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2
Repro Drug List
Long acting form of GnRH which down
regulates the GnRH receptors on the
gonadotropin cells (anterior pituitary) -
decrease respond to the normal cyclic
3 GnRH surges and LH (and FSH) will not
be produced. Because of lack of LH,
Leydig cells will not produce testicular and prostate cancer, polycystic ovary dz, as well
testosterone. Suppression of the as endometriosis in women (testosterone is a precursor for
Leuprolide HPGonadal axis estrogen); uterine fibroids, precocious puberty; (BPH?)
Treat BPH, Hirsutism and Other Disorders of Androgen
4
Flutamide Androgen receptor antagonist Excess; tx prostatic carcinoma
Potassium sparing diuretic with
5 Androgen receptor blocking function,
Spironolactone see diuretics Hirsutism and Other Disorders of Androgen Excess
Ornithine decarboxylase inhibitor;
6 mechanism of retarding hair growth is not
Eflornithine cream clear FDA approved for treating hirsutism
Selective 1A blocker - contracts Benign prostatic hypertrophy, prostate has greater number
Tamsulosin prostate smooth muscle of 1A receptors expressed than other tissues.
A B C
10
Hypertension. See adrengic blockers
Benign prostatic hypertrophy: This use is rapidly being
1-Selective Blockers, see adrenergic supplanted by the 1A selective agents (tamsulosin) which
Terazosin (Hytrin) blockers does not produce orthostatic hypotension
15
Vardenafil (Levitra) phosphodiesterase inhibitor Erectile Dysfuntion (4 hr duration), faster onset
16
22
Replacement of estrogen, see extra Menopause: vasomotor flushes, atrophic vaginitis, osteoporsis
Estrogen (HRT - hormonal notes for physiologic effect and (contoversial, and effectiveness gradually decreases),
replacement therapy) preparations coronary artery disease
23
Ethinyl Estradiol
24 Diethylstilbestrol (DES) Non-steroidal estrogen Post coital contraceptive (eg used after rape)
A B C
25
34
Plan B post coital contraceptive
Levonorgestrel (Plan B) Progesterone derivative Contains high concentration of levonorgestrel (P)
35
Testosterone Androgen
36 Dihydrotestosterone Androgen
44
synthetic Prostaglandin F2alpha lifesaving tx. of postpartum hemorrhage due to uterine atony
Hemabate (PGF2alpha) via myometrial contraction
48
hydralazine or labetalol Control BP in pergnancy
49 Pitocin Synthetic oxytocin
50
54
Renal Drug List
55 Diuretics
A B C
Extremely efficacious
1. Emergency & Chronic Tx of edematous states (eg M.I.,
CHF; Pulmonary; Ascites secondary to cirrhosis, Renal failure)
- most efficacious under low Creatinine clearance
conditions; Loop diuretics are used for hypertension with
renal insufficiency; used i.v. for hypertensive emergency
2. Hypercalcemia: causes increased Mg++ and Ca++ loss
(Cause of elevated Ca++ is usually hyperparathyroidism or
malignancy, which must be Tx surgically).
56 Loop diuretics can be used as a temporary measure to reduce
hypercalcemia
3. Hypertension: Use for cases that are not responsive to
thiazides (e.g, HTN in the presence of chronic renal failure)
4. Hyperkalemia: Usually occurs secondary to insufficient
renal excretion, causes loss of resting membrane potential
Sulfonamide; loop diuretic: acting in (cardiac problems). Tx is complex. Loop diuretics are useful
loop of Henle because treating chronic renal failure with a diuretic corrects
Inhibit Na+,K+,2Cl- cotransporter the hyperkalemia (see hypokalemia Side-Effects).
(symporter - transports cations and anion 5. Anion poisoning (eg Fluoride, iodide, bromide); symporter
in the same direction with no counter-ion also reabsorbs these anions, give loop agent with NaCl)
Furosemide (lasix, transport) - transporter used by macula 6. Drug of choice for treating HTN in pts with chronic renal
prototype) densa insufficiency or heart failure.
58
Torsemide Loop diuretic Once daily dosing
59 Bumetanide Loop diuretic
60
66
Metolazone thiazide-like
A B C
68 Potassium-sparing diuretic:
aldosterone receptor competitive
Eplerenone antagonist see spironalactone
74
Calcium Channel Blocker (CCB), a 1. Hypertension (generally preferred for treating hypertension
dyhydropyridine: a member of the over verapamil and diltiazem), efficacious, particularly for
77 dihydropyridines class; decrease Ca++ isolated systolic HTN (esp in diabetics)
influx, resulting in smooth muscle Because of their higher profile of side-effects related to
relaxation; vascular sm selective; therapeutic vasodilation, less preferred than ACE-I or ARBs
Nifedipine Block L-type Ca++ Channels
A B C
78
1. Angina (esp Prinzmetal variant angina)
Calcium Channel Blocker, a 2. Hypertension (Nifedipine is better; Efficacious, particularly
nondyhydropyridine: decrease cardiac for isolated systolic hypertension
contractility and cardiac output, cardiac Because of their higher profile of side-effects related to
myocytes selective (blocks L-type Ca++ therapeutic vasodilation, less preferred than ACE-I or ARBs
Diltiazem Channels)
86
Uses:
Venoarterial dilator: NO formation by Hypertensive emergencies (see extra note), IV - monitor
increasing cGMP which causes pressure
relaxation; dilates arterioles and veins, CHF (with hydralazine), Short-term therapy in acute HF
Nitroprusside (Sodium) decreasing myocardial oxygen demand Surgery (controlled hypotension)
87
Isosorbide dinitrate see nitroprusside CHF (with hydralazine), Short-term therapy in acute HF
A B C
Nitroglycerin (NTG, see Vasodilator, a nitric oxide (NO) donor,
88
NTG cardio) see cardiac drugs for more detail Angina pectoris (ischaemic heart disease, MI)
89 Labetalol see adrenergics HTN emergencies & drug-induced HTN
90
Na Polystyrene Sulfonate Resin that exchanges Na ions for K in
91
[Kayexalate] large intestine Treat hyperkalemia
92
94
Structural analogues of p-aminobenzoic
acid (PABA)
Block the incorporation of PABA into folic
acid (dihydrofolic acid) by inhibiting the
Sulfonamide (class) enzyme dihydropteroate synthetase see Co-Trimoxazole
Folate Antagonist - inhibits synthesis of
95 folate; Mechanism of action of
Sulfamethoxazole (SMX) sulfonamide see Co-Trimoxazole
97
Uncomplicated UTI: E.coli
Complicated UTI: Klebsilla pneumonia & Staphyloccous
saprophyticus & Enterobacter & Acinetobacter
Prostatitis
Acute pyelonephritis.
Used to treat E. coli acute UTI
Cystitis
Combination of TMP and SMX Chronic suppressive therapy for recurrent urinary tract
Co-Trimoxazole (aka Sulfonamide & trimethoprim act infection
TMP/SMX) synergistically Usually oral
99 Prostatitis
Gonorrhea
Ciprofloxacin Fluroquinolone
100 Norfloxacin Fluroquinolone
101 Ofloxzcin Fluroquinolone
Beta-lactam antibiotics
Inhibits bacterial cell wall
peptidoglycan synthesis (cross- DOC for STD caused by Treponema pallidum (syphilis)
linking) Augmentin = Amoxicillin + clavulanate are given orally to treat
102 Inhibits transpeptidase reaction urinary tract infection
Activates autolytic enzyme (autolysin) Not effective against:
Bactericidal agent Klebsiella
Highest activity against G (+), some G Pseudomonas
Penicillin G (-) Indole-positive Proteus
A B C
Uncomplicated UTI by Proteus mirabilis, Enterococcus
103 faecalis
Acute pyelonephritis
Ampicillin a penicillin UTI with pregnancy
104 Amoxicillin a penicillin Greater bioavailability than ampicillin
Ticarcillin, Carbencillin & anit-Pseudomonas penicillins; not Complicated UTI: Pseudomonas (give with penicllin and
105
Azlocillin beta-lactamase resistant clavulanate acid)
110
Beta-lactam antibiotics: Inhibition of
cell wall (peptidoglycan) synthesis (cidal); Complicated UTI: E.coli, Klebsiella pneumoniae (cefazolin),
Cephalosporins (class) does not cross BBB(??) Proteus mirabilis (ceftriaxone)
First line drugs to treat gonorrhea (Neisseria)
111 Complicated UTI: Indole positive Proteus mirabilis,
3rd generation Cephalosporin, good Serratia
Ceftriaxone CNS penetration Acute pyelonephritis; Meningitis; Infectivie Endocarditis
A B C
112
3rd generation Cephalosporin, good First line drugs to treat gonorrhea
Cefixime oral
Used to treat UTI caused by E. coli and Klebsiella in pregnant
patients because co-trimoxazole cannot be used due to risk of
113 kernicterus to the fetus
pneumoniae, Staphylococcus saprophyticus
Uncomplicated UTI: E.coli, Klebsiella pneumoniae!!,
Cefazolin 1st Generation Cephalosporin Staphylococcus saprophyticus!!
114
115
121
Caspofungin Disrupts fungal cell wall sythesis
A B C
enters cell and releases nitro moiety
122 which reacts with DNA and inhibits
Metronidazole duplication of bacteria (bacteriacidal) Trichomonas vaginalis (protozoa) Infection
treat Chronic UTI
123 Daily oral dose (100 mg) for adults in UTI
Nitrofurantoin unknown mech Given for months for chronic UTI
126
Gastrointestinal Drugs
127
132
136
145
Dopamine Antagonists; Prokinetic (Pro- Parkinson's dz (counteracting the GI effects of levodopa and
Domperidone motility) Agents - D2 antagonist which bromocriptine); for nausea and vomiting associated with
(MOTILIUM) does not penetrate CNS well gastric stasis
147
150
Macrolide Antibiotics; Prokinetic (Pro-
motility) Agents - macrolide antibiotic
that binds to motilin receptors -
erythromycin increases the frequency
Erythromycin (many and amplitude of antral contractions and Intravenous erythromycin may be useful short-term for an
brands) initiates gastric phase III contractions. acute exacerbation of diabetic gastroparesis.
152
Diphenoxylate (LOMOTIL) Opioid agonist Diarrhea; use for Irritable Bowel Syndrome (IBS)
153
Difenoxin (MOTOFEN) Opioid agonist Diarrhea
Paregoric (generic,
154 camphorated opium Opioid agonist - antidiarrheal,
tincture, morphine) antitussive, and analgesic properties Diarrhea
158
160
171 Prototypical muscarinic cholinergic prevention of motion sickness (for rough seas and extended
Scopolamine receptor antagonist, see journeys, transdermal patch is more convenient; less sedation
(TRANSDERM-SCOP) antimuscarinics than dimenhydrinate or promethazine)
178
Alosetron (LOTRONEX) 5HT3 Antagonist Irritable Bowel Syndrome with diarrhea (second line)
179
182
183
5-ASA Compound; Anti-inflammatory Inflammatory Bowel Disease, especially Ulcerative cholitis;
Sulfasalazine (Azulfidine) Drug treatment of Rheumatoid arthritis
184
Olsalazine 5-ASA dimer; Anti-inflammatory Drug Inflammatory Bowel Disease (UC and CD)
A B C
185
198
Liver Drugs
A B C
Synthetic guanosine nucleoside 1. Respiratory syncytial virus (RSV) in infants and young
200 analog children
Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV
201 Interferon -2b See Interferon- Treatment of Hepatitis B
203
Interferon -2b combined
with oral ribavirin See Interferon- Treatment of Hepatitis C
Interferon alfacon-1
204 combined with oral
ribavirin See Interferon- Treatment of Hepatitis C
206
inhibits reverse transcriptase activity of Treatment of Hepatitis B (long term therapy relative to
Lamivudine both HIV and HBV interferon alfa)
207
phosphonate nucleoside analog,
Adefovir Dipivoxil administered as the oral prodrug, Treatment of Hepatitis B (including variants resistant to
(Hepsera) inhibits replication of HBV lamivudine)
208
211
Cardio drugs
A B C
213
Digitoxin (Digitalis) see digoxin see digoxin
Phosphodiesterase inhibitors:
Inhibition of cAMP phosphosdiesterase Inotropic used in CHF
(PDE)- Increases cAMP: In heart Vasodilatory
218 (increase cardiac output) & in vasculature For short-term therapy
(decrease systemic vascular resistance) Parenteral use
& decrease pulmonary capillary wedge Acute heart failure
Imamrinone (aka pressure Available only in IV formulations
amrinone) Net result: improved hemodynamics Requires a large initial dose for positive inotropic effect
221
Antiarrhythmics
no longer used for rhythm control, modestly effective, very
toxic
222 Moderate Na channel Blocker which supraventricular and ventricular arrhythmias like atrial
also blocks K channelsprolongs fibrillation & atrial flutter (moderately effective), ventricular
QRS&QTaction potential; reduce extrasystoles and VT(poorly effective)
Quinidine (Antiarrhythmic automaticity and conduction velocity Major clinical use: atrial fibrillation, atrial flutter, &
Class IA) (Phase 0 and phase 3) ventricular tachcycardia
A B C
225 modest Na channel blockers (both acute rapid suppression of V arrhythmias, raises
active and inactive Na channels) ventricular fibrillation threshold as well as suppresses
Reduce automaticity arrhythmias caused by abnormal automaticity (observed pt
Lidocaine (Antiarrhythmic Shorten APD (narrow QRS) continuoulsy for SE), no atria effect; very effective membrane
Class IB) Slow conduction velocity stabilizer (numbing)
235
Amiodarone & K & Na & Ca channel blocker; ONLY used for life-threatening (refractory) Ventricular
(Antiarrhythmic Class III; prolongs PR and QT; slows sinus rate arrhythmias or Atrial fibrillation unresponsive to other
has class I, II, III, and IV (slows repolarization); prolongs AP in antiarrhythmatics (AV nodal re-rentrant tach and Wolff-
activity) fast-response AP Parkinson-White syndrome and sudden death post MI or HF)
236
Ibutilide (Antiarrhythmic K channel blocker; prolongs PR and QT
class III) (slows repolarization) atrial fibrillation or flutter
237
Dofetilide (Antiarrhythmic atrial flutter and atrial fibrillation; maintenance of sinus
class III) K channel blocker; prolongs QT rhythm after reversion
Dihydropyridine group
(nifedipine, amlodipine,
238 nitrendipine, isradipine, Ca channel blockers (CCB), SM
nisoldipine -- selective; see renal CCB; slow
Antiarrhythmic class IVs) conduction velocity, phase 0 of node small effect on AV conduction and arrhythmia
Ca channel blocker; slows AV node
239 Diltiazem (non- conduction (moderately), myocardial
dihydropyridine selective; slows conduction velocity, slows vent rate with atrial fibrillation or flutter and
antiarrhythmic class IV) phase 0 of node prevents AV nodal re-entrant tach
261
Direct thrombin inhibitor: direct binding Tx of heparin-induced thrombocytopenia (HIT) see extra
Lepirudin to thrombin note
A B C
262
264
265
Thrombolytic: Activator of plasminogen,
Reteplase (r-PA) dissolve formed fibrin clots Acute myocardial infarction
267
1. Acute myocardial infarction
Thrombolytic: Nonenzymatic activator 2. Pulmonary embolism
of plasminogen; stimulates dissolution 3. Deep venous thrombosis
Streptokinase of fibrin clots. 4. Arterial thrombosis
1. Acute myocardial infarction
268 2. Pulmonary embolism
3. Deep venous thrombosis
Urokinase Thrombolytic 4. Arterial thrombosis (?)
269
Thrombolytic: Streptokinase
plasminogen complex, dissolve formed
Anistreplase (APSAC) fibrin clots Acute myocardial infarction
271
Drotrecogin Alfa [Xigris] Activated protein C Tx of sepsis and DIC
272
273 Antihyperlipidemics
A B C
274
Uses:
1. Elevated cholesterol of all types. Particularly effective at
lowering levels of LDL. If the primary problem is too much
cholesterol, statins are good choices.
HMG-coA Reductase Inhibitor: decrease cholesterol by increasing LDL receptors in the liver
Inhibition of 3-hydroxy-3-methylglutaryl- causing decreased LDL cholesterol (often see a small
coenzyme A (HMG-CoA reductase) from decrease in triglycerides and a small increase in HDL
converting HMG-CoA to Mevalonic acid cholesterol)
-- essential step in cholesterol synthesis. 2. Aggressive therapy in high risk populations: With 2
These drugs are structural analogs of risks, e.g., ischemic disease and diabetes, goal is to reduce
the HMG-CoA intermediate. LDL<70 mg/dL (desirable level without these risk factors is
Leads to increased synthesis of LDL <130); Recent data have shown a 25% reduction in stroke (no
receptors (liver attempts to get more reduction in brain hemorrhage) in at risk populations
Lovastatin (Mevacor) cholesterol from plasma) maintained on statins
275 Atorvastatin
282
Inhibits VLDL secretion (probable main Used for both hypercholesterolemia and
mechanism not entirely understood), hypertriglyceridemia - Any lipoprotein disorder, particularly
which leads to decreases VLDL, mixed hyperlipidemia with elevated triglycerides
decreased LDL and increased HDL Have to take gram quantities (NOT acting as a vitamin)
Niacin (Vitamin B3) (catabolism of HDL is decreased) Decreases triglyerides!!
287
288
Hematopoiesis; production of epithelial
cells; maintenance of myelin. Vitamin
B12 is essential for the synthesis of the
biologically active form of folic acid,
tetrahydrofolate (essential for DNA
Vitamin B12 synthesis). Thus, in vitamin B12
Cyanocobalamin (i.m.) deficiency, there is an internal folate Megaloblastosis Vitamin B12 deficiency, including
Hydroxocobalamin (i.m.) deficiency. pernicious anemia
A B C
289
Purine and pyrimidine synthesis; amino
acid interconversions. Folate is required
for the synthesis of deoxythymidylate
monophosphate, which in turn is required
Folic Acid (p.o./i.m.) for DNA synthesis. Megaloblastosis due to folate deficiency
290
291
308
a Biguanide; antihyperglycemic agent, Oral hypoglycemic agent; treat Type 2 DM, patients with
decreases hepatic glucose production refractory obesity whose hyperglycemia is due to "insulin
& increases the binding of insulin to resistance", also has significant lipid-lowering effect, does
Metformin [Glucophage] its receptor not increase weight; hirsutism
-Glucosidase inhibitor:
oligosaccharide analogs that bind to the
intestinal brush border enzymes that
309 digest complex sugars (disaccharidases
such as -glucosidase). The competitive
inhibition of sugar digestion by these Oral hypoglycemic agent: The effects of -glucosidase
drugs delays the absorption of inhibitors on HbA1c are modest, so these drugs are most
carbohydrates and limits the postprandial useful for newly diagnosed Type 2 patients with mild
Acarbose [Precose] rise in glucose. hyperglycemia.
310 Miglitol -Glucosidase inhibitor
320
Indications for Insulin Therapy:
SQ (or IV) injections of insulin are the primary therapy for:
1. All Type 1 patients
2. Type 2 patients not controlled by diet and/or oral
hypoglycemic agents
3. Patients following pancreatectomy or with gestational
diabetes.
4. Management of diabetic ketoacidosis.
5. Treatment of hyperglycemic, nonketotic coma.
Lispro [Humalog] Ultra-Short-Acting Insulin (human) 6. Perioperative management of Type 1 and Type 2 patients.
321
Aspart [Novolog] Ultra-Short-Acting Insulin (human) See Lispro
322
Glulisine [Apidra] Ultra-Short-Acting Insulin (human) See Lispro
323
Inhaled insulin [Exubera] Ultra-Short-Acting Insulin (human) See Lispro
324
325
NPH (neutral protamine
Hagedorn) or Isophane
insulin Intermediate insulin (human) See Lispro
326 Lente Intermediate insulin (human?) See Lispro
A B C
327
331
Levothyroxine [generic,
Synthroid, Levoxyl, DOC for hypothyroid states (always give solucortef first!! -
Levothroid, Unithroid] Natural isomer of thyroxine (T4) reason? Ask Dr. Tanner)
345 Vasopressin, aka ADH used in pts witout P-Pit function. ADH can be insuffalated
Antidiuretic Hormone V1 (vascular receptor, IP3), V2 (renal as powder, injected i.m. for longer control (2-8 hrs) or injected
(ADH) receptor, cAMP) i.m as a tannate derivative for longest control (1-3 days)
346 Bromocryptine & both are alkaloids, stimulate dopamine Treatment of the prolactinoma depress prolactin secretion (a
Ergonovine receptors. prolactin inhibiting factor or PIF)
347 Cabergaline Treatment of the prolactinoma
359
Calcitonin inhibits bone resorption
while formation continues causing a net
increase in bone Ca deposition. Synthetic salmon calcitonin (more potent than human) used to
Calcitionin also lowers Ca by increasing treat bone disease (eg Pagets disease, hypercalcemia,
Calcimar (fish calcitonin) Ca renal clearance (excretion) osteoporosis)
364
366
Pulmonary Drugs
367 Bronchiodilators
368
374 Long-acting (~12 hrs), selective 2- It is not suitable for treatment of acute bronchospasm.
Salmeterol xinafoate adrenergic agonist with slow onset of Salmeterol is useful for prevention of nighttime asthma
(Serevent) action, Bronchodilator attacks and prophylactic brochodilation (BID)
Long-acting, dry powder inhaler for maintenance therapy
375 of asthma or prevention of bronchospasm in COPD &
2-selective adrenergic agonists, exercise-induced asthma. Not for treatment of acute
Formoterol (Foradil) Bronchodilator attacks.
381 Nonselective agonist, see Asthma; nonselective and has a still shorter duration of action
Isoproterenol adrenergics (than albuterol), very potent
A B C
389
Anti-Inflammatory Agent,
Flunisolide (Aerobid) Corticosteroid Asthma (twice daily), inhaled
Triamcinolone acetonide Anti-Inflammatory Agent,
390
(Azmacort) Corticosteroid Asthma (initially given 3 to 4 times daily), inhaled
391
Budesonide Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis, inhaled; tx of
diproprionate (Pulmicort) Corticosteroid cough-variant asthma
393 Mometasone furoate Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis only; (No growth
(Nasonex) Corticosteroid suppression detected in children)
A B C
402
405
408
Guaifenesin (Glyceryl
Guaiacolate) Expectorant - mech unknown Chronic irritating cough
Expectorants: Iodides enhance the
secretion of respiratory fluids, thus
409 decreasing the mucus viscosity. In
addition, iodides may stimulate
Potassium iodide & breakdown of fibrinoid material in
Iodinated glycerol inflammatory exudates. Chronic irritating cough
A B C
Mucolytic agent - acts by facilitating the
410 depolymerization of Chronic irritating cough (COPD); an effective mucolytic
N-Acetylcysteine mucopolysaccharides in dried airway agent but causes irritation. Use is not currently recommended.
(Mucomyst) secretions. May benefit bronchiectasis when delivered by nebulization
411
Mucolytic agent - acts by facilitating the
depolymerization of
Recombinant DNAase mucopolysaccharides in dried airway
(Dornase alpha) secretions. Cystic fibrosis (Chronic irritating cough)
412
Opioid used as an antitussive (cough
suppressant); believed to act at the CNS
level, by suppression of the cough
reflex. May act at non-opioid receptor Acute control of nonproductive cough; often used for in-
Codeine site. See opioids patient treatment.
Non-opioid used as an antitussive - the
d-stereoisomer of methorphan Acute control of nonproductive cough; has no analgesic
413 structurally related to levorphanol, a or addictive properties and does not act through opioid
narcotic (opioid) analgesic (no opioid receptors. Nearly as potent as codeine and produces fewer
receptor activity); NMDA receptor subjective and GI side effects. Available in many over-the-
Dextromethorphan glutamate receptor? counter preparations.
415
Diphenhydramine Non-opioid used as an antitussive; see Acute control of nonproductive cough; Control of minor
(Benyline) Antihistamines transient cough; H1 histamine receptor antagonist
416
Ranitidine H2 antagonist, see antihistamines
A B C
417 Smoking Cessation pharmacologic intervention
418 Nicotine polacrilex Nicotine replacement chewing gum; to reduce withdrawl symptoms and relapse
Transdermal nicotine
419 patch (Nicoderm, Nicotrol,
Habitrol) Nicotine replacement to reduce withdrawl symptoms and relapse
420 (see) Antidepressant; enhances CNS nonnicotine aid to smoking cessation, aid to pt who have not
Bupropion (Zyban) nonadrenergic function been able to quit smoking with nicotine replacement therapy
Smoking cessation: is the first treatment that specifically
targets the neurobiological mechanism of nicotine
421 dependence - reduces nicotine withdrawal symptoms and
Stimulates dopamine and blocks nicotine cravings, helping to prevent a full relapse; also blocks the
Varenicline (Chantrix) receptors effects of nicotine if patient begins smoking again.
422
Antimycobacterials
DOC, first line for TB disease (According to NEJM)
1. Isonizid alone should be given for 18mo (recommended
given in conjunction with other drugs)
2. Isoniazid + rifampin given for 9mo
3. Isoniazid + rifampin + pyrazinamide for first 2mo,
423 followed by 4mo of continued Isoniazid + rifampin (total of
6mo, ideal treatment)
4. Unless rate of resistance to isoniazid is known to be <4% in
Bacterialcidal; Inhibits mycolic acid community, add ethambutol or streptomycin until susceptbility
formation in outer membrane (mycolic is known
acid is unique to Mycobacteria). Kills both DOC, first line for TB latent infection, treat for 6-9mo
Isoniazid (INH) intra- and extracellular bacteria Safe for latent TB in pregnancy
433
Antifungal Agents
434
435 block the activity of an enzyme Itraconazole has the broader spectrum of activity and is
necessary for ergosterol synthesis available both orally and IV (of azole's)
Itraconazole
436
Flucytosinne Interferes with thymidylate synnthetase Tx cryptococcosis
block the activity of an enzyme
437
Fluconazole necessary for ergosterol synthesis
block the activity of an enzyme
438
Voriconazole necessary for ergosterol synthesis
A B C
block the activity of an enzyme Tx systemic fungal infections, used to treat Cushings
439
Ketoconazole necessary for ergosterol synthesis disease
Applied topical to skin and mucous membranes
440 complexes with ergosterol (primary Used to treat local candidiasis (thrush, vaginal, etc)
membrane sterol of fungi) and causes Polyene macrolide like Amphotericin B but too toxic for
Nystatin the membrane to become leaky parenteral administration
441 Clotrimazole, Miconazole Topical Azoles
Used for systemic treatment of dermatophytosis (griseofulivin
442
Griseofulvin Interfers with mitotic spindle funtion concentrates inn the stratum corneum)
Used for systemic treatment of dermatophytosis (especially
443
Terbinafine blocks ergosterol synthesis tinea unguium/neil infection)
444
445
Antiviral Agents
446 Prophylaxis of type A influenza; Treatment initiated within 48
Inhibit uncoating of RNA viral nucleic hours after initial appearance of symptoms is effective; Tx
Amantadine acids, Inhibit viral replication Parkinson's dz
447 Inhibit uncoating of RNA viral nucleic Prophylaxis of type A influenza; Treatment initiated within 48
Rimantadine acids, Inhibit viral replication hours after initial appearance of symptoms is effective
inhibits neuraminidase (Ez necessary
448 for viral replication and for release of
Zanamirvir infected cell) Tx and prophylaxis of both influenza A and B
449 Oseltamivir inhibits neuraminidase Tx and prophylaxis of both influenza A and B
1. Respiratory syncytial virus (RSV) in infants and young
Synthetic guanosine analog children
450 Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV
457
Antihistamines
463
Topical Nasal Spray Antihistamine: given intranasally, with
the advantage of rapid onset of action and the disadvantages
of twice-daily dosing; may be useful in pts with mucosal
Azelastine (Astelin) H1 receptor antagonists irritation and/or epistaxis from nasal corticosteroids.
Promethazine
465 (Phenergan, first
generation, Phenothiazine
derivatives) H1 receptor antagonists See diphenhydramine
Ophthamlmic H1 receptor
466 noncompetitive antagonists and
stabilizes mast cells, long duration of
Ketotifen action, little systemic absorption Allergic conjunctivitis
467
Fexofenadine (Allegra,
2nd generation,
Piperidines class) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis
468
Desloratidine (2nd Gen) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis
Loratadine (Claritin, 2nd See diphenhydramine; Newer agent; longer action; Allergic
469
Gen) H1 receptor antagonists Conjunctivitis
472
ranitidine (Zantac) H2 receptor antagonists, see cimetidine see cimetidine
473
famotidine (Pepcid) H2 receptor antagonists, see cimetidine see cimetidine
474
nizatidine (Axid) H2 receptor antagonists, see cimetidine see cimetidine
475
477
Induces vasoconstriction
Increases BP (arterioles) & Increases cardiac return (veins)
Expect reflex bradycardia. Also
1. Nasal decongestant
2. Infiltration with local anesthetics.
Phenylephrine - Non 3. Pressor agent (drug that increases bp) to maintain bp
Catecholamine Agonist 4. Ocular examination. Mydriasis without affecting
(selective) selective 1 agonist accommodation.
A B C
481
Albuterol - Direct Acting
2 Agents (Selective 2
adrenergic agonist) see
extra notes for additional Direct Acting 2 Agents (Selective 2 Used in bronchial asthma. Aerosol for acute effects and p.o.
beta 2 agonists adrenergic agonist) (post op) for chronic treatment. (see Pulmonary drugs)
482
De-carboxylated tyrosine
No direct effect on receptors
Enters nerve terminal via the re-uptake
483 pump. Massive NE releases
Does not cross BBB to any significant
extent (no CNS effects, contrast this to
amphetamine derivatives, which do cross
Tyramine - Indirect Acting BBB and do cause profound CNS
Sympathomimetic effects)
Agonist at D1 (& D2) receptors Shock, particularly Hypovolemic shock (and cardiogenic in
D1 (& D2) receptors in kidney; leads to the early stages)
vasodilation in the kidney 1 effects benefit cardiac output
486 Agonist at 1, leads to increased cardiac 1 effects increase blood pressure
output (D1 vasodilation prevents renal failure)
Agonist at 1 (less potent than for D1 Short-term therapy only
and 1), which can lead to Especially useful to increase splanchnic and renal blood
Dopamine (Intropin) vasoconstriction flow
490
Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
494 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the
control mechanism regulating HTN emergencies, used for drug-induced HTN (for limited
sympathetic nerve activity. The brainstem duration only), such as cocaine/amphetamine overdose;
is the main site of action as anti- Withdrawal symptom treatment for opiates and sedatives
hypertensive. Part of effect may be via (noradrenergic neurons in the locus ceruleus), see opioids;
Clonidine imidazoline receptors in brainstem May be helpful in reducing craving for cigarettes.
Extremely well studied in pregnancy. If a woman is
495 Methyldopa (aka alpha- Alpha2 agonists (central acting); Pro- hypertensive prior to the start of pregnancy, this is the drug
methyl-DOPA) drug of choice during the pregnancy.
496 Guanfacine Centrally acting alpha-2 agonist Tx of mild to moderate HTN
502
Non-Selective, Block 1 & 2
Affinity is 1 = 2 (non-selective)
Also is an agonist at muscarinic and
histamine receptors Pheochromocytoma (see extra notes)-- control acute
Phentolamine is a competitive blocker of hypertensive crisis
alpha receptors. It shifts the NE dose- Treat necrosis due to vasoconstrictors such as NE and
Phentolamine - non- effect curve to the right. Note that the full phenylephrine (should be rare)
selective alpha blocker effect of NE can be re-obtained with Note: non-selective alpha blockers have essentially no use in
(competitively binds) higher NE dose essential hypertension (see extra note).
A B C
505 Non-Selective Beta Blockers (similar to Actions and uses are much like propranolol
Nadolol (Corgard) propranolol); long 14-24hr half-life Very long duration of action (once daily dosing)
Much like other beta blockers for systemic uses (eg HTN,
angina)
506 Treats glaucoma by decreasing synthesis of aqueous humor.
Timolol (Blocarden; Non-Selective Beta Blockers (similar to Administered topically as Timoptic or in various combinations
Timoptic) propranolol) with other drugs.
A B C
507
hypertension, angina & CHF
Slightly preferred (compared to propranolol) in individuals
who also have: asthma, diabetes, peripheral vascular disease
1 (Cardioselective) Blocker; Short (Usual recommendation is to avoid beta blockers in these
Metoprolol half-life limits utility patients if possible)
510
513
515
517 Tamsulosin (selective 1A Benign prostatic hypertrophy, prostate has greater number
blocker) Selective 1A blocker of 1A receptors expressed than other tissues.
Same uses and liabilities as terazosin or prazosin
518 Long elimination half-life (24 hr) makes once daily dosing
Doxazosin (Cardura) 1-Selective Blockers feasible
523
Cholinergic agonist (Muscarinic Receptor Agonis
Drugs which produce effects similar to those observed during the stimulation of postganglionic parasympathetic fibers i.e., drugs which exert their effec
muscarinic receptors. (Typically) Parasympathetic postganglionic innervation to a muscarinic receptor on cardiac & smooth muscle, gland cells and nerve
have sympathetic muscarinic receptors).
531
Methacholine (Choline stimulates sm contractions in the Diagnostic applications: Provocholine (methacholine) for
esters) bronchioles diagnosis of subclinical asthma
532
545 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
cyclopentolate - ocular Amines) little cycloplegia are preferred. Duration of Action 12-24 hr
A B C
546 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
tropicamide - ocular Amines) little cycloplegia are preferred. Duration of Action 1-2 hr
547
548
Anticholinesterase (Cholinemimetics):
DEFINITION: Drugs that inhibit cholinesterase enzymes and allow acetylcholine released from cholinergic nerves to accumulate, bind to and stimulate posts
are indirectly acting.
571
mivacurium (non- Non-depolarizing blockers, see
depolarizing blockers) tubocurarine see tubocurarine
Non-depolarizing blockers, see
572
Vecuronium tubocurarine
Non-depolarizing blockers, see
573
Atracurium tubocurarine
577
Local anesthetic, Amide class; blocks
Lidocaine (class IB) voltage-dependent Na+ channels Local anesthetics, see antiarrhythmics
578 Bupivacaine Amide class Local anesthetic
579 Etidocaine Amide class Local anesthetic
580 Prilocaine Amide class Local anesthetic
581 Ropivacaine Amide class Local anesthetic
582 Mepivacaine Amide class
583
Procaine Ester class Local anesthetic
584 Benzocaine Ester class Local anesthetic
A B C
585 Chloroprocaine Ester class Local anesthetic
586 Cocaine Ester class Local anesthetic
587 Tetracaine Ester class Local anesthetic
588
Tetrodotoxin (puffer fish) Block voltage-dependent Na+ channels
600
602
Opioid Analgesics and Antagonists
A B C
603
607
Endogenous Compound - Kappa
Dynorphin B receptor activation No clinical use found
A B C
609
Meperidine (Demerol) Analgesia; given less due to:
HEO High efficacy mu opioid Shorter elimination half-life
610
High efficacy mu opioid, synthetic, also
blocks NMDA receptors and More efficacious than morphine in difficult to treat pain -
Methadone (Dolophine) monoamine reuptake pumps enhanced by antidepressant effects. Opioid abuse treatment
HEO (antidepressant mechanism) programs
611 High efficacy mu opioid; most lipid Surgery analgesia (particularly cardiovascular) with minimal
soluble, highest potency agents (~100 cardiodepressant effects (due to low dose requirement);
Fentanyl (Sublimaze) HEO x more potent than morphine) transdermal patch for vomiting pts
High efficacy mu opioid; Diacetyl
612 morphine - gets to brain quickly, and is
Heroin (Schedule 1) HEO deacetylated to morphine No clinical use; see No No's
613 High efficacy kappa opioids (& partial Post surgery pain with less potential for respiratory
Butorphanol (Stadol) HEO agonists at mu receptors) depression
614
Post surgery, when patients have respiratory depression,
High efficacy kappa opioids & mu often used to remove the respiratory depressant effects of mu
Nalbuphine (Nubain) HEO antagonist agonists given prior to surgery (still provides analgesia)
A B C
615
Hydrocodone Analgesia: Efficacy is enhanced by adding aspirin or
(Intermediate efficacy acetaminophen. (Numerous formulations exist, including
opioid (IEO)) Partial -opiate agonist Vicodin; Lortab).
616
Oxycodone (Percocet)
IEO See Hydrocodone
Propoxyphene Napsylate/
618 Acetaminophen Tablets
[Darvocet] Low efficacy Primarily affects -opioid receptors, Not recommended for use, low analgesic acitivity, unsuitable
Opioid (LEO) partial agonist for severe pain
626
Opioid Antagonist; Prototype, blocks DOC opioid overdose (or even slight possiblitiy, ie coma)
effects of full agonists, blocks mu useful in treating some drug-free addicts
Naloxone (Narcan) receptors Short acting, injected/parentral only (inactive oral)
627
Naltrexone (Revia, Opioid Antagonist; blocks effects of full
Trexan) agonists, block mu receptors Long acting, oral route only
628 Nalmefene (Revex) Opioid Antagonist
A B C
Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
629 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the HTN emergencies, used for drug-induced HTN (for limited
control mechanism regulating duration only), such as cocaine/amphetamine overdose;
sympathetic nerve activity. The brainstem Withdrawal symptom treatment for opiates and sedatives
is the main site of action as anti- (clonidine compensates for lack of inhibition in the locus
hypertensive. Part of effect may be via ceruleus (noradrenergic outflow));
Clonidine imidazoline receptors in brainstem. May be helpful in reducing craving for cigarettes.
630 L-alpha-acetylmethadol
acetate (LAMM) Synthetic opioid Prevent heroin relapse (substitution)
631 Non-opioid available OTC; binds NMDA Cough, and when used with opioids increases the cough
Dextromethorphan receptors suppressant activity of the opioid
632
633
Rheumatic Disease & Gout
634 Rheumatic Disease Drugs
635
Hydrochloroquine Malaria tx; mild to moderate (early) rheumatoid arthritis
(Plaquenil) Mechanism of action unknown (rapidly absorbed), safe and convenient
A B C
636
640
RA (usually given with methotrexate) and used for active
Rituximab (Rituxan) Reduces B lympocytes (targets CD20- moderater to severe RA that does not respond to TNF alpha
DMARD containing B lymphocytes) drugs
641
Infliximab (Remicade) Monoclonal antibody which binds TNF- RA Tx - given as an IV infusion every several weeks with
Anti-TNF- (chimeric mouse/human) methotrexate usually
Recombinant protein (genetically
engineered) consisting of the two soluble
642 portions of the TNF- receptor molecule
Etanercept (Enbrel) Anti- and the Fc portion of human IgG. It
TNF- binds two molecules of TNF- RA Tx - injected sub Q twice a week
644
Recombinant form of human interleukin-1
Anakinra (Kineret) Anti-IL1 receptor antagonist (IL-1ra) Efficacy as good as DMARD for RA Tx
Cyclosporine inhibits T lymphocytes, see Organ transplants & for RA when it fails to respond to
645
(Sandimmune) Immunosuppressants other therapies
Purine antimetabolite that interferes
with purine synthesis and also causes
646 DNA damage through formation of false
nucleotide substrates for DNA synthesis, Cancer, transplant rejection, SLE, and severe refractory
Azathioprine (Imuran) see Immunosuppressants RA
A B C
651 Gold salts probably inhibit the Suppress but do not cure RA. Early active arthritis
maturation and function of especially for diseases which progress despiite NSAID use.
mononuclear phagocytes and of T Water soluble used in intramuscular injections given weekly
Aurothioglucose cells, thereby suppressing immune until 1 gram has been achieved leading to accumulation of
(Solganal) Gold Salt responsiveness gold in the tissue
Gold salts probably inhibit the Suppress but do not cure RA. Early active arthritis
maturation and function of especially for diseases which progress despiite NSAID use.
652 mononuclear phagocytes and of T Water soluble used in intramuscular injections given weekly
Gold sodium thiomalate cells, thereby suppressing immune until 1 gram has been achieved leading to accumulation of
(Myochysine) Gold Salt responsiveness gold in the tissue
Gold salts probably inhibit the
maturation and function of Suppress but do not cure RA. Early active arthritis
653 mononuclear phagocytes and of T especially for diseases which progress despiite NSAID use.
Auranofin (Ridaura) Gold cells, thereby suppressing immune Hydrophobic administerd as oral dose for about 6-9 months
Salt responsiveness better tolerated than injectable but less efficacious
treat tenderness, swelling and pain caused by the
654
Meloxicam [Mobic] inflammation of osteoarthritis and rheumatoid arthritis
655 Gout Drugs
A B C
656 Xanthine oxidase inhibitor (purine DOC for chronic gout (intercritical or tophacious) and
analog competetively inhibits), reduces treats hyperuricemia primary to gout or from malignancy or
Allopurinol (Zyloprim) uric acid production renal failure. Once daily oral dose
657
Uricosuric - block proximal tubular
secretion (low dose) and resorption (both
Probenecid (Benemid) occur at high dose) of uric acid Gout; delayed excretion (secretion) of penicillin
662
Non-Steroidal Anti-Inflammatory Drugs
A B C
671
672
Refocoxib [Vioxx] Selective COX-2 Inhibitors, Withdrawn
673 1. Commonly used for relief of pain and fever as over the
counter medications; useful analgesic/antipyretic for
children and those with contraindications to aspirin.
Non-NSAID antipyretic/analgesic, a 2. Initial DOC for treatment of pain in osteoarthritis (which
non-narcotic analgesic; is a non-inflammatory condition)
Very weak anti-inflammartory activity 3. Combined with opioid agonists for additive postoperative
Acetaminophen [Tylenol] - (unknown mech; not used for pain relief [Percocet, Lortab, Vicodin, Darvocet, Tylenol with
non-narcotic, non-NSAID inflammation) Codeine]
Zafirlukast [ACCOLATE] & prophylactic treatment of chronic asthma in patients >
674 Montelukast Anti-leukotriene Drugs - LTD4- 12 years old. As yet, these agents are not approved for
[SINGULAIR] leukotriene receptor antagonists treatment of other inflammatory conditions
675 Sulindac
treat tenderness, swelling and pain caused by the
676
Meloxicam [Mobic] inflammation of osteoarthritis and rheumatoid arthritis
677
678
Corticosteroid Drugs
Glucocorticoids (metabolic) inhibit the production and release of many different cytokines that normally would stimulate the proliferation and function of B and T lym
phospholipase A2 from forming arachidonic acid from phosphoipids.
O=oral; I=injectable; T=topical; Inh=inhaler; E= eye drops
A B C
680
Prednisolone Intermediate acting (12-36 hrs) (O, I, E)
Intermediate acting (12-36 hrs) (O); 4
681 times more potent than cortisol, about a
Prednisone third of the mineralcorticoid effect see Immunosuppressant drugs bellow
682 Methylprednisolone Intermediate acting (12-36 hrs) (T, I) Used for spinal injuries, slows progression of degeration
Intermediate acting (12-36 hrs) (O, T, I,
683
Triamcinolone Inh)
684 Beclomethasone Long acting (36-54 hrs) (Inh) See pulmonary drugs
A B C
695
Immunosuppressant Drugs
A B C
Glucocorticosteroid:
1. can reduce the size and number of
cells in the lymph nodes and spleen,
with little effect on erythoid stem cells in
the bone marrow.
2. are cytotoxic to subsets of T cells.
However, immunosuppressive effects are
predominantly due to the modification of 1. suppress organ rejection
function rather than cytotoxicity. a. allergic reactions bee stings, contact dermatitis, allergic
708
4. inhibit the production of drug reactions, allergic rhinitis
inflammatory mediators, such as b. collagen-vascular disorders lupus erythematosus
leukotrienes, prostaglandins, histamine rheumatoid arthritis
and bradykinnin. c. eye disorders allergic conjunctivitis, optic neuritis
5. attenuate chemotaxis and impair d. GI disorders inflammatory bowel disease
bactericidal and fungicidal activity of e. hematologic disorders and malignancies leukemia,
monocytes and neurtrophils, without autoimmune hemolytic anemia, multiple myeloma
altering phagocytic activity. f. Systemic inflammation acute respiratory distress syndrome,
6. can alter leukocyte and neurtorphil gram (-) septicemia to suppress excessive inflammation
distribution causing cells to sequester h. joint inflammatory disorders arthritis, bursitits
in lymphoid tissue. i. neurlogical disorders cerebral edema (to minimize
7. inhibit IL-1 production, leading to postoperative cerebral edema), multiple sclerosis
reduced IL-2 & IFN- production. j. pulmonary disorders bronchial astma, infant respiratory
8. attenuate both cellular and humoral distress syndrome
Prednisone mediated immune responses. k. skin disorders dermatitis xerosis
A B C
710
1. control a wide number of disease states which are
characterized by excessive inflammation, including, a) severe
allergic reactions, b) inflammation of the lungs in asthma and
c) inflammation of the joints in arthritis.
2. decrease the numbers of white blood cells and is used
to prevent the rejection of organ transplants
3. treat cancers, including acute lymphatic leukaemia and
myelomas
Glucocorticoids: meachnism of action 4. treat some autoimmune diseases, including systemic lupus
Deflazacort is similar to prednisone erythematosus and rheumatoid arthritis.
711
713
715
most commonly in the treatment of multiple myeloma or non-
Melphalan Alkylating Agent resectable epithelial carcinoma of the ovary
Alkylating Agent: a Platinum
716
Carboplatin compounds
723 Atypical Alkylators: old alkylator, used in breast cancer or ovarian cancer and can be given
Thiotepa CCNS intravesically for bladder cancer. It can be given intrathecally.
They are the most lipid soluble and also are among the most
carcinogenic.
725 They are used for brain tumors and BCNU has activity
against lymphomas, Hodgkins Disease and melanoma.
They arent used very frequently, except BCNU comes in a
Nitrosureas - alkylating agent; cross wafer form placed in the brain after resection of brain
Carmustine the BBB, CCNS tumors.
726 Lomustine Nitrosureas, see carmustine see carmustine
used in metastatic islet cell tumors of the pancreas
727 Nitrosurea antibiotic: Potent inhibitor (insulinomas!). It also has some activity in lymphomas and
of alkyltransferase, the DNA repair carcinoid tumors.
Streptozotocin enzyme, CCNS Poorly tolerated
Immunotherapy: creates an
733 inflammatory cascade, attracting
chemokines, cytokines which attract
BCG (Bacillus Calmette- macrophages and T cells which kill tumor originally developed as TB vaccine. Its use is in the bladder
Guerin) cells and provides immunologic memory against superficial bladder cancers.
743
Levamisole enhances cell-mediated immunity Used in combination with 5FU to tx certain colon cancers
Hormonal agent: an
adrenocorticosteroids - Lympholytic
750 effects and suppress mitosis in ALL; CLL; Non-Hodgkins lymphoma - very useful in Tx of
lymphocytes; CCNS. See acute leukemia & malignant lymphoma in children and adults.
immunosuppressants or corticosteroids Also useful to reduce edema related to tumors in critical areas,
Prednisone above i.e., mediastinum, brain, spinal cord.
751 Dexamethasone see prednisone see prednisone
756
Plant alkaloid: a Vinca alkaloid, see Acute lymphoblastic leukemia, Hodgkin's disease, non-
Vincristine vinblastine Hodgkin's lymphoma, metastatic testicular tumors
Camptothecins: function as
topoisomerase I inhibitors. Topo I
induces single strand breaks in
757 supercoiled DNA. Topoisomerase I (II??)
reseals the break when unwound; block
the dissociation of TOPOI from the DNA
and a double strand break occurs,
Topotecan, irinotecan leading to cell death.
(epi)Podophyllotoxin: a Topoisomerase
II inhibitor. TOPOII is a repair enzyme
that binds, DNA, cleaves the double
strands, causes one strand to pass
758 through the break, and then reseals the
cut. Etoposide inhibits the resealing of
cleaved DNA, leading to irreparable DNA
damage and cell death. S-G2 phase
Etoposide specific Testicular and small cell carcinoma
A monoclonal mouse antibody directed at Diffuse Large B Cell Lymphoma when given with CHOP
759 CD20-positive lymphocytic disease (B (Cyclophosphamide, adriamycin, vincristine and Prednisone),
Rituximab cell) ITP
A B C
760
761
Tretinoin or ATRA (all- combination with idarubicin for treatment of promyelocytic
trans retinoic acid) leukemia
762
Imatinib mesylate Interfere with the action of the CML; Gleevec treatment has led to hematologic remission
(Gleevac) abnormal Bcr-Abl tyrosine kinase (control of WBC levels) in almost all patients.
treatment for malignant hypercalcemia from bone mets or from
763 Alendronate, clodrinate, Bisphosphonates - turn off paraneoplastic syndromes such as increased PTH-like
etidronate and osteoclasts; leading increased bone peptide production from squamous cell lung cancer;
pamidronate strength and stabilization Osteoporosis, Paget's dz of the bone
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
764 blocking the conversion of adrenal
androgens into estrogens (non-
Anastrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
765 blocking the conversion of adrenal
androgens into estrogens (non-
Letrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Prostate Hormonal Agents: LH/RH
analogs that inhibit gonadotropin
766 secretion, preventing production of
testosterone, which is the source of
Goserelin, leuprolide growth for majority of prostate cancers.
Vascular Endothelial Growth Factor
767
Bevacizumab Receptor Inhibitors
A B C
Epithelial Growth Factor Receptor
768
cetuximab or erlotinib Inhibitors
769 sorafenib or sunitinib Multikinase inhibitors renal cell cancer and melanoma
771
Antibiotics
772 Beta Lactams
Competetive inhibitor of the
773 transpeptidase enzyme; inhibits bacterial
Penicillin G cell wall synthesis Strep pneumonia
774 Penicillin V Same
775 Aminopenicillins
776 Amoxicillin Same
777 Ampicillin Same
778 Penicillinase resistant
779 Methicillin Same
780
Nafcillin Same
781 Oxacillin Same
782 Cloxacillin Same
783 Dicloxacillin Same
784 Antipseudomonal
785 Carbenicillin Same
786 Ticarcillin Same
787 Pipercillin Same
788 Mezlocillin Same
789
Cephalosporons
Cephalosporin 1st
790
generation Gram +
791
Cephalothin-1st generation Same
792
Cephalexin-1st generation Same
793 Cefazolin-1st generation Same
794 Cefadroxil-1st generation Same
A B C
Cephalosporin-2nd
795
generation Klebsilla, H. influenzae, and anaerobes
796 Cefamandole Same
797 Ceflacor Same
798 Cefuroxime Same
799 Cefoxitin Same
800 Cefotetan Same
801 Cefmetazole Same
802 Cefonicid Same
803 Loracarbef
Cephalosporin 3rd
804
generation Gram -
805 cefixime Same
806 cefotaxime Same Severely ill ICU patients with pneumonia
807 ceftazidime Same
808 ceftizoxime Same
818
Bacitracin
819
AntiRibosomal
820 50S-CLEAN
A B C
822 Lincosamide; Bind irreversibly to a site Excellent anaerobic coverage, most useful "aboe the
on the 50S subunit of the bacterial diaphragm" anaerobic infections (in part becasuse of the
Clindamycin ribosome, thus inhibiting translocation polymicrobial nature of lung absceseses)
826
Linezolid Blocks initiation complex formation, 50S Used for vancomycin-resistant infectons
827 30S-TAG
828
Tetracyclines
Ambulatory pneumonia; Used for renal insufficienct pts,
829 excreted in feces; used prophylactically for chloroquine-
Doxycycline see tetracycline resistant strains of plasmodia/Malaria
Used for renal insufficienct pts, excreted in feces; tx acne
830
Minocycline see tetracycline vulgaris
831 Methacycline see tetracycline
832 Oxytetracycline see tetracycline
833 Demeclocycline see tetracycline
834
A B C
841
DNA Gyrase
MC used agent for traveler's diarrhea, UTI, URT, gonococcal
infections, atypical pneumonia; gram negatives
842 (Pseudomonas, Neisseria, Haemophilus, Enterobacter,
Fluoroquinolones Inhibit bacterial DNA gyrase thus causing Legionella, Mycoplasma)
(quinolone) breaks in the DNA DOC for complicated UTI
843
(quinolone) Inhibit bacterial DNA gyrase
Ciprofloxacin thus causing breaks in the DNA Anthrax
Newer quinolone - additional gram-positive
844 coverage/increased activity, especially to S. pneumonia!
Levofloxacin quinolone (some Staph), also covers P. aerguinosa
Newer quinolone - additional gram-positive coverage (S.
845
Gatifloxacin quinolone pneumonia, some Staph
Newer quinolone - additional gram-positive coverage (S.
846
Moxifloxacin quinolone pneumonia, some Staph; Anaerobe coverage
Gets gram + and - including pseudomonas only for severe
847
Trovafloxacin quinolone pnumonia due to LIVER TOXICITY
848
Sparfloxacin quinolone CAP - increased activity, especially to S. pneumonia!
849 Nalidixic acid quinolone Excreted rapidly, rarely used
A B C
metabolized to a compound that
850
Nitrofurantoin damages bacterial DNA Used for recurrent UTI
851
Vaccinations
852
854
856
Yellow-fever vaccine Yellow fever
857 Tyhoid vaccine Thyroid fever
858
Pertussis vaccine
859
Tetanus vaccine Tetanus
860 Varicella vaccine Chickenpox
861
862
Neurologic Drugs
863 Headaches
864
Tension Headaches (Combination: NSAIDS + Butalbital +
NSAIDs (non-steroidal see NSAIDs above; inhibit prostaglandin Caffeine); Tx of Migraine (must be taken very early in the
anti-inflammatories) synthesis attack to be effective!)
A B C
867
869
Imipramine TCA, see antidepressants Prophylactic Tx of Tension HA
870
Sumatriptan (prototype,
Imitrex) (Sumatriptan is prototype) 5HT1 Agent, Tx of Migrane (acute tx, take during prodromal phase);
Rizatriptan (Maxalt) Agonists at 5-HT1b & 5-HT1d sites (Gi Sumatriptan has ~2hr effect (so usually taken several times
Zolmitriptan (Zomig) coupled receptor) - inhibits vasodilation per episode), given both orally and parenterally, not used
Naratriptan (Amerge) (Sub P & CGRP, see extra notes) (5- prophylactically for migrane
Frovatriptan (Frova) Hydroxytryptamine (aka serotonin)) Tx for acute Cluster HA
A B C
871
873
878
Valproate see Seizure Medication Prophylaxis of Migraine; Prophylaxis of Cluster
A B C
879
Prophylaxis of Migraine:
Ergot derivative; blockade of 5-HT2a and Without benefit when given during an attack
5-HT2c receptors (blocks serotonin Protective effect develops over 1-2 days.
Methysergide receptors) Prophylaxis of Cluster HA
880
881
884
Antimuscarinic (Anticholinergic):
Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Biperiden muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia.
Antimuscarinic (Anticholinergic):
885 Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Trihexyphenidyl muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia
Antimuscarinic (Anticholinergic):
886 Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Benztropine muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia
A B C
888
Rasagiline (Azilect) Selective inhibitor of MAO-B Early stage treatment of Parkinson's Dz (neuroprotective?)
892
Dopamine replacement (D2); ergot
Bromocriptine alkaloid (Old) Treatments for Disabling-Parkinsonism
893
Dopamine replacement (D1/D2); ergot
Pergolide alkaloid (Old) Treatments for Disabling-Parkinsonism
A B C
894
New Treatments for Disabling-Parkinsonism (especially
akinesia/bradykinesia); Possibly a neuroprotective agent.
Dopamine replacement (D3, part of the Effective in both early and advanced PD as monotherapy or in
D2 family); Non-ergot dopamine combination with levadopa. Neuroprotective as it is an
Pramipexole agonists; (antioxidant) antioxidant. Midigates on-off phenomenon
Dopamine replacement (Relatively Effective in early or advanced PD alone or in combination;
895
Ropinrole selective D2 agonist) Midigates on-off phenomenon
Catechol-O-Methyltransferase
inhibitors (COMT inhibitor): Inhibition of
dopa decarboxylase causes activation of
COMT pathway, increasing 3-O-
896 methyldopa (3OMD); 3OMD is
associated with poor therapeutic
response to levodopa (competes for the capones may smooth response to levodopa and may
absorption into brain); only active in the permit lowering of levodopa dose for PD (only used with L-
Entacapone periphery DOPA); typically started with L-DOPA/carbidopa therapy
906
Mineralocorticoid, see corticosteroids;
resorbing Na at kidney (K and H lost) Treat orthostatic hypotension due to autonomic
Fludrocortisone causing retension of water dysfunticon
907
Midodrine Alpha agonist (see adrenergics) Treat orthostatic hypotension due to autonomic dysfunticon
908 Benzodiazepines Dystonias
909 Botox Dystonias
910 Anticholinergic drugs Dystonias
911 Alprazolam Essential Tremor
912 Propranolol Essential Tremor
913 Primidone Essential Tremor (usually given with propranolol)
914 Seizure Medication
A B C
915
919
less potent, fewer adverse effects, fewer drug interactions than
Oxcarbazepine Voltage gated Na+ Channel Blocker Carbamazepine; 3/d dosing - compliance issue
926
Benzodiazepines - direct GABA(A), see
Lorazepam!! (Ativan) Diazepam Status epilepticus
A B C
absence; myoclonic, akinetic, atonic seizures
927
Clonazepam (Klonopin) Benzodiazepines - direct GABA(A) Infantile Spasms (Wests Syndrome)
Benzodiazepine - indirect GABA(A);
928
tiagabine Uptake inhibition
930
Enhances GABA activity; Blocks
glutamate activity; but many other
mechanisms, including other ion
Alcohol channels Good Anticonvulsant?
Antiseizure drug; has been studied in patients with MS with
931 Benzodiazepine - indirect GABA(A); positive results
Gabapentin (Neurontin) unknown mech; Spasmolytics of the CNS Neuropathic pain, Trigeminal Neuralgia
932
Corticosteroids (eg
corticotropin, prednisone,
dexamethasone) (Mechanism unknown) Infantile Spasms (Wests Syndrome)
933 Multiple Sclerosis Drugs & Myasthenia Gravis
943
see Anticholinesterases above; DOC for Myasthenia Gravis (long acting); Use in conjunction
Quaternary drugs do not penetrate with an antimuscarinic to block excess ACh in the
Pyridostigmine CNS, so no intoxication/seizure problem parasympathetic nervous system
944 see Anticholinesterases above; Used for Myasthenia Gravis; Use in conjunction with an
Quaternary drugs do not penetrate antimuscarinic to block excess ACh in the parasympathetic
Neostigmine CNS, so no intoxication/seizure problem nervous system
945
Uses
Diagnostic aid for myasthenia gravis (not primary
diagnostic, but useful for distinguishing MG from other
Alcohol; see Anticholinesterases neurological disorders)
above; brief duration of action, rapid Differentiation of myasthenic crisis from cholinergic crisis
Edrophonium (Tensilon) onset (iatragenic). see Tensilon test extra notes
946 Alzhemier Drugs
947
Tacrine Acetylcholinesterase Symptomatic Tx of Alzhemier dz
A B C
948 Donepezil Delays progression of Alzheimer dementia
949
950
Antidepressant Drugs
951
952
953
954
Citalopram (generic,
Celexa) SSRI Treat depression
955
Escitalopram (Lexapro) SSRI Treat depression
A B C
Heterocyclic anti-depressant;
959 Marketed as an SSNRI (selective
serotonin and norephinephrine
reuptake inhibitor - inhibits 5-HT and
NE reuptake); more potent at 5-HT site;
Venlafaxine (Effexor) hence, at low doses acts like an SSRI Treat depression
inhibits neuronal uptake of serotonin
and NE; acts as an antagonist of
960 postsynaptic 5-HTA receptors and of
alpha1-adrenergic receptors. Not
chemically related to SSRI, tricyclic,
Nefazodone tetracyclic, or MAOI Tx depression and anxiety; no sexual SE or weight gain
Heterocyclic anti-depressant;
marketed as an NaSSA (Noradrenergic
and Specific Serotonergic
Antidepressant),
963 Blocks 2-adrenergic autoreceptors
which increases NE release; & increase
in 5-HT cell firing due to increase NE
release and block of 2-adrenergic
heteroreceptors on 5-HT nerve terminals
Selective stimulation of 5-HT1
Mirtazapine (generic, receptors due to blockade of 5-HT2 & Treat depression (refractory major depression who need to
Remeron) 5-HT3 receptors. gain weight)
Treat depression!
964 Other Clinical Uses:
Tricyclic Antidepressant (TCA): block chronic pain!
monoamine reuptake (NE, 5-HT, DA), Enuresis
Amitriptyline (generic, down-regulate NE and/or 5-HT Panic disorder
Elavil) receptors Attention deficit hyperkinetic disorder
Nortriptyline (generic,
965
Aventyl, Pamelor) TCA see amitriptyline
966 Imipramine TCA see amitriptyline
967 Clomipramine TCA Tx obsessive-compulsive disorder
968
972
Selective norepinephrine uptake
Atomoxetine (Strattera) inhibitor Treatment of attention deficit hyperactivity disorder (ADHD)
A B C
973
Mood Stabilizers
975 Valproic Acid + Sodium Mood Stabilizing Drug: May act through Anticonvulsant mood stabilizer and the combo of these two
Valproate = Divalproex increasing GABA, see Seizure causes less GI distress. Both for acute and maintenance
Sodium Medication above therapy (see notes about therapy approaches)
981
Antipsychotics
982
984
Atypical Antipsychotic: blocking D2
receptors & block 5-HT2 receptors;
Olanzapine is rapidly becoming the
standard against which both typical and Tx of Psychosis and Schizophrenia
Olanzapine (Zyprexa) atypical antipsychotics are judged Bipolar dz - primarily for acute mania
987
Ziprasidone Atypical Antipsyychotic - IM formula Rapid relief of agitation and distress; weight neutral
A B C
988
992
Thioridazine Typical Antipsychotic - Phenothiazine Tx of Psychosis and Schizophrenia
994 Prochlorperazine
(Compazine special use) Typical Antipsychotic - Phenothiazine Anti-nausea use; Tx of Psychosis and Schizophrenia
996
Anxiolytics & Hypnotics
997 Anxiolytics
A B C
998
BZD are generally used for situational care (and not long term
care)
Anxiolytic, hypnotic
Muscle relaxant
Pre-anesthetic (anesthetic + above)
Blocks convulsions in ethanol or BZD withdrawal
Benzodiaezepin (BZD) - prototype: 2nd line status epilepticus (given i.v.; Second behind
Increases Cl- conductance on GABA lorazepam - see extra notes)
Diazepam (Valium) channels; long half-life (approx 50+ hrs) - Alcohol withdrawal
Prazepam, quazepam,
999
and flurazepam See diazepam See diazepam
Used for anxiolytic and hypnotic effect
some potential for early morning awakening
1000 said to be less sedative than other BZDs (use as hypnotic
Benzodiaezepin - Increases Cl- may be based on anxiolytic effect)
conductance on GABA channels; Often a BZD of choice for pts PRN (eg fear of flying)
Alprazolam (Xanax) Intermediate acting Panic disorder; generalized anxiety
1002
Benzodiaezepin - Increases Cl-
conductance on GABA channels;
reliable pharmokinetics, especially for Anxiolytic and for sleep induction
Oxazepam (serax) the elderly; intermediate acting Alcohol withdrawal (with liver dz)
A B C
Temazepam and
1003
chlordiazepoxide Benzodiaezepines
1010
1012 Sleep (shorter half life though than zolpidem) Pushed as PRN
before bedtime or upon awakening in the middle of the
Zaleplon (Sonata) Same as zolpidem; very short half life night (if more than 4 hours remain in sleep cycle)
1013
Pineal hormone that regulates useful for sleep problems related to jet-lag or changing
Melatonin sleep/wake cycle (peaks at 2 am) day/night working hours
1014
Binds melatonin receptors (MT1 and
Ramelteon (Rozerem) MT2) and not GABA Sleep
1019
Additional Psych Drugs
1020 ADHD Drugs
1024
Structurally similar to methylphenidate;
Pemoline (Cylert) relatively long duration of action (7-h) ADHD; essentailly no abuse potential
1028
Methylphenidate (Ritalin) See above ADHD drugs Narcolpesy
1029
Amphetamine related by structure, DEA DOC for narcolpesy and sleep disturbances associated with
Modafinil (Provigil) Schedule IV drug jobs that involve shift changes (day shift to night shift)
1030 Appetite Control
A B C
1031
Amphetamine-related anorexiant:
Modification of NE and dopamine; work Weight loss, decreased appetite, loss of interest in food, less
in appetite control centers of the pleasure from eating, increased satiety with eating, decrease
Benzphetamine (Didrex) hypothalamus (likely a NE mechanism) in total energy intake
1032
Diethylproprion (Tenuate) See Benzphetamine Extended release available, See Benzphetamine
Previosly used with fenfluramine (Fen-Phen) popularity
1033 See Benzphetamine; Long acting increased once fenfluramine removed from market; See
Phentermine (Fastin) sympathomimetic Benzphetamine
1034 Fenfluramine (Not avail) See Benzphetamine No longer available
Non-sympathomimetic anorexiant:
1036 Inhibits reuptake of 5HT and NE (SNRI
reuptake inhibitor), as well as being an
Sibutramine (Meridia) MAOI Weight loss; take without regards to meals
1038
Herbals See extra notes Weight loss
A B C
1040
Drugs of Abuse & Treatment
1041 Alcohol
1042
1045
1048
Psychostimulants; blocks DA
transporter (also binds NE and 5-HT
transporters); (benzoylecgonine
Cocaine metabolie in plasma 1-3 days) Local anesthetic effect
A B C
1049
1051
1052
1053
1054
1055
Methylenedioxy-
methamphetamine
(MDMA) Hallucinogen
1059
Related to GABA, but mechanism not
Gamma-hydroxybutyric known; detectable in plasma only for
acid (GHB) hours
A B C
1060
BZD; detectable in plasma less than 7
Flunitrazepam days
1061
Inhalants: Organic
solvents
1062 Inhalants: Used medically to relieve pain in people with heart disease,
Nitrates/Nitrites (amyl amyl is a vasodilator -- it causes blood vessels to open wider,
nitrite, butyl nitrite and easing the heart's labors, allowing blood to flow more freely,
isobutyl nitrite) Amyl is a vasodilator and temporarily increasing the pulse rate.
D E F
1 Side Effects & Toxicies Contraindications Memory Technique
st 2
10
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose);
Asthenia ("feel" weak, will not show
objective evidence); Stuffy nose
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose)
11 though this is minimal with time; Asthenia
("feel" weak, will not show objective
evidence); Stuffy nose
12
Rem: "clone me friend, many times." (Clo - mi
Multiple births - phene)
13
Tx with nitrites/nitrates,
Patients with angina are at
14 Blindness is rare (unique to Sildenafil), risk; BP < 90/55
some pt complain of a "blue aura" in visual Warning: ED drugs of sildenafil-
field and decreased visual accuity; type should not be used within 4
Headache (15%), Flushing, G.I. upset, hrs of alpha blockers (does not Put your penis on the (window) sill, then the fill
Nasal congestion (4%), priapism apply to tamsulosin) (of the vagina with semen)Sill-den -da -fill
Headache (15%), Flushing, G.I. upset,
15
Nasal congestion (4%), priapism see sildenafil
16
Headache (15%), Flushing, G.I. upset,
Nasal congestion (4%), priapism see sildenafil
17
18
plagued by high incidence of nausea and
vomiting
D E F
19
21
23
24
D E F
DVT is absolute
25 contraindiction; Pregnancy;
Women with Hx of E-dependent
Thromboembolism, Cardiovascular risk, neoplasms or breast cancer; Hx
Hypertension. Because high doses of thromboembolic disorder or liver
steroids, side effects range from minor disease; Heavy smokers
discomfort (water retention, nausea) to (cardiovascular risk is higher if
cosmetic (chloasma) to dangerous >35yrs of age) (big
(hypertension, embolic disorders) contraindication); Migrane HA
26
Some women may hoave moral or ethical
objections to the mini pill but not the standar pill
27
N/V!
Weight gain, 5lbs at 1 year, lbs by the
2nd, 12lbs by the 5th.
Massive weight gain in 1-2 % of patients.
Bone loss!
28 Should use for no longer than 2 years
without a break
Slow return to fertility
average 10 months, can be as long as 2
years
Some metabolise quickly, some very slow
Pt keeps eatting heavily too
29
Androgenic effects such as hirsutism
30
higher risk of thromboembolism
31
D E F
32
very high androgenicity
33
34
35
36
37
38
39
40
Rem: Are you for 86ing this pregnancy (RU486)
41
Rem: Dan - you have endometriosis??; Dan-an
tagonist (Danazol)
42
43
D E F
Rem: abate/stop the hemorrhage (Hemabate);
44 Rem: PGF2 For Fucks sake, save that
woman; or Fuck that baby (2nd trimester
pregnancy termination)
45
Rem: PGE2 E-gads, get that baby out
46
47
48
49
50
52
53
st 54
55
D E F
57
58
59
61
63
64 a sulfa based drug
thiazide-like; have key portion of Remember: India (indapamide) produces
65 sulfonamide structure hypersensitivity cheap thiazide knockoffs (thiazide-like), many
cross-reactions people allergic (HS)
Remember: thiazide ring made from metal
66 thiazide-like; have key portion of (Metolazone), many people have allergy (HS);
sulfonamide structure hypersensitivity or me to lazy to get up and go to bathroom so
cross-reactions I'll pee right here
D E F
73
see losartan
D E F
75
76
78
1. Constipation!!
2. headache; flushing; orthostatic
problems
79 3. potential problem of heart block if
verapamil and diltiazem are used with Remember: a bear (ver) rapping (rap), falls with
beta-blockers pain of angia, chocking on Ca so bad that he
4. CHF can't poop
80
81
1. Hypotension (orthostatic) is a
significant side-effect for most patients.
Profound reflex SNS activation and
tachycardia as well as peripehal edema.
Consequences of increased myocardial O2
consumption - angina; increased
myocardial work - induction of CHF is more
82 likely; hypotension side-effects such as
palpitation, pounding headache,
flushing; edema secondary to Na+ and
H20 retention; GI
2. tachyphylaxis
3. Drug induced systemic lupus (hapten
mech - high doses, slow acetylators,
reversible)
4. Coronary Steal syndrome in pts with remember: pregnant hydra with using visin for
ischemic dz the butterfly rash around face
D E F
83
see hydralazine
Adverse effects: SNS activation, angina,
edema, hirsutism
84
see hydralazine Remember: an ox in the day opening all of the
window (arteries)
Remember: "Fen? old o pam, she's D one
85 Typical arteriodilator toxicities who's got the HTN problem, but great kidneys",
says her old friend
86
excessive hypotension
cyanide/thiocyanate toxicity with
prolonged use
Tolerance!!
87
I 93
ng and females
er persons, males
Drug interactions of
sulfonamides - Displace
bilirubin from plasma albumin -
94 bilirubin is then free to pass into
central nervous system, cause
Act synergistically with sulfonylurea kernicterus (neural symptoms
hypoglycemia by increasing the release of associated with high levels of Rem: Sulfonamides (eg Sulfamethoxazole)
insulin bilirubin) - contraindicated block dihydropteroate Synthase, TRimethoprim
reduce blood glucose level during pregnancy blocks dihydrofolate Reductase
95
96
D E F
97
Toxicity:
Crystalluria Drug interactions of
Hemolytic anemia in G6PD deficient sulfonamides - Displace
patients (Afro Americans) bilirubin from plasma albumin - Remember: TMX/SMX: T = tree or respiration
Stevens-Johnson syndrome: severe and bilirubin is then free to pass into (S. pneumonia and H. inflenazae); Mouth = GI,
usually fatal conditions involving blistering central nervous system, cause diarrhea (Shigella, Salmonella, E.coli); Pee =
of the skin, mouth, eyes and genitalia, often kernicterus (neural symptoms UTI, urethritis, prostatitis (enterics such as E.
accompanied by fever, polyarthritis, and associated with high levels of coli); SMX = Syndrome or AIDS (profolactive to
kidney failure bilirubin) - contraindicated prevent P. Carinii when T count below 200, also
Hyperkalemia during pregnancy T gondii)
Toxicity: n, v, d
98 Achilles tendonitis, tendon rupture
CNS such as HA, insominai, restlessness Contraindicated with patients
Epigastric distress under 18 years of age;
Damage cartilage do not give to children as
Suprainfection with streptococci, Candida causes cartilage damage
102
103
Allergy and hypersensitivity
104
105
108
109
Remember: You 'spectin to get gonorrhea
110
Relatively toxic
Contraindicated during
pregnancy
cross the placenta to reach the
114 fetus and cause deformity and
Teeth discoloration, bone deformity in growth inhibition
children, Fanconi's syndrome damage to teeth, bones, and Remember: VACUUM your Bed Room Tonight:
(aminoaciduria, phosphaturia, acidosis, and nails of the fetus Vibro cholera, Acne, Chlamidia, Ureaplasma
glycosuria), photosensitityity Renal toxicity Urealyticum, Mycoplasma pneumonia, Borrelia,
Suprainfection Rickettsia, Tularemia,
Do not give during pregnancy:
Congenital limb abnormalities,
115 tooth discoloration, inhibition of remember: a daschund (dog, doxicycline) on
bone growth in fetus, bicycle coming out of your ass (excreted in
suprainfection. feces)
116
117
118
119
Oral therapy causes GI disturbances. Remember: clostridium for clottage cheeze
120
Remember: Miconazole for fungus of the toe;
severe GI disterubances also Azoles hate ergosteroles
Rem: Casper the ghost messin with the fungus
121 wall synthesis (moving around all the pieces
needed), the fungus just doesn't get why it can't
complete its wall
D E F
123
124
Drugs
126
127
Generally well tolerated; occasional
nausea, diarrhea, abdominal colic,
headache, dizziness, skin rash. PPIs are
metabolized and can inhibit cytochrome
P450 (CYP2C19 & CYP3A4, especially
omeprazole) and therefore decrease the Prazole = PPI; Rem: pray so (pra-zole) the
clearance of other drugs such as pumps stop pumping acid onto our heads;
benzodiazepines, warfarin, phenytoin, and Rem: put your H. pylori CAP on (tx with
others. clarithromycin, amoxicillin, and PPI)
128
see Omeprazole
D E F
129
see Omeprazole
130
see Omeprazole
131
see Omeprazole
133
Very little SE
134
Very little SE
135
Very little SE
137
138
140
Rem: Ralph was sucking (Suc-ral-fate) on a
sticky viscous sucrose and aluminum sucker
that coated his stomach and relieved him of the
Constipatoin fate of his ulcer just to give him constipation
141
potential abortifacient, Rem: Miso-prostol is Prosta-glandin soup, but
therefore it is contraindicated in causes Japanese baby abortions; miso is good
Causes diarrhea in 30% of patients pregnancy. for the belly; prost = prostaglandin
142
D E F
143
Side effects are significant, especially
with chronic treatment, and include: Rem: Me is such a dope (anti-D2) that me toe I
hyperprolactinemia, galactorrhea, breast cloped (Me-to-clop-ramide), screaming like a
tenderness, menstrual irregularities, girl (giving me girly stuff (SE)) while my GI
extrapyramidal symptoms, anxiety, and functions better with the diabetes. Rem: Me to
depression. D 2 (D2 and DM2)
Rem: try meth Ben (Trimethobenzamide), its a
144 dope (dopamine) used to prevent vomiting and
nausea "2 dope" he exclaims
145
Rem: the PD pt cracked open a bottle of
central side effects less than (Domperidone) now that his gastric stasis is
metoclopramide solved
146
SLE SE
147
148
149
D E F
151
Prolongs fever in pts with shigellosis, toxic Rem: the pt took Loperamide and is now
megacolon in pts with C. difficile; and HUS lopping around from the opioid (opioids work at
in children infected with Shiga toxin- Ulcerative colitis, or acute the MD receptos, mu and delta); or Rem: (the)
producing E. coli. Should be avoided in pts bacillary or amoebic dysentery; l'opera makes you slow, opiods make on lop;
with bloody diarrhea bloody diarrhea lopping amide the diarrhea in the streets
154
Schedule II
156
158
159
160
161
Rem: a prep for chemo puking - Aprepitant, "No
Kidding" as he pokes you (NK1 antagonist)
162
setron = antiemetic; Rem: seeing Tron won't
make you puke, in fact, it will make you feel
pretty good (seritonin receptor); Rem: Tron
throwing his frisbee at the seritonin receptor
inhibiting it; or Rem: O' dan is so strong
(Ondansetron), you can give him 5 hits in 3
rounds (5HT3)
163
164
165
D E F
166
Rem: Men die from saying hi to nate, (Di-men-
hy-dri-nate, Hi is H1 antagonist)
167
168
169
Rem: zine = H1 blocker
173
174
178
This drug was previously withdrawn due to
very serious adverse effects, including setron = antiemetic; Rem: seeing Tron won't
ischemic colitis and serious make you puke, in fact, it will make you feel
complications of constipation. pretty good (seritonin receptor);
179
180
181
182
184
D E F
185
Must check for latent TB and other
infections before administration. One side
effect is a lupus-like syndrome, which is
rare and reversible after stopping the drug.
Anti-double-stranded DNA antibodies occur Rem: to fix CD, inflict a flick to their bowel
in 9% but are not associated with clinical (Infliximab), don't flick too hard or will give them
lupus. TB SLE or knock free the TB
186
187
188
189
190
191
192
193
194
195
196
197
198
D E F
202
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
203 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.
204
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
205 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.
D E F
206
Negligible
208
209
210
s 211
D E F
212
213
see digoxin
214
216
See NTG
217
cs 221
223
Salty (Na) old man weiding his cain in NAPA
valley, whacking hot Lupus chick, giving her
lupus-like syndrome!! arrhythmia may be Do not use in pt with long QT butterfly rash; Rem: its not HIPP to get drug
aggravated, development of TdP; syndrom, TdP history, or induced-LE - (Hydralizine, INH, Phenytoin,
agranulocytosis, BM depression hypokalemia Procainamide)
224
227
228
Remember: die laughing so had a seizure
D E F
230
proarrhythmia!!
232
similar to Flecainide
238
reflex tach due to vasodilation; edema
and orthostatic hypotension
239
moderate in LV contractility,
bradycardia and hypotension
facial flushing, dyspnea, or chest pressure dont use for AFib, sick sinus
242 lasts <60 sec; sometimes nausea, syndrome, or 2 and 3 heart
lightheadedness, headache, sweating, block unless they have a
palpitation, hypotension and blurred vision pacemaker
243
247
Bleeding
248 Bleeding Rem: Enoxaparin = LMWHeparin
D E F
250
252
Rem: Love cAMPing outside a pyramide,
planned go into the pyramide but passout from
vasodilation and die from eatting spicy mole
(though drug prevents stroke)
255
258
Remember: a pent up ox in a RBC that that is
doing yoga to become more flexible
262
264
266
hemorrhage
D E F
267
269
271
272
273
D E F
280
same as Cholestyramine same as Cholestyramine
281
same as Cholestyramine same as Cholestyramine
285
286
D E F
287
288
289
290
291
293
MC SE include myelosuppression
(leukopenia, thrombocytopenia, anemia),
GI symptoms (eg n/v, stomatitis, anorexia,
appetite disturbances), and dermatologic
toxicity (eg rashes, skin ulcerations, facial
erythema). Rarely (at high doses)
295 neurologic disturbances (eg drowsiness,
dizziness, HA, and convulsions, altered
renal function, alopecia). Mutagenic
potential is unknown, avoid when possible
in pregnant women. Causes
macrocytosis, may mask the incidental Rem: hydrated urine (hyrdoxy-urea), when
development of folic acid deficiency, give pissed on R to D 2 (ribonucleotide to
prophylactic folic acid deoxyribonucleotide) shuts him down
296
List
297
298
Rem: first generation sulfonylureas have
299
-amide
300
alcohol-induced flush!!
301
302
D E F
303
304
Hepatic insufficiency, sulfa
See Glimepiride allergies, pregnancy Rem: Glee (Glipizide) and ide
305
See Glimepiride See Glimepiride Rem: Glee (Glyburide) and ide
306
309
Rem: a car and bus (Acarbose) filled with
diabetic ketoacidosis, cirrhosis, people with explosive diarrhea, their splatter
inflammatory bowel disease, splattering their sugar lolly pops such that they
flatulence, diarrhea and GI upset due to colonic ulcers, or partial don't want to eat them (inhibits glucose
undigested carbohydrate intestinal obstruction. digestion)
310
311
moderate weight gain, edema and mild Rem: the glitter zone (glitazone), everyone is
anemia, all due at least partly to fluid here in the nuclear gliter zone, sensitized to
retention; can precipitate frank anemia. insulin's hypnotic music - P-party!! (PPAR-) -
Potential liver damage Heart dz and liver dz! the heart and liver weren't invited
312
See rosiglitazone Heart dz and liver dz!
313
Hepatotoxic (monitor LFTs) Heart dz and liver dz!
D E F
314
Risk of hypoglycemia and nausea. Other
side effects include decreased appetite, Rem: the new baby Amylin in the pram
vomiting, stomach pain, tiredness, (flatbottom boat or baby carrige, Pram-lintide)
dizziness, or indigestion. is so fat it already has DM
315
Nausea, vomiting, diarrhea and upper
respiratory symptoms are the most Rem: I threw my ex in the tide (Ex-en-a-tide) to
common adverse effects. Incidents of drowned because of her glib tongue (GLP), that
hypoglycemia are relatively low. fat diabetic bitch
316
317
320
323
324
325
326
D E F
327
331
332
Toxicity to thioamide drugs occur in 3-12%
of treated patients. The most common
adverse effect is a maculopapular pruritic
rash (super itchy!!). The most dangerous Rem: they are for (pro) piling (pyl) up the iodine
(potentially fatal) complication occurring in because drug blocks Ez that forms MIT, DIT,
0.3 0.6% of patients is agranulocytosis and thyronines. Rem: Theo Huxtable amist
(BM failure) heralded by a sore throat (thio-amide) all the trendies with ther peroxide
and fever. Goiterogen bleached hair (peroxidase)
D E F
334
335
336
337
338
339
340
341
Remember: Perchlorate prefers it makes active
Goitrogen receptors to chocolate than iodine
342
D E F
Remember:: the orc tree had acromegaly so
343 was chopped down to prevent it from growing
(GH inhibiter) taller - Octreotide
Rem: a ginormous Peg (Pegvisomant) standing
344 on Camp bowie blocking traffic (blocks GH
receptors)
345
349
Adverse effects. Hot flashes and leg
cramps. Also increase risk of
thromboembolic disorders.
355
356
Remember: flood (flud) the mineral mine
359
361
362
363
Dry skin and chelitis!! Pseudotumor
cerebri, vision impairment, HA, myalgias,
364 arthralgias; also BM suppresion, Teratogen - must confirm pt is
hepatotoxicity, hypertriglyceridemia and not pregnant with two negative
pancreatitis; depression and suicide pregnancy tests
D E F
365
gs
366
367
371
see albuterol, use with caution in pts with Remember: Terbutaline - tear a butt to help
CHF or history of arrhythmias person breath and delay pregnancy
D E F
372
376
378
379
380
382
Quaternary compounds can block nicotinic
receptors and may have ganglion or a rat from Ip was rowing his boat with four
neuromuscular blocking action paddles (quaternary) because he thought the
Overdose with quaternary more likely to be sea air would open his lungs (reverse bronchial
fatal because of neuromuscular constriction), his boat was overflowing with
blockade. sizziling mushrooms
Tio is spanish for uncle, the uncle of
383 ipratropium who tries to spit, but sizzling
see ipratropium mushrooms in his mouth wont let him
385
Corticosteroids
386
D E F
388
See corticosteroid SE
389
See corticosteroid SE
390
See corticosteroid SE
391
Budda is so nice (Budesonide) to alleve pt of
See corticosteroid SE allergic/sesonal rhinitis
flew to kazakhstan (Flu-ti-casone propionate) to
392 apropriate drugs for my rhino (seasonal/allergic
See corticosteroid SE rhinitis)
mo' meat is on (Mometasone) this rhino
393 (allergic/seasonal rhinitis), let your kid ride on
See corticosteroid SE his back (no growth retardation)
D E F
394
See corticosteroid SE
395 See corticosteroid SE
396 See corticosteroid SE
397
398
399
401
D E F
404
405
Dyspepsia (indigestion) is the most
common side effect. Liver toxicity has lukast - inhibits leukotriens. Monte is a young
been noted in some patients and the drugs boy (6-12yo) with asprin triggered asthma, so
are contraindicated in patients with he takes lukast but gets a stomach ache
abnormal liver function. instead.
406
see Montelukast
407
408
Rem: fence in the throat guana (sputum),
delivered from throat (Gua-i-fenesin)
409
Because of the potential for adverse effects
(?), other agents are usually preferred.
D E F
410
causes irritation
411
419
local skin irritation
420
421
nausea, vomiting, gas, headache and Rem: I am very inclined to stop smoking (Var-
insomnia. enicline)
ials
422
nts
433
437
438
D E F
439
440
441
442
Pregnancy
443
444
ts 445
447
CNS SE in elderly
448
449
450
anemia teratogenic
451
454
es 457
461
see diphenhydramine
D E F
462
see diphenhydramine
463
Rem: has a lasting (az-e-lastine) effect when
At very high doses (280x), is squirt this up the rhino's nose (allergic rhinits),
sometimes leaving a bitter taste, and teratogenic in mice; dont use but he gets pissed cause the bitter taste in his
sometimes causing sedation. during pregnancy. mouth
466
467
468
Rem: Lo-ratidine is lo-nger actingin 2nd gen H1
469
little sedation. antagonist
470
D E F
473
see cimetidine
474
see cimetidine
475
pathomimetics):
476
amine vs. non-Catecholamine, Direct vs. indirect acting, Re-uptake inhibitors)
477
Increases BP (arterioles)
Expect reflex bradycardia. Remember: phenylephrine is a picky hot bitch
Increases cardiac return (veins) who feels (phenyl) out ephrine (who is similar
to epinephrine) and only takes his 1 qualities.
D E F
478
Contraindications
1. Hypertension
2. Shock (non-anaphylactic??)
3. Hyperthyroidism - E may have
enhanced cardivascular actions
in pt with hyperthyroidism. If E
1. Arrhythmias - particularly in conjunction is required in such an indivildual,
with the gaseous anesthetic halothane; E the dose must be reduced. The
increases the frequency of ectopic beats in mechanism appears to involve
Purkinje fibers by accelerating spontaneous increased production of
depolarization. adrenergic receptors on the
2. Cerebral hemorrhage vasculature of the hyperthyroid
3. Necrosis distal to site of injection individual leading to a Rem: I had a cat named NED
(potential problem with infiltration) hypersensitive response. (Catecholamines; NE, E, Dopamine) - all
4. CNS effects: anxiety, headache 4. Angina pectoris derived from tyrosine (which is derived from
phenylalanine)
479
slow, forceful (pounding) heart beat,
elevated BP, anxiety, headache.
D E F
480
485
D E F
487
Atrial fibrillation; Tachycardia with possible
increase in myocardial oxygen
consumption (angina)
Side effects:
488 insomnia, anxiety, arrhythmias, nausea,
vomiting
Toxicity:
Acute: convulsions, coma, death
Chronic: abnormal mental state (paranoia),
weight loss, psychotic reactions.
emicals
493
tivity or of sympathomimetic drugs
495 May cause autoimmune hemolytic Remember: give meth and dopa to pregnant
anemia and SLE woman with high bp
496
499
500
g Agents
501
502
Orthostatic hypotension
Tachycardia
Combined alpha blocking and
muscarinic/histamine agonist actions Remember: the phens are hens that are bitchy
Diarrhea and charge a tole to all the alpha males that is
Nausea too steep for them to pay, so they keep them
out/block them.
D E F
503
1. Cardiac. Reflex tachycardia.
Reducing BP causes sympathetic
activation. Because 2 receptors on
adrenergic nerves are blocked, this further
increases NE release at the heart, where Remember: Phen is Hen and
NE can act on beta-1 receptors. they're bitchy birds that block all
2. CNS. Lipophilic agent that crosses blood alpha's, and the word is
brain barrier. impressive -
Nausea, vomiting and weakness may be PhenoxyBENZAMINE -
signs of non-specific CNS effects. showing its strength to
3. Others: miosis, inhibition of ejaculation, irreversibly bind to the alpha
stuffy nose. receptors covalently
D E F
506
Dyslipidemia
AV block!!
All 1-selective drugs lose selectivity at
high doses.
507
Use very cautiously if at all in patients with
reactive (asthma) airways.
Symptomatic hypotension common initially
Fluid retention: may have to increase
diuretics remember: lol blocks beta, me too (meto)
Heart failure may worsen initially selective for beta 1
Rem: Aten, very selective for who he is a god
of (beta 1), he is a (long lasting) god; Rem:
508 beta1 blockers is "A BEAM" straight to the
heart (cardioselective; acebutolol, betaxolol,
esmolol, atenolol, metoprolol)
511
512
513
514
516
Note: non-selective alpha blockers have
essentially no use in essential hypertension
(see extra note at phentolamine).
D E F
517
518
520
Orthostatic hypotension - alpha blocking
effects make this more likely than with pure
beta blockers contraindication similar to
Others side effects are like propranolol. propranolol
Receptor Agonists):
523 i.e., drugs which exert their effects largely via activation of peripheral
tic fibers
c & smooth muscle, gland cells and nerve terminals. (Notice eccrine sweat gland
ors).
Contraindications for
cholinoceptor agonist drugs
Potential Side Effects of Muscarinic Bronchial asthma (constricts
Agonists bronchiols)
Bradycardia Urinary obstruction (force urine
524 Syncope (caused by asystole) against ob)
Orthostatic hypotension Peptic ulcer (already too much
Cardiac dysrhythmias acid secr.)
Gut or urinary urgency Gastrointestinal lesion or
Diaphoretic effects (sweating) obstruction
Sialogogic effects (salivation) Hyperthyroidism (precipitates
Abdominal cramping arhythmia)
Coronary insufficiency (would
slow heart further)
D E F
526
see muscarine
See Muscarin side effects contraindications
527
See Muscarin side effects, also no nicotinic see muscarine Beth-ann was agonizing over lossing her
effect contraindications boyfriend, who started dating a mushroom
529
530
see muscarine s'have (cev) you eat a melon (meline) for you
See Muscarin side effects contraindications dry mouth.
531
see muscarine Remember: the method (Metha) to diagnose
See Muscarin side effects contraindications asthama.
532
ceptor antagonist):
533
er muscarinic agonists. Antimuscarinics exert their effects through competitive
inic receptors.
D E F
534
538
Contraindications for bunch of ladies standing in line picketing (pro)
Antimuscarinics: Glaucoma for pans and have 4 (quaternary) pans each
Prostatic hypertrophy that are frying mushrooms (muscarinic
Toxicity more severe in children antagonist)
Contraindications for
539 Antimuscarinics: Glaucoma
Prostatic hypertrophy
Toxicity more severe in children
540
541
542
543
544
remember: can drive home (hom) after
contraindicated in pt with BPH ophthamologist treats eye with hom-atropine
546
Got eyes checked to see well in the tropics
547
nemimetics):
548
o accumulate, bind to and stimulate postsynaptic cholinergic receptors. Thus, they
549
550
551
554
556
557
558
559
561
562
Rem: 0ligomycin inhibits the F0
566
Rem: LEAD - EDTA
567
568
ng drugs:
569
olinergic neurotransmission and produce muscle paralysis.
D E F
571
Release of histamine (also resulting in
hypotension) (tubocurarine, mivacurium)
572
573
575
Depolarizing blocker (succinylcholine)
(effects predictable based on similarity to
acetylcholine)
1. Stimulates SA node muscarinic
receptors and ganglionic nicotinic receptors
and may produce various cardiac
arrhythmias.
2. Low doses produce negative
chronotropic effect (blocked by atropine)
whereas higher doses may produce
positive inotropic and chronotropic effects Psuedocholinesterase
via activation of ganglia. deficiency - idosyncratic apnea
Malignant hyperthermia, see extra notes (monogenetic response) (this is
Hyperkalemia (succinylcholine promote K not predictable); Malignant
efflux from muscle cells) hyperthermia
576
Amazonian Indian arrow poisons
577
puffer fish has needles filled with lidocaine
578
579
580
581
582
592
593
594
Remember: an blackwidow storm
595
(acetylcholine storm)
Beavis saying "bungaro" with a smoke (nicotine
596
receptor) as he is bitten by a snake
597
598
599
Antagonists
602
D E F
603
604
605
606
607
D E F
610
612
Schedule 1
Rem: Bo tore his flannel (Bu-tor-phanol) in his
613 state of dysphoria after Luke was capped
Dysphoria (kappa agonists) Schedule 4 (kappa), trying to be a HErO
615
616
618
Abuse potential is higher than analgesia Rem: a pox on any physician who recommends
potential propoxyphene
619
Rem: give Buprenorphine to the orphine to
Not readily reversed by an opioid treat his drug habit, but only give him a partial
antagonist (e.g., naloxone); difficult to dose (partial mu agonist) cause he's weak
reverse respiratory depression (LEO)
620
Seizures epilepsy
D E F
621
Non mu receptor action may cause
unpleasant side effects and limit abuse
potential (ceiling of efficacy due to sigma?
mediated SE)
622
Prolongs fever in pts with shigellosis, toxic Rem: the pt took Loperamide and is now
megacolon in pts with C. difficile; and HUS lopping around from the opioid (opioids work at
in children infected with Shiga toxin- the M/D receptors, mu and delta); or Rem: (the)
producing E. coli. Should be avoided in pts l'opera makes you slow, opiods make one lop;
with bloody diarrhea lopping amide the diarrhea in the streets
625
Schedule II
626
Precipitate withdrawal symptoms on
individuals dependent on mu agonists
(chronic users of opioids)
627
628
D E F
629
CNS: drowsiness, dry mouth, depression
Rebound hypertension (from abrupt
discontinued oral administration, can elicit
hypertensive crisis, common board Rem: the clone goes into the bank to make a
question) withdrawal so he can buy cigarettes, cocaine,
Do not give with beta blocker because heroine, (used to treat drug withdrawl) and he
excessive bradycardia is agonizing over his need (alpha 2 agonist)
630
631
Less constipation than codeine
632
& Gout
633
s 634
639
Rem: take a bat and beat the T cells 80 to 86
times, to stop them (A-baT-acept blocks
CD80/86) from harming the RA pt; but a COPD
pt jumps you first smashing the back of your
COPD as it can make it worse head with his O2 tank (COPD contraindicated)
D E F
643
Rem: add the whole Ab for less IR (Ad-alimum-
Ab)
645
Expensive and renal toxicity
648
hemorrhagic cystitis
649 hemorrhagic cystitis
650
652
See Aurothioglucose
653
See Aurothioglucose
654
NSAID gastropathy
655
D E F
MC hypersensitivity reactions (rashes),
656 precipitate an acute attack of gout (low Acute attack (increases pain
dose to minimize this). Hepatotoxicity even though decreasing uric
(rare, lethal) acid)
657
Low incidence of GI irritation, used with
caution in pts with history of ulcers. Impaired renal function or
Hypersensitivity, sulfa allergies patients prone to urate stones
May induce hypoglycemia by inhibiting
metabolism of oral hypoglycemics.
658 Hepatic metabolism of warfarin
impaired. GI irritation in 10-15%; sulfa
allergies
660
GI toxicities; BM suppression and renal do not give with renal
damage insufficiency
661
matory Drugs
662
D E F
Hypersensitivity to aspirin.
Patients intolerant of aspirin also
may suffer a severe reaction
from ibuprofen-like drugs. Alter
664 platelet function and prolong
bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
D E F
668
Hypersensitivity to aspirin
669
Rem: key-toe roll ack (Ketorolac) is an attack
that is so effect that it actually eliminates pain,
Hematologic toxicity minor or chronic pain but its so strong it cause blood toxicities
670
Contraindicated in aspirin
HS reaction to sulfa allergy, 3rd trimester pregnancy,
No effect on platelets and bleeding time. and pts with a family Hx of
But caution with patients on warfarin. CAD!
D E F
Valdecoxib is associated with an increased
rate of serious and potentially life-
671 threatening skin reactions (e.g., toxic Lesser incidence and less serious GI side
epidermal necrolysis, Stevens-Johnson effects (than aspirin and other non-COX2
syndrome, erythema multiforme) Hypersensitivity to aspirin inhibitor NSAIDs)
672
Hypersensitivity to aspirin
673
Well tolerated, lacks many of the side
effects of aspirin (especially GI, platelet
(bleeding), uric acid excretion)
Acute Overdose: can be fatal due to
delayed liver damage (fatal hepatic
damage, self-poisonings and suicides
has grown), see Liver drugs
674
675
676
677
rugs 678
e the proliferation and function of B and T lymphocytes. Also Corticosteroids inhibit
m phosphoipids.
= eye drops
D E F
680
681
682
683
684
D E F
685
Rem: I'll bet-a deck-a cards that I can piss
further (Betamethasone and Dexamethasone;
longest half-life)
686
687
688
689
690
gynecomastia
691
692
693
694
t Drugs
695
D E F
696
Toxicites are numerous and frequent. They
include a) nephrotoxicity, b) HTN c)
hyperglycemia, d) liver dysfunction, e)
hirsutism and f) hyperkalemia
Increased risk of lymphoma, karposi's
sarcoma and skin cancer have also been
documented.
also toxic to nerves, kidneys, and can
cause diabetes; metabolized by P450
697
also toxic to nerves, kidneys, and can
cause diabetes and hyperkalemia; HTN;
risk of developing post transplant Remember: an organ rolling in tacks, creating a
lymphoproliferative disorders & tack shield that prevent IL-2 from reaching T
lymphomas & de novo nonlymphoma cells inside, steps on some kidneys while he
solid tumors; neutropenia is a rare does it
698
699
Lymphopenia
D E F
702
703
Rem: Dac-LI2-zu-mab Daclizumab
Rem: fresh basil growning on a T cell IL-2
704 receptor, and Basiliximab comes along and just
puts his mouth right on it and sits there
minimal renal toxicity, though synergistic
705 renal toxicity if mixed with cyclosporine;
hyperlipidemia, thrombocytopenia, and
lekopenia
D E F
erapy
712
D E F
713
714
BM suppression and GI upset
716
BM toxicity!! Rem: -plantin = Platinum Alkylating Agent
Renal tubular damage, ototoxicity Rem: Plantin' (Cis-platin) a platinum tree with
718 Extremely toxic CH3s hanging off branches (alkylating agent),
Nausea & vomiting!! and its roots form an X (cross-links). The tree
Bone marrow suppression! is so beautiful it causes you to vomit up your
GI irritation kidney (renal failure), which causes you to
Gonadal suppression sceam, however it only falls on deaf ears
Secondary leukemias (ototoxicity)
Hemorrhagic cystitis!!
719 Extremely toxic
Nausea & vomiting
Bone marrow suppression
GI irritation
Gonadal suppression
Secondary leukemias see immunosuppresant
720 See cyclophosphamide
721
722
Rem: tx ChLorambuciL
723
727
N/V!
728
Rem: the bison (ru-bicin) rode his bike (anthra-
cycline) over topo (Topoisomerase inhibitor)
Nausea & vomiting, Bone marrow because it was infected with anthrax (anthra-
depression; cardiotoxicity (especially cycline) which caused his giant heart to
dysrhythmias); alopecia; stomatitis; explode from his little body (cardiotoxicity) thus
hyperuricemia,; leukemia freeing the radicals from his tyranny
729
730
731
732
733
736
737
Inhibits T cells (sim to AiDS pt) Rem: ribine/rabine are antimetabolites
Rem: clay dripping from your hair; ribine/rabine
738 are antimetabolites; give the man 2CD-A
Very toxic in large dose, give in short doses (canadian saying it) for catching the hairy
over several days monster
739
D E F
740
Profound myelosuppression
GI toxicity, oral mucositis Rem: ribine/rabine are antimetabolites
742
Rem: ribine/rabine are antimetabolites
Rem: Levi missles (Leva-misole) will make your
743
immune system bad ass
744
Nausea & vomiting, oral and GI
ulceration, bone marrow depression Rem: Me so tricky/tricksie (Methotrexate), I
(anemia and thrombocytopenia), convinced cancer to die by giving it a
pulmonary infiltrates & fibrosis, liver water/folate reduction sauce (dihydrofolate
cirrhosis, renal toxicity, osteoporosis, reductase) over its fibrotic lung dinner, but
alopecia, others Leucovorin came to its recue
747
748
749
750
Fluid retention (?used to reduce edema??),
hypertension, diabetes, increased
susceptibility to infection, moon facies.
751 see prednisone
752
Hot flashes; thrombo-embolism; vaginal
bleeding & discharge (vaginitis);
thrombocytopenia peripheral edema, Rem: Tammy on an ox with big ol lumpy
increased risk of endometrial cancer breasts covered with estrogen receptors
755
757
758
760
761
762
763
Rem: -dronate ~ bisphosphonate
766
767
D E F
768
769
770 Rem: I'll just dust some IL-2 on your back and
then whipe the melanoma right off. (al-des-
leukin)
771
772
773
Allergic reaction; rare hemolytic anemia
774
775
776
777
778
779 Interstitial nephritis!! I met a nasty ox
780
Interstitial nephritis!! Also neutropenia I met a nasty ox
781 I met a nasty ox
782
783
784
785
786
787
788
789
790
791
792
793
794
D E F
Rem: I met man tanned the foxes fur; all have
795
f's - all 2nd generations
796
797
798
799
800
801
802
803
804
805
806
807
808
809
Eosinophilia, thrombocytosis, and
leukopenia
810
811
812
Seizures (especially renal insufficency pts
813 or previous CNS pathology), allergic
reaction Rem: see, it stays in (C-il-istat-in)
814 See imipenem
815
816
817
818
l 819
820
D E F
821
822
824
inhibit p450
825 inhibit p450
826
HA Rem: the Godzilla Lizard (linezolid)
827
829
830
831
832
833
834
D E F
840
841
847
PHOTOSENSITIVITY and prolongs the QT Sun burned boxer gyrating and sparring for a
848
interval QT
849
D E F
GI upset, neuropathy, hemolytic anemia in
850
G6DP
s 851
852
853
854
855
856
857
858
859
860
861
gs 862
863
864
865
Rebound HA (with overuse); abuse Do not take with alcohol Rem: (But-al-bital) , Barbiturate - relaxes
potential (schedule 3 with tylenol) (additive effects) muscles
872
see Ergotamine, less nausea than
ergotamine, but still requires anti-emetic Rem: Dihydroergotamine is an ergot alkaloid
874
See Metoclopramide, drug induced SLE
875
See Metoclopramide
876
see CCB above
877
asthmatics, COPD
hepatotoxicity & thrombocytopeina, weight
878
gain
D E F
880
882
city 883
Drugs
884
Classic side effects of antimuscarinics (dry
mouth, urinary retention, constipation etc). Prostatic hyperplasia,
Will make dementia worse (especially obstructive GI disease,
Alzehimers, antimuscarin exacerbates). glaucoma
885
See Biperiden See Biperiden
886
See Biperiden See Biperiden
D E F
erythromelalgia, vasospasm;
892 Psychotomimetic and dyskinetic effects
typical of dopaminergic treatment of PD;
Postural hypotension nausea, somnolence,
mental disturbances, hallucinations
See bromocriptine; also cardiac Rem: (Pergolide) Pergo lied about her age, she
valvulopathy involving one or more valves said she was 21 (D1/D2) but she was really old
893 - consistent with the valvulopathy (old treatment of PD), you could tell by the
associated with carcinoid syndrome and horrendous sound of her cardic valve
with the use of other ergot alkaloids. flapping/snapping
D E F
894
No ergot associated side effects; postural
hypotension (D2 agonists are hypotensive
via peripheral DA receptors in vasculature), Rem: the Parkinson's pt felt so good after
dyskinesi, nausea, somnolence, Mental taking his Pramipexole he primed his pecks
disturbances, hallucinations, etc. (Pra-mi-pex-ole) for his new date tonight.
895
See Pramipexole
897
898
900
D E F
903
905
906
(if give at night, it will cause really high bp,
so only give in morning and at noon)
907
908
909
910
911
912
913
914
D E F
916
Antiepileptic drug idiosyncratic rxns (see Rem: zepine and zepam seems to be generic
extra note) Toxicity: ataxia, rash, blood for seizure; Rem: A car exploded (Car-bam-a-
917 dyscrasias (leukopenia or aplastic zepine), set by a group of salt mine workers
anemia!!), diplopia, teratogen (Na) who are angery and protesting because
Induce P450 (increases metab of they got seizures from their working conditions;
contraceptives); also increase steroid H FDA pregnancy category D Rem: RC PP induces P450 (rifampin,
binding protein. Hyponatremia carbamazepine, phenobarbital, phenytoin)
918 Sedation, weight loss, nephrolithiasis
Rem: the ox driving the car (Ox-car-bazepine)
919 eating fries, heavily salted (Na channel blocker)
Serious: Hyponatremia (more common in - the ox keeps dumping more Na on to fix his
elderly), rash hyponatremia
932
Idiosyncratic rxn
enia933
Gravis
936
938
939
Bone marrow suppression (leukopenia), GI
signs (diarrhea, vomiting typical of high
dose); Allopurinol increases 6-
mercaptopurine levels
Toxicities are numerous and frequent;
nephrotoxicity and hypertension are
940 notable -- limits use in patients with pre- Toxicities are numerous and frequent;
existing renal disease or uncontrolled nephrotoxicity and hypertension are notable --
hypertension. See Immunosuppresants limits use in patients with pre-existing renal
above disease or uncontrolled hypertension.
D E F
943
944
see Anticholinesterases above
945
947
D E F
948
949
rugs
950
954
957
958
960
963
969
See Phenelzine SSRI
970 See Phenelzine SSRI
971 See Phenelzine SSRI
rs
973
978
979
980
cs 981
982
983
Somewhat more sedative (give at night); Rem: Quetiapine quites the voices in the
Implicated in type 2 diabetes incidence schizo's head
D E F
986
Remarkably low incidence of SE, including Rem: Ari only gave the schizo a partial slice of
no tardive, and less weight gain than pie (Ari-pi-prazole; partial D2 agonist), even
olanzapine; No incidence of Type 2 though he wasn't gonna get the diabetes or get
diabetes; akathisia very common fat
Potential for polongation of QTc intervals
987 (caution pts with hx of AV block and
arrhythmia)
D E F
989
991
See Chlorpromazine
992
See Chlorpromazine
994
See Chlorpromazine
notics
996
997
D E F
998
999
See diazepam
1000
Potential for early morning awakening,
tolerance/dependence if over used Rem: -am = BZD
1001
Leukopenia; mild elevation of lactate
dehydrogenase
1002
D E F
1003
1005
1007 10% can't tolerate because it increasses Rem: can drive the bus (no motor impairment,
anxiety; High dose can cause anxiety. Bus-pirone), to the zoo to see the Piranhas (no
Poor patient acceptance, dizziness, anxiety to see them) and throw 5 partial
nausea, vomiting. MAOI will increase BP bananas (K+) to the monkeys
1008
1009
1013
Depression or hx of depression
is contraindicated
Drugs
1019
1020
1023
Schedule II agent - potential for
abuse/dependence.
Insomnia!!, reduced weight, emotional
lability (flip flop), significant potential for
diversion (parents, ADHD patient, other
siblings) HIGH ABUSE POTENTIAL
Rem: pommelling the liver (Pemoline,
1024 hepatoxicity), riddling (same as ridalin) your
Less used due to hepatotoxicity but no liver with bruises (no abuse, or can't see
abuse potential (essentially) abuse)
1028
1033 Primary pulmonary HTN, See Rem: it's fun to mine (Phen-ter-mine), cause
Benzphetamine See Benzphetamine you lose weight
1034 Lethal SE
1035
Tolerance develops within days or weeks
Rem: Sir Butt Rammin' (Sibutramine) is taken
Serah (serotonin) in the @$$, (though he can
1036 Dry mouth, headache, constipation, F&%k NEbody), he's thinking she needs to loss
insomnia, some risk of increased BP weight - maybe she will after she fixes the
(monitoring required) constipation
1037
Initial flautlence and loose stools which
may occur after high fat meals
(steatorrhea)
1038
D E F
Rem: Meg wanted to eat, so she eat Mega-
1039 struddles (Meg-e-strol)and gained all sorts of
weight
eatment
1040
1041
1042
1045
1046
Rem: my piss is foamy from the antifreeze in it
(Fome-piz-ole)
No's
1047
1048
D E F
1049
1050
1051
1052
D E F
1053
1054
1055
1056
1057
1058
1059
D E F
1060
Rem: Flunitrazepam is the flun (fun)
benzodiazepine
1061
1062
Toxicity related to vasodilation -
headache, peripheral pooling of blood, combination of Viagra and
decreased myocardial flow poppers can be deadly
G H
1 Extra Notes Extra Note
BPH S&S:
More frequent urination, especially at night
Sub sets of alpha1A, B, and D (all three seen in prostate, alpha1A Feeling an urgent need to urinate
9 predominates in prostate; alpha1B predominates with arterials) Having difficulty urinating or straining
both have mosaics of receptors. There is also an alpha2 family (A, Pause/prolonged amount of time before the urine flow starts
B, and D); all of these receptors are most likely expressed on A very weak urinary stream
receptive tissues, but the relative amount changes (eg A urine stream that starts and stops
preponderance of alpha1B in arterials) Feeling of incomplete emptying of the bladder
G H
10
Relaxation of muscle (Relatively few alpha-1 receptors in the body
of the bladder)
Sympathetic stimulation causes contraction of trigone, therefore Symptomatic improvement
blocking this results in relaxation and hence voiding Does not arrest or reverse the underlying prostatic hyperplasia
11
15
Tadalafil:
Much longer lasting, with a significantly greater likelihood of
16 priapism
Much less visual disturbance (if any)
Higher incidence of muscle ache complaints (5%)
One advantage with this drug, the mother may change her mind
17
and suckling will usually override the effect.
Bromocriptine and Cabergoline can be taken orally, or
administered intra-vaginally to reduce nausea. Nausea associated
18 with bromocriptine is due to: effect of Dopamine on CTZ
(chemoreceptor trigger zone) via D2 receptors. The CTZ is a
group of cells situated close to the area postrema on the floor of
the fourth ventricle
G H
20
21
25
The progestagenic component should have low androgenic
activity (ex. Desogestrel)
Reduce free androgens by increasing the amount of plasma
SHBG
The pill does not stop follicular development and when not taken Sequential (E, then P) or E alone oral contraceptives will
for one or more days ovulation may occur. Must be taken faithfully inhibit the H-P-G axis, thus reducing ovarian androgen
(99% effective) production
26
Norplant system:
Injectalbe effective for long-term contraception Also effective for long term contraception - releases much
27 Not good for women who want to get pregnant soon after less steroid as oral agents;
discontinuation of treatment Disadvantages include need for surgical implantation and
Takes awhile for H to be cleared removal, and some irregular bleeding
29
31
Prodrug: Norgestimate converted to L-norgestrel
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32
Rank order of androgenicity:
Norgestrel >> norgestimate > norethindrone > desogestrel
35
Sources for testosterone:
In male: Testosterone is principally bound to SHBG (sex H binding
- produced primarily by testis (Leydig cells) globulin) or albumin (only about 2% is free-circulating
- only about 5% produced by adrenals hormone the bioavailable amount). Converted to DHT
Levels in women: ~0.03ug/dL (dihydrotestosterone) by 5-reductase type II (but also by
Levels in men (post-pubertal): 0.6ug/dL type I, especially CNS)
36
Propionate, cypionate esters of testosterone can be administered
37 parenterally. While they have greater activity, they have prolonged
absorption times
39
40
41
Danazol: Can bind to AR, GR and PR, but not ER;
By binding to SHBG, may increase clearance of hormones
42
43
G H
44
Rem: hem-abate = blood stop
PGE2 keeps ductus arteriosus open, thus large ingestion of
45 aspirin may cause fetal death
46
48
49
51
Tell pt to stop taking multi vitamins (for the folate)
52
53
54
55
G H
Drug Interactions:
Aminoglycosides: Ototoxicity!! Normal physiology: Symporter is electrically neutral,
Digitalis (digoxin/digitoxin)!!: Enhanced efficacy of digitalis however, net result is excess K+ in the ascending loop cell.
56 (mechanism related to hypokalemia) enhanced likelihood of K+ follows concentration gradient back into lumen. Therefore,
arrhythmias the lumen become positively charged. Positive lumen charge
Sulfonylureas used for Type II diabetes: Hyperglycemia drives divalent cations out of the lumen via paracellular
Lithium (used in treating bipolar disorder): Na is preferentially pathway.
excreted Loop Diuretic: Na+, K+ transport is blocked. Note: Almost
NSAIDs (e.g., aspirin, ibuprofen): Blunted diuretic response; also immediately after the (blocked) symporter segment of the thick
blunts response to loop's ability to reduce pulmonary edema ascending loop, a different transporter exists for K+. K+ is
(mech related to prostaglandins released by the kidneys to cause essentially entirely reabsorbed at this site . Net loop diuretic
vasodilation and rapidly reduce pulmonary edema) result across these segments is increased loss of Na+ without
Thiazides: Diuretic synergism - use thiazide and loop diuretic loss of K+; block of Na+, K+ transport leads to a relative loss
together to help tx CHF refractory to loops alone (thiazide blocks of positive charge in the lumen (less driving force for K+ to
distal Na resorption) back diffuse). This in turn leads to less reabsorption (potential
for greater urinary loss) of Ca++ and Mg++
57
60
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61
Note there are 2 sites of action (both are important): Net effect is
reduced HCO3- going back into blood, and less H+ available in Carbonic anhydrase is also present in the eye, where it is
nephron to serve as counter ion for Na+ reabsorption. involved in the production of aqueous humor
63
64
65
68
69
70
71
73
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74
ACE is also the same enzyme as Kininase II, which is the enzyme
that inactivates bradykinin. Note that bradykinin is: Tissue irritant, Mechanism and Effects:
vasodilator, a candidate for why ACE-I drugs inhibit cardiac Block conversion of angiotensin I to angiotensin II by inhibiting
hypertrophy Angiotensin Converting Enzyme (ACE):
ACEI cough: 3-39% of pts decrease angiotensin II-mediated release of aldosterone
Elevated bradykinin in the lungs produce dry, non-productive, decrease breakdown of bradykinin
Irritating cough; dose-related, but seen in the therapeutic range; decrease overly active SNS (little reflex tachycardia),
not seen with ARBs; elevated bradykinins!! also may rarely decreasing preload, decreasing afterload which then
cause angioedema (Remember: Greg Brady entering the vessels decreases BP
and tissue swells with his offspring abundance)
75
Remember: not anal (Enalapril) cause its pro-drug, pril - ACEI
76
78
Advantages:
Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Diltiazem and verapamil are relatively selective for cardiac
myocyte Ca channels
Advantages:
79 Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Not used with pt with CHF (actually accelerates CHF, has
negative inotropic effect)
80
Not associated with AV block (as beta blockers)
81
82
Mechanism is unknown
Decreases systemic vascular resistance (decreases
General effect: afterload), which leads to increased stroke volume
decrease PR, causes compensatory responses (initiated by Has minimal effects on venous capacitance. Therefore, most
baroreceptors) of increased SNS and increased RAS. effective when combined with venodilators
Consequences of SNS and RAS activation: increased SNS with When combined with isosorbide dinitrate, the
arterial block but venous constriction, increased HR and CO, Na+ combination has been shown to decrease mortality in
and H2O retention CHF (but not as effective as ACEIs)
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83
84
85
93
94
95
Does not work on anaerobes
96
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97
Pharmacokinetics
98 Rapid absorption following oral administration
Oral absorption impaired by divalent cations-antacids
Excellent tissue/fluid distribution
Excreted mainly through kidney by tubular secretion & by
glomerular filtration
99
100
101
Resistance
Mainly due to production of beta-lactamases; Due to reduction of Blood level of penicillin can be raised by simultaneous
102 permeability of the outer (porin pores) of gram negative bacteria; administration of probenicid, impairs tubular secretion of
Due to modified penicillin-binding sites penicillin
Pharmacokinetics Susceptible to beta-lactamases, used in combination with
Excreted rapidly via the urine; 10% glomerular filtration; 90% beta-lactamase inhibitors such as clavulanic acid,
tubular excretion; probenecid prevents tubular secretion sulbactam, and tazobactam
G H
103
104
105
106
107 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug
P/C open bacteria to allow AMP to reach target
108 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug Antibiotics causing poluria: demeclocycline, methacillin,
gentamicin
109
Note the difference between spectinomycin and streptomycin
110
Resistance
Very similar to penicillin
Degraded by beta-lactamases
111
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112
113
Most effective against Klebsiella (even though first gen are most
effective against gram +)
Resistance
114 Transmitted by plasmids TC affects both pro- and eukaryotic cells
TC resistance genes are closely associated with those of AMG, Mammalian cells have both the uptake and the efflux systems
sulfonamides, CAP for TC
Plasmids usually transmits resistance to multiple drugs rather than Bacteria have only uptake system. Can concentrate TC
TC alone Resistance bacteria have active efflux system
116
117
118
119
120
121
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122
123
124
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
Safe during pregnancy
125
126
128
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129
130
131
133
134
135
136
Antacids should be prescribed on an as-needed-basis for During anesthesia, coma, cesarean section, or
symptom relief, but only if the patient reports symptomatic relief endoscopy, aspiration of gastric contents can cause
after antacid administration. Drawbacks include: lack of patient aspiration pneumonitis - sodium citrate (Bicitra, a clear liquid
compliance, nocturnal acid secretion, and interaction of antacids antacid) is used prophylactically to neutralize gastric contents
with other medications. Antacids typically only provide short-term in these situations. Oral or IV administration of H2 blockers is
symptom relief but act rapidly. also used for this purpose.
G H
137
138
139
140
141
Misoprostol and H2 antagonists are the only agents with proved
efficacy in preventing NSAID-induced mucosal injury.
Pirenzepine is an antagonist relatively selective for the M1 receptor subtype in the stomach and is being tested as a potential
antisecretory drug. Other, older compounds, particularly quaternary amines with few CNS side effects find limited use as GI
142 antispasmodic agents, e.g. dicyclomine (Bentyl). Other available cholinergic antagonists such as hyoscyamine sulfate (Levsin,
IB-Stat) glycopyrrolate (Robinul) are still used occasionally for their GI antispasmodic activity but are associated with typical
anticholinergic side effects such as dry mouth, urinary retention, and tachycardia. Muscarinic agonists, such as bethanechol, find
some limited use for stimulating GI motility.
G H
144
146
148
149
G H
These opiodes penetrate into the CNS poorly and can inhibit
151 diarrhea at doses that produce few central effects.
Atropine is added to diphenoxylate and difenoxin preparations,
primarily so that the unpleasant anticholinergic side effects will Agents Used to Treat Diarrhea - General Considerations:
discourage abuse. Atropine may have some capacity to slow Excessive fecal loss of fluid and electrolytes that characterizes
motility, but usually much higher doses are required to achieve this diarrhea is an important aspect of many infectious and non-
effect. Loperamide alone or in combination with antibiotics infectious GI diseases. Although nonspecific drug therapy for
(trimethoprim, trimethoprim-sulfamethoxazole, or a diarrhea is the norm clinically, knowledge of the types of
fluoroquinolone) has been effective in controlling the symptoms of diarrhea can help determine when to use nonspecific agents
travelers diarrhea. or more specific agents.
Atropine is added to diphenoxylate and difenoxin preparations,
152 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.
Atropine is added to diphenoxylate and difenoxin preparations,
153 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.
154
peptide must be given parenterally (SQ); useful for treating the symptoms of tumors of the GI tract (carcinoid, VIPoma,
glucagonoma, gastrinoma, insulinoma), AIDS-related diarrhea, and various motility disorders. Octreotide can inhibit the secretion
of hormones involved in vasodilation. This property makes octreotide useful in treating variceal bleeding and orthostatic
155 hypotension. Octreotide increases splanchnic arteriolar resistance and decreases gastrointestinal blood flow, hepatic-vein
wedge pressure, hepatic blood flow, portal vein pressure, and intravariceal pressure. Decreased blood flow to the portal vein
reduces portal venous pressure in patients with cirrhosis or portal hypertension. A majority of patients with portal hypertension
have a reduction in variceal bleeding when given octreotide.
G H
Stimulant Laxatives
1) Diphenylmethane derivatives: phenolphthalein (Modane, Ex-Lax, Feen-a-Mint, Correctol, etc.) and bisacodyl (Dulcolax,
157 Carters Little Pill). Effective doses vary widely among patients. Soft or semiliquid stool occurs within 6-24 hours.
Phenolphthalein causes pink to red colored urine and feces. Can cause gastric irritation, electrolyte imbalance, and allergic
reactions are possible. Use of these agents should be limited to 7 days at most.
2) Anthraquinone derivatives: senna, cascara, rheum (rhubarb), and aloe. Produce laxation after about 6 hours. These agents
may produce an excessive laxative effect and abdominal pain and yellowish brown to red urine. May cause nephritis.
Saline laxatives:
Magnesium sulfate (Epsom salt) - intensely bitter taste may
produce nausea; magnesium hydroxide (Milk of Magnesia)
liquid suspension of Mg(OH)2 or as tablets; magnesium citrate
oral solution, or sodium phosphates oral solution (FLEET
158
PHOSPHO-SODA) is relatively pleasant tasting
Sodium phosphate (FLEET) enema is the DOC for fecal
impaction.
Saline laxatives produce laxation with a delay of 6 to 8 hours in
lower laxative doses and a thorough fluid evacuation in less than
3 hrs when administered at higher cathartic doses.
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Osmotic laxatives
a) are not absorbed and are resistant to digestion, increase osmotic pressure in lumen and water content of stools.
b) Lactulose is a disaccharide broken down by bacteria in the GI to fructose and galactose. These metabolites are only partially
absorbed and increase osmotic pressure in the GI lumen. Used to lower blood ammonia levels in patients with portal
hypertension and hepatic encephalopathy.
159
c) Glycerin administered as a rectal suppository softens and lubricates the passage of hard stool.
d) Sorbitol and mannitol are sugars administered rectally, orally, or as an enema.
e) Polyethylene glycol-electrolyte solutions (Colyte, GoLYTELY) are the drug of choice for bowel preparation for colonoscopy,
barium enema, or colorectal surgery. These preparations are mixtures of sodium sulfate, bicarbonate, and chloride, and
potassium chloride in an isotonic solution containing ethylene glycol. Patient drinks four liters of solution over 3-5 hours. Causes
most complete evacuation of GI tract; copious, watery diarrhea.
161
167
168
169
170
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174
175
176
180
181
184
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186
187
188
189
190
191
192
193
194
195
196
197
198
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202
203
204
209
210
211
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212
216
217
218
219
220
221
Class 1A:
222 1. Reduce automaticity (phase 4, reduce slope of upstroke,
AP becomes broader)
Rarely used;has a vasodilator effect so can be used in reduced 2. Prolong action potential duration
vent function or HF; also has a indirect anticholinergic effect that 3. Reduce conduction velocity (phase 0, slope also reduced)
will decrease vagal tone and may facilitate condion in the AV node Note: (phase 3 affected, not 4, according to Lange)
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Class 1B
Reduce automaticity
Shorten APD (narrow QRS)
225 Slow conduction velocity
Have little or no effect on atrial tissue Antiarrhythmic Class Class IB include lidocain, mexiletine,
all other classes work above ventricles and tocainide - modest Na channel blockers that shorten
Moderately effective for ventricular arrhythmia the action potential duration (APD) and refractoriness with
only used for V!! little effect on PR, QRS, or QT intervals
227
228
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230
231
eliminated by the liver CYP2D6; if CYP2D6 deficiency have slow
elimination of propafenone and develop significant receptor
antagonism at low doses
232
Amiodarone:
prolonged half-life of 30 days - makes difficult to use to
reach steady state (4-5 half lives) requires half a year (3
months for effect), and if make a mistake, takes 5 half lives to
get ride of , must follow pt closely (have foresight)
235
Rapid effect when given IV
Side Effects
Hepatotoxicity
Hypo and hyperthyroidism
metabolized to desethyl metabolite (DEA) in the liver; half life of Corneal deposits
5hrs to 30days (Cecil says 103days); IV HAS A RAPID EFFECT Irreversible pulmonary fibrosis (permanent)
236
oxidative hepatic metabolism and cleared by the kidney
237
eliminated by liver (CYP3A4) and kidney; half life=8-10 hrs but
12% to 18% lower in women
Antiarrhythmic Class IV: Ca channel antagonists; dont
affect the Phase2 plateau???; poor effect as direct
238 antiarrhythmic for atrial or vent arrhythmias, most effective
on slowing conduction velocity (Phase 0) in nodal
tissues; useful for the control of vent rate in SVT
239 CCB and beta blockers have ~same effect in heart - slow
conduction velocity in the AV node (prevent SVT from getting
to V)
240
241
243
250
Clopidogrel:
Alternate to, or additive with, aspirin Approved for the prophylaxis of stroke, MI, peripheral arterial
Inhibits ADP pathway in platelets disease, and acute coronary syndrome. This drug
251 Reduces platelet aggregation irreversibly inhibits platelet fibrinogen binding. Clopidogrel
NO EFFECT ON PROSTAGLANDINS preferred over aspirin: selectively inhibits the binding of adenosine diphosphate
if loop diuretic is being used (ADP) to its platelet receptor and the subsequent ADP-
if kidney disease is present mediated activation of the glycoprotein GPIIb/IIIa
Particularly useful in unstable angina complex, thereby inhibiting platelet aggregation.
253
Ticlopidine (Ticlid) inhibits the platelet ADP receptor and inhibits
the binding of fibrinogen to activated platelets, and thus blocks
platelet aggregation and clot retraction. The effect on platelet
function is irreversible for the life of the platelet.
G H
257
258
260
263
266
G H
268
270
271
Also give broad spectrum Abx and Xigris for sepsis and DIC
272
273
G H
274
275
276
G H
277
278
280
281
282
283
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285
286
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287
Treatment of Iron Deficiency Anemia Prophylaxis: Generally, prophylactic use of iron preparations
The severity and cause will determine the appropriate approach should be reserved for individuals at high risk; pregnant and
to treatment. lactating women, low birth weight infants and infants
Symptomatic elderly patients with severe iron deficiency anemia maintained on unsupplemented milk formulas. Other
and cardiovascular instability may require red cell transfusions. patients at high risk include rapidly growing children (low
For the majority of cases, oral iron therapy is sufficient. meat diets) and in adults with chronic blood loss.
All dividing cells are undergoing DNA synthesis and require the
precursors and cofactors necessary for synthesizing the purine
and pyrimidine bases in DNA. Two of these essential factors are
288 vitamin B12 and folic acid. Deficiencies in either of these two
substances lead to impaired DNA synthesis and abnormal
maturation and functioning of cells. These changes occur in Megaloblastic anemia: In vitamin B12 or folic acid deficiency
any dividing cells, but tissues which normally undergo rapid cell there is decreased DNA synthesis, but continued RNA and
division, i.e., hemopoietic cells and GI epithelium, are the most protein synthesis which leads to a characteristic production of
susceptible. Anemia is the chief finding in patients with Vitamin large (macrocytic) red blood cell precursors (megaloblasts)
B12 or folic acid deficiency; GI symptoms may also occur. that do not mature properly into circulating red cells. The
Neurological abnormalities may also occur in Vitamin B12 bone marrow is hypercellular and the red cells formed are
deficiency, but not usually in folic acid deficiency. more susceptible to destruction.
G H
Colony stimulating factors (CSFs) have only been recently purified and their physiologic functions and mechanisms of action are
incompletely understood, but these molecules hold great promise for treating anemias and myelodysplastic disorders.
a. SCF (Multi CSF): stimulates bone marrow production of RBCs, granulocytes, macrophages, and platelets.
290
b. GM CSF: stimulates production of granulocytes and macrophages.
c. G CSF: stimulates granulocyte proliferation and differentiation.
d. M CSF: stimulates monocyte macrophage proliferation.
e. Other cytokines: numerous other factors influence bone marrow derived cell proliferation, differentiation, and function
including the interferons (alpha, beta, gamma), the interleukins (1-12), and other factors.
293
297
298
First-generation sulfonylureas vary considerably in their half lives,
299
duration of action, and extent of metabolism
300
301
302
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304
305
Repaglinide & nateglinide are structurally different from Repaglinide and nateglinide were developed to manage meal
sulfonylurea drugs; they are meglitinides. Meglitinides binds to the related glucose loads. The rapid action of these drugs
ATP-sensitive potassium channel on pancreatic beta cells at a (taken right before a meal) makes them useful for patients
different site than sulfonylureas. The subsequent who are erratic eaters. For example, if a meal is skipped so is
306
depolarization of the beta cell opens the Ca channel and rapidly that dose of drug and hypoglycemia is avoided. Only the first
increases insulin secretion. Thus, these drugs are sometimes phase of insulin secretion is stimulated because of the rapid
called non-sulfonylurea secretagogues. Both of these drugs are metabolism of the drugs. These drugs are approved for
well absorbed and reach peak levels within 30 to 60 minutes. monotherapy or combined with metformin. Adverse effects
These drugs are rapidly metabolized by the liver to inactive are comparable to sulfonylureas but these drugs should be
metabolites that are excreted in the bile or urine. used cautiously in the elderly and those with liver dysfunction.
307
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309
311
312
313
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321
322
323
333
334
335
339
340
343
344
345
348
Osteoprosis Tx: Combination of estrogen-calcium or estrogen-
BPs; Statins also prevent fractures and enhance bone formation in
rodents
Combination of estrogen-calcitonin or estrogen-BPs appears to
have additive effects in increasing BMD.
349
355
356
357
358
361
362
363
364
Monitoring required the following: pregnancy test, CBC, liver tests,
lipid panel and psychiatric symptoms
G H
365
366
367
371
Terbutaline can also be given orally, or as subcutaneous injection,
or IV infusion.
G H
374
Over use may lead to tolerance, some data suggests overuse of
beta agonist may worsen condition, still debated
375
376
377
378
MAO breaks E down very rapidly, short acting
379
380
381
G H
385
386
G H
387
1. The development of aerosol formulations or aqueous
intranasal sprays significantly improved the safety of
corticosteroid treatment for moderate asthma or other respiratory
disease. 2. Asthmatics who require inhaled -adrenergic
agonists four or more times weekly are viewed as candidates
for inhaled corticosteroid. 3. Available preparations are viewed Asthmatic patients maintained on inhaled corticosteroids show
as being equivalent in efficacy and potential adverse effects, but improvement of symptoms and lowered requirements for
vary considerably in amount of drug aerosolized per inhaler rescue with -adrenergic agonists. Improvement may be
activation. Therefore, the dose of inhaled steroid must be seen within one week, may continue for up 2 years or longer,
empirically determined for each patient. and reductions in dose over time are often possible.
388
389 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema)
from inflammed turbinantes (anti-histamines do not)
390
391 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema) All inhaled glucocorticoids are effective give twice a day
from inflammed turbinantes (anti-histamines do not) (budesonide can be given once a day for mild asthma)
392
393
G H
397
398
400
401
G H
402
Stimulate vasoconstriction in the nasal mucosa, primarily
Nasal decongestants that are -adrenergic agonists that cause on venous sinusoids, resulting reduced edema, i.e.,
vasoconstriction via activation of 1-adrenergic receptors are decongestions; They are effective only for relief of nasal
found in many, many over-the-counter preparations. congestion and (not?) for sneezing, itching, or discharge.
403
404
406
Inhibits P450
407
413
Opioids are orally active, metabolized in the liver and renally
excreted.
414
416
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417
418
419
420
422
Mycobacterium tuberculosis
Tuberculosis still the leading cause of death by infectious disease
throughout the world
Increasing incidence in USA, AIDS patients, homeless, immigrants
423 Difficult to stain & acid-fast
Grows slowly and are relatively resistant to most antibiotics,
therefore must treat for months - years
Lipid-rich cell wall impermeable to many agents
Substantial portion of organisms are intracellular, so inaccessible Treatment divided into:
to drugs which penetrate poorly 1. treatment of latent infection diagnosed by a positive PPD
Many resistant strains so use multiple drug therapy 2. treatment of active clinical TB
424 For patients who cannot tolerate rifampin: 9-12 months of INH
+ ethambutol + pyrazinamide +/- a fluoroquinolone (levofloxacin,
moxifloxacin, gatifloxacin)
Rifabutin has been substituted for rifampin in some patients who
could not take rifampin because of drug interactions (HIV patients Resistance to rifampin: isoniazid + ethambutol for 18mo or
on multiple drugs) isoniazid + pyrazinamide + streptomycin for 9mo
425
Do not use rifobutin with ritonavir or delaviridine (protease inhibitor
and NNRTI respectfully)
G H
426
429
Other second line drugs include: Ethionamide, Aminosalicylic Acid, Streptomycin bacteriacidal for actively growing extracellular
Capreomycin, Cycloserine organism
430
431
432
433
434
Conventional amphotericin deoxycholate (Fungizone) older, non-
lipid formulation, least expensive - Better tolerated, new
formulations replacing this drug
Lipid Formulations: three lipid formulations are available; generally
better tolerated, nephrotoxicity is less severe than with
conventional Ampho B
435
436
437
438
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439
440
441
442
443
444
445
446
447
448
449
450
451
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
G H
452
453
454
455
456
457
458
H1 receptors activation results in:
bronchoconstriction
Storage location of Histamine: exocrine excretion (?)
1. mast cells major source of stored histamine in mammalian increase capillary permeability
tissues contraction of intestinal smooth muscle
2. basophils basophilic leucocytes of the blood contain stored stimulation of sensory nerve endings
histamine Cellular signaling mechanism
3. CNS and peripheral nerves - increase phosphoinositol hydrolysis, increase intracellular
Histamine Receptors- H1, H2, and (H3 not relevant clinically); all Ca++
are G protein-coupled receptors Distribution: smooth muscle, endothelial cells, brain
459
460
461
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462
464
465
466
Second-Generation Antihistamines: These drugs penetrate Allergic Conjunctivitis: the most common form of ocular allergy, is usually associated with allergi
poorly into the brain and are much less likely than 1st-gens to seasonal or perennial. An oral antihistamine, a 2nd generation, relatively non-sedating drug such as
have adverse effects on the CNS; The oral drugs loratadine fexofenadine, or loratadine is recommended to relieve the main symptom, itching. Antihistamines fo
(generic [$21.30], Claritin [$27.30], Alavert [$16.50]) and also available.
467 desloratadine Clarinex [$63.29] are non-sedating in recommended Topical decongestants reduce erythema, congestion, and eyelid edema; their adverse effects includ
doses; with higher doses, sedation may occur; Fexofenadine rebound hyperemia and conjunctivitis medicamentosa.
(Allegra [$84.62]) has been free of sedative effects; Cetirizine Antihistamine/decongestant combinations such as pheniramine/naphazoline (Visine A, and others)
(Zyrtec [$63.29]) is sedating in some patients but has a better antazoline/naphazoline (Vasocon-A) available OTC may be more effective than either agent alone, b
established safety record in young children than the other drugs; of action and may cause rebound vasodilation with continued use.
No well-controlled trials have convincingly established that any one Topical corticosteroids should only be used as a last resort because they are associated wit
of the 2nd-generation drugs is more effective than the others. pressure, cataract formation and complications with viral infections.
468
469
471
472
473
474
475
476
477
Alpha1 Receptor Distribution and Effects of Stimulation:
Arterioles/Veins Constricts
Eye (Radial Muscle of the Iris) - Contracts (leads to pupil dilation Alpha2 Receptor Distribution and Effects of Stimulation:
mydriasis) NE Nerve Terminals - Decreases NE outflow (autoreceptor)
Intestine- Constricts sphincters, Decreases motility CNS - Decreases sympathetic outflow
(hyperpolarization leads to relaxation), Also : Inhibit release of insulin
Prostate (note: this is an 1A receptor; vascular alpha receptors Relaxes intestinal smooth muscle
are likely 1B) - Contraction, Promotes tissue growth
Urinary bladder sphincters - Constricts
G H
478
479
Net effect: Positive inotropic effect, but reflex bradycardia
because of increased systolic and diastolic blood pressure.
G H
481
2 Selective Adrenergic Agonists: As a group, 5-10X more
potent at 2 than 1 adrenergic receptors.
Therefore more selective for smooth than cardiac muscle.
Longer acting than catecholamines.
COMBIVENT = albuterol + Ipratropium bromide Tolerance may develop.
482
483
487
488
As non-catecholamines, they are metabolized slowly and are
effective p.o.; They are non-polar and penetrate the CNS;
Generally display a higher ratio of CNS to peripheral CV effects.
However, vasoconstriction and a positive inotropic effect are
present.
489
Relatively insensitive to degradation by MAO and COMT. Effective
p.o.
491
492
493
494
495
496
497
498
Adrenergic neuronal depleting agents. These should only be of Does NOT get into CNS (highly polar)
historical interest, but they still show up on Boards. Basis of Board questions concerning this agent vs. reserpine;
499
500
501
502
503
G H
505
506
G H
508
use very cautiously if at all in patients with reactive (asthma)
airways.
509
510
511
514
516
G H
Sub sets of alpha1A, B, and D (all three seen in prostate, alpha1A
517 predominates in prostate; alpha1B predominates with arterials)
both have mosaics of receptors.
518
520
Notice the RAS system and sympathetic tone is very high during Approved for class II and III heart failure
521 HF, so to give Carvedilol in the face of high sympathetic (acute Use results in decreased hospitalizations and all-cause
heart failure) are contraindicated because already high mortality
sympathetic with poor heart function, would percipitate acute HF. Improves symptoms and slows progression
Beta blocker improve mortality once HF is undercontrol.
522
523
524
Muscarinic Cholinergic Receptors
TOXICITY (controlled by atropine) Contract smooth muscle.
Syncope (caused by asystole) or orthostatic hypotension Apparent discrepancy ACh & muscarinic agonists given IV
Cardiac dysrhythmias (decreases refractory period in atria) cause vasodilation, due to release of nitric oxide (NO)
Gut or urinary urgency Smooth muscle sphincters can be relaxed by parasympathetic
Flushing, sweating, epigastric distress, abdominal cramps, stimulation, this is due to release of NO or other non-
salivation. adrenergic, non-cholinergic neurotransmitters (NANC) like
ATP
G H
525
see muscarine other effects
526
Although not normally evident, nicotinic effects of
acetylcholine can be observed when muscarinic receptors are
blocked by atropine ("unmasking" of nicotinic effect). In this
The choline esters are quaternary ammonium compounds; they do case, the effect of acetylcholine is to stimulate sympathetic
not penetrate the blood-brain-barrier and have little or no direct activity (via stimulation of nicotinic receptors at ganglia and
CNS actions following systemic administration. the adrenal medulla).
527
The choline esters are quaternary ammonium compounds; they do
not penetrate the blood-brain-barrier and have little or no direct
CNS actions following systemic administration.
The choline esters are quaternary ammonium compounds; they do
528 not penetrate the blood-brain-barrier and have little or no direct
CNS actions following systemic administration.
529
530
533
G H
534
535
537
538
539
540
541
542
543
544
545
G H
546
547
548
550
G H
552
The nerve agents are all liquids at room temperature and are
divided into two major categories. Those that are volatile and
nonpersistent are the G-agents. Those that are nonvolatile and
persistent - being VX. The G-agents, being volatile, represent
more of a vapor threat but also a liquid threat. If left over time they
553 will eventually evaporate and dissipate in an open environment
and therefore are considered nonpersisent. VX, on the other
hand, is more the consistency of cooking oil and is nonvolatile. It
does represent a vapor threat but represents a significant liquid
threat. The risk of secondary contamination exists with G and VX butyrylcholinesterase (major Plasma cholinesterase aka
agents but more so with VX. Both of these agents will produce pseudocholinesterase) preferentially binds many of the
vapor that is heavier than air and therefore should be taken into organophosphorous anti-AChE drugs and thus analysis of
account when at a scene to insure that there are not populations in plasma cholinesterase activity can be used to detect low-
danger in down-hill areas grade poisoning from this class of insecticides
554
556
Note: Leber's Heriditary Optic Neuopathy is a genetic mutation Note: Piericidin A is a more potent inhibitor and is a close
of complex I - a mitochondrial inheritance dz structural homologue of ubiquinone.
557
558
559
Note: CO and Cyanide act at same point - Complex IV Cyanide poisoning may have "bitter almond" scented breath
560
Treat with Dimercaprol and penicillamine - treats both lead and
arsenic Arsenic poisoning may have "garlic" scented breath
561
F0 "stalk" of ATP synthase (F1F0 ATPase) complex V, F1 is the
562
catalytic site, or "sphere" Causes increased H+ gradient, but no ATP is produced
563
564
565 Treat with Deferoxamine
566
Treat with Calcium EDTA, dimercaprol, or penicillamine. Note: Diagnose by blood lead levesl and free erythrocyte
Dimercaprol is also known as BAL (British Anti-Lewisite) protporphyrin
567 Treat with Penicillamine
568
569
G H
572
573
574
G H
575
576
583
584
G H
585
586
587
588
589
590
591
592
593
594
Causes flaccid descending paralysis
595
596
597
598
599
602
G H
603 Definitions
Analgesia: Attenuation of pain perception without the loss of
consciousness.
Narcotic: Archaic term, more legal than medical, referring to
any substance producing stupor associated with analgesia
(usually associated with derivatives of opium).
Pain has sensory and reactive components: Opiates: Natural products and derivatives obtained from the
Sensory - Pain is perceived as a result of direct stimulation of pain opium poppy (e.g., opium, morphine, heroin, codeine).
receptors and/or by the pattern of neural input from the periphery. Opioids: The class of compounds that bind to opioid
Reactive - Intensity of pain is dramatically altered by the level of receptors. Includes agonists, antagonists, partial agonists and
anxiety and the stress response related to the original insult. mixed agonist/antagonists. This is the preferred term.
Delta receptors may be more associated with euphoria than mu
604 receptors. No clinically useful drugs are selective for these Preproenkephalin gives 6 met enkephalin, 1 copy of
receptors leuenkephalin
605
Opioid Effects: Vascular System: Clinical Uses: Acute Pulmonary Edema (morphine)
Vasodilation - Morphine is by far the most efficacious opioid in Relief from dyspnea associated with left ventricular failure is
this regard (non-mu/non-kappa mediation), useful in pulmonary due to:
edema - 2 factors come together very nicely in this regard: (1) reduced perception of shortness of breath
608
morphine-induced vasodilation shifts fluid from the central to the anxiolytic effects (this effect is noted in many texts, but the
peripheral compartment; (2) opioids make the brainstem less evidence for direct anti-anxiety effects of opioids is nearly non-
responsive to pCO2, which results in reduced sympathetic tone existent. By reducing the perception of shortness of breath,
(patients dont care as much about difficulty breathing/SOB). With the anxiety accompanying that perception is reduced. This is a
relaxation of the sympathetics comes easier movement of fluid very different phenomenon than anti-anxiety effects per se.)
from central to peripheral compartment reduction in cardiac preload and afterload
609 Shorter elimination half life than morphine. Was once given more
frequently for pain than morphine, no longer however due to
negative SE
612 Heroine enters brain faster than morphine (higher abuse potential) Heroin withdrawal is considered brief lasting 5-10 days, and
where it is rapidly deacetylated to morphine is intense.
613
relatively pure kappa agonist
Drugs Classified as Mixed Agonist-Antagonists - these agents have variable actions at different receptor subtypes, examples:
614 Partial agonists at mu receptors: e.g., buprenorphine
full agonist at one receptor subtype and a partial agonist at another: e.g., pentazocine
agonist at one receptor subtype and an antagonist at another: e.g., nalbuphine
Remember: weak partial agonists act as antagonists when given with a full agonist.
G H
617
Would cause withdrawl if given after >7-8 days of morphine use.
618
Efficacy is no better than an NSAID alone and most authorities do
not recommend using this drug
620
622
623
combined with atropine (limits abuse potential)
624
combined with atropine (limits abuse potential)
625
627 Antagonist Therapy: primarily use naltrexone (ReVia) - long half Note - naltrexone does not stop runners high, will not stop
life (~10 hr), good oral absorption ; block rewarding effects of pleasure from life activities such as eating, sex, etc
agonists; patients must be highly motivated to remain drug free (theoretically it should, no evidence however that it does)
628
G H
629
630
633
634
635 Note that NSAIDs can address symptoms (ie pain) of RA, but do
nothing to slow progression of dz; Corticosteroids can both
decrease pain and slow progression of joint destruction, however,
no longer used on long term treatment do to imminent SE
G H
636
637
638
Sulfasalazine is a poorly absorbed and is metabolized by intestinal
bacteria to sulfapyridine, an active sulfonamide antibiotic, and 5-
aminosalicylate, a salicylate anti-inflammatory agent. Good Sulfasalazine can be given with methotrexate, or as
alternative to methotrexate for patients with liver disease alternative too, and can be given with other DMARD
639
640
TNF-alpha receptors are expressed on essentially all cells, and TNF-alpha plays an important role
TNF-is produced by macrophages and activated T-cells and microorganism (Listeria and mycobacteria). It is also important in cell apoptosis. Thus, there is sign
641 stimulates the release of inflammatory cytokines, including
agents may increase susceptibility to intracellular organisms and/or result in increased susceptibility
interleukins and proteases such as collagenase and neutral agents are being watched with particular attention to determine if they are associated with an increas
metalloproteinases. TNF-effects require activation of specific tubercular and/or fungal infections. Particularly for the murine-derived agents, immunogenicity is a co
membrane bound receptors (TNFR1). proteins that must be injected, and injection site reactions are common. They have good efficacy as
642
645
646
G H
647 Rem: use a Pen on the Ceiling of the cysteine chapel to draw
lesions on Adam, make him pee blood, and make him pale
(Penacillamine for Pen on Ceiling) is a cysteine analog and can
cause dermatologic probs (skin lesions) nephritis (peeing blood) Give B6 along with D-Penicillamine to prevent neurologic
and aplastic anemia (he is pale) symptoms
648
649
650
Hot peppers
652
653
654
655
G H
658
659
660
Low doses of salicylate NSAIDs (aspirin) must not be used to
treat gout because these drugs inhibit net uric acid excretion
Can also use naproxen; do not use aspirin for gout in the urine
661
662
G H
664
G H
665
666
667
668
669
670
G H
671
672
678
G H
Therapeutic Regimens:
Alternate Day Therapy
679 Use drug with shorter half-life (e.g., prednisone)
Give drug every other day
Minimizes HPA suppression
Pulse Therapy
life-threatening or serious disease
General Therapeutic Considerations: initial dose large
Individualize therapy always if insufficient benefit quickly, double or triple the dose
Reevaluate frequently Replacement Therapy
Except for replacement therapy, glucocorticoids are neither 1. For primary (adrenal) or secondary (anterior pituitary)
specific nor curative. adrenocortical insufficiency.
A single dose is without harmful side effects! 2. This remains the only application in which chronic
A short course is without harmful side effects. corticosteroid treatment is completely appropriate and
Longer than one week, adverse effects are very likely defensible.
their severity being dependent upon length of treatment and dose 3. When prolonged systemic glucocorticoid treatment is
start low, gradually taper up planned, alternate day therapy is recommended to reduce
taper down slowly toxicity and occurrence of iatrogenic secondary adrenocortical
Cortisol has modest but significant mineralocorticoid activity insufficiency.
680
modest but significant mineralocorticoid activity
681
modest but significant mineralocorticoid activity
682
683
684 methasone ending means long acting steroid
G H
685
686
687
688
689
690
691
692
693
694
695
G H
696
697
698
699
702
703
No known drug interactions; given IV
704
705
G H
706
708
G H
709
Prolonged use of methylprednisolone can depress the
ability of the body's adrenal glands to produce
Short courses of methylprednisolone usually are well-tolerated corticosteroids. Abruptly stopping methylprednisolone in
with few and mild side effects. Long term, high doses of these individuals can cause symptoms of corticosteroid
methylprednisolone usually will produce predictable and potentially insufficiency, with accompanying nausea, vomiting, and even
serious side effects. Whenever possible, the lowest effective shock. Therefore, withdrawal of methylprednisolone
doses of methylprednisolone should be used for the shortest usually is accomplished by gradual tapering the dose.
length of time to minimize side effects.
712
G H
714
715
716
717
G H
718
Cisplatin-induced nephrotoxicity has been largely overcome by the routine use of hydration and diuresis during therapy.
However, ototoxicity caused by cisplatin is unaffected by diuresis and is manifested by tinnitus and hearing loss in the high-
frequency range. The ototoxicity can be unilateral or bilateral, tends to be more frequent and severe with repeated doses, and
may be more pronounced in children. Other adverse effects commonly occur with cisplatin treatment; most notably, marked
nausea and vomiting occur in almost all patients, but usually can be controlled with ondansetron and/or high dose corticosteroids.
721
722
723
724
G H
725
726
727
728
May cause irreversible dilated cardiomyopathy, the occurrence of which is related to the total dose of the drug. Two types of
cardiomyopathy may occur. (1) An acute form is characterized by abnormal ECG changes and arrhythmias. This is brief and
usually not a serious problem. (2) Chronic, cumulative dose-related toxicity is manifested by CHF that is unresponsive to digitalis.
The mortality rate is >50%. The hazard is attributed to lipid peroxidation of myocyte membranes and nonspecific alterations in the
myocardium have been noted such as a decrease in the number of myofibrils, mitochondrial changes, and cellular degeneration.
Discontinuance of the drug can allow complete resolution of these changes, but there are currently no practical means for early
detection of the toxicity. Cardiac irradiation or administration of high does of cyclophosphamide increase the risk of cardiotoxicity.
729
730
731
G H
732
733
734
735
736
PRPP = phosphoribosyl pyrophosphate - which is a ribose 5- Allopurinol enhances the retention and potentiation of activity
phosphate from the hexose monophospate shunt activated with of 6-mercaptopurine (xanthine oxidase deactivated) -
addition of pyrophosphate from ATP increases chances of SE (pancytopenia)
737
738
739
G H
740
742
743
744
High dose regimens of methotrexate combined with co- Use of very high-dose methotrexate (>1000 mg/m2) requires the monitoring of serum methotrexate l
administration of a reduced folate, such as leucovorin (folinic acid, and schedule of leucovorin rescue. Methotrexate is cleared mainly by renal excretion, and patients w
citrovorum factor), that bypasses the block created by function require dosage adjustments. High-dose regimens have been associated with acute renal inj
methotrexate can prevent severe gastrointestinal toxicity or prevented by vigorous hydration and alkalinization of the urine. In the absence of normal renal functi
marked bone marrow hypoplasia. This is sometimes called satisfactory methods (including hemodialysis) to eliminate methotrexate. Acute or chronic administra
leucovorin rescue. been associated with hepatotoxicity and an idiosyncratic pneumonitis.
748
749
Adrenal and gonadal synthesis of testosterone are not affected, so
serum levels of T do not decrease, and may actually increase b/c
the dedication blocks the neg feedback in the hypothalamic-
pituitary axis, resulting in increased LH production
750
751
753
G H
754
755
757
Topoisomerase I & II introduce and then repair single or double
stranded DNA breaks
Essential during transcription and translation because of twisting
and untwisting of DNA
Cell lines that show MDR are resistant to natural product cytotoxic
agents such as vinca alkaloids, antitumor antibiotics,
epipodophyllotoxins, camptothecins, & taxanes. Mechanism is
758 increased tumor expression of p-glycoprotein, drug efflux pump.
Product of MDR-1 gene.
Another type of MDR is due to expression of a topoisomerase II
with altered drug binding properties resistant to anthracyclines &
epipodophyllotoxins.
759
G H
763
764
765
When giving LHRH analogs, one must first give adjunct drugs
766 such as bicalutamide for about 2 weeks before to prevent
testosterone storm, which can lead to heart attack and stroke from
malignant hypertension.
767
G H
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
790
791
792
793
794
G H
795
796
797
798
799
800
801
802
803
804
805
806
807
808
Ceftriazone is good for S. pneumonia and H. influenzae, and in
combination with azithromycin (expanded spectrum against gram
809 negatives) which covers Legionella and Moraxella - this
combination is good empiric coverage for community-acquired
pneumonia
810
811
812
Given with Cilistatin - inhibits enzymes in the kidney which
813 break down imipenem and protects kidney from toxicity caused
by imipenem
814
815
816
Considered safe for pregnant or nursing women and infants
817
Streptococcus pyogenes, or Group A b-hemolytic streptococci, can
818 be differentiated from the other b-hemolytic streptococci by its
exquisite sensitivity to bacitracin.
819
820
G H
823
Note: diphtheria toxin also inactivates the eukaryotic elongation
factor (eEF-2) thus preventing translocation
829
830
831
832
833
834
G H
835
Require O2 for uptake into the bacterial cell, thus ineffective Aminoglycosides include: tobramycin, gentamicin,
against anaerobes streptomycin, amikacin, and neomycin
836
837
838
839
840
841
842
Do not admin with antacids (binds in GI and prevents absorption) TMP-SMX is MC used for traveler's diarrhea in kids
843
845
846
847
848
849
G H
850
851
855
Tx travelers to SE Asia or Asian subcontinent
Gives immunity for 10 yrs, travelers to endemic areas should
856
receive a booster after 10yrs
857 Typhoid vaccine requires a booster every 3yrs
Not recommended after age 4-6. Administration of the vaccine is
858 usually during infancy, with four doses being received by age 18
mo
Should be administered every 10 yrs and may be given within that
859 period if quesiton of susceptibility of a person at high risk (ie after
an open trauma, stabbing, or gunshot wound)
860
861
862
863
Caffeine side-effects:
At doses prescribed for headache, caffeine is benign.
However, caffeine is a significant component in the diet of
866 many patients. Two problems result:
Combination products have greater efficacy than NSAIDs Excess dose. At high doses, caffeine causes palpitations and
alone: anxiety
NSAID + caffeine is more efficacious than either alone Termination of taking caffeine in patients who are dependent
Caffeine mech: Competitive antagonist at adenosine receptors on caffeine. This provokes headaches.
872
873
Most migraine symptoms can be provoked by dopaminergic
agonists. Migraine pts are abnormally reactive to low doses of Antagonists at D2 receptors which are older antipsychotic
dopamine agonists (they show yawning, nausea, vomiting, and drugs - Chlorpromazine (Thorazine), Prochlorperazine
hiccough, all of which are caused by dopamine stimulation of DA (Compazine), and Metoclopramide (Reglan) (Modern
receptors in the brainstem). Hence, it might be expected that antipsychotics have fewer side-effects, but the newer agents
dopamine antagonists would be beneficial. are not as efficacious in migraine)
874
875
877
Do not give to pt with low HR or seasonal allergies/asthma/COPD
878
G H
Cluster HA: The predominant form of treatment is prophylaxis. Cluster HA characteristics: Worst HA of life may be cluster;
When a bout occurs, oxygen is most efficacious, and triptans are alcohol is a vasodilator, single glass (red or white) can trigger
880 also a reasonable choice. Effective prophylactic drugs are cluster HA
prednisone, lithium, methysergide, ergotamine, valproate, and 15min to 5 hrs
verapamil. Lithium appears to be particularly useful for the chronic cluster very seasonal - common during Winter and Summer
form of the disorder (note: Li is ineffective in migraine do not Solstice (hypothalmus associated with cercadian rhythm); also
confuse the uses). may occure at the same time of day
882
883
884
885
886
G H
Inhibits DA metabolism in the striatum (MAO-B) without greatly Selegiline can delay need for aggressive pharmacotherapy,
affecting degradation of catecholamines in other brain regions or but does not prove that neurodegenerative process is
887 the periphery (by inhibition of MAO-A which would increase NE in delayed, since selegiline also has a direct symptomatic effect
the periphery). Little risk of hypertensive crisis due to by increasing availability of DA. Best documented use of
accumulation of peripheral NE as might occur with selegiline is as an adjunctive agent to improve response to
nonselective MAOI's (& tyramine) levodopa.
888
889
892
893
Association with cardiac valvulopathy associated with
Ergot alkaloid with similar side effects carcinoid syndrome
G H
895
898
899
900
G H
901
902
The effects are in the spinal cord dz, acts by increasing gabaergic
mediated presynaptic inhibition of internuncial neurons. Baclofen
by inhibiting release of excitatory transmitters on IA neurons
903 themselves. Excitation of GABA-A receptors causes
hyperpolarization by increased Cl- conductance (gamma subunit
for benzodiazepine facilitation).
Target is intrannuncial (inhibitory interneuron). decrease Ia
(intrafusal afferent) excitation of primary motoneuron.
904
Rem: doc said he would be weak, so they made Dan a bed in
whataburger closet so he didn't have to ambulate; he got liver sick
from eating the food
905
I. Symptomatic
A. Fluid balance, mineralocorticoids
906 (Fludrocortisone, midodrine)
B. Elastic stockings
II. Treatment of underlying disorder
A. Careful manipulation of ANS parameters
907
908
909
910
911
912
913
914
G H
Phenytoin: Pharmacokinetics
Absorption of oral dose slow and incomplete
70-90% bound; salicylates, phenylbutazone and thyroxine will
displace from albumin
915
Metabolized in liver; therefore, very susceptible to drugs such as
disulfiram and bishydroxycoumarin Seizure:
t1/2 is 24 hours, but is dose-dependent A transient loss of cerebral function caused by abnormal
At greater than 10 ug/ml = zero-order elimination, therefore synchronous electrical discharges from cortex.
best to measure plasma levels. (relatively low therapeutic index) 10% of population has had a seizure.
SE: megaloblastic anemia - check for low folate Epilepsy:
!!All antiepileptic drugs can cause idiosyncratic rxns (not A symptom complex characterized by recurrent paroxysmal
dose related, no lab test to predict): rash, Stevens-Johnson aberrations of brain function, usually brief and self-limited.
syndrome, agranulocytosis, thrombocytopenia, aplastic Note: Two million Americans have some form of epilepsy
anemia, hyponatremia, and hepatic failure!! (about 1 in 100).
916
917
918
919
Reduction of Ca2+ Entry: Molecular Actions via T-type (low Absence Seizures:
threshold) calcium channels: Effects on Brain Activity - failure to inactivate T-type
Ca2+ is necessary for neurotransmitter release. channels produces the rhythmic oscillations seen in absence
920 Concentration of Ca2+ is related to number of vesicles/packets of seizures, increased glutamate release, increased excitation
neurotransmitter released. and reduced inhibition of thalamic cells results in feedback
Reduced amounts of neurotransmitter release leads to less loop -- T-type Calcium channel blockers decrease
conduction. glutamate release in thalamus
G H
922
923
925
Benzodiazepines: Pharmacokinetics
Rapid onset, short duration
Highly bound (drug interactions)
Diazepam is relatively ineffective when given p.o.
928
929
930
931
Neutralizing Antibodies to IFN: The possibility of viral infection as a causative agent raised
Antibodies (neutralizing antibodies NAb) to -interferon (IFN) the possibility that gamma interferon, one of the body's natural
may occur during treatment weapons against viruses, might help MS sufferers. In 1984,
934 Presence of NAb may be associated with a reduction in clinical researchers first administered gamma interferon to humans.
effectiveness of IFN treatment Unfortunately, the patients' symptoms became even worse.
The rate of NAb production is probably less with IFN-1a This made researchers wonder if gamma interferon might be
treatment than with IFN-1b treatment directly involved in MS. Research showed that gamma
Clinical utility of measuring NAb in an individual on IFN therapy is interferon levels shot up just before and during MS
uncertain attacks.
G H
935
Originally intended to induce an animal model of multiple sclerosis Glatiramer - A random chain of 4 amino acids in a particular
(experimental autoimmune encephalomyelitis [EAE]) by sensitizing stoichiometery (the stoichiometry is shown below, and only
the immune system to a key component of myelin basic protein. To FYI), which mimic myelin basic protein.
the contrary, glatiramer reduces EAE severity. Alanine (5), Lysine (3), Glutamic Acid (1.5), Tyrosine (1)
936
937
940
Inhibits the production of helper T-cells.
Works more quickly than azathioprine, usually within one or two
months.
G H
941
944
Penetrate ganglia poorly, so little effects on blood pressure
950
951
SSRIs: Fluoxetine
longest half life!! (implications when switching to an MAOI) Selective Serotonin Reuptake Inhibitors (SSRIs):
t ~ 48 hr after a single dose newest generation of antidepressants
t ~ 84 hr after multiple doses selectively block serotonin reuptake
Steady state plasma levels not achieved for 4-5 weeks fewer side effects
Active Metabolite - Norfluoxetine much safer in overdose
t ~ 146 hr may be the first-choice for treatment of depression
SSRIs: Sertraline
952 long half life: t ~ 24 hr
Side effects: most likely of the SSRIs to produce GI disturbances
(diarrhea)
Low potential for drug interactions due to P450 interactions.
SSRIs: Paroxetine
long half life: t ~ 26 hr
953 One of the most serotonin selective of the SSRIs
Side effects: more weight gain, sexual dysfunction and
discontinuation symptoms than other SSRIs.
Potential for many drug interactions due to potent inhibition of 2D6.
SSRIs: Citalopram/Escitalopram
long half lives: t ~ 35 hr
citalopram is a racemic drug mixture (S-enantiomer, escitalopram,
954 is active)
Reportedly less likely to produce mania if given to a bipolar,
depressed patient.
Many reports in the literature where escitalopram treatment
induced mania
955
Escitalopram is the most serotonin selective of the SSRIs
G H
956 Tx OCD with SSRI (usually takes 4-6 wks for effect, but with
long half life: t ~ 22 hr OCD, SSRIs work in 4-6mo and must use aggressive doses)
957
958
960
Not associated with cardiovascular SE, nor sexual
dysfunction or weght gain!!
961
963
SE:
Antimuscarinic: blurred vision, dry mouth, constipation,
Tricyclic Antidepressants urinary hesitancy, confusion,
964 first generation antidepressants - 3-ring structure Metabolic/Endocrine: weight gain, sexual disturbances
block monoamine reuptake (NE, 5-HT, DA) SEDATION
down-regulate NE and/or 5-HT receptors Sympathomimetic: tremor and insomnia
lots of side effects Cardiovascular: orthostatic hypotension, conduction defects,
high toxicity in overdose arrythmias
965
966
967
969
970
971
972
973
976
99% is processed in the liver, adjunctive or 2nd line treatment.
Increasingly used as first line agent. Well tolerated in the elderly,
effective against absence seizures through calcium channel
mechanism) May have to withdraw immediately if they get a rash
977
978
979
980
981
983
G H
984
985
986
987
Will not cause weight gain in therapeutic does.
G H
988
Can give IV (or PO/IM) for acute aggitation (or violent
behavior - straight jacket effect), no recognized ceiling dose
(keep increasing until aggitation deminishes) - more
commonly give atypicial with a BZD now; note that the
aggitation can be addressed within a few hous, but the
delusional thought/psychosis will take the typical 1-3wks
Half-life of approximately 20 hours before drug effect.
989
990
991
992
993
994
995
996
997
G H
Definitions:
Anxiety: Signs and symptoms of anxiety can be useful for
meeting difficult situations; anxiety inhibits unwise action; in
998 the case of true danger, anxiety can be life saving
In the absence of an appropriate threat, or if the anxiety is
out of proportion to the threat, it can impair the individuals
Diazepam terminates status epilepticus, given i.v. - second ability to function
choice agent behind lorazepam. Diazepam is much more lipid Sedative:
soluble than lorazepam; so much so that diazepam requires a diminish awareness
special vehicle it precipitates from aqueous solution unless the cause drowsiness
concentration is very dilute. These physicochemical properties diminish motor activity
have caused the more water-soluble agent (lorazepam) to take Note: sedatives are generally anxiolytic, but sedation is not a
over this function. Not used as long-term therapy for seizures. desirable property of an anxiolytic
Profound tolerance that develops rapidly Hypnotic: an agent that promotes sleep and inhibits
wakefulness
999
1000 Perhaps less sedative than other BZDs, yet also effective for
hypnosis (pt is less anxious)
Relatively short half-life (12-15 hr)
1007
1008
1009
1011 Compared to BZDs, selective alpha1 subunit agonits is very Short half life 3-5 hours, less hangover than long acting BZDs,
hypnotic (nearly as efficacious at producing sleep) and much less no rebound insomnia even after 30 days of use. Abuse
anxiolytic, anticonvulsant, muscle relaxant dependence potential much lower than BZDs!!
1012
Shorter half-life than zolpidem (approx 1hr)
Argued that Ramelteon (melatonin agonist) is regulated by
FDA so consistent formula and thus can more accurately
1013 correct pts sleep schedule (as compare to OTC melatonin)
through strategic timing of administration (take at night) and
Works well, no probs with dependence, safetey standards not set have pt stay awake and be outside in sun to set internal clock
by FDA for travel/jet lag.
1014
1019
1020
1023
1024
1027
1028
1029
1030
G H
1031
1032
1036
1037
1039
1040
1041
1042
EtOH: Pharmacokinetics Oral Absorption
absorbed rapidly and completely
One Drink ~ 14 g EtOH Peak BEC seen at ~30 min (longer if taken with food)
1.5 oz 80 proof whiskey Primary site of absorption is in the small intestine
12 oz beer EtOH: Pharmacokinetics Distribution
4 oz glass of wine Rapid
note: some use 10 g as the definition of a drink Passes easily through membranes
Blood Ethanol Concentration Distributes with total body water
BEC = BAC = BEL = BAL Females on average have a higher fat composition, and,
Units: % (g/dL) or mg % (mg/dL) therefore, a smaller volume of distribution and a higher BEC
1-2 drinks produces a BEC of ~0.025 g/dL than males
1046
1047
Cocaine: Mechanisms
1048 Reinforcing effects correlated best with blocking DA transporter.
One of the most reinforcing substances identified in both humans
and animals. It is thus powerfully addictive.
20% of recreational users go on to serious heavy usage with
negative consequences. NIDA estimates 25+ million Americans
have used cocaine. Use has declined considerably from early 80s
to the 90s. Availability of free-base form (i.e., crack) has Cocaine: Neural Targets: Reward pathways (VTA and NA)
influenced use. (mesolimbic and mesocortical DA pathways); Arousal
Also binds NE and 5-HT transporters systems (NE pathways; Locus Ceruleus, dorsal bundle);
Reinforcing effects similar to i.v. amphetamines Autonomic nervous system (Potentiates the actions of NE in
Cocaine also has a local anesthetic action, which accounts the periphery. Particular concern for blood pressure and
for its convulsant effects in overdose. arrhythmias)
G H
Hallucinogens: Classification
Indoleamine-like:
Lysergic acid diethylamide (LSD)
Dimethyltryptamine (DMT)
1052 psilocybin (magic mushrooms)
Phenethylamine-like:
Dimethoxymethylamphetamine (DOM) (STP)
MDMA derivatives (Ecstasy, Eve) (mixed
stimulant/psychedelic)
Mescaline
G H
1056
Marijuana: Mechanism Most commonly used nonlegal drug in US,
Binding to cannabinoid receptors Usage peaked in 1970s 60% tried, 11% regular users
Diverse Physiological functions 40%, 2% in mid 90s
Anandamide endocannabinoids Use has leveled off as of 1998-2000
1057
1058 Detectable 12-36 hrs in plasma
8
Problems to Address:
Prostate size is a function of age + androgens!!
Obstruction-induced detrusor dysfunction
Neural alterations in the bladder and the prostate
Tx Options:
9 BPH age: Watchful Waiting
Rarely occurs <40 Surgery
50% older than 50 Pharmacotherapy (Alpha Blockers, Finasteride or
20 million American men are now over 50 Dutasteride (Anti-Androgen), Saw Palmetto (Anti-
80% older than 70 Androgen + ?))
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SOURCES OF ESTROGEN
In female: Physiological Effects of Estrogens:
- produced primarily by ovary, but some contribution by Female maturation - development of sex organs and
adrenals, and local production in such target tissues as the secondary sex characteristics.
22 brain Closure of the epiphyseal plates on long bones.
- during pregnancy, fetoplacental unit produces estrogen Endometrial effects (proliferative).
(estriol). Increase in risk of endometrial cancer (with unopposed
- postmenopausally, low levels of estrogen exist (mainly estrogen, no progesterone accompaning).
estrone and estriol from adrenals, adipose tissue) Metabolic and cardiovascular effects - Heart, bone, brain
In male: Estradiol made by testis (Sertoli cells), which also require estrongens.
aromatize testosterone (to estradiol) produced by Leydig cells; Reduce bone resorption (osteoporosis effect on both
also in the adrenals and local production osteoblasts and osteoclasts)
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Prodrug: Desogestrel converted to 3-keto desogestrel
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ipine drugs are relatively selective for vascular smooth Dihydorpyridines are more potent antihypertensive agents
muscle Ca channels (than non) but any direct negative chronotropic or inotropic
effects are offset by reflex sympatheitc activation.
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Bioavailability Issues: Fast and slow acetylators
Acetylated in bowel and liver
Acetylation inactivates
Dose necessary is much larger in fast acetylators
Indications
Typically used with isosorbide dinitrate after a failure of
ACEIs (most commonly because ACEIs produced
intolerable cough)
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Four generations:
First generation--very active against gram (+) cocci
Modestly active against gram (-) organisms
110 Second generation---have extended gram (-) coverage.
Moderate gram (+) activity
Third & Fourth generation--- very active against gram (-)
organisms. Less active against gram (+) activity.
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113
Pharmacokinetics
Oral administration
114 Forms chelate with Ca, Mg, Al ions, thus prevents TC
absorption
Not to be taken with antacids, laxatives
Doxycycline less effective than others
Doxycycline is excreted in feces
Other TCs is excreted through kidney
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In clinical studies, erythromycin accelerates gastric emptying,
particularly in the acute setting. The chronic use of
erythromycin is limited by its side effects. Intravenous
erythromycin may be useful short-term for an acute
exacerbation of diabetic gastroparesis.
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Corticosteroids: Oral (prednisone and controlled release Immunosuppressants: azathioprine and 6-mercaptopurine (6-MP) are purine analog immunosuppress
budesonide) and parenteral (hydrocortisone and employed in the management of glucocorticoid-dependent IBD. Azathioprine is converted to 6-MP after
182 methylprednisolone) are used to treat moderate to severe UC converted to a metabolite that inhibits purine ribonucleotide synthesis and thus cell proliferation. Use of
and CD. The anti-inflammatory properties of these many patients to be weaned from glucocorticoids. These drugs are usually well tolerated, but rarely
glucocorticoids allow induction of clinical remission during (4%). Other side effects include nausea, fever, rash, and hepatitis. Leukopenia which is dose-related an
flare-ups of the inflammatory disease. However, the serious so CBC should be regularly monitored. Methotrexate (MTX), an inhibitor of dihydrofolate reductase that
side effects of glucocorticoids prevent their use for DNA synthesis is sometimes used when either 6-MP or azathioprine are ineffective or poorly tolerated. C
maintenance therapy and limit their chronic use. Once clinical potent inhibitor of cell-mediated immune responses. It inhibits interleukin-2 production from T helper cell
remission is achieved, the dose of the steroid must be slowly recruitment of cytotoxic T cells and blocks other cytokines, including IL-3, IL-4, interferon , and TNF. Cy
tapered down over several months before it can be used to treat severe UC that is unresponsive to IV glucocorticoids. Cyclosporine may save the patient fro
discontinued altogether. the potential for significant toxicity.
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Treatment of Hepatitis: In about one third of adults and
children with chronic hepatitis B, treatment with interferon alfa-
2b leads to loss of HBeAg, return to normal aminotransferase
activity, sustained histological improvement and, in adults, a
lower risk of progressive liver disease. However, AIDS
patients co-infected with hepatitis B virus (HBV) generally
respond poorly to interferon. Hepatitis D (hepatitis delta
virus), which occurs only in patients infected with HBV, may
respond to treatment with high doses of interferon alfa, but Interferon- is usually combinated with ribavirin is more
relapse is common. effective than therapy with either agent alone.
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223 Class 1A effects also (procainamide is a mixed class drug) WPW syndrome is best txed with a class IA agent which increase refractoriness of the bypass track an
Reduce automaticity (phase 4, reduce slope of upstroke, AP tachyarrhythmia. Other agents (adenosine, BB, and digoxin (&CCB?) should be avoided in a wide comp
becomes broader) syndrome such as WPW because they may accelerate the ventricular rate and cause the rhythm to dege
Prolong action potential duration agents act by inhibiting the AV node and thus increase conduction down accessory pathway; also class IB
Reduce conduction velocity (phase 0, slope also reduced) repolarization by decreasing the AP duration and thus also can increase the ventricular response to an S
evidence of WPW on ECG and is hemodynamically unstable, DC cardioversion should be first-line thera
225
Synergistic depression of myocardial function with combo of Lidocaine works on slightly depolarrized or ischemic tissue
other antiarrhythmic agents (especially propranolol). Pts with more so than normal tissue, due to its state-dependent
heart failure (HF) achieve lidocaine levels that are double blocking. Therefore, use lidocaine (IV) to suppress acute
the levels of normal pts (reduce dose by half) MI-associated ventricular arrhythmias
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Class 1C
Reduce automaticity and conduction velocity in atria and Class IC do same thing as class1A, but more powerful
229 ventricles very powerful side effects, the worst SE is accutally
Prolong action potential duration worsening arrhythmia
Major side effect is proarrhythmia
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When macula densa sense increase NaCl, they send signal (via extraglomerular mesanginum) to granula
242 drug interactions: carbamazepine and dipyridamole adenosin which vasoconstricts primarily the afferent a. (know that in most areas of the body adenosin
pretreatment its potency; caffeine and theophylline not so in the kidneys), decreasing GFR (moderate constriction; if severe constriction then GFR decreas
antagonize it flow becomes so stagnent that proteins clog up on exam always assume moderate efferent a. constrict
Procainamide:
Moderately effective for atrial or ventricular arrhythmia
243 Metabolized in liver to active component NAPA
this metabolite is more effective (acetly group)
must check prodrug and metabolite to prevent toxcity
Reduce automaticity and conduction velocity
effects phase 4 and 0
Universal adverse effect is lupus
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247
No protein or endothelial binding of LMWH (as UFH), effects
kenetics - more predictable
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Cytochrome P-450 - a family of heme-containing Ez, found in Major Cytochrome P-450 inhibitors: FREaCKI
the liver and intestinal tract and are involved in phase I Grapefruit - Ketoconazole, Isoniazid, Cimetidine,
metabolism. Fluoxetine, Ritonavir, Erthyromycin, Grapefruit
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Other Cytokines:
Stem Cell Factor (SCF), Interleukins (IL1-12), Monocyte-
Macrophage Colony Stimulating Factor (M-CSF, CSF-1),
P1XY321 (GM-CSF/IL-3 fusion protein), Tumor Necrosis
290
Factor (TNF), Transforming Growth Factor (TGF-2) are all
cytokines with stimulatory activity on marrow precursor cells.
The clinical utility of many of these agents is already being
tested in clinical trials. It is likely that future research on these
compounds will yield important therapeutic agents.
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Meglitinides very fast acting, short half life (dont get into
trouble with low sugars over time)
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The pancreatic islets of Langerhans ( cells) are capable of Regulation of insulin release. Glucose is transported
sensing the plasma concentration of glucose. As glucose into the -cell by a specific glucose transporter protein
concentrations rise following a meal, insulin secretion is (GLUT-2 - on liver, pancreatic beta cells, and basolateral
stimulated. Glucose is the principal stimulus of insulin surface of the SI) on the cell surface. The glucokinase
320
secretion. Insulin secretion is a tightly regulated process phosphorylates glucose, forming glucose-6-P in the first
involving the coordinated interplay of nutrients, GI hormones, step of glycolysis. The generation of ATP by glycolysis and
pancreatic hormones, and autonomic neurotransmitters. the Krebs cycle leads to inhibition and closure of the
Glucose, amino acids, fatty acids, and ketone bodies ATP-sensitive potassium channels (the target of
promote insulin secretion. Stimulation of 2-adrenergic sulfonylurea drugs), depolarization of the plasma
receptors inhibits insulin secretion, whereas activation of membrane, and opening of the voltage-dependent Ca
2-adrenergic receptors and vagal nerve activity stimulate channels. The influx of extracellular Ca and mobilization
insulin secretion. In general, activation of the autonomic of Ca from intracellular stores lead to the fusion of insulin-
nervous system leads to inhibition of insulin secretion via 2- containing secretory granules with the plasma membrane
adrenergic receptors. and the release of insulin into the circulation.
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332
Grave's disease is an autoimmune disorder leading to Hyperthyroid diagnosis: High circulating levels of T3
synthesis of antibodies to thyroidal antigens. One of these and T4 (bound and free) and low TSH, also TSI and
antibodies, Thyroid stimulating immunoglobulin (TSI) binds antithyroglobulin antibodies present.
directly to the TSH receptor on the thyroid cell. TSI binding to Management of hyperthyroidism: the three primary
the receptor activates the cell just as TSH does, but this methods are antithyroid drug therapy, surgical removal of
activation is much more prolonged leading to excessive T3/T4 the thyroid, and destruction of the gland with radioactive
output and hyperplasia/hypertrophy (goiter) of the gland. iodine.
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368 1. Metered dose inhalers (MDI): a pressurized canister with a Rapid acting 2-selective agonists:
metering valve that delivers drug with CFC propellant, Albuterol, levalbuterol, terbutaline, pirbuterol, or
cosolvents, and/or surfactants. Advantages of MDIs are low bitolterol - all are 2-selective, and produce equivalent
cost and portability; disadvantages include need for hand-lung bronchodilation when inhaled with an onset of action of
coordination making it more difficult for young children and the <15 min and a duration of action ranging from 2 to 6
elderly to use. Spacer devices that attach to the MDI hours.
markedly improve the ratio of inhaled to swallowed drug and Albuterol and terbutaline are available in nebulizer
reduce need for coordination. 2. Nebulizers: preferred for solutions in addition to metered dose inhalers.
severe asthma exacerbations with poor inspiratory ability; do Albuterol is also available as a powder inhaler, and as
not require hand-lung coordination. Nebulizer therapy can be syrup, tablets, or extended release tablets for oral
delivered by face mask to young children or older patients who administration. Terbutaline can also be given orally, or
are confused. 3. Dry powder inhalers: require relatively high as subcutaneous injection, or IV infusion. Levalbuterol
air flow to suspend the powder and can be irritating when is the R-isomer of racemic (R+S) albuterol available only
inhaled. as a nebulized solution.
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Bronchodilation (smooth muscle relaxation) is a clinically relevant effect of theophylline. Other effects of theophylline
and some methylxanthines include CNS stimulation, cardiac stimulation, modest peripheral vasodilation, improved
skeletal muscle contractility, and a thiazide-like diuresis.
Theophylline was formerly a first-line therapy for asthma. It now has a far less prominent role in therapy because its
benefits are modest, it has a narrow therapeutic window, there is considerable variation in absorption and
elimination between patients, and monitoring of plasma drug levels is often required.
Nocturnal asthma can be improved with slow-release theophylline preparations (Theo-Dur, Slow-Bid), but inhaled
corticosteroids or salmeterol are probably more effective.
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High dose inhaled steroid preparations require the use of Beclomethasone and triamcinolone are initially given 3 to
a spacer device to limit side effects. 4 times daily; flunisolide is used twice daily. With high-
Asthmatic patients maintained on inhaled corticosteroids show dose inhaled corticosteroids, use of a spacer device
improvement of symptoms and lower requirements for will reduce the risk of adverse side effects and should
rescue with a bronchodilator. be considered mandatory.
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Cromolyn compounds do not directly relax smooth
muscle, therefore they are not useful for control of
Treatment of allergic rhinitis is similar to that for asthma. acute bronchospasm.
Topical corticosteroids delivered as an aqueous nasal spray Cromolyn compounds are primarily prophylactic. When
(beclamethasone, budesonide, flunisolide, fluticasone, inhaled several times daily, they inhibit both the
monetasone, triamcinolone) or cromolyn sodium can be highly immediate and late asthmatic responses to antigenic
effective with minimal side effects. challenge or exercise.
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o Intranasal decongestants should not be used for more These drugs are often given in combination with an H1-antihistamine, analgesics, cough suppressants, o
than 3 days in order to avoid rebound congestion, and with common OTC medications.
prolonged use, rhinitis medicamentosa. Rhinitis Actifed = pseudoephedrine + triprolidine HCl (H1 antihistamine)
402 medicamentosa is a complication of chronic use of Alka-Seltzer Plus Cold & Cough Liqui-Gels = Pseudoephedrine +Acetaminophen (analgesic) + Dex
vasoconstrictor nasal sprays or intranasal cocaine abuse. (cough suppressant) + Chlorpheniramine (H1 antihistamine)
Chronic nasal obstruction and nasal inflammation develop and Robitussin Cold & Congestion Liqui-Gels Caplets = Pseudoephedrine + Guaifenesin (expectorant
are manifest as beefy red nasal membranes on physical Dextromethorphan (cough suppressant)
examination. Sudafed Cold and Cough Liquid Caps = Pseudoephedrine + acetaminophen + guaifenesin + dextr
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433
Coccidioides immitis
Pneumocystis carinii (P. jiroveci) desert SW USA, Valley fever, fungal pneumonia
Approximately 15-30% of HIV-infected people develop P. carinii pneumonia Aspergillus spp.
434 Interstitial pneumonia with ground glass appearance Allergic bronchopulmonary aspergillosis, fungus balls, invasive
Candida albicans Aspergillosis pneumonia
Oral thrush, esophageal, tracheal, or pulmonary Blastomyces dermatitidis
Histoplasma capsulatum fungal pneumonia
Bird and bat-enriched soil, Ohio, Mississippi, & Missouri River beds, caves Histoplasma, Coccidiodes, & Blastomyces
and chicken coops Inhalation of spores cause asymptomatic or acute self-resolving fungal
Cryptococcus neoformans pneumonias (if not immunocompromised)
in pigeon droppings, also meningitis in AIDS patients Mucor, Rhizopus, Absidia
Rhinocerebral infections in ketoacidotic diabetics & cancer patients
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H2 receptors
458
Predominant effect of H2 activation is an increase in
gastric secretion
cardiac effects Pharmacological Effects of Histamine (next 2 slides
vasodilatory effects also)
Cellular signaling mechanism: 1. Role in allergy, anaphylaxis and inflammation -
stimulation of adenylate cyclase, increasing cAMP contributes to hypersensitivity phenomena and includes
Distribution: gastric mucosa, heart, mast cells, brain urticaria (e.g. hives), pruritis, allergic rhinitis (e.g. the runny
H3 receptors nose in hay fever); anaphylactic shock; inflammation -
Presynaptic auto-receptors on histamine-containing neurons, mast cells release histamine, causing local dilation and
produce feedback inhibition of histamine release increase blood flow in inflamed area
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n, and467
eyelid edema; their adverse effects include burning, stinging,
sa.
pheniramine/naphazoline (Visine A, and others) and
may be more effective than either agent alone, but have a short duration
ontinued use.
a last resort because they are associated with increased intraocular
with viral infections.
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473
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476
Beta Adrenergic:
Heart:
positive inotropic 1
positive chronotropic 1
increase AV node conduction
477 increase electrical excitability of the heart
Stimulate release of renin 1
Relaxation of certain blood vessels (skeletal muscle arterioles, Baroreceptor Control of BP (vagal acts like
coronary arterioles) 2 parasympathetic)
Lungs relaxation of bronchioles 2 Blood pressure increases suddenly:
Metabolic effects (glycogenolysis, 2) (lipolysis, 3) Sympathetic tone decreased & Vagal tone to the SA node
Stimulate release of insulin 2 increased
Relaxation of the uterus 2 Blood pressure decreases suddenly:
Relaxation of detrusor (bladder) 2 Sympathetic tone increased & Vagal tone to the SA node
Relaxation of intestinal smooth muscle 2 decreased
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504
Beta-Blockers in Chronic Stable Angina:
Indications:
monotherapy for mild to moderate angina of effort (not
for Prinzmetals)
combination therapy (angina of effort)
after MI
Limitations
bradyarrhythmias
Systolic BP x HR = Cardiac Output = Pressure-Rate congestive heart failure
Product (imprecise measure of CO, but close enough) extracardiac effects
Note that increasing doses of beta-blocker does nothing to In the acute stages of CHF, beta blockers are
the final level of CO that can be obtained (angina occurs at the contraindicated - sympathetics are highly active in acute
same CO). However, by decreasing HR and contractility, the HF - Beta-blocker poses a significant danger of reducing
beta-blocker facilitates exercise in a dose-related fashion. cardiac output to intolerable levels
505
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507
Approved drugs for HF (not all beta-blockers are
efficacious):
Carvedilol
Bisoprolol Metoprolol may cause dyslipidemia (elevated total
Sustained release metoprolol (metoprolol succinate) cholesterol, LDL, and triglyceride levels, and low HDL)
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548
SE:
SLUDGE mneumonic for muscarinic type
poisionings/overdoses
Salivation
Lacrimation
Urination
Deffication
549 Gastrointetinal cramping
Emesis
or DUMBBELLS
Diarrhea
Urination
Miosis
Bradycardia, Bronchoconstriction, Bronchorrhea
Emesis
Lacrimation
Salivations, Secretions, Sweating
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556
Note: can add succinate to chain which donates electrons
down stream from complex I (at complex II)
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Tx cyanide poisoning with nitrite
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High Efficacy mu Opioids:
Morphine
Meperidine (Demerol)
Binds to all opioid receptor subtypes, low oral:parenteral Methadone (Dolophine)
potency ratio (Highly polar so slowly and incompletely Fentanyl (Sublimaze; Duragesic)
absorbed orally) Heroin (Schedule 1)
609
Methadone: Its high bioavailability via the oral route and long
610 plasma half life (25-52 hr) renders it useful in replacement
therapy in addiction therapy as well as in opioid detox.
Racemic mix of d- and l-methadone has agonist activity as
well as NMDA and monoaminergic receptor blocking activity
non-opioid effects may enhance analgesic activity Replacement/maintenance therapy: see Buprenorphine
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Rem: You notice how nice your nails are buffed (Nal-buphine)
while kappin the cows that mu as they drop (kappa agonist,
mu antagonist)
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656 Thiazides stimulate proximal tubule reabsorption of uric acid Majority of gout sufferers do not secret uric acid effectively
(thiazide inhibits DT reabsorption of NaCl, causes elaboration (as compared to overproduction), though allopurinol is still
of more proteins in the PT) commonly used for chronic gout
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Substrates of p450:
cyclosporine
696 warfarin
phenytoin
tricyclic anti-depressants
theophlline
carbamazepine
beta-blockers
calcium channel blockers
haloperidol
benodiazepines
oral contraceptives
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DRUG INTERACTIONS:
Azathioprine can cause an increase in cancer risk when
used long-term. This particular risk increases in patients with a
prior history of treatment with other immunosuppressants. It
also increases the risk of serious infections.
700 Azathioprine can impair fertility by reducing sperm counts in
males.
Azathioprine's toxicity increases when taken with the gout
medication allopurinol, therefore its dose is reduced with
simultaneous use.
Severely low white blood counts can occur when taken
with other drugs that can affect the bone marrow or with patients with thiopurine methyltransferase (TPMT)
ACE-inhibitor class drugs used to treat elevated blood deficiency are at greater risk for developing
pressure. haematopoietic toxicity from therapy with azathioprine
701 To reduce the side effects, patients may be given a) an OKT3 is usually given once a day in a very fast
antihistamine to reduce the allergic reaction, b) Tylenol to intravenous dose. It usually must be given in a hospital for
prevent fever, and c) steroids such as to diminish the allergic the first three or four days and always requires close
response. These drugs are generally given 30 to 60 minutes medical supervision. The patient can form antibodies
before the OKT3. against OKT3. Therefore, blood tests are done during
treatment to watch for signs of antibodies.
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DRUG INTERACTIONS:
Troleandomycin, a macrolide antibiotic, reduces the liver's
ability to metabolize methylprednisolone. This interaction can
result in higher blood levels of methylprednisolone and a
higher probability of side effects. Erythromycin and
709 clarithromycin and ketoconazole also inhibits the
metabolism of methylprednisolone. Estrogens, including birth
control pills, can increase the effect of corticosteroids by 50%
by mechanisms that are not completely understood.
Phenobarbital can increase the metabolism of Methylprednisolone and other corticosteroids do not
methylprednisolone and other corticosteroids, resulting in appear to pose a risk to the developing fetus. The
lower blood levels and reduced effects. Therefore, the dose of amounts of methylprednisolone in mother's milk after
methylprednisolone may need to be increased if treatment consumption of standard doses are lower than the infants
with phenobarbital is begun. adrenal glands produce.
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Curable by chemotherapy
Acute lymphoblastic leukemia Chemotherapy has significant activity
Acute myeloid leukemia Anal carcinoma
Ewing's sarcoma Bladder carcinoma
Gestational trophoblastic carcinoma Breast carcinoma
Hodgkin's disease Chronic lymphocytic leukemia
Non-Hodgkin's lymphoma Chronic myelogenous leukemia
Burkitt's lymphoma Hairy cell leukemia
Diffuse large cell lymphoma Head and neck carcinoma
Follicular mixed lymphoma Lung (small cell) carcinoma
Lymphoblastic lymphoma Multiple myeloma
Rhabdomyosarcoma Non-Hodgkin's lymphoma
Testicular carcinoma Follicular lymphoma
Wilms's tumor Ovarian carcinoma
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Alkylating Agents: These compounds are chemically related to the mustard gases used in WWI. In general, these drugs
718 are highly reactive and spontaneously transfer their alkyl groups to DNA, protein, or other cell constituents producing
cytotoxic effects. The most important reaction is the alkylation of the "7 position" nitrogen of guanine in DNA. This
reaction leads to (a) cross linking with a second guanine residue, i.e., the two DNA strands become cross-linked (b)
abnormal base pairing; G instead of pairing with C, pairs with T, i.e., genetic code misread. Most of the alkylating agents
also modify adenine, cytosine, phosphates, or protein in DNA. Overall, these chemical defects lead to abnormal base
pairing, miscoding of DNA, RNA, and protein, inhibition of DNA replication, and can lead to DNA strand breakage.
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Doxorubicin has a broad spectrum of activity and is often
synergistic with other agents. It is used in combination
regimens against Hodgkin's and non-Hodgkin's lymphomas Hodgkins Lymphoma:
(ABVD regimen); carcinomas of the breast (CAF regimen), ABVD Regimen - Doxorubicin (Adriamycin), bleomycin,
ovary (PAC regimen), endometrium, ovary, testicle, lung, vinblastine, dacarbazine
prostate, cervix, head and neck; and osteogenic and soft- In Hodgkins disease, combo chemo results in long-term,
tissue sarcomas. disease-free survival in >60% of patients.
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requires the monitoring of serum methotrexate levels to adjust the dose
cleared mainly by renal excretion, and patients with impaired renal
mens have been associated with acute renal injury, which may be High-dose methotrexate with leucovorin rescue is an
the urine. In the absence of normal renal function, there are no alternative treatment for aggressive NHLs.
minate methotrexate. Acute or chronic administration of methotrexate has This treatment would be unaffected by the MDR gene
ratic pneumonitis. product.
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Dystonias I - Defined by body region affected: Dystonias II:
1. Torticollis (muscle contractions leading to twisting of the Opisthotonus -- whole body spasm
neck with an unnatural position of the head) Scoliosis -- bending of the spine
2. Facial distortion Oculogyric crisis -- rapid eye movements
3. Tongue protrusion Akathisia (Inability to sit; patient is constantly pacing,
4. Dysarthria (imperfect articulation of speech) restlessness; MC after about a week of treatment)
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879
Cluster cont: Male 4:1 cluster HA; aka suicidal HA (feels like
hot poker pt bangs head into tree to distract from HA)
880 HA comes on rapidly (little warning, little/no prodrome) by
time oral med works (if can be held down from vomiting) HA
may have remitted and med no good Cluster cont: accompanied by ipsilateral lacrimation,
Prophylactic agents reduce frequency (# of attacks) but if nasal congestion or discharge,and facial flushing (mixture
attack occurs, severity not decreased of para and sympathetic activation)
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890 Parkinson's Dz: Defect in extrapyramidal system that controls Parkinson's Dz cont:
involuntary movement, muscle tone and postural reflexes; 1% Difficulty initiating movement is overcome in emergency;
of adults over 65 i.e., by potent stimuli.
paralysis agitans (shaking palsy) James parkinson, 1817 Festinations: short, accelerating steps, festinating gait.
Extrapyramidal is literally all CNS but corticosplinal. In Dyskinesias: (in TD, HC, or PD at peak levodopa dose):
practice, means Basal ganglia coordinate large muscle Choreiform: involuntary, complex movements
movements, initiating and terminating them." Athetosis: slow writhing movements of the hands Athetoid
Bradykinesia- slowness of movement Dyskinesia: impaired movement, fragmentary or
Tremor mostly at rest when patient sits quietly. incomplete
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esic/anti-inflammatory treatment
ys: corticospinal, reticulospinal, vestibulospinal. (i.e., upper motor neuron
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A patient can have true petit mal and be treated with ethosuximide, but then one day have a grand mal (G
920 Ethosuximide: Pharmacokinetics part of the idiopathic epileptic syndrome (but now it is atypical), and you would have to change the AED t
Completely absorbed after oral dose DOC, for petit mal with GTCS. Alternatively, you could have treated the patient in the first place with valpr
Not significantly bound though they had never had a GTCS.
t1/2 is 30 hours in children and 40-60 hours in adults GTCS can occur with petit mal, but it is the atypical presentation.
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GABA(A) drugs
Direct:
Facilitation of GABA Barbiturates: phenobarbital
924 Directly: Enhancing Receptor Activity generalized tonic-clonic seizures
BZD allosteric site Alternative for febrile convulsions in children <5 years
Barb allosteric site Benzodiazepines
Indirectly: Increasing GABA Levels diazepam (Valium), lorazepam (Ativan)
Uptake inhibition status epilepticus
Inhibit degradation clonazepam (Klonopin)
absence; myoclonic, akinetic, atonic seizures
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In the first stage of CNS myelination, the axon at a particular site is enclosed by the process of the myelin-forming
oligodendrocyte. The process completely envelopes the axon and its lips come together to form a mesaxon. With
increased myelination (oligodendrocyte process elongation), cytoplasmic faces of most portions of the plasma membrane
of each side of the process become positioned very close together forming the major dense line (MDL). The process of
935 MDL formation is called compaction. Formation of MDL is essential for myelination. If MDL does not form (dysfunctional
or lacking myelin basic protein (MBP)), myelin becomes loosely wrapped around the axon. Close apposition of the outer
faces of the plasma membrane of two adjacent oligodendrocyte processes forms the intraperiod line (IPL).
In humans with multiple sclerosis (MS), many nerve fibers become devoid of myelin. There is evidence that MS is an
autoimmune disease. The myelin has been observed to be stripped from the axons by M0. The space created by the
loss of myelin is taken up by astrocytic processes (astrocytic hyperplasia or hypertrophy).
This region is referred to as an MS plaque. MBP is 30-35% of total myelin protein and MBP is located in the MDL.
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Lorazepam used short term, tremendous tolerance within
48hrs, usually switched to phenobarbial)
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No dependence or tolerance, no cross tolerancce with other Buspirone - clear consciousness, no dependence or
BZDs, does not alleviate BZD or EtOH withdrawal withdrawal - but its efficacy as an anxiolylitic is poor.
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Children have increased suicidal thoughts with atomoxetine 2/3 of ADHD kids continue with it to adults
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Ethanol Metabolism: first step - primary route
ADH = Alcohol Dehydrogenase
EtOH: Pharmacokinetics Metabolism and Elimination ADH is inhibited by 4-methylpyrazole (Fomepizole)
Small, predictable amounts excreted through the lungs, urine First step in EtOH metabolism (90-98% of ingested
and sweat (2-10%), basis of breathalyzer tests EtOH), occurs in the cytosol
Primarily metabolized by oxidation in the liver (>90%) Acetaldehyde may be partly responsible for headache
EtOH elimination follows - ZERO ORDER KINETICS - which is characteristic of hangovers
Independent of concentration nicotinamide adenine dinucleotide (NAD) is a cofactor,
Elimination rate is dependent on body weight or liver weight availability of NAD may be rate limiting
An average adult metabolizes 7-10 g/hr (~0.7 drinks/hr) some ADH activity in the stomach (higher for men than
for women)
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Marijuana: Pharmacokinetics
Rapid absorption following inhalation
Euphoria onset after 10-30 minutes lasting 3-4 h
1056 Delta-9-THC is highly lipid soluble; accumulation in fatty
tissue
In some states, marijuana is legal for appetite stimulation Active and inactive metabolites
among AIDs patients. 10-15% urinary excretion- detectable up to 30 days after
use.
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Similar S&S to opioid OD - respirtory depression, coma, and
brandycardia; no response to naloxone or flumazenil
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1
7 Decreases PSA about 50%. PSA test is still valid, but data have to
be interpreted differently. Get a PSA before starting.
Get base line, so when on 5a reductase blocker, would double Notice: alpha blockers have fast onset, 5a reductase
PSA score to correct inhibitors have slow onset
Watchful Waiting
If no signs, or if minimally disrupting, simply wait. Patient training
to: Tamsulosin:
9 Restrict caffeine at night Competitive alpha blocker; binds a1A (and a1D) with
Phosphodiesterase inhibitor little a1B binding
Stimulants cardiac output (more fluid to glomeruli) Highly efficacious in benign prostatic hyperplasia.
Restrict fluid at night Very limited (if any) vascular effects, Well tolerated,
Do not delay voiding Effectiveness is maintained for years (little tolerance)
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10
Asthenia loss of strength, pt will complain of weakness, but Notice: Terazosin SE similar to doxazosin, but side-
strenght tests will be normal effect profile is perhaps more severe.
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OC (Estrogen) SE cont
Nausea related to amount of estrogen; Heightened sense of Side effects of OCs associated with progestin
smell (sickenly sweet to woman) Cardiovascular disease: depends on age of subject
Headache or worsening of migraine has been suggested to and genetic factors (thromboembolic factors, liver Ez)
be related to the influence of estrogen on tryptophan metabolism Stroke (thromboembolic factors)
(tryptophan has been used to treat migranes) Increased appetite may be a result of the glucose
25 Edema (Bloating) associated with estrogens ability to promote intolerance, and consequent increase in the amount of
sodium retention insulin which influences satiety centers in the brain.
Breast tenderness or fullness Weight gain may be more prevalent with the
Cancer (?, depends on type) more likely with the higher androgenic progestins (they are anabolic)
concentration and/or alternate preparation of hormone used in HT Fatigue
or ET; Reduced exposure and dose helps Depression may be related to the ratio of
OC may improve risks for ovarian cancer (higher the dose of Progesterone to Estrogen
progestin, the lower the ovarian cancer) Breast regression
26
27
28
Medroxyprogesterone acetate (MPA): Progestoren Challenge test: progestoren which will
t of 38-46hrs (long half life) stimulate the endometrium to change from proliferative
Elimination: phase to secretory phase and then slough off (+
Renal (minor) withdrawl bleed). Give for 7 days then stop (mimics
Fecal (major) corpus luteum) woman should have menstruation if
she has sufficient estrogen and vaginal patency.
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ACEI advantages: Predictable, typically mild, dose-related side- Contraindication: ACEI with renal a. stenosis
effects (bilateral, eg atherosclerosis or fibromuscular
Blunt the hypokalemia caused by diuretics dysplasia): Stenosis must be removed by surgery; renin
Decrease aldosterone release levels are high in this condition; ACE-I will further dilate
Little orthostatic hypotension or SNS activation the efferent arteriole, resulting in even less pressure in
No effect on triglycerides, cholesterol the glomerulus (rise in serum creatinine).
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NSAIDs are ulcerogenic. NSAIDs aggravate mucosal damage,
delay healing, and predispose to bleeding. Prolonged ingestion of
NSAIDs is one of the primary causes of gastric ulcer and, to a
lesser extent, duodenal ulcers. NSAIDs should either be avoided
or reduced in dose in ulcer patients. COX-2 selective NSAIDS
(e.g., celecoxib), have a lesser incidence of ulcer formation than
nonselective NSAIDs. However, recent reports of increased risk
of adverse cardiovascular events with these agents have
significantly limited their use. Rofecoxib, valdecoxib have been
withdrawn from the market.
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s:
ng, high136
neutralizing capacity, causes constipation.
moderate acting, high neutralizing capacity; causes diarrhea.
act acting, moderate neutralizing capacity; releases CO2 causing distention SINCE ALUMINA COMPOUNDS DECREASE
ated and sustained rebound acid secretion. MOTILITY AND CAUSE CONSTIPATION, AND
high neutralizing capacity; rapidly cleared from the stomach and presents MAGNESIUM COMPOUNDS INCREASE MOBILITY
mic alkalosis; releases CO2. AND CAUSE DIARRHEA, MOST COMMERCIAL
mulations to decrease foaming and reflux. PRODUCTS CONTAIN A COMBINATION OF THE TWO
cid; forms a foam that floats on the gastric contents and protects the mucosa INGREDIENTS TO MINIMIZE EFFECTS ON BOWEL
MOTILITY.
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Nitrate therapy in chronic stable angina NTG primarily works on venous side (dilation),
Short-acting: Relief during acute episodes, Prophylaxis of acute however, large enough dose will dilate arterials also.
episodes, Venodilator drugs reduce preload by redistributing blood
Long-acting: monotherapy for mild angina, adjunctive for more away from the chest into peripheral viens
severe angina Arteriodilators decrease afterload (eg Hydralazine)
Limitations: side-effects & tolerance Venodilators decrease preload (eg Organic nitrates)
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221
Action Potential
Electrolyte shifts create electrical activity
222 Four phase action potential demonstrates the various
stages of activity
Electrolytes associated with each phase differ in nodal
eliminated mainly by the liver and some by the kidney; elderly vs. non-nodal tissue
requires lower dose due to reduced clearance
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ent which
223 increase refractoriness of the bypass track and "break" the reentry
and digoxin (&CCB?) should be avoided in a wide complex preexcitation
elerate the ventricular rate and cause the rhythm to degenerate to Vfib (these
rease conduction down accessory pathway; also class IB agents shorten the
thus also can increase the ventricular response to an SVT). If a pt has
ally unstable, DC cardioversion should be first-line therapy
Disopyramide:
Moderately effective for atrial arrhythmia and poorly effective for
224 ventricular arrhythmia
Reduces automaticity and conduction velocity
Side effects include decreased contractility and urinary retention
has anticholinergic effects - stops peeing, pooping, salivating
225
Note: Infiltration of inflammation mediators and necrotic materials
lower tissue pH (eg abcess) and render lidocain anestheic less
effective (lidocaine is a weak base, does not work when
protonated)
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Class IC kills people; thus, they are not used as first line agents
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233
BB are beneficial in longterm tx of pts follwing MI if they have
evidence of recurrent ischemia or have sustained a Q-wave MI
(give BB, ACEI and ASA). Howevere, BB have no benefit in pts
with small or non-Q-wave MI (give ACEI and ASA)
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ptake (may increase insulin responsive genes and increase GLUT-1 and
ecrease triglycerides, FFA, increase HDL, in increase large fluffy LDL. If pt continues to eat poorly, they will dramatically gain
l effect. weight if they are prescribed TZD!! Do not prescibe if pt
lin dose or facilitate discontinuation of insulin. clearly has no intention of improving diet (and excersize)
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Causes of Hyperthyroidism:
* Graves' Disease (toxic diffuse goiter)
Hyperthyroid Symptoms: Heat Intolerance, Weight loss * Toxic uninodular goiter (Plummer's disease)
332 common; or weight gain due to increased appetite, increased * Toxic multinodular goiter
sweating, palpitations, Pedal edema, Diarrhea/frequent bowel * Nodular goiter with hyperthyroidism due to exogenous
movements, Amenorrhea/light menses, Tremor, Weakness, iodine (Jod-Basedow)
fatigue * Exogenous thyroid excess through self-administration
Physical Findings: Thinning of hair (fine), Proptosis, lid lag, lid (factitious hyperthyroidism)
retraction, conjunctivitis, stare, periorbital edema, loss of ocular * Tumors (thyroid adenoma, follicular carcinoma,
movements, Diffusely enlarged goiter, bruits, thrills, Wide pulse thyrotropin secreting tumor of the pituitary, and
pressure, Pretibial myxedema!!, Plummer's nails, Flushed, moist hydatiform mole with secretion of a thyroid stimulating
skin, Palmar erythema, increased Deep tendon reflexes substance)
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360 Nutritional Rickets: Treat with Vit D and diet having adequate Ca
and phosphate.
Chronic Renal Disease: Reduced synthesis of 1,25 and 24,25
(OH)2, retention of phosphate and secondary
hyperparathyroidism leading to renal osteodystrophy
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an H1-antihistamine, analgesics, cough suppressants, or expectorants in Pseudoephedrine and Methamphetamine: Pseudoephedrine obtained OTC is the major ingredien
make methamphetamine (Meth, Ice; see No No's) in illegal labs (cars, motel rooms, basements, g
(H1 antihistamine) Meth is a major drug abuse problem. Efforts are underway at both the national and various state legis
402
= Pseudoephedrine +Acetaminophen (analgesic) + Dextromethorphan to restrict the use and availability of pseudoephedrine. Several states (Oklahoma) restrict sales or no
tihistamine) pharmacies to place medications containing pseudoephedrine behind the counter. Most drug manufa
Caplets = Pseudoephedrine + Guaifenesin (expectorant) + reformulating their OTC medications to replace pseudoephedrine with phenylephrine. Phenyleph
be easily converted to methamphetamine. Long-term changes in the laws and availability of drugs
seudoephedrine + acetaminophen + guaifenesin + dextromethorphan determined.
403
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615
616
617
618
619
Partial agonist action decreases some of the craving for HEO Remember weak partial agonists work as antagonists
opioid when given with a full agonist
620
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623
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629
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K L
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663
Analgesia: PGE2 sensitizes pain nerve endings to the action of
bradykinin, histamine, substance P and other mediators and thus
blockade of PGE2 synthesis prevents this hyperalgesia.
Antipyresis: Temperature control center in hypothalamus
regulates body temperature. Pyrogens (cytokines) from
lymphocytes lead to higher temperature set point, i.e., fever - heat
generation (metabolism) increases and heat loss (vasodilation)
decreases. NSAIDs (that can cross BBB effectively) suppress this
response but do not effect normal body temperature. Anti- Gastrointestinal Effects: PGI2 inhibits gastric acid
inflammatory: PGE2 and PGI2 (prostacyclin) cause vasodilatation secretion.
and are important mediators of localized erythema and edema in PGE2 and PGF2a stimulate synthesis of bicarbonate and
inflammation. NSAIDs inhibit their formation. Also, it has been mucus.
proposed that NSAIDs directly inhibit activation and function of PGE2 promotes mucosal blood flow.
neutophils, stabilize lysosomal membranes, and inhibit leukocyte NSAIDs inhibit all of these effects which leads to GI
phagocytosis. irritation.
664
K L
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666
667
668
669
670
K L
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673
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675
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K L
Receptor Mechanism:
Steroid hormone receptors are located in the cytoplasm
of cells (they are soluble, mobile proteins; not
679 membrane-associated). The receptors are associated in
a complex with a number of other proteins (heat shock
proteins; hsp); these proteins dissociate from the
receptor upon binding of the steroid. The activated
receptor moves to the nucleus of the cell where it binds
to specific sequences of DNA. termed glucocorticoid-
Therapeutic Uses and Diagnostic Applications of ACTH responsive elements (GREs). Receptor binding at the
All of the known therapeutic effects of ACTH also can be achieved GRE site can either activate or inhibit transcription of
with appropriate doses of corticosteroids that are more convenient specific genes. The hormone-receptor complex also
to administer. Therefore, ACTH has very limited therapeutic use. can regulate gene transcription by binding to other
A synthetic analog (Cosyntropin) is available for diagnostic tests nuclear transcription factors (regulatory proteins) or to
of adrenal function. ACTH plasma concentrations can be their promoter/regulator regions on the DNA.
measured by an immunoradiometric assay. Metyrapone Because the metabolic and antiinflammatory effects
stimulation test is used to test for ACTH deficiency. It works by are mediated by the same receptor, none of
inhibiting cortisol synthesis, which should result in an increase in glucocorticoid derivatives have selective anti-
ACTH levels by reduced negative feedback. It is used to evaluate inflammatory activity without also affecting
the HPA axis and not used for the diagnosis of Cushing syndrome carbohydrate, protein, and fat metabolism.
680
681
682
683
684
K L
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688
689
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714
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719
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721
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723
724
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728
Principles defining drug selection:
1. Single agents should have known activity against the tumor
2. all agents in the regimen should have different mechanisms of Anthracycline Antibiotics mech: planar multi-ring
action structures that are active by insertion of the planar ring
3. Agents should not have overlapping toxicities so that the between base pairs (G-C sequence) of DNA and
duration of acute and chronic toxicities are minimized. interferes with DNA function. Other minor activities are
4. All should be used in their optimal dose and schedule. TOPOII inhibition, and free radical formation.
729
730
731
K L
732
733
734
735
736
737
738
739
K L
740
742
743
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K L
746
747
748
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K L
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760
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764
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766
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768
769
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772
773
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776
777
778
779
780
781
782
783
784
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786
787
788
789
790
791
792
793
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K L
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
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818
819
820
K L
821
822
823
824
825
826
827
828
829
830
831
832
833
834
K L
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
K L
850
851
852
853
854
855
856
857
858
859
860
861
862
863
865
866
867
868
869
871
872
874
875
876
877
878
K L
879
880
881
882
883
885
886
K L
888
889
891
892
893
K L
894
895
896
The effects of these drugs are primarily in the spinal cord; targets
897 are Ia fibers that excite the primary motorneuron Baclofen inhibits
release of excitatory transmitters from IA neurons themselves.
Excitation of GABA-B receptors causes hyperpolarization by
increased K+ conductance. Baclofen inhibits both monosynaptic
and polysynaptic spinal reflexes
898
899
900
K L
901
902
903
904
905
906
907
908
909
910
911
912
913
914
K L
915
Partial Seizures:
Simple Partial (single focus):
no abnormality of consciousness
motor, sensory, autonomic, psychic (??effected or
not??)
Seizure types: Complex Partial (multiple foci):
Partial seizuresBegin locally at some focus quality of consciousness impaired
Generalized seizuresInvolve both hemispheres; no local onset psychomotor
ContinuousNot transient or self-limited Partial seizures secondarily generalized (Spread)
916
917
918
919
with ethosuximide, but then one day have a grand mal (GTCS) that is actually
920
w it is atypical), and you would have to change the AED to valproic acid, the
could have treated the patient in the first place with valproic acid, even
cal presentation.
K L
921
922
923
924
925
926
K L
927
928
929
930
931
932
933
Interferon: 1a and1b
Reduce the attack rate in MS, whether measured clinically or by
MRI
934 For relapsing/remitting MS & secondarily progressive MS.
Both of these forms of MS are characterized by relapses
These drugs slow the accumulation of physical disability and
decrease the frequency of clinical exacerbations.
In patients with chronic progressive multiple sclerosis, safety and INF-beta (anti-inflammation) has opposite effect of INF-
efficacy have not been established. gamma (inflammation)
K L
936
937
938
939
940
K L
941
942
943
944
945
946
947
K L
948
949
950
952
953
954
955
K L
956
957
958
959
960
961
962
K L
963
964
Tricyclinics used to treat chronic pain disorders (NE blocking Tricyclics tx of Enuresis: reduce bed-wetting by
effect) reduction of delta sleep (note - this is not a long term
solution, only treats symptom)
965
966
967
969
970
971
972
K L
973
975
976
977
K L
978
979
980
981
983
K L
984
985
986
987
K L
988
989
990
991
992
993
994
995
996
997
K L
GABAa Structure
Alpha unit binds GABA
GABAa Receptor Complex - A critical receptor complex for the Alpha/beta junction seems to be BZD binding site
anxiolytic/sedative-hypnotic effects of gamma unit must be present for BZDs to modulate
benzodiazepines GABA
barbiturates Channel opens to Cl- ions when GABA binds
ethanol Increased Cl- conductance inhibits neural firing
998 GABAa Structure - 7 families Decreased Cl- conductance excites neurons (seizures)
Receptors containing alpha, beta, gamma, and delta are most Binding Sites on the GABA Receptor
frequent in CNS True Receptor Site - GABA
15 total subunits Sites that Modulate GABA binding:
e.g., 6 alpha subunits (alpha1, alpha2, etc) BZDs
5 subunits come together to form the receptor complex, barbiturates (and alcohol)
approximately 2000 variants of GABAa receptor possible, several neurosteroids
subtypes exist in the mammalian CNS; Usual stoichiometry is picrotoxin (a convulsant you are not responsible for
limited, composition of 2alpha,2beta,1gamma is most frequent. this agent)
Within a receptor, the alpha, beta, gamma subunit families are Note - the modulators have no effect on neuron without
identical (e.g., both alpha might be alpha1, or both might be the presence of GABA, they do not have a true receptor
alpha3, etc) site, only modulate GABA's effect
999
1000
1001
1002
K L
1003
1004
1005
1006
1007
1008
1009
1010
Primates have been shown to distain marijuana and LSD, but love
everything else.
K L
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
K L
1022
1023 Mech is still not quit known seems to interfer with active
uptake (at presynaptic neuron membrane as well as at the
transporter into the vessicle) amphetamine interfers with both
processes some claim it actually reverses these transporters Amphetamine enhance both DA (abuse) and NE (so
increases concentration in both cytoplasm (and extracellular increase BP (peripheral) and activate sleep wakefulness
space?) (note: coke only blocks the uptake mech of DA or NE, not in RAS (central))
the vessicular transport).
1024
1025
Note: all drugs of abuse increase DA somehow (either block DA
reuptake or release it) - no DA release with Atomoxetine
1026
1027
1028
1029
1030
K L
1032
1033
1034
1035
1036
1037
1038
K L
1039
1040
1041
1043
1044
K L
1045
1046
1047
Amphetamine-type drugs:
d-amphetamine (Dexedrine)
methamphetamine (Desoxyn) - favorite of the biker set, and a
drug of abuse that waxes and wanes in popularity among other Psychostimulants: Uses
folks. Its long duration of action makes profound sleep disruption Commercial availability of amphetamines carefully controlled since 1972
1049 more likely than with cocaine, which is a negative for those trying Weight control (Not amphetamine or methamphetamine) - derivatives of amphetamine that are sch
to maintain work habits. Methamphetamine has become an IV agents that are used for weight control; they have very little abuse potential compared to d-amphe
epidemic in rural America. Ice is methamphetamine that is methamphetamine.
smoked Anti-fatigue - e.g., military uses amphetamine for this purpose. Penalty is a rebound effect = need t
Methylphenidate (Ritalin) - extremely limited in abuse potential crash
compared to amphetamines Enhance Athletic performance - actually, they improve tasks where boredom is a factor, but are no
Phenmetrazine (Preludin) - not readily available other tasks.
1050
1051
e within a pressure sensitive resin, to minimize the risk of accidental
essary for activation. Mildly unpleasant tasting (to reduce risk of accidental Nicotine use amoung Mental Illness:
cosa. Take every 1-2 hours. Dont chew constantly. Soften it up and then 50% of all psychiatric patients
plus this leads to upset stomach, nausea, etc. Large first-pass metabolism if 70% of patients with Bipolar Disorder
90% of patients with Schizophrenia
(weak base) (reduces outside sensory stimuli and increase
sufficiently high dose of nicotine. 24-h and 16-h systems. Each comes with concentration)
icotine)
1052
K L
1053
1054
1055
1059
K L
1060
1061
1062
M N
1
11
12
13
14
15
16
17
18
M N
19
20
21
23
24
M N
25
Progestins SE cont
Post-partum depression Progestins can increase blood pressure in certain
Therory: ratio of E:P, P gets converted to individuals, especially obese (Not a problem unless pt is
allopregnenolone by 5alpah-reductase, alloP is the obese)
most potent positive allosteric modulator of the GABAa The more androgenic progestins may reduce HDL levels
receptor (sedation/anxiolysis). Enhances GABAa May increase CV risk
currents, increasing sedation/depression Remember that testosteone (an androgen) decreases HDLs
26
27
29
30
31
M N
32
33
34
35
36
37
38
39
40
41
42
43
M N
44
45
46
47
48
49
50
51
52
53
54
55
M N
56
57
58
59
60
M N
61
62
63
64
65
66
M N
67
68
69
70
71
72
73
M N
74
If a blockage in an artery to the kidney is suspected, the
captopril test may be done. The captopril test involves
taking a dose of the medication captopril following a
plasma renin activity (PRA) test and baseline blood
pressure measurement. Then follow-up blood pressure
measurements and a PRA test done 60 minutes later
screen for high blood pressure. Deterioration of renal
function in a pt suggests bilateral renal a. stenosis or
stenosis in a single functioning kidney. The increase Note: ACEIs and ARBs selectively dilate the efferent
after captopril of PRA is higher in unilateral significant arterioles, dihydropyridine CCB selectively dilate the
lesions. More commonly MRA imaging is used today. afferent arterioles.
75
76
77
Most dihydropyridine calcium channel blockers (arterial Note: ACEIs and ARBs selectively dilate the efferent
dilation) induce a reflex increase in heart rate in the arterioles, dihydropyridine CCB selectively dilate the
absence of -blockade afferent arterioles.
M N
79
80
81
82
M N
83
84
85
86
87
M N
88
89
90
91
92
93
94
95
96
M N
98
99
100
101
102
M N
103
104
105
106
107
108
109
110
111
M N
112
113
114
115
116
117
118
119
120
121
M N
122
123
124
125
126
127
128
M N
129
130
131
132
Drugs that inhibit P450:
Cimetidine
isoniazid
fluoxetine
erthromycin
ketoconazole
ritonavir
grapefruit juice
133
134
135
136
M N
137
138
139
140
141
142
M N
143
144
145
146
147
148
149
M N
150
151
Drug-induced diarrhea: A number of drugs can cause
diarrhea: reserpine, guanethidine, sulfonamides,
tetracyclines, most broad-spectrum antibiotics,
cholinergic agonists, osmotic and stimulant laxatives,
prokinetic agents (metoclopramide, domperidone),
prostaglandins, quinidine. Adjustment of dosage or
change in medication is preferred to co-
administration of an anti-diarrheal drug.
152
153
154
155
M N
156
157
158
M N
159
160
161
162
163
164
165
M N
166
167
168
169
170
171
172
173
174
175
176
177
M N
178
179
180
181
182
183
184
M N
185
186
187
188
189
190
191
192
193
194
195
196
197
198
M N
200
201
202
203
204
205
M N
206
207
208
209
210
211
M N
212
EKG effects of glycosides:
S-T segment depression
Inversion of T wave
Preceding two effects normally first to appear
Prolongs P-R interval
Decease conduction velocity at AV node
Up to 0.25 sec, followed by block as dose increases
Shortens Q-T interval
Due to accelerated ventricular repolarization ADDITIONAL USES OF DIGOXIN
Because of digoxins many effects, many types of Atrial arrhythmias: 1. Fibrillation, flutter (Blocks the AV node,
dysrhythmia are possible Increases contractility of ventricle) 2. Paroxysmal
tachycardia (Make sure it is not caused by digoxin)
213
214
M N
215
NTG: reduces preload and afterload and myocardial oxygen consumption. Also, it directly dilates coronary stenoses
and increases oxygen delivery to the ischemic region.
Nitroglycerin increases collateral flow and favorably redistributes regional coronary flow.
In contrast to other vasodilators, it does not induce a coronary steal
Nitroglycerin inhibits platelet aggregation and, in experimental models, reduces platelet thrombus deposition.
The most common adverse effects are headache, nausea, dizziness, hypotension, and reflex tachycardia.
216
217
218
219
220
221
All phases common to nodal and non-nodal Electrolyte shift in Atrial or Ventricular tissue (non-nodal)
Phase 0: Rapid depolarization Phase 0: Sodium
222 Phase 1: Depolarization overshoot Phase 1: Sodium channel closes
Phase 2: Plateau Phase 2: Calcium channel open
Phase 3: Repolarization Phase 3: Potassium rectifier
Phase 4: Instrinsic depolarization Phase 4: Sodium leak
M N
223
224
225
226
227
228
M N
229
230
231
232
233
234
M N
235
236
237
238
239
240
241
M N
242
243
244
245
247
248
M N
249 Distribution:
rapid and complete absorption
Onset: considerably delayed (36 - 72 hours), delay in highly fat-soluble
onset is due to long t1/2 of warfarin and the fact that pre- 99% bound to plasma albumin
existing clotting factors are slowly cleared from the blood Termination: delayed (2 -5 days)
(t1/2 for VII = 6 hours) liver and kidney metabolism
Duration: prolonged, proportional to the elimination long elimination t1/2
t1/2 (25-60 hours) new, active clotting factor must be synthesized
250
251
252
253
M N
254
255
256
257
258
259
260
261
M N
262
263
264
265
266
M N
267
268
269
270
271
272
273
M N
274
275
276
M N
277
278
279
280
281
282
283
M N
284
285
286
M N
287
Circulating iron-bound transferrin (TF) is bound to
Storage forms: Hemoglobin represents the largest specific receptors on the surface of red blood cell
pool of iron in the body. Iron is also stored in the precursors in the marrow. Most of this iron is incorporated
intestinal mucosal cells, plasma, and macrophages of into hemoglobin; the remainder is stored as ferritin.
the liver, spleen, and bone marrow in the form of ferritin. Following maturation of the erythroid precursor cell, the
Ferritin is the most readily available stored form of iron. nucleus is shed and the red blood cell emerges from the
It consists of a water soluble complex of ferric hydroxide marrow into the plasma where it circulates for approximately
crystals covered with a shell of the protein apoferritin. 120 days. The senescent red blood cell is taken up by the
Hemosiderin is the name given to the (insoluble) ferric monomuclear phagocyte system and is destroyed. The
core crystals without apoferritin; iron is stored in this heme iron is initially incorporated into ferritin. This storage
form in macrophages. iron is available for transport to the marrow via transferrin.
289
290
291
292
293
M N
294
295
296
297
298
299
300
301
302
M N
304
305
306
307
M N
308
309
310
311
312
313
M N
314
315
316
317
318
319
M N
321
322
323
324
325
326
M N
327
328
329
330
Iodide Uptake: Iodide is an essential component of the Synthesis: The enzyme peroxidase oxidizes iodide to
T3 and T4 molecule. Iodide (I-) is present in the normal oxidized iodine (Io) which rapidly bonds with tyrosine
diet (recommended daily adult intake = 150 microg), is residues on the large protein thyroglobulin forming
331 rapidly absorbed, and concentrated from the blood by monoiodotyrosine (MIT) and diiodotyrosine (DIT). Two
the thyroid gland by an active uptake mechanism. The molecules of DIT combine on the thyroglobulin molecule to
thyroid can concentrate iodide 20 to 50, or even a 100 form one molecule of thyroxine (T4). One MIT and one
times over the plasma concentration. TSH (thyrotropin) DIT combine to form T3. This process of synthesizing
stimulates iodide uptake. Cardiac glycosides iodinated amino acid residues on the protein is sometimes
(ouabain) can inhibit uptake. Uptake is also controlled referred to as "iodide organification and coupling". The
by autoregulatory mechanisms; if stores of iodide antithyroid thioureylene drugs (propylthiouracil and
decrease, uptake is stimulated; excess iodide methimazole) inhibit peroxidase and thus block synthesis
decreases uptake. of T3 and T4.
333
334
335
336
337
338
339
340
341
342
M N
343
344
345
346
347
348
349
350
351
352
353
354
M N
355
356
357
358
359
360
361
362
363
364
M N
365
366
367
369
370
371
M N
372
373
374
375
376
377
378
379
380
381
M N
382
383
384
385
386
M N
387
388
389
390
391
392
393
M N
394
395
396
397
398
399
400
401
M N
403
404
406
407
408
409
M N
410
411
412
413
414
415
416
M N
417
418
419
420
421
422
423
424
425
M N
426
427
428
429
430
431
432
433
434
435
436
437
438
M N
439
440
441
442
443
444
445
446
447
448
449
450
451
M N
452
453
454
455
456
457
459
460
461
M N
462
463
464
465
466
467
468
469
470
M N
471
472
473
474
475
476
477
M N
478
479
M N
480
481
482
483
485
M N
486
487
488
489
490
M N
491
492
493
494
495
496
497
M N
498
499
500
501
502
M N
503
M N
504
505
506
M N
507
508
509
510
511
512
M N
513
514
515
516
M N
517
518
520
521
522
523
524
M N
525
526
527
528
529
530
531
532
533
M N
534
535
536
M N
537
538
539
540
541
542
543
544
545
M N
546
547
548
549
550
M N
551
552
553
554
M N
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
M N
570
571
572
573
574
M N
575
576
577
578
579
580
581
582
583
584
M N
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
M N
kappa receptors:
less involvement in abuse potential and physical
603 dependence
important for effects of non-selective and some of the mixed
Opioid Receptor Subtypes: mu receptors agonist-antagonist opioids including:
important for most of the classical effects described for dysphoria
opioids including: psychotomimetic responses (disoriented to
analgesia person/place/time or depersonalized feelings)
euphoria less miosis and respiratory depression than mu agonists
miosis analgesia
respiratory depression sedation
physiological dependence vasodilation
reduced GI motility (constipation) increased urinary output
604
605
606
607
M N
Morphine:
equivalent analgesic dose = 10 mg
608
maximum efficacy = high
oral: parenteral potency ratio: low
duration of analgesia = 4-5 hours
addiction/abuse liability = high
Abuse potential is decreased by slower rates of infusion oral and suppository preparations available
(eg morphine pump in hospital) - no rush
609
610
611
612
613
614
M N
615
616
617
618
619
620
M N
621
622
623
624
625
626
627
628
M N
629
630
631
632
633
634
635
M N
636
637
638
639
M N
640
641
642
643
644
645
646
M N
647
648
649
650
651
652
653
654
655
M N
656
657
658
659
660
661
662
M N
664
M N
665
666
667
668
669
670
M N
671
672
673
674
675
676
677
678
M N
680
681
682
683
684
M N
685
686
687
688
689
690
691
692
693
694
695
M N
696
697
698
699
M N
700
701
702
703
704
705
M N
706
707
708
M N
709
710
711
712
M N
714
715
716
717
M N
718
Cisplatin causes severe n/v. The recommended initial
regimen would be ondansetron (consider the most The most common drugs that are cycle dependent are the
effective, or other other 5-HT3 antagonist) plus antimetabolites. The most common drugs that are cycle
dexamethasone plus lorazepam. Independent are the alkylating agents.
719
720
721
722
723
724
M N
725
726
727
728
729
730
731
M N
732
733
734
735
736
737
738
739
M N
740
741
742
743
744
745
M N
746
747
748
749
750
751
752
753
M N
754
755
756
757
758
759
M N
760
761
762
763
764
765
766
767
M N
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
M N
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
M N
821
822
823
824
825
826
827
828
829
830
831
832
833
834
M N
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
M N
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
M N
865
866
867
868
869
871
872
873
plicated in NMS have dopamine D2-receptor antagonist properties.
of anti-Parkinson medication. The clinical syndrome is thought to
n the central nervous system (CNS), either from blockade of
ty of dopamine itself, and shares similarities with malignant
ckade of dopamine neurotransmission in the nigrostriatum and
nd altered thermoregulation, respectively. There is evidence that
unction may play a significant role in the pathogenesis of NMS.
874
875
876
877
878
M N
879
880
881
882
883
884
885
886
M N
887
888
889
891
892
893
M N
894
895
896
897
898
899
900
M N
901
902
903
904
905
906
907
908
909
910
911
912
913
914
M N
916
917
918
919
920
M N
921
922
923
924
925
926
M N
927
928
929
930
931
932
933
934
M N
936
937
938
939
940
M N
941
942
943
944
945
946
947
M N
948
949
950
952
953
954
955
M N
956
957
958
959
960
961
962
M N
963
965
966
967
968
969
970
971
972
M N
973
974
975
976
977
M N
978
979
980
981
982
Mechanism of Action of Typical Antipsychotics
Drug Terminology: Antipsychotics as a term refers to All block DA receptors, particularly the D2 receptor. Their
both the entire class of these drugs as well as to an clinical efficacy against positive symptoms is relatively well
older set of drugs that should now be seen as a correlated with this action. Not particularly efficacious
subclass (a class sometimes described as Neuroleptics against negative symptoms. Many side-effects are well
or Typical Antipsychotics, eg Chlorpromazine and correlated with this action. Note that drugs do not well-
Haloperidol). At one time this subclass comprised scores differentiate the subtypes of the D2-receptor-family (D2, D3
of drugs. You should know only some of them. This and D4). Within the family, D2 predominates in terms of
subclass is rapidly being supplanted by a new subclass, number of receptors. Hence, the D2 receptor per se is
the so-called Atypical Antipsychotics (Olanzapine, usually the one specified for mediating the effects of
Risperidone, Clozapine, Arapiprazole). antipsychotics.
983
M N
984
985
986
987
M N
988
989
990
991
992
993
994
995
996
997
M N
998
Note: BZD have a celling/plateau to effect (so much Benzodiazepines (BZDs) - 3 Types of Drugs:
safer drug), where both alcohol and barbituates do not; Agonists (therapeutic agents) - facilitate GABA action at
also note that (though considered modultor drugs with GABAa receptors by increasing the frequency of Cl-
no true receptor) barbiturates and alcohol can directly channel openings
increase Cl- flux into cell (where BZD cannot, indirect Antagonists - competitively antagonize BZD agonists
effect, also makes safer). A true receptor must have a Inverse Agonists - decrease Cl- conductance; inhibit
binding site and activate a secondary messanger system GABA in a non-competitive fashion
of cell
999
1000
1001
1002
M N
1003
1004
1005
1006
1007
1008
1009
1010
M N
1011
FDA reports that pts using hypnotics may develop
amnesia during usage.
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
M N
1022
1024
1025
1026
1027
1028
1029
1030
M N
1031
1032
1033
1034
1035
1036
1037
1038
M N
1039
1040
1041
1042
Acute EtOH: liver
Increased oxygen utilization
Ethanol metabolism can produce an excess of decreased gluconeogenesis
reducing agents - during EtOH metabolism, excess decreased production of glucose from glycogen
NADH and NADPH are formed; involved in EtOH- increased lactate production
induced metabolic disorders including: decreased oxidation of fatty acids
reduced gluconeogenesis increased fat accumulation
hypoglycemia
ketoacidosis Acute EtOH effects on ion channels - 2 major:
increased triglyceride synthesis from free fatty acids GABA gated Cl- channel is facilitated;
Glutamate gated Ca++ channel is inhibited
1043
1044
M N
1045
1046
1047
1048
Cocaine: Interactions
Opioids (speedball)
Alcohol, where it condenses covalently to form
cocaethylene - produced by use of alcohol in
combination with abuse of cocaine; covalent linkage of
ethanol and cocaine; this compound has a much longer Cocaine: Tolerance: occurs to euphoric effects; however,
half-life than cocaine. Like cocaine, cocaethylene blocks very little carryover over tolerance from one session of use
the dopamine transporter, which accounts for its to another. Does not result in significant escalation of
euphoric effects dosage across sessions of use
M N
e for this purpose. Penalty is a rebound effect = need to sleep and a Psychostimulants: Uses
Narcolepsy - Legitimate use
ey improve tasks where boredom is a factor, but are not helpful on ADHD - Legitimate use, but watch for diversion
1050
1051
Nicotine Neuropharmacology: Binds to the cell bodies Epidemiological studies have found that smokers have a
in the VTA (ventral tegmental area) as well as the reduced risk of developing Parkinson's disease,
dopaminergic terminal of the nucleus accumbens (Brain Alzheimer's disease, and ulcerative colitis. A nicotine
stem to Cortex). Stimulates the release of dopamine analogue that stimulates dopamine release is under study
and glutamate. Also releases or causes increases in: B- for treatment of Parkinson's disease, and the nicotine
endorphin, epinephrine, vasopressin, norepinephrine, transdermal patch is being studied to counteract the
adrencorticotropin, Cortisol, Glutamate cognitive impairment caused by treatment with haloperidol.
1052
M N
1053
1054
1055
Marijuana: Dependence
Tolerance reported Marijuana: Overdosage
Withdrawal syndrome: anorexia, nausea, vomiting, Euphoria, time-space distortion, tachycardia, fever
1056 diarrhea, irritability, restlessness, insomnia - observed Psychosis (visual and auditory hallucinations,
after sudden discontinuance of prolonged use of high depersonalization)
doses (difficult to demonstrate in clinical populations) Treatment
Withdrawal does not appear to be major factor in haloperidol or diazepam for agitation
maintaining use. propranolol for cardiovascular effects
1057
1058
1059
M N
1060
1061
1062
O P Q
1
10
11
12
13
14
15
16
17
18
O P Q
19
20
21
23
24
O P Q
26
27
28
29
30
31
O P Q
32
33
34
35
36
37
38
39
40
41
42
43
O P Q
44
45
46
47
48
49
50
51
52
53
54
55
O P Q
56
57
58
59
60
O P Q
61
62
63
64
65
66
O P Q
67
68
69
70
71
72
73
O P Q
75
76
77
O P Q
78
79
80
81
82
O P Q
83
84
85
86
87
O P Q
88
89
90
91
92
93
94
95
96
O P Q
98
99
100
101
102
O P Q
103
104
105
106
107
108
109
110
111
O P Q
112
113
114
115
116
117
118
119
120
121
O P Q
122
123
124
125
126
127
128
O P Q
129
130
131
132
133
134
135
136
O P Q
137
138
139
140
141
142
O P Q
143
144
145
146
147
148
149
O P Q
150
151
152
153
154
155
O P Q
156
157
158
O P Q
159
160
161
162
163
164
165
O P Q
166
167
168
169
170
171
172
173
174
175
176
177
O P Q
178
179
180
181
182
183
184
O P Q
185
186
187
188
189
190
191
192
193
194
195
196
197
198
O P Q
200
201
202
203
204
205
O P Q
206
207
208
209
210
211
O P Q
212
213
214
O P Q
215
216
217
218
219
220
221
223
224
225
226
227
228
O P Q
229
230
231
232
233
234
O P Q
235
236
237
238
239
240
241
O P Q
242
243
244
245
246
247
248
O P Q
Platelet Count:
(Normal Values = 130,000-400,000 per
microliter)
Thrombocytopenia = low platelets (<100,000/
ml, severe < 50,000/ml)
249 Bleeding Time:
Spring-loaded device makes incisions on volar Individual patient variation is very high
surface of the forearm with pressure cuff at 40 Due to differences in absorption, elimination, liver
mm Hg function, and drug-drug interactions.
excess blood is blotted away every 30 sec. Noncompliant and unreliable patients are not good
Normal = 7 min (2-9 min) candidates for warfarin therapy
Measures adequacy of platelet plugs Potential drug-drug interactions are numerous When ever hear Vit K think Warfarin and
Highly variable results vice versa
250
251
252
253
O P Q
254
255
256
257
258
259
260
261
O P Q
262
263
264
265
266
O P Q
267
268
269
270
271
272
273
O P Q
274
275
276
O P Q
277
278
279
280
281
282
283
O P Q
284
285
286
O P Q
288
289
290
291
292
293
O P Q
294
295
296
297
298
299
300
301
302
O P Q
304
305
306
307
O P Q
308
309
310
311
312
313
O P Q
314
315
316
317
318
319
O P Q
321
322
323
324
325
326
O P Q
327
328
329
330
333
334
335
336
337
338
339
340
341
342
O P Q
343
344
345
346
347
348
349
350
351
352
353
354
O P Q
355
356
357
358
359
360
361
362
363
364
O P Q
365
366
367
368
Only relieves bronchospasm, not used for beta-blocker induced asthma (seen in eye
treatment of underlying inflammatory Beta-agonist, steroids, and theophylline are drops for glacoma) - contraindication in pt
disease mainstays in the treatment of status asthmaticus with asthma or history of atopy
369
370
371
O P Q
372
373
374
375
376
377
378
379
380
381
O P Q
382
383
384
385
386
O P Q
387
388
389
390
391
392
393
O P Q
394
395
396
397
398
399
400
401
O P Q
402
403
404
405
406
407
408
409
O P Q
410
411
412
413
414
415
416
O P Q
417
418
419
420
421
422
423
424
425
O P Q
426
427
428
429
430
431
432
433
434
435
436
437
438
O P Q
439
440
441
442
443
444
445
446
447
448
449
450
451
O P Q
452
453
454
455
456
457
459
460
461
O P Q
462
463
464
465
466
467
468
469
470
O P Q
471
472
473
474
475
476
477
O P Q
478
479
O P Q
480
481
482
483
485
O P Q
486
487
488
489
490
O P Q
491
492
493
494
495
496
497
O P Q
498
499
500
501
502
O P Q
503
O P Q
504
505
506
O P Q
507
508
509
510
511
512
O P Q
513
514
515
516
O P Q
517
518
520
521
522
523
524
O P Q
525
526
527
528
529
530
531
532
533
O P Q
534
535
536
O P Q
537
538
539
540
541
542
543
544
545
O P Q
546
547
548
549
550
O P Q
551
552
553
554
O P Q
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
O P Q
570
571
572
573
574
O P Q
575
576
577
578
579
580
581
582
583
584
O P Q
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
O P Q
General:
603 Euphoria - Mu receptors
Dysphoria - Kappa receptors (predom)
Psychotomimetic - Kappa receptors (and
sigma for some drugs)
Notes on Clinical Uses: Analgesia
Best with severe, constant, dull pain (eg bone Opioid Effects - Therapeutic uses and
fracture). Not as effective with sharp, intermittent, side-effects are confined to actions in:
As a general rule, the greater the opioid's brilliant pain (eg knife pain). CNS
efficacy against pain, the greater the abuse Although dulled, pain is still perceived. Reaction to G.I.
potential pain is diminished. Vasculature
Match drug to intensity of pain Kidney (kappa agonists)
604
605
606
607
O P Q
608
609
610
611
612
613
614
O P Q
615
616
617
618
619
620
O P Q
621
622
623
624
625
626
627
628
O P Q
629
630
631
632
633
634
635
O P Q
636
637
638
639
O P Q
640
641
642
643
644
645
646
O P Q
647
648
649
650
651
652
653
654
655
O P Q
656
657
658
659
660
661
662
O P Q
663
Dysmenorrhea
Prostaglandins released by the endometrium during
menstration contribute to severe cramps and pain.
NSAIDs have proven very effective for treatment
664
O P Q
665
666
667
668
669
670
O P Q
671
672
673
674
675
676
677
678
O P Q
Cardiovascular System
1. Mineralocorticoid-induced hypertension can
contribute to atherosclerosis, cerebral Formed Elements of Blood
hemorrhage, stroke, and cardiomyopathy. The administration of glucocorticoids leads to a
Restriction of dietary Na+ can lower the blood decreased number of circulating lymphocytes,
pressure considerably. eosinophils, monocytes, and basophils. This effect is
2. Corticosteroids enhance vascular reactivity to due to redistribution of cells away from the periphery
other vasoactive substances. Glucocorticoids rather than from increased destruction. In contrast,
increase expression of adrenergic receptors glucocorticoids increase circulating PMN leukocytes.
in the vascular wall. Anti-inflammatory and Immunosuppressive
G. Skeletal Muscle Actions Transport, Metabolism, and Excretion
1. Permissive concentrations of corticosteroids 1. Corticosteroids profoundly alter the immune 1. Following absorption, 90% of cortisol is
are required for normal function of skeletal responses of lymphocytes and can prevent or bound to protein. The extent of protein
muscle; diminished work capacity is a prominent suppress inflammation in response to any number of binding varies among different steroid
679 sign of adrenocortical insufficiency. inciting stimuli (radiant, mechanical, chemical, analogs. Only unbound hormone or drug is
2. Chronic glucocorticoid excess causes skeletal infectious, and immunological). free to enter cells and affect function.
muscle wasting. 2. Glucocorticoids inhibit the production and release 2. Two plasma proteins bind glucocorticoids,
H. Central Nervous System of many different cytokines that normally would albumin and corticosteroid-binding
1. Indirect effects are important for maintenance stimulate the proliferation and function of B and T globulin (CBG or transcortin).
of the CNS, including effects on blood pressure, lymphocytes. Glucocorticoids suppress interferon, 3. At low steroid levels, most of the hormone
glucose levels, and electrolyte concentrations. GM-CSF, interleukins, tumor necrosis factor, is protein bound; at higher levels, the binding
2. Clinical administration of glucocorticoids can prostaglandins and leukotrienes. capacity of albumin and CBG is exceeded
induce mood elevation or more pronounced 3. The HPA axis and the immune system are capable and a much higher fraction of steroid exits in
behavioral changes, such as euphoria, of bidirectional interactions during the stress the free state.
insomnia, restlessness, and increased motor response. Several cytokines, e.g., IL-1, stimulate 4. CBG has high affinity for cortisol and low
activity. A smaller percentage of patients treated release of CRH and ACTH. This centrally mediated affinity for aldosterone. Corticosteroids
with glucocorticoids become anxious, feedback by the immune system stimulates compete with each other for binding to CBG.
depressed, or overtly psychotic. glucocorticoid release which inhibits the immune / 5. In general, metabolism of these steroids
3. Recent studies suggest that steroids inflammatory response and helps protect the involves oxidation or reduction followed by
produced locally in the brain (neurosteroids) organism from the potentially life-threatening conjugation in the liver to more water-soluble
may regulate neuronal excitability. consequences of a full-blown inflammatory reaction. metabolites which are excreted in the urine.
680
681
682
683
684
O P Q
685
686
687
688
689
690
691
692
693
694
695
O P Q
696
697
698
699
O P Q
700
701
702
703
704
705
O P Q
706
707
708
O P Q
709
710
711
712
O P Q
714
715
716
717
O P Q
718
719
720
721
722
723
724
O P Q
725
726
727
728
729
730
731
O P Q
732
733
734
735
736
737
738
739
O P Q
740
741
742
743
744
745
O P Q
746
747
748
749
750
751
752
753
O P Q
754
755
756
757
758
759
O P Q
760
761
762
763
764
765
766
767
O P Q
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
O P Q
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
O P Q
821
822
823
824
825
826
827
828
829
830
831
832
833
834
O P Q
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
O P Q
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
O P Q
865
866
867
868
869
870
O P Q
871
872
873
874
875
876
877
878
O P Q
879
880
881
882
883
884
885
886
O P Q
887
888
889
891
892
893
O P Q
894
895
896
897
898
899
900
O P Q
901
902
903
904
905
906
907
908
909
910
911
912
913
914
O P Q
Continuous Seizures:
Generalized status epilepticus:
Absence status epilepticus
915
Generalized tonic-clonic status epilepticus
Clonic status epilepticus
Tonic status epilepticus
Typical Absence Seizure (petit mal): Benign Febrile Convulsion: Myoclonic status epilepticus
3/second spike & wave (dome) activity brief generalized seizure Partial status epilepticus:
brief loss of consciousness without loss of during first day of febrile illness not due to meningitis Epilepsia partialis continua of Kojevnikov
postural tone or encephalitis Aura continua
blinking, licking lips, head turning only in children 6 months to 5 years of age Limbic status epilepticus (psychomotor
No aura Good prognosis unless have mutation on SCN2A status)
Abrupt onset, brief duration, prompt recovery gene Hemiconvulsive status with hemiparesis
916
917
918
919
920
O P Q
921
922
923
924
925
926
O P Q
927
928
929
930
931
932
933
934
O P Q
935
936
937
938
939
940
O P Q
941
942
943
944
945
946
947
O P Q
948
949
950
952
953
954
955
O P Q
956
957
958
959
960
961
962
O P Q
963
964
965
966
967
968
969
970
971
972
O P Q
973
974
975
976
977
O P Q
978
979
980
981
983
O P Q
984
985
986
987
O P Q
988
989
990
991
992
993
994
995
996
997
O P Q
999
1000
1001
1002
O P Q
1003
1004
1005
1006
1007
1008
1009
1010
O P Q
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
O P Q
1022
1024
1025
1026
1027
1028
1029
1030
O P Q
1031
1032
1033
1034
1035
1036
1037
1038
O P Q
1039
1040
1041
1043
1044
O P Q
1045
1046
1047
1049
1050
1052
O P Q
1053
1054
1055
1056
1057
1058
1059
O P Q
1060
1061
1062
R S
1
9
R S
10
11
12
13
14
15
16
17
18
R S
19
20
21
22
23
24
R S
25
26
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31
R S
32
33
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36
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40
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42
43
R S
44
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50
51
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53
54
55
R S
56
57
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R S
61
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66
R S
67
68
69
70
71
72
73
R S
75
76
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R S
78
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81
82
R S
83
84
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86
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R S
88
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91
92
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96
R S
98
99
100
101
102
R S
103
104
105
106
107
108
109
110
111
R S
112
113
114
115
116
117
118
119
120
121
R S
122
123
124
125
126
127
128
R S
129
130
131
132
133
134
135
136
R S
137
138
139
140
141
142
R S
143
144
145
146
147
148
149
R S
150
151
152
153
154
155
R S
156
157
158
R S
159
160
161
162
163
164
165
R S
166
167
168
169
170
171
172
173
174
175
176
177
R S
178
179
180
181
182
183
184
R S
185
186
187
188
189
190
191
192
193
194
195
196
197
198
R S
199
200
201
202
203
204
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R S
206
207
208
209
210
211
R S
212
213
214
R S
215
216
217
218
219
220
221
222
R S
223
224
225
226
227
228
R S
229
230
231
232
233
234
R S
235
236
237
238
239
240
241
R S
242
243
244
245
246
247
248
R S
249
Vitamins, especially vit E, can increase the risk of
bleeding in pt taking warfarin; foods high in vit K (eg
Supratherapeutic INR (eg pt has ecchymoses which is a minor bleeding complication but brussels sprouts, green tea, and spinach, organ meat,
wanting to maintain anticoagulation) - stop the warfarin and give oral vit K and continue to alfalfa, asparagus, broccoli, cabbage, cauliflower, kale,
follow INR to theraputic levels. Warfarin Overdose (ie serious bleeding) - no antedote - turnip greens, and watercress) can reduce the efficacy
can only give back clotting factors (FFP, danger of clotting), stop warfain, oral vit K of warfarin.
250
251
252
253
R S
254
255
256
257
258
259
260
261
R S
262
263
264
265
266
R S
267
268
269
270
271
272
273
R S
274
275
276
R S
277
278
279
280
281
282
283
R S
284
285
286
R S
Acute Iron Toxicity - seen almost exclusively in children. Adults can usually tolerate
large doses of oral iron without serious consequences. Consider the following scenario:
excess iron tablets, e.g., prescribed during pregnancy but no longer needed, are left in the
medicine cabinet; curious child sees what looks like M&M candies, child eats tablets and
becomes severely ill. Parenteral iron therapy is used only if oral
Ingestion of as few as 10 tablets of the commonly prescribed oral iron preparations can preparations cannot be tolerated, absorbed, or if
287 be lethal if ingested by a small child. Large amounts of oral iron cause necrotizing untoward reactions occur by this route. Iron
gastroenteritis, with vomiting, abdominal pain, and bloody diarrhea followed by shock, dextran complex is usually given IV (less tissue
lethargy, and dyspnea. Subsequently, improvement is often noted, but may be followed by staining), but also can be injected IM. Parenteral iron
severe metabolic acidosis, coma, and death. Urgent treatment of acute iron toxicity is use has been rising rapidly in the last several years with
necessary, especially in young children. Gastric aspiration, followed by lavage with the recognition that recombinant erythropoietin therapy
carbonate solutions to promote formation of insoluble iron compounds is the usual initial induces a large demand for iron that frequently cannot
treatment. Deferoxamine (Desferal), a potent and specific iron chelating compound be met through the physiologic release of iron from
should be given systemically by intermittent IM injection or by continuous IV infusion to reticuloendothelial sources. Allergic hypersensitivity
bind iron that has already been absorbed. Deferoxamine can also be given via gastric reactions and hypotension, vascular collapse,
tube to chelate any remaining iron in the GI tract, but this is controversial. General headache, nausea are adverse reactions. Never
supportive measures for GI bleeding, metabolic acidosis, and shock must also be administer concomitantly with oral iron
provided. preparations.
288
R S
289
290
291
292
293
R S
294
295
296
297
298
299
300
301
302
R S
303
304
305
306
307
R S
308
309
310
311
312
313
R S
314
315
316
317
318
319
R S
321
322
323
324
325
326
R S
327
328
329
330
331
TBG levels may be altered in certain conditions, thus changing the total circulating pool of
thyroid hormones. For example, TBG levels are elevated during pregnancy in
response to high estrogen levels; this increases the serum concentrations of both
protein bound and total T4 and T3 but not the concentrations of free hormones. Biotransformation: T3 and T4 are deiodinated and/or
Since free concentrations are the relevant factor for biological activity and do not change, conjugated to their respective glucuronate and sulfate
thyroid function and action during pregnancy are not normally affected. The opposite conjugates and excreted in the bile. Half-life for T4 is 6
situation occurs during androgen therapy, when TBG levels are reduced. - 7 days; T3 has a much shorter half-life 1.5 days.
332
R S
333
334
335
336
337
338
339
340
341
342
R S
343
344
345
346
347
348
349
350
351
352
353
354
R S
355
356
357
358
359
360
361
362
363
364
R S
365
366
367
368
369
370
371
R S
372
373
374
375
376
377
378
379
380
381
R S
382
383
384
385
386
R S
387
388
389
390
391
392
393
R S
394
395
396
397
398
399
400
401
R S
402
403
404
405
406
407
408
409
R S
410
411
412
413
414
415
416
R S
417
418
419
420
421
422
423
424
425
R S
426
427
428
429
430
431
432
433
434
435
436
437
438
R S
439
440
441
442
443
444
445
446
447
448
449
450
451
R S
452
453
454
455
456
457
458
*Terfenadine (Seldane) and Astemizole (Hismanal) were voluntarily withdrawn from the
market in 1998. These drugs produce the potentially fatal torsades de pointes cardiac
arrhythmia is the presence of other drugs that affect their metabolism. These agents
accumulate, usually a consequence of the simultaneous administration of a second agent
that competitively inhibits their metabolic degradation by the cytochrome P-450
isoenzyme 3A4. Other agents metabolized by this isoenzyme include macrolide
antibiotics (except erythromycin and azithromycin), the imidazole antifungals (e.g.,
fluconazole), HIV protease inhibitors (indinavir, ritonavir, saquinavir, and nelfinavir),
serotonin reuptake inhibitors (fluvoxamine, nefazodone, and sertraline), zileuton,
cisapride, sparfloxacin, mibefradil, and grapefruit juice.
459
460
461
R S
462
463
464
465
466
467
468
469
470
R S
471
472
473
474
475
476
477
R S
478
479
R S
480
481
482
483
485
R S
486
487
488
489
490
R S
491
492
493
494
495
496
497
R S
498
499
500
501
502
R S
503
R S
504
505
506
R S
507
508
509
510
511
512
R S
513
514
515
516
R S
517
518
520
521
522
523
524
R S
525
526
527
528
529
530
531
532
533
R S
534
535
536
R S
537
538
539
540
541
542
543
544
545
R S
546
547
548
549
550
R S
551
552
553
554
R S
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
R S
570
571
572
573
574
R S
575
576
577
578
579
580
581
582
583
584
R S
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
R S
604
605
606
607
R S
608
609
610
611
612
613
614
R S
615
616
617
618
619
620
R S
621
622
623
624
625
626
627
628
R S
629
630
631
632
633
634
635
R S
636
637
638
639
R S
640
641
642
643
644
645
646
R S
647
648
649
650
651
652
653
654
655
R S
656
657
658
659
660
661
662
R S
663
Aspirin absorption
Since aspirin is an acid, it exists principally as
unionized drug at the low stomach pH and is readily
absorbed by passive diffusion into the mucosal cells of
the stomach. Once it diffuses into the cells it
becomes ionized and trapped. This process may lead
to accumulation of the drug and may contribute to the
toxic effects on the stomach lining. Aspirin should be
taken with food or large volumes of fluid. Enteric coated
tablets (Ecotrin) do not dissolve until reaching the small
intestine; this helps minimize, but does not eliminate, GI
toxicity (toxicity due to prostaglandin inhibition is still a
Avoid use during third trimester unless absolutely necessary: key factor). Misoprostol, an analog of PGE 1, is
low birth weight, increased perinatal mortality, anemia, antepartum and postpartum sometimes prescribed for patients who must take
hemorrhage, prolonged gestation, premature closure of ductus arteriosus NSAIDs chronically.
664
R S
665
666
667
668
669
670
R S
671
672
673
674
675
676
677
678
R S
680
681
682
683
684
R S
685
686
687
688
689
690
691
692
693
694
695
R S
696
697
698
699
R S
700
701
702
703
704
705
R S
706
707
708
R S
709
710
711
712
R S
714
715
716
717
R S
718
719
720
721
722
723
724
R S
725
726
727
728
729
730
731
R S
732
733
734
735
736
737
738
739
R S
740
741
742
743
744
745
R S
746
747
748
749
750
751
752
753
R S
754
755
756
757
758
759
R S
760
761
762
763
764
765
766
767
R S
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
R S
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
R S
821
822
823
824
825
826
827
828
829
830
831
832
833
834
R S
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
R S
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
R S
865
866
867
868
869
870
R S
871
872
873
874
875
876
877
878
R S
879
880
881
882
883
884
885
886
R S
887
888
889
890
Simplified Neurotransmitter Schematic for Predicting Therapeutic Effects: In Consider impact of pharmacotherapy in three
Huntingtons chorea, there is primarily a GABAergic loss in the indirect pathway, dopaminergic pathways in relation to their function and
leading to a loss of inhibition of thalamic activity. Cholinergic neurons may also be lost; involvement in different pathology:
that reinforces the effect, and dopamine is left to inhibit whatever is left. Huntingtons Nigrostriatal (motor function; Parkinsonism)
disease symptoms involve increased and dysregulated output of the extrapyramidal Mesolimbic (reward function; schizophrenia)
circuitry and can be viewed as opposite those of Parkinsonism. Mesocortical (reward function; schizophrenia)
891
892
893
R S
894
895
896
897
898
899
900
R S
901
902
903
904
905
906
907
908
909
910
911
912
913
914
R S
915
916
917
918
919
920
R S
921
922
923
924
925
926
R S
927
928
929
930
931
932
933
934
R S
935
936
937
938
939
940
R S
941
942
943
944
945
946
947
R S
948
949
950
952
953
954
955
R S
956
957
958
959
960
961
962
R S
963
964
965
966
967
968
969
970
971
972
R S
973
974
975
976
977
R S
978
979
980
981
983
R S
984
985
986
987
R S
988
989
990
991
992
993
994
995
996
997
R S
999
1000
1001
1002
R S
1003
1004
1005
1006
1007
1008
1009
1010
R S
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
R S
1022
1023
1024
1025
1026
1027
1028
1029
1030
R S
1031
1032
1033
1034
1035
1036
1037
1038
R S
1039
1040
1041
1042
Management of acute alcohol intoxication:
Prevent severe respiratory depression Progress of EtOH Liver Disease
Prevent aspiration of vomitus alcoholic steatosis (fatty liver) - reversible; 90% of
Give thiamine (depleted in alcoholism) heavy consumers of alcohol
May need to treat hypoglycemia and ketosis alcoholic hepatitis and fibrosis (replacement of healthy
If patient is hypoglycemic, give thiamine before glucose - with thiamine deficiency, tissue with scar tissue) - 40% of heavy consumers of
glucose may result in lactate acidosis and Wernickes encephalopathy. alcohol
May need to treat electrolyte and phosphate imbalances cirrhosis and liver failure - 15-30% of heavy consumers
of alcohol
Intoxication is more pronounced when BEC is rising than when falling
1043
1044
R S
1045
1046
1047
1049
1050
1051
1052
R S
1053
1054
1055
1056
1057
1058
1059
R S
1060
1061
1062
T U V
1
9
T U V
10
11
12
13
14
15
16
17
18
T U V
19
20
21
22
23
24
T U V
26
27
28
29
30
31
T U V
32
33
34
35
36
37
38
39
40
41
42
43
T U V
44
45
46
47
48
49
50
51
52
53
54
55
T U V
56
57
58
59
60
T U V
61
62
63
64
65
66
T U V
67
68
69
70
71
72
73
T U V
74
Angioneurotic edema
Rapid swelling in the upper respiratory tract DRUGS THAT REDUCE THE RATE OF CARDIAC
life-threatening REMODELING
0.1-0.2% incidence ACE-I
Typically occurs within first week of therapy, Hydralizine/Isosorbide (in ACEI intolerant Many patients tx with ACEIs show return to
often with the first dose individuals) near baseline levels of angiotensin II, which
Not immune mediated BETA-BLOCKERS occurs by activation of the chymase pathway.
Bradykinin is listed as a culprit, but the evidence ALDOSTERONE ANTAGONISTS Nonetheless, the ACEIs continue to be
is not compelling Remember: triple A HIB (ACEI, Aldosterone efficacious.
Antagonists, hydralizine isosorbide, beta blockers
75
76
77
T U V
78
79
80
81
82
T U V
83
84
85
86
87
T U V
88
89
90
91
92
93
94
95
96
T U V
97
98
99
100
101
102
T U V
103
104
105
106
107
108
109
110
111
T U V
112
113
114
115
116
117
118
119
120
121
T U V
122
123
124
125
126
127
128
T U V
129
130
131
132
133
134
135
136
T U V
137
138
139
140
141
142
T U V
143
144
145
146
147
148
149
T U V
150
151
152
153
154
155
T U V
156
157
158
T U V
159
160
161
162
163
164
165
T U V
166
167
168
169
170
171
172
173
174
175
176
177
T U V
178
179
180
181
182
183
184
T U V
185
186
187
188
189
190
191
192
193
194
195
196
197
198
T U V
199
200
201
202
203
204
205
T U V
206
207
208
209
210
211
T U V
212
213
214
T U V
215
216
217
218
219
220
221
222
T U V
223
224
225
226
227
228
T U V
229
230
231
232
233
234
T U V
235
236
237
238
239
240
241
T U V
242
243
244
245
246
247
248
T U V
249
250
251
252
253
T U V
254
255
256
257
258
259
260
261
T U V
262
263
264
265
266
T U V
267
268
269
270
271
272
273
T U V
274
275
276
T U V
277
278
279
280
281
282
283
T U V
284
285
286
T U V
288
T U V
289
290
291
292
293
T U V
294
295
296
297
298
299
300
301
302
T U V
303
304
305
306
307
T U V
308
309
310
311
312
313
T U V
314
315
316
317
318
319
T U V
321
322
323
324
325
326
T U V
327
328
329
330
332
T U V
333
334
335
336
337
338
339
340
341
342
T U V
343
344
345
346
347
348
349
350
351
352
353
354
T U V
355
356
357
358
359
360
361
362
363
364
T U V
365
366
367
368
369
370
371
T U V
372
373
374
375
376
377
378
379
380
381
T U V
382
383
384
385
386
T U V
387
388
389
390
391
392
393
T U V
394
395
396
397
398
399
400
401
T U V
402
403
404
405
406
407
408
409
T U V
410
411
412
413
414
415
416
T U V
417
418
419
420
421
422
423
424
425
T U V
426
427
428
429
430
431
432
433
434
435
436
437
438
T U V
439
440
441
442
443
444
445
446
447
448
449
450
451
T U V
452
453
454
455
456
457
458
459
460
461
T U V
462
463
464
465
466
467
468
469
470
T U V
471
472
473
474
475
476
477
T U V
478
479
T U V
480
481
482
483
485
T U V
486
487
488
489
490
T U V
491
492
493
494
495
496
497
T U V
498
499
500
501
502
T U V
503
T U V
504
505
506
T U V
507
508
509
510
511
512
T U V
513
514
515
516
T U V
517
518
520
521
522
523
524
T U V
525
526
527
528
529
530
531
532
533
T U V
534
535
536
T U V
537
538
539
540
541
542
543
544
545
T U V
546
547
548
549
550
T U V
551
552
553
554
T U V
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
T U V
570
571
572
573
574
T U V
575
576
577
578
579
580
581
582
583
584
T U V
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
T U V
Opioid Tolerance
Tolerance, with cross-tolerance, can develop to
all opioid agonists
rate of development varies among agents but
603 generally develops faster with more potent
drugs and/or higher doses
starts with first dose but doesnt become
Opioid Effects: GI System clinically relevant for 2-3 weeks (@ normal
Constipation - decreased motility secondary Opioids: Excessive Use and Abuse therapeutic doses)
to increased tone (due to effects both in the Tolerance - Occurs even with the lowest there is specificity of tolerance development
CNS and on the local enteric nervous system). therapeutic doses and increases as dose and tolerance can be profound (as great as 35-fold)
The tone is sometimes described as spasm it duration of treatment increase No tolerance develops for constipation nor
is not coordinated contraction Dependence/Withdrawal miosis! - presence of constipation/miosis
Little or no tolerance development Overdose indicates opioid use, but not degree pain nor
Maintenance Treatment dose taken
604
605
606
607
T U V
608
609
610
611
612
613
614
T U V
615
616
617
618
619
620
T U V
621
622
623
624
625
626
627
628
T U V
629
630
631
632
633
634
635
T U V
636
637
638
639
T U V
640
641
642
643
644
645
646
T U V
647
648
649
650
651
652
653
654
655
T U V
656
657
658
659
660
661
662
T U V
664
T U V
665
666
667
668
669
670
T U V
671
672
673
674
675
676
677
678
T U V
680
681
682
683
684
T U V
685
686
687
688
689
690
691
692
693
694
695
T U V
696
697
698
699
T U V
700
701
702
703
704
705
T U V
706
707
708
T U V
709
710
711
712
T U V
714
715
716
717
T U V
718
719
720
721
722
723
724
T U V
725
726
727
728
729
730
731
T U V
732
733
734
735
736
737
738
739
T U V
740
741
742
743
744
745
T U V
746
747
748
749
750
751
752
753
T U V
754
755
756
757
758
759
T U V
760
761
762
763
764
765
766
767
T U V
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
T U V
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
T U V
821
822
823
824
825
826
827
828
829
830
831
832
833
834
T U V
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
T U V
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
T U V
865
866
867
868
869
870
T U V
871
872
873
874
875
876
877
878
T U V
879
880
881
882
883
884
885
886
T U V
887
888
889
891
892
893
T U V
894
895
896
897
898
899
900
T U V
901
902
903
904
905
906
907
908
909
910
911
912
913
914
T U V
915
Old classic drugs still appear to be the most Treatments:
effective Do not have to sedate patient to control
Have adverse effects Pharmacotherapy: seizures
However, newer drugs not as effective and/or Seizure type determines treatment Require careful monitoring of blood levels
adverse effects worse More than one type of seizure may be present of drug and seizure frequency!!
Most newer drugs best used as adjuncts Treat all seizures Never discontinue drug abruptly, and shift
Starting to identify which drugs best for certain Multi-drug therapy may be necessary from one drug to another gradually (Allergic
syndromesmany of which are refractory to Nearly all anti-convulsants make some kind of rxn is the only reason to stop immediately)
standard treatment seizure worse Continue therapy until seizures absent for ~4
years
916
917
918
919
920
T U V
921
922
923
924
925
926
T U V
927
928
929
930
931
932
933
934
T U V
935
936
937
938
939
940
T U V
941
942
943
944
945
946
947
T U V
948
949
950
952
953
954
955
T U V
956
957
958
959
960
961
962
T U V
963
964
965
966
967
968
969
970
971
972
T U V
973
974
975
976
977
T U V
978
979
980
981
983
T U V
984
985
986
987
T U V
988
989
990
991
992
993
994
995
996
997
T U V
998
BZD Dependence
Shorter elimination half-life drugs give nastier Management of EtOH Withdrawal
signs and symptoms of withdrawal Benzodiazepines may be administered as a
Longer half-life drugs give less severe signs FDA warning: BZD and BZD alpha 1 subunit drugs substitute for EtOH followed by tapering.
and symptoms of withdrawal, but they are more are capable of producing anterograde amnesia Long acting BZDs like diazepam and
protracted. (short term memory) in large enough dose (dose to chlorazepate may be used because long half
If withdrawal is threatening to become produce muscle relaxation/hypnosis/surgery, not lives provide a built-in tapering effect.
intolerable or if seizures are likely, consider usually at dose used for anxiety) With liver disease, a short-acting BZD such
administering a longer acting BZD as oxazepam or lorazepam may be used
999
1000
1001
1002
T U V
1003
1004
1005
1006
1007
1008
1009
1010
T U V
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
T U V
1022
1023
1024
1025
1026
1027
1028
1029
1030
T U V
1031
1032
1033
1034
1035
1036
1037
1038
T U V
1039
1040
1041
1043
1044
T U V
1045
1046
1047
1049
1050
1052
T U V
1053
1054
1055
1056
1057
1058
1059
T U V
1060
1061
1062
W X Y
1
9
W X Y
10
11
12
13
14
15
16
17
18
W X Y
19
20
21
22
23
24
W X Y
25
Older combined formulas had 50 micrograms
of estrogen (and had higher incident of MI in
Migrane HA are CI with OC - d/t association of smokers); newer formulations usually have 35
migrane, OC, and stroke (2 to 4 fold increase). microg (new studies show no increased
Greatest risk in pts with aura and and focal incidence of MI in any age, but guide lines
neurologic symptoms. No risk associated with remain that OC should not be given to >35 yo
tension HA smokers)
26
27
28
29
30
31
W X Y
32
33
34
35
36
37
38
39
40
41
42
43
W X Y
44
45
46
47
48
49
50
51
52
53
54
55
W X Y
56
57
58
59
60
W X Y
61
62
63
64
65
66
W X Y
67
68
69
70
71
72
73
W X Y
74
75
76
77
W X Y
78
79
80
81
82
W X Y
83
84
85
86
87
W X Y
88
89
90
91
92
93
94
95
96
W X Y
97
98
99
100
101
102
W X Y
103
104
105
106
107
108
109
110
111
W X Y
112
113
114
115
116
117
118
119
120
121
W X Y
122
123
124
125
126
127
128
W X Y
129
130
131
132
133
134
135
136
W X Y
137
138
139
140
141
142
W X Y
143
144
145
146
147
148
149
W X Y
150
151
152
153
154
155
W X Y
156
157
158
W X Y
159
160
161
162
163
164
165
W X Y
166
167
168
169
170
171
172
173
174
175
176
177
W X Y
178
179
180
181
182
183
184
W X Y
185
186
187
188
189
190
191
192
193
194
195
196
197
198
W X Y
199
200
201
202
203
204
205
W X Y
206
207
208
209
210
211
W X Y
212
213
214
W X Y
215
216
217
218
219
220
221
222
W X Y
223
224
225
226
227
228
W X Y
229
230
231
232
233
234
W X Y
235
236
237
238
239
240
241
W X Y
242
243
244
245
246
247
248
W X Y
249
250
251
252
253
W X Y
254
255
256
257
258
259
260
261
W X Y
262
263
264
265
266
W X Y
267
268
269
270
271
272
273
W X Y
274
275
276
W X Y
277
278
279
280
281
282
283
W X Y
284
285
286
W X Y
287
288
W X Y
289
290
291
292
293
W X Y
294
295
296
297
298
299
300
301
302
W X Y
303
304
305
306
307
W X Y
308
309
310
311
312
313
W X Y
314
315
316
317
318
319
W X Y
321
322
323
324
325
326
W X Y
327
328
329
330
332
W X Y
333
334
335
336
337
338
339
340
341
342
W X Y
343
344
345
346
347
348
349
350
351
352
353
354
W X Y
355
356
357
358
359
360
361
362
363
364
W X Y
365
366
367
368
369
370
371
W X Y
372
373
374
375
376
377
378
379
380
381
W X Y
382
383
384
385
386
W X Y
387
388
389
390
391
392
393
W X Y
394
395
396
397
398
399
400
401
W X Y
402
403
404
405
406
407
408
409
W X Y
410
411
412
413
414
415
416
W X Y
417
418
419
420
421
422
423
424
425
W X Y
426
427
428
429
430
431
432
433
434
435
436
437
438
W X Y
439
440
441
442
443
444
445
446
447
448
449
450
451
W X Y
452
453
454
455
456
457
458
459
460
461
W X Y
462
463
464
465
466
467
468
469
470
W X Y
471
472
473
474
475
476
477
W X Y
478
479
W X Y
480
481
482
483
485
W X Y
486
487
488
489
490
W X Y
491
492
493
494
495
496
497
W X Y
498
499
500
501
502
W X Y
503
W X Y
504
505
506
W X Y
507
508
509
510
511
512
W X Y
513
514
515
516
W X Y
517
518
520
521
522
523
524
W X Y
525
526
527
528
529
530
531
532
533
W X Y
534
535
536
W X Y
537
538
539
540
541
542
543
544
545
W X Y
546
547
548
549
550
W X Y
551
552
553
554
W X Y
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
W X Y
570
571
572
573
574
W X Y
575
576
577
578
579
580
581
582
583
584
W X Y
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
W X Y
604
605
606
607
W X Y
608
609
610
611
612
613
614
W X Y
615
616
617
618
619
620
W X Y
621
622
623
624
625
626
627
628
W X Y
629
630
631
632
633
634
635
W X Y
636
637
638
639
W X Y
640
641
642
643
644
645
646
W X Y
647
648
649
650
651
652
653
654
655
W X Y
656
657
658
659
660
661
662
Drug-drug interactions: potential drug-drug
interactions with aspirin, salicylates, and other
NSAIDs are numerous. W Notable examples X Y
include:a. Antacids (given for relief of NSAID- Aspirin as a Therapeutic Agent in
induced ulceration) delay NSAID absorption. b. Cardiovascular Disease
NSAIDs may displace other protein bound 1. Aspirin therapy confers conclusive benefits
drugs and vice versa, e.g., phenytoin, thyroxine, in the acute phase of evolving myocardial
thiopental. c. Aspirin increases the risk of infarction (MI) and should be administered
bleeding for patients taking heparin or warfarin routinely to virtually all patients with
anticoagulants. d. Aspirin and salicylates block evolving MI.
the uricosuric effects (to increase excretion of uric 2. Secondary prevention of MI and Stroke:
acid) of probenecid and can worsen the Long-term aspirin therapy confers conclusive
symptoms of gout. net benefits on risk of subsequent MI, stroke,
Toxicity: and vascular death among patients with a wide
a. Salicylism is the term used for mild salicylate range of manifestations of cardiovascular
intoxication and is characterized by nausea, disease. Daily aspirin (75-325 mg/d) should be
vomiting, tinnitus (ringing in the ears), strongly considered for all patients (men and
hyperventilation, headache, mental confusion, women) who have experienced chronic stable
and dizziness. Tinnitus begins to appear at the angina, MI, TIA, or occlusive stroke and who
663 top of the therapeutic range and is a reliable are at elevated risk of subsequent vascular
indicator of plasma concentration range. events.
b. Severe toxicity due to overdose: accidental or 3. Primary prevention of Cardiovascular
intentional overdose with aspirin is not Disease: Currently, the use of aspirin therapy
uncommon. Under these conditions, the for primary prevention remains inconclusive.
symptoms listed above are followed by fever, Additional clinical trials are necessary to firmly
dehydration, delirium, hallucinations, convulsions, establish the benefit-to-risk ratio of long-term
coma, respiratory and metabolic acidosis, and aspirin in apparently healthy persons. Taking
death. Children are especially vulnerable to into account an individual patient's particular
salicylate induced intoxication and death which cardiovascular risk profile, aspirin may be NSAIDs inhibit renal Na excretion, and can impair the
can occur with ingestion of as few as 30 adult warranted. antihypertensive action of diuretics as well as drugs that
tablets or 4-5 ml of methyl salicylate found in 4. Additional proven benefits: reduction of block the RAS. Becase a fall in renin & AII levels is a
liniments. Aspirin overdose is an acute medical thromboembolic complications associated with compensatory mech that normally serves to counter
emergency. Treatment consists of cardiovascular artificial heart valves; decrease in thrombotic volume-dependent HTN, the bp-raising effects of
and respiratory support, correction of acid-base occlusion of uremic patients undergoing NSAIDs are problematic with ACEI-based therapy
imbalance, and enhancement of elimination hemodialysis; increased potency of coronary (interruption of mech). Also occurs with asprin > 325mg
(lavage with activated charcoal, i.v. bicarbonate). bypass grafts. (not with 81mg/d) (Cecil 358)
664
W X Y
665
666
667
668
669
670
W X Y
671
672
673
674
675
676
677
678
W X Y
679
680
681
682
683
684
W X Y
685
686
687
688
689
690
691
692
693
694
695
W X Y
696
697
698
699
W X Y
700
701
702
703
704
705
W X Y
706
707
708
W X Y
709
710
711
712
W X Y
714
715
716
717
W X Y
718
719
720
721
722
723
724
W X Y
725
726
727
728
729
730
731
W X Y
732
733
734
735
736
737
738
739
W X Y
740
741
742
743
744
745
W X Y
746
747
748
749
750
751
752
753
W X Y
754
755
756
757
758
759
W X Y
760
761
762
763
764
765
766
767
W X Y
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
W X Y
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
W X Y
821
822
823
824
825
826
827
828
829
830
831
832
833
834
W X Y
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
W X Y
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
W X Y
865
866
867
868
869
870
W X Y
871
872
873
874
875
876
877
878
W X Y
879
880
881
882
883
884
885
886
W X Y
887
888
889
891
892
893
W X Y
894
895
896
897
898
899
900
W X Y
901
902
903
904
905
906
907
908
909
910
911
912
913
914
W X Y
916
917
918
919
920
W X Y
921
922
923
924
925
926
W X Y
927
928
929
930
931
932
933
934
W X Y
935
936
937
938
939
940
W X Y
941
942
943
944
945
946
947
W X Y
948
949
950
951
952
953
954
955
W X Y
956
957
958
959
960
961
962
W X Y
963
964
965
966
967
968
969
970
971
972
W X Y
973
974
975
976
977
W X Y
978
979
980
981
983
W X Y
984
985
986
987
W X Y
988
989
990
991
992
993
994
995
996
997
W X Y
998
999
1000
1001
1002
W X Y
1003
1004
1005
1006
1007
1008
1009
1010
W X Y
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
W X Y
1022
1023
1024
1025
1026
1027
1028
1029
1030
W X Y
1031
1032
1033
1034
1035
1036
1037
1038
W X Y
1039
1040
1041
1043
1044
W X Y
1045
1046
1047
1049
1050
1052
W X Y
1053
1054
1055
1056
1057
1058
1059
W X Y
1060
1061
1062
Z AA
1
9
Z AA
10
11
12
13
14
15
16
17
18
Z AA
19
20
21
22
23
24
Z AA
25
26
27
28
29
30
31
Z AA
32
33
34
35
36
37
38
39
40
41
42
43
Z AA
44
45
46
47
48
49
50
51
52
53
54
55
Z AA
56
57
58
59
60
Z AA
61
62
63
64
65
66
Z AA
67
68
69
70
71
72
73
Z AA
74
75
76
77
Z AA
78
79
80
81
82
Z AA
83
84
85
86
87
Z AA
88
89
90
91
92
93
94
95
96
Z AA
97
98
99
100
101
102
Z AA
103
104
105
106
107
108
109
110
111
Z AA
112
113
114
115
116
117
118
119
120
121
Z AA
122
123
124
125
126
127
128
Z AA
129
130
131
132
133
134
135
136
Z AA
137
138
139
140
141
142
Z AA
143
144
145
146
147
148
149
Z AA
150
151
152
153
154
155
Z AA
156
157
158
Z AA
159
160
161
162
163
164
165
Z AA
166
167
168
169
170
171
172
173
174
175
176
177
Z AA
178
179
180
181
182
183
184
Z AA
185
186
187
188
189
190
191
192
193
194
195
196
197
198
Z AA
199
200
201
202
203
204
205
Z AA
206
207
208
209
210
211
Z AA
212
213
214
Z AA
215
216
217
218
219
220
221
222
Z AA
223
224
225
226
227
228
Z AA
229
230
231
232
233
234
Z AA
235
236
237
238
239
240
241
Z AA
242
243
244
245
246
247
248
Z AA
249
250
251
252
253
Z AA
254
255
256
257
258
259
260
261
Z AA
262
263
264
265
266
Z AA
267
268
269
270
271
272
273
Z AA
274
275
276
Z AA
277
278
279
280
281
282
283
Z AA
284
285
286
Z AA
287
288
Z AA
289
290
291
292
293
Z AA
294
295
296
297
298
299
300
301
302
Z AA
303
304
305
306
307
Z AA
308
309
310
311
312
313
Z AA
314
315
316
317
318
319
Z AA
321
322
323
324
325
326
Z AA
327
328
329
330
331
Myxedema Coma: is the end stage of untreated Cretinism: Early diagnosis and treatment are essential. Most of
hypothyroidism. Immediate T3 or T4 replacement is adverse effects of cretinism can be minimized or avoided if treatment is
required along with general supportive procedures. begun immediately after birth. Treatment initiated after about 1.5
These patients have a large pool of empty TBG binding months of age fails to reverse all of the intellectual impairment that has
sites that must be filled with a loading dose. already occurred but does reverse the physical defects.
332
Z AA
333
334
335
336
337
338
339
340
341
342
Z AA
343
344
345
346
347
348
349
350
351
352
353
354
Z AA
355
356
357
358
359
360
361
362
363
364
Z AA
365
366
367
368
369
370
371
Z AA
372
373
374
375
376
377
378
379
380
381
Z AA
382
383
384
385
386
Z AA
387
388
389
390
391
392
393
Z AA
394
395
396
397
398
399
400
401
Z AA
402
403
404
405
406
407
408
409
Z AA
410
411
412
413
414
415
416
Z AA
417
418
419
420
421
422
423
424
425
Z AA
426
427
428
429
430
431
432
433
434
435
436
437
438
Z AA
439
440
441
442
443
444
445
446
447
448
449
450
451
Z AA
452
453
454
455
456
457
458
459
460
461
Z AA
462
463
464
465
466
467
468
469
470
Z AA
471
472
473
474
475
476
477
Z AA
478
479
Z AA
480
481
482
483
485
Z AA
486
487
488
489
490
Z AA
491
492
493
494
495
496
497
Z AA
498
499
500
501
502
Z AA
503
Z AA
504
505
506
Z AA
507
508
509
510
511
512
Z AA
513
514
515
516
Z AA
517
518
520
521
522
523
524
Z AA
525
526
527
528
529
530
531
532
533
Z AA
534
535
536
Z AA
537
538
539
540
541
542
543
544
545
Z AA
546
547
548
549
550
Z AA
551
552
553
554
Z AA
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
Z AA
570
571
572
573
574
Z AA
575
576
577
578
579
580
581
582
583
584
Z AA
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
Z AA
604
605
606
607
Z AA
608
609
610
611
612
613
614
Z AA
615
616
617
618
619
620
Z AA
621
622
623
624
625
626
627
628
Z AA
629
630
631
632
633
634
635
Z AA
636
637
638
639
Z AA
640
641
642
643
644
645
646
Z AA
647
648
649
650
651
652
653
654
655
Z AA
656
657
658
659
660
661
662
Z AA
663
664
Z AA
665
666
667
668
669
670
Z AA
671
672
673
674
675
676
677
678
Z AA
679
680
681
682
683
684
Z AA
685
686
687
688
689
690
691
692
693
694
695
Z AA
696
697
698
699
Z AA
700
701
702
703
704
705
Z AA
706
707
708
Z AA
709
710
711
712
Z AA
713
Alopecia: chemotherapy-induced hair loss is one of the
most distressing aspects of cancer treatment for some
patients. It is due to the cytotoxic effects of
antineoplastic agents on the hair follicle. The hair loss
tends to be patchy and most severe on the scalp, and it
is usually noticeable 1 to 2 weeks after the beginning of
therapy. After the cessation of chemotherapy, the hair
should eventually return to pretreatment levels,
although it may be different in texture and color.
Cyclophosphamide, dactinomycin, doxorubicin,
paclitaxel, and vincristine generally cause the most
profound alopecia. Scalp-cooling devices, which
apparently decrease scalp perfusion, have been
employed with mixed results.
714
715
716
717
Z AA
718
719
720
721
722
723
724
Z AA
725
726
727
728
729
730
731
Z AA
732
733
734
735
736
737
738
739
Z AA
740
741
742
743
744
745
Z AA
746
747
748
749
750
751
752
753
Z AA
754
755
756
757
758
759
Z AA
760
761
762
763
764
765
766
767
Z AA
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
Z AA
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
Z AA
821
822
823
824
825
826
827
828
829
830
831
832
833
834
Z AA
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
Z AA
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
Z AA
865
866
867
868
869
870
Z AA
871
872
873
874
875
876
877
878
Z AA
879
880
881
882
883
884
885
886
Z AA
887
888
889
891
892
893
Z AA
894
895
896
897
898
899
900
Z AA
901
902
903
904
905
906
907
908
909
910
911
912
913
914
Z AA
Status Epilepticus:
Most commonly due to cessation of anti-convulsant
915
medication
In infants, likely due to high fever
Initial treatment - IV diazepam or lorazepam (longer-
acting)
Continuing treatment: Teratogens: Drugs for monotherapy of epilepsies are teratogens
IV phenytoin (phenytoin, phenobarbital, carbamazepine, valproic acid)
IV fosphenytoin may be safer Designated FDA category D (benefits outweigh risks) based on
IV phenobarbital may be used if patient unresponsive to considerably greater pregnancy risk associated with uncontrolled
phenytoin seizures
916
917
918
919
920
Z AA
921
922
923
924
925
926
Z AA
927
928
929
930
931
932
933
934
Z AA
935
936
937
938
939
940
Z AA
941
942
943
944
945
946
947
Z AA
948
949
950
951
952
953
954
955
Z AA
956
957
958
959
960
961
962
Z AA
963
964
965
966
967
968
969
970
971
972
Z AA
973
974
975
976
977
Z AA
978
979
980
981
983
Z AA
984
985
986
987
Z AA
988
989
990
991
992
993
994
995
996
997
Z AA
998
999
1000
1001
1002
Z AA
1003
1004
1005
1006
1007
1008
1009
1010
Z AA
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
Z AA
1022
1023
1024
1025
1026
1027
1028
1029
1030
Z AA
1031
1032
1033
1034
1035
1036
1037
1038
Z AA
1039
1040
1041
1043
1044
Z AA
1045
1046
1047
1049
1050
1052
Z AA
1053
1054
1055
1056
1057
1058
1059
Z AA
1060
1061
1062
AB AC
1
9
AB AC
10
11
12
13
14
15
16
17
18
AB AC
19
20
21
22
23
24
AB AC
25
26
27
28
29
30
31
AB AC
32
33
34
35
36
37
38
39
40
41
42
43
AB AC
44
45
46
47
48
49
50
51
52
53
54
55
AB AC
56
57
58
59
60
AB AC
61
62
63
64
65
66
AB AC
67
68
69
70
71
72
73
AB AC
74
75
76
77
AB AC
78
79
80
81
82
AB AC
83
84
85
86
87
AB AC
88
89
90
91
92
93
94
95
96
AB AC
97
98
99
100
101
102
AB AC
103
104
105
106
107
108
109
110
111
AB AC
112
113
114
115
116
117
118
119
120
121
AB AC
122
123
124
125
126
127
128
AB AC
129
130
131
132
133
134
135
136
AB AC
137
138
139
140
141
142
AB AC
143
144
145
146
147
148
149
AB AC
150
151
152
153
154
155
AB AC
156
157
158
AB AC
159
160
161
162
163
164
165
AB AC
166
167
168
169
170
171
172
173
174
175
176
177
AB AC
178
179
180
181
182
183
184
AB AC
185
186
187
188
189
190
191
192
193
194
195
196
197
198
AB AC
199
200
201
202
203
204
205
AB AC
206
207
208
209
210
211
AB AC
212
213
214
AB AC
215
216
217
218
219
220
221
222
AB AC
223
224
225
226
227
228
AB AC
229
230
231
232
233
234
AB AC
235
236
237
238
239
240
241
AB AC
242
243
244
245
246
247
248
AB AC
249
250
251
252
253
AB AC
254
255
256
257
258
259
260
261
AB AC
262
263
264
265
266
AB AC
267
268
269
270
271
272
273
AB AC
274
275
276
AB AC
277
278
279
280
281
282
283
AB AC
284
285
286
AB AC
287
288
AB AC
289
290
291
292
293
AB AC
294
295
296
297
298
299
300
301
302
AB AC
303
304
305
306
307
AB AC
308
309
310
311
312
313
AB AC
314
315
316
317
318
319
AB AC
320
321
322
323
324
325
326
AB AC
327
328
329
330
331
332
AB AC
333
334
335
336
337
338
339
340
341
342
AB AC
343
344
345
346
347
348
349
350
351
352
353
354
AB AC
355
356
357
358
359
360
361
362
363
364
AB AC
365
366
367
368
369
370
371
AB AC
372
373
374
375
376
377
378
379
380
381
AB AC
382
383
384
385
386
AB AC
387
388
389
390
391
392
393
AB AC
394
395
396
397
398
399
400
401
AB AC
402
403
404
405
406
407
408
409
AB AC
410
411
412
413
414
415
416
AB AC
417
418
419
420
421
422
423
424
425
AB AC
426
427
428
429
430
431
432
433
434
435
436
437
438
AB AC
439
440
441
442
443
444
445
446
447
448
449
450
451
AB AC
452
453
454
455
456
457
458
459
460
461
AB AC
462
463
464
465
466
467
468
469
470
AB AC
471
472
473
474
475
476
477
AB AC
478
479
AB AC
480
481
482
483
485
AB AC
486
487
488
489
490
AB AC
491
492
493
494
495
496
497
AB AC
498
499
500
501
502
AB AC
503
AB AC
504
505
506
AB AC
507
508
509
510
511
512
AB AC
513
514
515
516
AB AC
517
518
520
521
522
523
524
AB AC
525
526
527
528
529
530
531
532
533
AB AC
534
535
536
AB AC
537
538
539
540
541
542
543
544
545
AB AC
546
547
548
549
550
AB AC
551
552
553
554
AB AC
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
AB AC
570
571
572
573
574
AB AC
575
576
577
578
579
580
581
582
583
584
AB AC
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
AB AC
604
605
606
607
AB AC
608
609
610
611
612
613
614
AB AC
615
616
617
618
619
620
AB AC
621
622
623
624
625
626
627
628
AB AC
629
630
631
632
633
634
635
AB AC
636
637
638
639
AB AC
640
641
642
643
644
645
646
AB AC
647
648
649
650
651
652
653
654
655
AB AC
656
657
658
659
660
661
662
AB AC
663
664
AB AC
665
666
667
668
669
670
AB AC
671
672
673
674
675
676
677
678
AB AC
679
680
681
682
683
684
AB AC
685
686
687
688
689
690
691
692
693
694
695
AB AC
696
697
698
699
AB AC
700
701
702
703
704
705
AB AC
706
707
708
AB AC
709
710
711
712
AB AC
713
714
715
716
717
AB AC
718
719
720
721
722
723
724
AB AC
725
726
727
728
729
730
731
AB AC
732
733
734
735
736
737
738
739
AB AC
740
741
742
743
744
745
AB AC
746
747
748
749
750
751
752
753
AB AC
754
755
756
757
758
759
AB AC
760
761
762
763
764
765
766
767
AB AC
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
AB AC
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
AB AC
821
822
823
824
825
826
827
828
829
830
831
832
833
834
AB AC
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
AB AC
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
AB AC
865
866
867
868
869
870
AB AC
871
872
873
874
875
876
877
878
AB AC
879
880
881
882
883
884
885
886
AB AC
887
888
889
890
891
892
893
AB AC
894
895
896
897
898
899
900
AB AC
901
902
903
904
905
906
907
908
909
910
911
912
913
914
AB AC
915
All seizure drugs can effect Bone Marrow and Liver!! Also: Dose-dependent - Nystagmus, ataxia, dizziness!
916
917
918
919
920
AB AC
921
922
923
924
925
926
AB AC
927
928
929
930
931
932
933
934
AB AC
935
936
937
938
939
940
AB AC
941
942
943
944
945
946
947
AB AC
948
949
950
951
952
953
954
955
AB AC
956
957
958
959
960
961
962
AB AC
963
964
965
966
967
968
969
970
971
972
AB AC
973
974
975
976
977
AB AC
978
979
980
981
982
Other SE - all antipsychotics lower the seizure threshhold - must Note: anxiolytic drugs have no effect on schizophrenia, only causes
consider if Hx of seizures an intoxicated crazy person (does not calm aggitated behavior)
983
AB AC
984
985
986
987
AB AC
988
989
990
991
992
993
994
995
996
997
AB AC
998
999
1000
1001
1002
AB AC
1003
1004
1005
1006
1007
1008
1009
1010
AB AC
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
AB AC
1022
1023
1024
1025
1026
1027
1028
1029
1030
AB AC
1031
1032
1033
1034
1035
1036
1037
1038
AB AC
1039
1040
1041
Alcoholism:
No standard definition.
pharmacological definition: 1 pint of hard liquor daily for at least 30
days.
1042 dependence
LOSS OF CONTROL
Fetal Alcohol Syndrome societal problems
Greatest preventable cause of mental retardation CHRONIC/RELAPSING DISORDER
Symptoms: AA is still the treatment of choice
midfacial abnormalities
retarded body growth Alcoholism: Genetics & Prevalence
microcephaly higher concordance for monozygotic versus dizygotic twins
poor coordination Four fold increased risk in children of alcoholics even if adopted at
minor joint anomalies birth.
heart & kidney defects Prevalence is about 20% even in affluent areas
1043
1044
AB AC
1045
1046
1047
1049
1050
Behavioral Therapy
1051 discover high-risk relapse situations,
create an aversion to smoking,
develop self-monitoring of smoking behavior, and
establish competing coping responses The combined use of systemic nicotine administration and
The most effective behavioral support programs address such issues behavioral counseling has resulted in sustained abstinence rates of
as how to perform common daily activities (such as eating, driving, and 60 percent in well-controlled clinical trials.
socializing) without smoking and how to cope with the dysphoric mood Dependence on these ystemic nicotine products has been reported
and the weight gain that can accompany smoking cessation. in up to 20 percent of patients; therefore, careful supervision by the
physician of amount and duration of use is necessary.
1052
AB AC
1053
1054
1055
1056
1057
1058
1059
AB AC
1060
1061
1062
AD AE
1
9
AD AE
10
11
12
13
14
15
16
17
18
AD AE
19
20
21
22
23
24
AD AE
25
26
27
28
29
30
31
AD AE
32
33
34
35
36
37
38
39
40
41
42
43
AD AE
44
45
46
47
48
49
50
51
52
53
54
55
AD AE
56
57
58
59
60
AD AE
61
62
63
64
65
66
AD AE
67
68
69
70
71
72
73
AD AE
74
75
76
77
AD AE
78
79
80
81
82
AD AE
83
84
85
86
87
AD AE
88
89
90
91
92
93
94
95
96
AD AE
97
98
99
100
101
102
AD AE
103
104
105
106
107
108
109
110
111
AD AE
112
113
114
115
116
117
118
119
120
121
AD AE
122
123
124
125
126
127
128
AD AE
129
130
131
132
133
134
135
136
AD AE
137
138
139
140
141
142
AD AE
143
144
145
146
147
148
149
AD AE
150
151
152
153
154
155
AD AE
156
157
158
AD AE
159
160
161
162
163
164
165
AD AE
166
167
168
169
170
171
172
173
174
175
176
177
AD AE
178
179
180
181
182
183
184
AD AE
185
186
187
188
189
190
191
192
193
194
195
196
197
198
AD AE
199
200
201
202
203
204
205
AD AE
206
207
208
209
210
211
AD AE
212
213
214
AD AE
215
216
217
218
219
220
221
222
AD AE
223
224
225
226
227
228
AD AE
229
230
231
232
233
234
AD AE
235
236
237
238
239
240
241
AD AE
242
243
244
245
246
247
248
AD AE
249
250
251
252
253
AD AE
254
255
256
257
258
259
260
261
AD AE
262
263
264
265
266
AD AE
267
268
269
270
271
272
273
AD AE
274
275
276
AD AE
277
278
279
280
281
282
283
AD AE
284
285
286
AD AE
287
288
AD AE
289
290
291
292
293
AD AE
294
295
296
297
298
299
300
301
302
AD AE
303
304
305
306
307
AD AE
308
309
310
311
312
313
AD AE
314
315
316
317
318
319
AD AE
320
321
322
323
324
325
326
AD AE
327
328
329
330
331
Levothyroxine Sodium USP (generic, Synthroid, and other trade
names) - Sodium salt of natural isomer of thyroxine (T4) available as
tablets or powder for injection. Peak effect occurs after 9 days,
declines to one half maximum in 12 15 days. Absorption is variable.
In most cases, this is the drug of choice because of its stability,
content uniformity, low cost, lack of allergenic foreign protein, easy Suppression therapy with levothyroxin of benign nodules is no
lab interpretation, and long half life that allows for once daily longer recommended
administration.
332
AD AE
333
334
335
336
337
338
339
340
341
342
AD AE
343
344
345
346
347
348
349
350
351
352
353
354
AD AE
355
356
357
358
359
360
361
362
363
364
AD AE
365
366
367
368
369
370
371
AD AE
372
373
374
375
376
377
378
379
380
381
AD AE
382
383
384
385
386
AD AE
387
388
389
390
391
392
393
AD AE
394
395
396
397
398
399
400
401
AD AE
402
403
404
405
406
407
408
409
AD AE
410
411
412
413
414
415
416
AD AE
417
418
419
420
421
422
423
424
425
AD AE
426
427
428
429
430
431
432
433
434
435
436
437
438
AD AE
439
440
441
442
443
444
445
446
447
448
449
450
451
AD AE
452
453
454
455
456
457
458
459
460
461
AD AE
462
463
464
465
466
467
468
469
470
AD AE
471
472
473
474
475
476
477
AD AE
478
479
AD AE
480
481
482
483
485
AD AE
486
487
488
489
490
AD AE
491
492
493
494
495
496
497
AD AE
498
499
500
501
502
AD AE
503
AD AE
504
505
506
AD AE
507
508
509
510
511
512
AD AE
513
514
515
516
AD AE
517
518
520
521
522
523
524
AD AE
525
526
527
528
529
530
531
532
533
AD AE
534
535
536
AD AE
537
538
539
540
541
542
543
544
545
AD AE
546
547
548
549
550
AD AE
551
552
553
554
AD AE
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
AD AE
570
571
572
573
574
AD AE
575
576
577
578
579
580
581
582
583
584
AD AE
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
AD AE
603
604
605
606
607
AD AE
608
609
610
611
612
613
614
AD AE
615
616
617
618
619
620
AD AE
621
622
623
624
625
626
627
628
AD AE
629
630
631
632
633
634
635
AD AE
636
637
638
639
AD AE
640
641
642
643
644
645
646
AD AE
647
648
649
650
651
652
653
654
655
AD AE
656
657
658
659
660
661
662
AD AE
663
664
AD AE
665
666
667
668
669
670
AD AE
671
672
673
674
675
676
677
678
AD AE
679
680
681
682
683
684
AD AE
685
686
687
688
689
690
691
692
693
694
695
AD AE
696
697
698
699
AD AE
700
701
702
703
704
705
AD AE
706
707
708
AD AE
709
710
711
712
AD AE
713
714
715
716
717
AD AE
718
719
720
721
722
723
724
AD AE
725
726
727
728
729
730
731
AD AE
732
733
734
735
736
737
738
739
AD AE
740
741
742
743
744
745
AD AE
746
747
748
749
750
751
752
753
AD AE
754
755
756
757
758
759
AD AE
760
761
762
763
764
765
766
767
AD AE
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
AD AE
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
AD AE
821
822
823
824
825
826
827
828
829
830
831
832
833
834
AD AE
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
AD AE
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
AD AE
865
866
867
868
869
870
AD AE
871
872
873
874
875
876
877
878
AD AE
879
880
881
882
883
884
885
886
AD AE
887
888
889
890
891
892
893
AD AE
894
895
896
897
898
899
900
AD AE
901
902
903
904
905
906
907
908
909
910
911
912
913
914
AD AE
Seizure Pearls:
915
Anti-Seizure Side Effects:
Sedation
Ataxia
Nystagmus
Diplopia
If you do not know the answer and Valproic acid is a choice, default
your answer to valproic acid!!!
When in doubt monitor the levelsmany of these drugs must be
monitored regularly.
916
917
918
919
920
AD AE
921
922
923
924
925
926
AD AE
927
928
929
930
931
932
933
934
AD AE
935
936
937
938
939
940
AD AE
941
942
943
944
945
946
947
AD AE
948
949
950
951
952
953
954
955
AD AE
956
957
958
959
960
961
962
AD AE
963
964
965
966
967
968
969
970
971
972
AD AE
973
974
975
976
977
AD AE
978
979
980
981
982
983
AD AE
984
985
986
987
AD AE
988
989
990
991
992
993
994
995
996
997
AD AE
998
999
1000
1001
1002
AD AE
1003
1004
1005
1006
1007
1008
1009
1010
AD AE
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
AD AE
1022
1023
1024
1025
1026
1027
1028
1029
1030
AD AE
1031
1032
1033
1034
1035
1036
1037
1038
AD AE
1039
1040
1041
1042
1043
1044
AD AE
1045
1046
1047
1048
Sensitization (Reverse tolerance): An increase in the response to
a drug after repeated administrations ; may take form of an increase
in potency, efficacy, or both. (ie graphically a leftward, upward shift, Withdrawal and Physical Dependence
in potency and in efficacy, respectfully) Physical dependence is a state that develops as a result of an
Associated with psychostimulants such as cocaine and adaptation produced by resetting of homeostatic mechanisms in
methamphetamine. Increase is seen in motor stimulant effect of the presence of the drug. Tolerance to the drug may reflect the
drug, but humans do not report increase in euphoric effect. The adaptation that produces the state of physical dependence.
sensitization phenomenon has instead been related to development Appearance of a withdrawal syndrome upon cessation of the
of psychotomimetic effects with repeated use of cocaine or drug is the only true evidence of physical dependence.
methamphetamine. Withdrawal is characteristic for drug classes.
AD AE
1049
1050
1051
Women who stop smoking before pregnancy or during the first People who successfully discontinue smoking are likely to have
3 to 4 months of pregnancy reduce their risk for having low- been encouraged by someone close to them (such as a spouse or
birth-weight infants to that of women who never smoked. children), to have been fearful of the ill effects of smoking, and to
The health benefits of smoking cessation substantially exceed any have joined a support group of some type for ex-smokers.
risks from the average 5-pound (2.3-kg) weight gain or any adverse Encouragement from a nonsmoking physician is also highly
psychological effects after quitting. correlated with abstinence.
1052
AD AE
1053
1054
1055
1056
1057
1058
1059
AD AE
1060
1061
1062
AF AG
1
9
AF AG
10
11
12
13
14
15
16
17
18
AF AG
19
20
21
22
23
24
AF AG
25
26
27
28
29
30
31
AF AG
32
33
34
35
36
37
38
39
40
41
42
43
AF AG
44
45
46
47
48
49
50
51
52
53
54
55
AF AG
56
57
58
59
60
AF AG
61
62
63
64
65
66
AF AG
67
68
69
70
71
72
73
AF AG
74
75
76
77
AF AG
78
79
80
81
82
AF AG
83
84
85
86
87
AF AG
88
89
90
91
92
93
94
95
96
AF AG
97
98
99
100
101
102
AF AG
103
104
105
106
107
108
109
110
111
AF AG
112
113
114
115
116
117
118
119
120
121
AF AG
122
123
124
125
126
127
128
AF AG
129
130
131
132
133
134
135
136
AF AG
137
138
139
140
141
142
AF AG
143
144
145
146
147
148
149
AF AG
150
151
152
153
154
155
AF AG
156
157
158
AF AG
159
160
161
162
163
164
165
AF AG
166
167
168
169
170
171
172
173
174
175
176
177
AF AG
178
179
180
181
182
183
184
AF AG
185
186
187
188
189
190
191
192
193
194
195
196
197
198
AF AG
199
200
201
202
203
204
205
AF AG
206
207
208
209
210
211
AF AG
212
213
214
AF AG
215
216
217
218
219
220
221
222
AF AG
223
224
225
226
227
228
AF AG
229
230
231
232
233
234
AF AG
235
236
237
238
239
240
241
AF AG
242
243
244
245
246
247
248
AF AG
249
250
251
252
253
AF AG
254
255
256
257
258
259
260
261
AF AG
262
263
264
265
266
AF AG
267
268
269
270
271
272
273
AF AG
274
275
276
AF AG
277
278
279
280
281
282
283
AF AG
284
285
286
AF AG
287
288
AF AG
289
290
291
292
293
AF AG
294
295
296
297
298
299
300
301
302
AF AG
303
304
305
306
307
AF AG
308
309
310
311
312
313
AF AG
314
315
316
317
318
319
AF AG
320
321
322
323
324
325
326
AF AG
327
328
329
330
331
332
AF AG
333
334
335
336
337
338
339
340
341
342
AF AG
343
344
345
346
347
348
349
350
351
352
353
354
AF AG
355
356
357
358
359
360
361
362
363
364
AF AG
365
366
367
368
369
370
371
AF AG
372
373
374
375
376
377
378
379
380
381
AF AG
382
383
384
385
386
AF AG
387
388
389
390
391
392
393
AF AG
394
395
396
397
398
399
400
401
AF AG
402
403
404
405
406
407
408
409
AF AG
410
411
412
413
414
415
416
AF AG
417
418
419
420
421
422
423
424
425
AF AG
426
427
428
429
430
431
432
433
434
435
436
437
438
AF AG
439
440
441
442
443
444
445
446
447
448
449
450
451
AF AG
452
453
454
455
456
457
458
459
460
461
AF AG
462
463
464
465
466
467
468
469
470
AF AG
471
472
473
474
475
476
477
AF AG
478
479
AF AG
480
481
482
483
485
AF AG
486
487
488
489
490
AF AG
491
492
493
494
495
496
497
AF AG
498
499
500
501
502
AF AG
503
AF AG
504
505
506
AF AG
507
508
509
510
511
512
AF AG
513
514
515
516
AF AG
517
518
520
521
522
523
524
AF AG
525
526
527
528
529
530
531
532
533
AF AG
534
535
536
AF AG
537
538
539
540
541
542
543
544
545
AF AG
546
547
548
549
550
AF AG
551
552
553
554
AF AG
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
AF AG
570
571
572
573
574
AF AG
575
576
577
578
579
580
581
582
583
584
AF AG
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
AF AG
603
604
605
606
607
AF AG
608
609
610
611
612
613
614
AF AG
615
616
617
618
619
620
AF AG
621
622
623
624
625
626
627
628
AF AG
629
630
631
632
633
634
635
AF AG
636
637
638
639
AF AG
640
641
642
643
644
645
646
AF AG
647
648
649
650
651
652
653
654
655
AF AG
656
657
658
659
660
661
662
AF AG
663
664
AF AG
665
666
667
668
669
670
AF AG
671
672
673
674
675
676
677
678
AF AG
679
680
681
682
683
684
AF AG
685
686
687
688
689
690
691
692
693
694
695
AF AG
696
697
698
699
AF AG
700
701
702
703
704
705
AF AG
706
707
708
AF AG
709
710
711
712
AF AG
713
714
715
716
717
AF AG
718
719
720
721
722
723
724
AF AG
725
726
727
728
729
730
731
AF AG
732
733
734
735
736
737
738
739
AF AG
740
741
742
743
744
745
AF AG
746
747
748
749
750
751
752
753
AF AG
754
755
756
757
758
759
AF AG
760
761
762
763
764
765
766
767
AF AG
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
AF AG
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
AF AG
821
822
823
824
825
826
827
828
829
830
831
832
833
834
AF AG
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
AF AG
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
AF AG
865
866
867
868
869
870
AF AG
871
872
873
874
875
876
877
878
AF AG
879
880
881
882
883
884
885
886
AF AG
887
888
889
890
891
892
893
AF AG
894
895
896
897
898
899
900
AF AG
901
902
903
904
905
906
907
908
909
910
911
912
913
914
AF AG
915
916
917
918
919
920
AF AG
921
922
923
924
925
926
AF AG
927
928
929
930
931
932
933
934
AF AG
935
936
937
938
939
940
AF AG
941
942
943
944
945
946
947
AF AG
948
949
950
951
952
953
954
955
AF AG
956
957
958
959
960
961
962
AF AG
963
964
965
966
967
968
969
970
971
972
AF AG
973
974
975
976
977
AF AG
978
979
980
981
982
983
AF AG
984
985
986
987
AF AG
988
989
990
991
992
993
994
995
996
997
AF AG
998
999
1000
1001
1002
AF AG
1003
1004
1005
1006
1007
1008
1009
1010
AF AG
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
AF AG
1022
1023
1024
1025
1026
1027
1028
1029
1030
AF AG
1031
1032
1033
1034
1035
1036
1037
1038
AF AG
1039
1040
1041
1042
1043
1044
AF AG
1045
1046
1047
1049
1050
1051
1052
AF AG
1053
1054
1055
1056
1057
1058
1059
AF AG
1060
1061
1062
AH
1
9
AH
10
11
12
13
14
15
16
17
18
AH
19
20
21
22
23
24
AH
25
26
27
28
29
30
31
AH
32
33
34
35
36
37
38
39
40
41
42
43
AH
44
45
46
47
48
49
50
51
52
53
54
55
AH
56
57
58
59
60
AH
61
62
63
64
65
66
AH
67
68
69
70
71
72
73
AH
74
75
76
77
AH
78
79
80
81
82
AH
83
84
85
86
87
AH
88
89
90
91
92
93
94
95
96
AH
97
98
99
100
101
102
AH
103
104
105
106
107
108
109
110
111
AH
112
113
114
115
116
117
118
119
120
121
AH
122
123
124
125
126
127
128
AH
129
130
131
132
133
134
135
136
AH
137
138
139
140
141
142
AH
143
144
145
146
147
148
149
AH
150
151
152
153
154
155
AH
156
157
158
AH
159
160
161
162
163
164
165
AH
166
167
168
169
170
171
172
173
174
175
176
177
AH
178
179
180
181
182
183
184
AH
185
186
187
188
189
190
191
192
193
194
195
196
197
198
AH
199
200
201
202
203
204
205
AH
206
207
208
209
210
211
AH
212
213
214
AH
215
216
217
218
219
220
221
222
AH
223
224
225
226
227
228
AH
229
230
231
232
233
234
AH
235
236
237
238
239
240
241
AH
242
243
244
245
246
247
248
AH
249
250
251
252
253
AH
254
255
256
257
258
259
260
261
AH
262
263
264
265
266
AH
267
268
269
270
271
272
273
AH
274
275
276
AH
277
278
279
280
281
282
283
AH
284
285
286
AH
287
288
AH
289
290
291
292
293
AH
294
295
296
297
298
299
300
301
302
AH
303
304
305
306
307
AH
308
309
310
311
312
313
AH
314
315
316
317
318
319
AH
320
321
322
323
324
325
326
AH
327
328
329
330
331
332
AH
333
334
335
336
337
338
339
340
341
342
AH
343
344
345
346
347
348
349
350
351
352
353
354
AH
355
356
357
358
359
360
361
362
363
364
AH
365
366
367
368
369
370
371
AH
372
373
374
375
376
377
378
379
380
381
AH
382
383
384
385
386
AH
387
388
389
390
391
392
393
AH
394
395
396
397
398
399
400
401
AH
402
403
404
405
406
407
408
409
AH
410
411
412
413
414
415
416
AH
417
418
419
420
421
422
423
424
425
AH
426
427
428
429
430
431
432
433
434
435
436
437
438
AH
439
440
441
442
443
444
445
446
447
448
449
450
451
AH
452
453
454
455
456
457
458
459
460
461
AH
462
463
464
465
466
467
468
469
470
AH
471
472
473
474
475
476
477
AH
478
479
AH
480
481
482
483
485
AH
486
487
488
489
490
AH
491
492
493
494
495
496
497
AH
498
499
500
501
502
AH
503
AH
504
505
506
AH
507
508
509
510
511
512
AH
513
514
515
516
AH
517
518
520
521
522
523
524
AH
525
526
527
528
529
530
531
532
533
AH
534
535
536
AH
537
538
539
540
541
542
543
544
545
AH
546
547
548
549
550
AH
551
552
553
554
AH
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
AH
570
571
572
573
574
AH
575
576
577
578
579
580
581
582
583
584
AH
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
AH
603
604
605
606
607
AH
608
609
610
611
612
613
614
AH
615
616
617
618
619
620
AH
621
622
623
624
625
626
627
628
AH
629
630
631
632
633
634
635
AH
636
637
638
639
AH
640
641
642
643
644
645
646
AH
647
648
649
650
651
652
653
654
655
AH
656
657
658
659
660
661
662
AH
663
664
AH
665
666
667
668
669
670
AH
671
672
673
674
675
676
677
678
AH
679
680
681
682
683
684
AH
685
686
687
688
689
690
691
692
693
694
695
AH
696
697
698
699
AH
700
701
702
703
704
705
AH
706
707
708
AH
709
710
711
712
AH
713
714
715
716
717
AH
718
719
720
721
722
723
724
AH
725
726
727
728
729
730
731
AH
732
733
734
735
736
737
738
739
AH
740
741
742
743
744
745
AH
746
747
748
749
750
751
752
753
AH
754
755
756
757
758
759
AH
760
761
762
763
764
765
766
767
AH
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
AH
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
AH
821
822
823
824
825
826
827
828
829
830
831
832
833
834
AH
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
AH
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
AH
865
866
867
868
869
870
AH
871
872
873
874
875
876
877
878
AH
879
880
881
882
883
884
885
886
AH
887
888
889
890
891
892
893
AH
894
895
896
897
898
899
900
AH
901
902
903
904
905
906
907
908
909
910
911
912
913
914
AH
915
916
917
918
919
920
AH
921
922
923
924
925
926
AH
927
928
929
930
931
932
933
934
AH
935
936
937
938
939
940
AH
941
942
943
944
945
946
947
AH
948
949
950
951
952
953
954
955
AH
956
957
958
959
960
961
962
AH
963
964
965
966
967
968
969
970
971
972
AH
973
974
975
976
977
AH
978
979
980
981
982
983
AH
984
985
986
987
AH
988
989
990
991
992
993
994
995
996
997
AH
998
999
1000
1001
1002
AH
1003
1004
1005
1006
1007
1008
1009
1010
AH
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
AH
1022
1023
1024
1025
1026
1027
1028
1029
1030
AH
1031
1032
1033
1034
1035
1036
1037
1038
AH
1039
1040
1041
1042
1043
1044
AH
1045
1046
1047
1048
1049
1050
1051
1052
AH
1053
1054
1055
1056
1057
1058
1059
AH
1060
1061
1062