z Class Drug MOA Indications Adverse Reactions

ANTIINLAMMATORY DRUGS
-Eicosanoids -G-protein binding, involved in
-PG, TXA and LT inflammation, toxins, trauma, IgE
reactions
-PGE1 -protective to the gastric mucosa -Abortificient and
contraindicated for
pregnancy.
-Misoprostol -)) -Rx for NSAIDs ulcers
-Alprostadil -Maintains PDA
-PGE2 -uterine contraction
-Dinoprostone -Cervical ripening
during parturition
-PGF2 -uterine and bronchiolar muscle -abortificient
contraction
-Dino/carbaprost -))
-Latanopost Rx of glaucoma
-PGI2 -Vasodilator and inhibits platelet
aggregation
-Activates cAMP - Ca2+ uptake
- intracellular Ca2+ - platelets
stability
-Epoprostenol -Rx for pulmonary HTN
-TXA2 -opposite of PGI2 function
-Activates PLC - IP3 - free
Ca2+ - platelet aggregation
-LT blockers -Headache, dental
pain GI distress and
rash.
-Zileuton -inhibits lipoxygenase Prophylaxis for Asthma -Increases Liver
(immunosuppression) Function Tests
-Montelukast -All lukast drugs are antagonist -)) -headaches, dental
for LTs and block their receptors. pain, GI distress and
-Antagonists for LTD4 receptors rash
-NSAIDs -inhibitors of cyclooxygenase
pathway (Cox1 and Cox2).
 -Aspirin -Irreversible noncompetitive -Post MI: baby aspirin -Hypersensitivity
inhibitor of COX 1&2. triad: asthma, nasal
-Works by acetylating the serine polyps and atrophic
residue on the binding site on rhinitis.
COX. -Increases warfarin
-antipyretic, analgesic, anti- toxicity, uricosurics
inflammatory, and antiplatelet and hypoglycemic
aggregation agents.
-Reyes Syndrome:
Aspirin + viral
infection
-Salicylism: chronic
dosing leading to
tinnitus, vertigo and
decreased hearing.
-Acetaminophen -Inhibits COX in the CNS and -Hepatotoxicity:
NOT in the periphery metabolized by
-Therefore only analgesic and Cp450 into reactive
antipyretic metabolite that
damages the liver.
-Antidote overdose:
Acetylcycteine SH
group that inactivates
metabolite
-Reversible -Side effects:
NSAIDs Dyspepsia and
interstitial nephritis
-Ibuprofen -does not affect warfarin and -#1 over the counter pain
hypoglycemic agents unlike reliever
aspirin
-Naproxen -for gout
-Indomethacin -Closing PDA and gout -Thrombocytopenia,
agranulocytosis
-Sulindac -does not affect the kidney -Pancreatitis
-Ketoro/etodo-lac
-Nebumetone
-Diclofenac -hepatotoxicity
 -Tolmentin -does not affect oral hypoglycemic
agents.

-Selective COX2 -Good for GI and

inhibitors antiinflammatory
-Inhibits COX 2 and spares COX
1
-Rofecoxib -Arthritis (chronic -Causes platelet
inflammation) aggregation leading
to MI and blood clot
-Celecoxib -Cross allergy with
sulfonamides.
- Migraine drugs -Triptans: suma, zolmi -Agonist at 5HT1D receptors in -Migraine -Possible asthenia,
and frova triptan cerebral BV throat pressure
-Ergotamine and -Partial agonist for alpha1 and -Acute Migraine attack
Methysergide 5HT2 in BV
-Drugs for Asthma
Bronchodilators -Binds to 2 receptors in the lung
adenylyl cyclase cAMP
bronchodilation.
-Albuterol, -2 agonist, fast and short acting -Acute asthma attack
metaproterenol and (inhaled)
Terbutamine
-Salmeterol -long lasting and slow acting 2 -Prophylaxis for
agonist bronchospasm
-Isoproterenol -1,2 agonist - Anxiety, tremors,
-Contraindication: uncontrolled headache,
arrhythmia palpitations
tachycardia,
hypertension and
arrhythmia
-Epinephrine -1,1,2 agonist -))
-Xanthine -Theophyilline and - Competitively inhibits -Has a low
Bronchodilators aminophylline phosphodiesterase increase therapeutic index.
cAMP bronchodilation. -Cp450 down
regulators, increases
its toxicity and
 Cp450 up regulators
decreases its action
Anticholinergic -Ipratropium -Local bronchodilator after -For blocker induced Like atropium: Dry
bronchodilators inhalation bronchospasms. mouth, miadrisis,
(M Blockers) -Bronchodilator in constipation, urinary
asthma in COPD retention, sweating,
tachycardia
-Corticosteroids -Inhibits PLA2 and decreasing -Inflammation, Asthma, -ACTH depression
the production of LT, PG and Autoimmune disease -Susceptibility to
TXA infections
- Beclomethasone, -Inhaled corticosteroids - Chronic bronchitis -Contraindicated for
Fluticasone, Bronchial Asthma, acute bronchospasms
Triamcinolone Allergic rhinitis - abdominal distress,
anorexia, oral fungal
infection or
candidiasis
-Prednisone -Oral corticosteroid
-LT antagonist **REFER TO LT CLASS
ABOVE
-Mast cell -Cromolyn and -Prevents the degranulation of -Prevention for Exercise -bad taste in the
Stabilizers Nedocromil mast cells and the release of induced asthma mouth, cough,
histamine and LTs by blocking diarrhea, myalgia,
calcium channels which is hoarseness
essential for degranulation.
-Monoclonal -Omalizumab -Binds to IgE receptor on mast -prophylaxis Rx for mild -increase viral and
Antibodies cell to moderate asthma resp tract infections.

-Cough Medications -Usually contain codeine (opioids)

Antussives (non- -Dextrometorphan -Suppresses cough reflex - Treat nonproductive
opoid) And benzonatate cough and cough that
interfere with sleep or
daily activites
-Expectorants -Guaifenesin - Decrease the viscosity of the - Treat cough associated
secretions with common cold and
upper respiratory
infections.
-Mucolytics - Acetylcysteine -Break down the mucoprotein -Treatment for thick or
(Mucomyst) molecules abnormal mucus in
 -Antidote for tylenol Cystic Fibrosis and
(acetaminophen) overdose atelectasis
-Dornase -Recombinant human DNase -Cystic fibrosis
-administered using a nebulizer
-Decongestants -Pseudoephedrine -Stimulate 1 receptors -Nasal congestion
(Sudafed), vasoconstriction.
Phenylephrine

-Rheumatoid
Arthritis drugs
DMARDs
-Methotrexate -Inhibits Dihydrofolate reductase -Also anticancer -Bone marrow
-Cytotoxic to lymphocytes suppression, Hair
loss, mucositis,
Worsens Nodules
Hydroxychloroquine -Stabilizes lysosomes and decrease -Also for malaria - Cinchonism: GI
chemotaxis distress and visual
dysfunction.
-Hemolysis in G6PD
deficiency
- Sulfasalazine -ASA inhibits COX2 -ASA: GI distress
-Sulfapyridine: decrease B cell -Sulfapyridine: Rash,
functions hemolysis, SLE like
syndrome
-Corticosteroids **REFER TO ASTHMA
ABOVE
-Gold salts -Decrease lysosomal and -Stomatitis, rash,
macrophages functions bone marrow
depression,
Proteinuria and
nephrotic syndrome
-D-Penicillamine -Suppresses T-cell and decreases -Also for Wilsonss -Aplastic anemia,
Rheumatoid factor disease myasthenia gravis
-Suppresses copper metabolites in
Wilsons disease
-Cyclophosphamide -Alkylating agents used in severe -anticancer -Hemorrhagic cystitis
cases
 -Azathioprine -Metabolized to 6-Mecaptopurine -Bone marrow
-Inhibits purine synthesis therefore suppression,
immunosuppressive. Leukopenia,
thrombocytopenia,
-hepatotoxicity
-New FDA
DMARDs
1. Infliximab -Monoclonal antibody, Decrease -Infusion reactions,
(Remicaids) TNF infections
2. Etanercept (Enbrel) -A recombinant of TNF receptor -Also for treating -Hypersensitivity,
that Binds to TNF Psoriasis infections
3. Leflunomide -Pyrimidine synthesis inhibitor -Alopecia, rash,
-Inhibits dihydro-orotic acid hepatotoxicity.
dehydrogenase decreased UMP
decreased RNA.
4. Anakinra -IL-1 receptor antagonist -Reaction at injection
site, infection
5. Adalimumab -Recombinant Monoclonal
(Humira). antibodies
Binds to TNF
-Osteoarthritis drugs -Tylenol and Celecoxib **REFER TO NSAID AND COX
2
-Osteomyelitis -Ox/Clox/Diclox and -For Staph Aureus
drugs Naf
-Fibromyalgia drugs -Cymbalta (duloxetine) -SNRIs antidepressant -Also for chronic pain
and DM neuropathy.
-Pregabalin (Lyrica)
-Polymyalgia -Steroids -Give 15mg initially, taper off. If -usually present with
Rheumatica drugs symptom persists, give 40mg, if temporal (giant cell)
not they go blind. arteritis.
-Gout (Crystal
induced Arthritis)
NSAIDs -Indomethacin, **REFER NSAID ABOVE -initial treatment
Sulindac, Naproxen
-Colchicine -binds to tubulin decreases -Acute gouty attack -Acute: Diarrhea and
microtubule formation GI pain
-decreases LTB4 -Chronic:
Mylosuppression,
 -Inhibits leukocyte and peripheral
granulocyte migration neuropathy,
hematuria and
alopecia
` -Allopurinol -Inhibits Xanthine Oxidase via -Chronic gouty arthritis -Peripheral
suicide inhibition neuropathy, stone
-*inhibits 6-mecarptopurine formation, rash,
metabolism vasculitis
-Probenicid -Inhibits proximal tubular -)) -urate crystals in the
reabsorption of urate kidney
-inhibits secretion of acidic drugs:
Penicillins
-Sulfinpyrazone -similar to Probenicid. -GI distress, rash,
-Activity is GFR dependent (not nephrotic syndrome
good below 30ml/min)
-Inhibits platelet aggregation

DRUGS IN IMMUNOLOGY
-For organ
transplant
1. Cyclosporine -Binds to cyclophillin leads to - Nephrotoxicity,
decrease calcineurin - inhibition Gingival Hyperplasia
of transcription factors IL-2, IL-
3 and INF
-usually administered with
corticosteroids
2. Azathioprine -*REFER TO DMARDS
3. Muromonab-CD3 -Monoclonal antibody -Acute renal transplant
-Must administer rejection
methylprednisone before IV
Muromonab-CD3 (to counteract
initial flaring and prevent cytokine
release syndrome)
4. Sirolimus -it inhibits signal transduction -Nephrotoxicity
(Rapamycin) -Sirolimus is metabolized by
cytochrome P450
 5. Tacrolimus (FK506) -calcineurin inhibitors -renal and liver
transplants
6. Mycophenolate -inhibits de novo synthesis of
Mofetil (MMF) purine by inhibiting IMP
dehydrogenase
-Used in combination with
cyclosporine
-Rh Incompatibility RhoGAM -Administer at 28wks of
pregnancy and 72 hrs after
parturition if the baby is positive
ONLY if the mother didnt
develop antibodies and therefore
still negative
-If mum Rh is positive, then titer
measure
-Cytokines in
Clinical Use
-INF -Hepatitis, leukemia
-INF -MS
-INF -Chronic Granulomatous
Disease
-IL-11 -Thrombocytopenia
-Thrombopoietin -Thrombocytopenia
-Erythropoietin -Anemia
- Aldesleukin (IL-2) - Renal cell Carcinoma
- Filgrastim (G-CSF) -bone marrow recovery
- Sargramostim (GM- - bone marrow recovery
CSF)
Monoclonal
Antibodies in
Clinical Use
- Abciximab - IIb/IIIa receptors inhibitor - antiplatelet indicated
after PCI (stent)
-Infliximab -Rheumatoid arthritis
-Omalizumab -Asthma
-Trastuzumab -Breast Cancer
-Daclizumab -Renal transplants
-Muromonab -Renal transplants
 -Palivizumab -RSV(repiratory
syncytial virus)
-Rituximab -Non-Hodgkin
Lymphoma, lymphoma
-Adalimumab -Rheumatoid arthritis

-Bevacizumab -Metastatic cancer

-Visilizumab -Crohns disease

Antibiotics
1. Inhibition of cell -Penicillins -Bind to cytoplasmic-penicillin- -Penicillin: gram ve,
wall synthesis Cephalosporins binding proteins (PBPs) Neisseria, syphilis,
Imipenem, meropenem, Inhibit transpeptidation Rheumatic fever
aztreonam inhibit cross-linking of bacterial
cell wall

-Bactericidal

-Vancomycin - Inhibits peptidoglycan synthase, -Rx MRSA

binds to D-Alanine -Enterococci
- Listeria
-Pseudomembranous
colitis
2. Inhibition of
Protein Synthesis

A. Interfere with -Aminoglycoside (30S) -Bactericidal: Misread of genetic

the formation of -Linezolid (50S) code carried by mRNA
initiation complex incorporation of wrong Amino
acid
- Binds to peptide site
 B. Interfere with -Tetracyclines (30S) -Bacteristatic: Inhibit the
incorporation of -Dalfopristin & insertion of aminoacyl t-RNA into
next amino acid Quinupristin (50S) "A" site
(streptogramins)

C. Interfere with the -Chloramphenicol -Bacteriostatic How?: Inhibition -Gray baby syndrome
formation of of peptidyltransferase
peptide bond

D. Interefere with -Macrolide (50S) -Bacteriostatic How?: Inhibit

Translocation -Clindamycin (50S) translocation of peptidyl-tRNA
from acceptor to donor site

3. Inhibition of Folic - Sulfonamide - Inhibits Dihydropteroate

acid Synthesis synthetase

- Trimethoprim and - Inhibits Dihydrofolate reductase

Pyrimethamine

4. Inhibition of - Fluoroquinolones - Inhibit DNA gyrase

Nucleic Acid (Topoisomerase II)
Synthesis

- Rifampin Inhibits DNA-dependant RNA

polymerase

Mechanism of resistance by bacteria

-Penicillins & 1. B-lactamase cleavage of drugs
Cephalosporins B-lactam ring

-Aminoglycosides 2. Production of conjugating

enzymes that increase drugs
clearance

-Chloramphenicol 3. Formation of acetylating

enzymes that inactivate drugs
 -Macrolides 4. Methylation of base in RNA
that alter drugs binding (M&M)

-Tetracyclines 5. Production of active transport

systems that push drugs out of the
cell (cycled out)

-Sulfonamides 6. Formation of PABA, increase

resistance to inhibition of
dihydropteroate synthetase

-Fluoroquinolones 7. Increase transport systems to

push drugs out and Increase
resistance to inhibition of
topoisomerase II

The resistance story and how new antibiotics came to be

-Staphylococcus -Penicillin -**Refer to penicillin above 1. Nonpenicillinase
aureus producing

-Methicillin (Oxcillin, -group of penicillinase resistant 2. Penicillinase

Cloxcillin, Dicloxcillin, penicillin producing
Nafcillin)
-Vancomycin **refer above 3. Methicillin Resistant
Staph Aureus (MRSA)

-Linezolid **refer above 4. Vancomycin Resistant

-streptogramins Staph Aureus (VRSA),
(dalphopristin and VRE : Vancomycin
quiniopristin) Resistant Enterococcus
-Daptomycin,
tigecycline ( for cSSSi)
cefteroline
 3. Broad spectrum -Amoxacillin and -Good against strep and
antibiotics Ampicillin gram-ve bacteria but
(aminopenicillins) NOT staph aureus

4. Extended -Piperacillin- Ticarcillin- -Good against strep and

spectrum penicillins Carbenicillin gram-ve (including
(antipseudomonads) pseudomonas) but NOT
staph aureus

5. So they came up -Clavulanate and -inhibit B-lactamase inhibitors - and combined it with
with B-lactamase sulbuctam, Tazobuctam broad spectrum and
inhibitors extended spectrum to
cover everything
including staph aureus

6. So we got.. - - Good against

Amoxacillin/Clavulanate gram+ve and gram-ve
Ampicillin/Sulbactam but not MRSA
Piperacillin/Tazobactam
Ticarcillin/Clavulunate

Cautions with Antibiotics

1. Always, always, always assess for Allergies
2. If allergic to penicillin also allergic to cephalosporins
3. If normal flora is disturbed during antibiotic therapy: Superinfection
Caused by microorganisms resistant to the given antibiotics
Signs of superinfection:
black, furry overgrowth on the tongue, loose or foul smelling stools, (woman) vaginal itching or discharge
4. Avoid taking oral penicillin and acidic juices or soda why? reduce drug absorption
5. Always, always, always teach the patient about completing the full therapeutic course, even if feeling better. Why? risk for resistant organism
Buzz words for Bacterial Resistance:
1. Patient stop taking antibiotics
2. Environmental dispersion of liquid antibiotics
3. Antibiotics are prescribed to Rx viral infection
-There are 5 1. First generation -No CNS entry - good against gram+ve
generations
cephalosporins
 - Cefazolin - Surgical prophylaxis

- Cephalothin - renal tubular

necrosis

- 2. Second -No CNS entry except Cefuroxime -good against gram-ve

generation
- ***Cefotetan -Rx Bacteroid fragilis -***Disulfiram like
action

- Cefaclor -some serum sickness

3. **Third -Enter CNS except Cefoperazone -good against gram-ve -
generation and pseudomonas *Pseudomembranou
-Neisseria and s colitis
pseudomonas.

-*Ceftriaxone IV/IM --Ceftriaxone is usually given with -single dose for

doxycycline 100mg X 10days gonorrhea
(for chlamydia)
-Excreted in the bile with
cefoperazone

-Cefixime (PO) -**Biliary sludge

with cholecystitis
like illness

4. Fourth -Cefepime IV -as good as third

generation generation and good
against gram+ve

5. Fifth Generation -Ceftaroline -**good for MRSA

Cephalosporins Buzz word:
Dose adjustment in renal impairment Except: Ceftriaxone & Cefoperazone
If patient is Allergic to penicillins: Don't prescribe cephalosporins
If gram +ve: Use Macrolides; If Gram-ve rods: Use Aztreonam. Cephalosporins are not effective against: Chlamydia (doxycycline), Mycoplasma
(macrolide), Listeria (aminoglycosides or vancomycin), MRSA (Vancomycin), Enterococci (Vancomycin)
s-New Beta Lactams

1. Monobactam -Aztreonam -Binds to PBP's 1a&3 and inhibits -**Given IV against

transpeptidation gram-ve
-**No cross sensitivity to -FYI: Pseudomonas:
penicillins. aztreonam, extended
-Resistant to B-lactamase spectrum and 3rd
-Synergistic to aminoglycosides generation
cephalosporins
2. Carbapenem -Carbapenem are resistant to B- -Given IV against
lactamase Gram+ve, Gram-ve, and
anaerobes

-Imipenem&cilastatin -Imipenem is rapidly metabolized -Seizure with renal

by renal dipeptidase dysfunction
-Cilastatin is a specific inhibitor (Imipenem)
of dipeptidase; Increase
duration of action of Imipenem

-Meropenem -Rx of serious infections

-Vancomycin -It is not penicillin or -**Against Gram+ve 1."Red man

cephalosporins only syndrome"
-It inhibits bacterial cell wall -IV effective against chills - fever - rash -
-Inhibits elongation of MRSA red face and neck
Peptidoglycan chains -Oral effective against why? histamine
-It is bactericidal clostridium difficile release
-Vancomycin is not effective (pseudomembranous 2. Ototoxicity
against gram-ve colitis) 3. Hypersensitivity
-Inhibits D-ala D-ala crosslinking 4. Nephrotoxicity

-Inhibit -Macrolides -Erythromycin -Community acquired -**Binds to motilin

translocation -Azithromycin pneumonia receptors -Diarrhea
-Clarithromycin -Mycoplasma -Reversible
pneumoniae Ototoxicity
 -**It inhibits
cytochrome P450
(all)

-Erythromycin -Indicated for pregnancy: grp b -Good against staph- -Erythromycin

strep. agalactia strep - Mycoplasma estolate causes
and Legionella cholestatic jaundice
- (diarrhea and
vomiting)
-High dose
(prolonged QT
interval)

-Azithromycin -As Good as -Less side effects

erythromycin + than erythromycin
Chlamydial urethritis

-Clarithromycin: -As good as

Erythromycin + H.
Influenza and H. pylori
-Good against MAC
Mycobacterium avium
complex in AIDS patient

-New class of -Telithromycin -Similar to Azithromycin -Prolonged QT

macrolides interval
-Inhibits
cytochrome P450

-Anaerobic -Clindamycin -Oral infections (above -risk for AAPMC

infections the esophagus) Antibiotic Associated
PseudoMembranous
Colitis
 -Metronidazole -**chosen over Vancomycin for -Intraabdominal -Furry tongue,
AAMPC treatment because its infections (below the glossitis
cost effective esophagus) -Peripheral
-Bactericidal: Mechanism -Rx of AAPMC neuropathy
unknown -Drug of choice: -Disulfiram like
-MOA: produces oxidative free -Protozoa: action
radicals that is cytotoxic to - Giardia Lamblia,
pathogens -Trichomonas vaginalis
-Entamoeba histolytica
-Bacterial: AAPMC
-Bacteroids Fragilis
-G. Vaginalis

Disulfiram drug action drugs:

Metronidazole, Cefamandole, Cefoperazone, Cefotetan, Griseofulvin

-Inhibitors of the -Tetracycline (both Tetracycline - -Used in patients allergic to -Good for chlamydia, 1. Contraindicated in
A site generic and brand Doxycycline- penicillin Rickettsia, Mycoplasma, children younger than
name) Minocycline- -Dairy product should be avoided Brucella, Yersinia and 8y/old why?
Demeclocycline with Tetracycline why? reduce Vibrio cholera, lyme permanent
absorption (Chelators) Except disease discoloration of
doxycycline & Minocycline teeth

2. Use sunscreen and

protective clothing
when outdoors is
advised why?
Photosensitivity

3. Out dated
Tetracycline:
Fanconi like
syndrome

4. Hepatotoxicity:
more in pregnant
women
-Tetracycline
 -Demeclocycline -inhibits ADH -and used to Rx SIADH 5. Nephrogenic
seen in small cell lung diabetes insipidus
cancer.
-Doxycycline -penetrates the prostate
and used in Prostatitis
-chlamydia

-mostly intracellular
microbes (obligate
intracellular)
-Minocycline 6. Vestibular
Ototoxicity
(Minocycline)

All tetracyclines, except doxycycline (fecal excretion) require dose adjustment in renal impairment

-Inhibitors of DNA -Fluoroquinolones -Ciprofloxacin, -Inhibit DNA gyrase -Drug of choice: -contraindicated for
synthesis Norfloxacin, Ofloxacin (topoisomerase II) Anthrax pregnancy
Enoxacin, Trovafloxacin -2nd choice: Penicillins -Careful <18y/old
or tetracyclines why? inhibit
-Good against Gram-ve chondrocytes
sepsis (PO)

-Cipro & Oflo -Single dose for

gonorrhea

-Sparfloxacin -Resistant
pneumococcus
-Ofloxacin -Chlamydia
-Inhibitors of -Aminoglycosides -Gentamycin - -Active transport by O2 -gram-ve infections 1. Ototoxicity (2%)
Initiation Tobramycin - dependant system Auditory:
Paromomycin Irreversible
Amikacin- Neomycin- -***Cannot be used to treat (cochlear), high pitch
Kanamycin- anaerobic infections 1st
Streptomycin Vestibular:
-All aminoglycosides require Reversible
dose adjustment in renal failure
 2. Nephrotoxicity:
(7%)
Proteinuria,
hypokalemia, and
acute tubular necrosis

3. Neuromuscular
blockade
Decrease
prejunctional release
of Acetylcholine

Used in -Triple antibiotics 1.Endometritis

combination: Gentamycin +
Ampicillin +
Metronidazole

-Synergistic with 2. Enterococcus

ampicillin infection

-Synergistic with 3. Pseudomonal

Extended spectrum infection
penicillin

-Drug interaction -Furosemide, ethacrynic 1. Enhanced

acid Ototoxicity

-Amphotericin B, 2. Enhanced
Vancomycin, Cisplatin, Nephrotoxicity
cyclosporin

**Spectinomycin is not an aminoglycoside

**Used in Rx of Gonorrhea alone
MOA: inhibits protein synthesis by binding to (30S)
Doesn't cause misreading of the genetic code
-Inhibition of folic -Sulfonamides - 1. Hypersensitivity:
acid synthesis Rash to Steven
Johnson Syndrome

2. Hemolysis in
G6PD deficiency

3. Photosensitivity

4. Crystalluria

1. Sulfisoxazole -: Rx of UTI &

Norcardial infection
2.Sulfasalazine -Rx of Ulcerative colitis
3. Sulfacetamide -Rx of Trachoma
(Topical)
4. Silver sulfadiazine -**Rx of Trachoma
(Topical)

5. Sulfadiazine & - Rx of Toxoplasmosis

Pyrimethamine

6. Trimethoprin -prophylaxis & Rx of -Thrombocytopenia,

Sulfamethoxazole PCP (pneumocystis leukopenia
(TMP-SMX) pneumonia) -GI distress in AIDS
co-trimoxazole -2nd choice: Rx of patients
Salmonella, Chancroid, F
MRSA

Contraindication: 3rd trimester of pregnancy

Cross BBB leading to kernicterus (by displacing bilirubin bound to albumin)
Drug interactions:
-Increase warfarin activity
-Increase phenytoin activity

Urinary Tract Antiseptics

-Methenamine mandelate and Nitrofurantoin
Urinary Tract Anelgesics
 -Phenazopyridine
-Buzz word: Produce orange to red urine that may stain clothing
Broad spectrum antibacterial
-Chloramphenicol
-Buzz word: Aplastic anemia (side effects), Gray baby syndrome.

Antituberculous drugs
1. Isoniazid (INH) -MOA: Inhibition of mycolic acid -Hepatitis
synthesis (Cell wall synthesis) -Neuritis
-Hemolysis in G6PD
-Resistance: deficiency
Low resistance: Deletion in INHA -SLE in slow
gene; gene encoding acyl carrier acetylators
protein (Target)

High Resitance: Deletion in katG

gene; encode catalase enzyme
needed for INH bioactivation

-Why is Pyridoxine (Vit B6) used

with INH?
Helps prevent numbness and
tingling that occur secondary to
Isoniazid neuritis.
2. Rifampin -MOA: inhibits DNA-dependant -Red-orange
RNA polymerase by binding to discoloration of
the beta subunit. urine
sweat, and tears
-Resistance: Mutation in -Proteinuria
polymerase enzyme -Flu-like symptoms
-Thrombocytopenia
-Induces CP450

3. Ethambutol -MOA: Inhibits synthesis of -Loss of red green

Arabinogalactan (Component of acuity
cell wall) -Retrobulbar
neuritis
 4. Pyrazinamide -MOA: Unknown -Arthralgia due to
hyperuricemia
-Hepatotoxicity
-Increase porphyrin
synthesis

5. Aminoglycosides -MOA: Inhibit protein synthesis -Streptomycin:

Hearing loss, ataxia,
nephrotoxicity
-Amikacin:
Nystagmus
-Kanamycin:
Electrolyte
abnormalities

6. Capreomycin -Buzz word: No cross resistance -Hearing loss, ataxia

Not an aminoglycoside with aminoglycosides
-Used as 2nd line for Rx of
resistant TB with Aminosalicylic
acid and cycloserine

-DMAC: -Azithromycin +
Disseminated Rifabutin + Ethambutol
Mycobacterium
Avium Complex

Rifabutin -Similar to Rifampin -Rashes, GI effects

-Neutropenia
-Induces p450
-No Hepatotoxicity

***Refer to ppt for clinical screening and TB treatment guideline

*Psych Medications
The Neurotransmitter story (Amine hypothesis)
 Norepinephrine + Serotonin Depression
Norepinephrine + Serotonin Bipolar (mania )
Dopamine Psychosis (hallucinations)
GABA (Gamma Amino Butyric Acid) Anxiety
-Bipolar disorders: fluctuations of Norepi and serotonin
-Antipsychotics

- Typical -also called Neuroleptics -Antidopaminergics (Block D2A)

Antipsychotics -work only on the positive
symptoms
- (not experienced by
normal individuals but are
present in schizophrenia) eg
Hallucinations,
Delusions, Agitation

1. Phenothiazines -may discolor the

(less potent) urine to pink or red-
brown

-Chlorpromazine -Aliphatic side chain -used as antiemetic -blocks alpha

-Antiemetics: used to receptors
treat nausea and -can cause deposits
vomiting on the Cornea or lens

-Fluphenazine -Long acting available

-piperazine

-Mesoridazine -**Prolonged QT
interval
- Torsade de pointes

-***Thioridazine -piperidine -**Prolonged QT

interval (black box
warning)
 - Torsade de pointes
- reTinal deposits

-Perphenazine - Low cardiac risk

2. Butyrophenones -Haloperidol -Haloperidol should be withheld -Psychosis,

(more potent) 48 Hrs before and 24 hrs after -Tourette syndrome
myelography with metrizamide -Hyperactivity in
(radio opaque contrast media) children ADHD
why? risk of seizures

3. Other Typical - Loxapine -Low cardiac risk

antipsychotics -less likely to increase weight

- Molindone - Low cardiac risk

- Pimozide -tourettes -**Prolonged QT

interval
- Torsade de pointes

All Typical Antipsychotics have a big adverse reaction

EPS = Extra Pyramidal Side effects (why? decrease of dopamine in the CN); blocking of receptors elsewhere than the intended site of action
1. Pseudoparkinsonism: bradykinesia, rigidity, tremor, mask like face, shuffling gait
2. Akathisia: Inability to stand still
3. **Acute Muscle dystonia: Muscle spasms facial grimacing, torticollis, oculogyric crisis, locked jaw, opisthotonus (backward bending of the spine)
4. Tardive dyskinesia: involuntary choreiform movements of the face & limb (occurs later in months)
5. Neuroleptic malignant syndrome: very rare but fatal (occurs late); severe muscle rigidity, can have increased CK & WBC, Hyperpyrexia, Tachycardia
Rx: diazepam, dantrolene (inhibits release of calcium from the SR (sarco. Ret.))

Other Adverse reactions

1. Anticholinergics: Dry mouth and constipation
2. Orthostatic hypotension why? alpha blockade
Patients complains of tachycardia?? Reflex
Impaired ejaculation
3. Photosensitivity and rashes - Sunburn
4. Increase appetite and weight gain
-Glucose intolerance and diabetes (most psychotic drugs)
5. Endocrine: increase prolactin release: Amenorrhea-galactorrhea, infertility, impotence
 The more potent the antipsychotic the more the EPS and the less the anticholinergic side effects
Buzz word: Haloperidol and fluphenazine, triflu, pimozide and thiothixene
The less potent the antipsychotic the less the EPS and the more the anticholinergic side effects
Buzz word: Chlorpromazine, mesoridazine and thioridazine

Management of patients on Antipsychotics

1. tell the patient that phenothiazines may discolor the urine to pink or red-brown
2. Avoid OTC or herbal medications
3. Monitor QT interval: Risk for cardiotoxicity: Torsades de points
4. Haloperidol should be withheld 48 Hrs before and 24 hrs after myelography with metrizamide (radio opaque contrast media) why? risk of seizures
5. Avoid Alcohol and other CNS depressants
6. If EPS occur, switch to a different Antipsychotics and administer Benztropine or diphenhydramine (acute dystonia)
7. What we do if a schizophrenic on antipsychotic meds comes back to the ER at Bellevue claiming that the voices are back and telling him to kill himself????
-Switch drugs
-Atypical -No or less EPS because they are
Antipsychotics more effective on 5HT2A
receptors than Dopamine (D2)
-Atypical because it treats both
positive and negative [(deficits of
normal emotional responses) eg
flat affect, social withdrawal and
poor speech)] symptoms

-Its atypical for old closets to

quietly risper from A - Z

-Clozapine -***Agranulocytosis,
weight gain, seizure

-Olanzapine -Weight gain and

DM

-Quetiapine -Rx of Autism in

children

-Risperidone -Rx aggression in autism -EPS with high doses

 -Ziprasidone -blocks dopamine and serotonin
-?
-Aripiprazole -dopamine agonist/antagonist -nausea and akithisia
activity
-partial agonist of D2.

-Antidepressants
1. Tricyclic [TCAs] -Inhibit reuptake of NE, serotonin
-SNDRIs and dopamine
-contraindicated in pregnancy
-All triptyline and pramines
are TCAs except for Doxepin
-Amitriptyline -used for chronic pain
-Nortriptyline (DM pains and shingles
zoster pain, or pain
without etiology)

-Clomipramine -FDA approved for

OCD
-Imipramine -Used for enuresis
(night time bedwetting)
-Trimipramine -No GI upset

-Doxepin -potently anti-histamine -Used for anxiety

And insomnia
-hives (behave)
-Desipramine -Sudden cardiac
death in children due
to prolonged q-t
interval

2. Tetracyclics -Amoxapine -Dopamine blockers

-Maprotiline -seizures
 -Mirtazapine -Potent anxiolytic drug (behave) -Anxiety, anorexia and -seizures and
insomnia agranulocytosis

-Bupropion -Smoking Cessation -it lowers threshold

-might improve sexual for seizures
function

3. Second -Nefazodone -irreversible

generation Hepatotoxicity
tetracyclics

-Trazodone -Priapism: sustained

painful erection
-Postural hypotension
Adverse effects of TCAs:
1.Anticholinergic: dry mouth, epigastric distress, constipation, tachycardia, palpitation, blurred vision, and urinary retention (especially in elderly males)
2.CNS: sedation, confusion, Seizure threshold is lowered
3.CVS: orthostatic hypotension, sinus tachycardia, cardiac arrhythmias, conduction defects (intraventricular) prolonged QRS interval

4.SNRI -Venlafaxine (for -Dose dependent -Severe withdrawal

behave) -Fast acting serotonin and symptoms
norepi reuptake inhibitor
-*Most potent antidepressant
-Duloxetine (Cymbalta) -Acts more on norepinephrine -Fibromyalgia and
diabetic peripheral
neuropathy
5.MOA inhibitors - (MonoAmine Oxidase) Inhibitors -Hypertensive crisis
--MOA inhibitor are nonselective with food containing
thus inhibit isoform A and B tyramine, Cheese
-Contraindicated with SSRIs to and wine
prevent serotonin syndrome

-Phenelzine,
isocarbazide,
selegiline(MOA-B)
-Tranylcypromine
 6. RIMA -Moclobemide -Reversible Inhibitors of MAO-
Broforamine A
7. SSRI -Selective Serotonin Reuptake -GI symptoms (rare)
Inhibitors -Sexual dysfunction
-All SSRI are safe in Pregnancy, -Insomnia
less side effects

-Fluoxetine (Prozac) -Agitation and

restlessness
Paroxetine (Paxil) -Slight weight gain,

-Sertraline (Zoloft)

-Fluvoxamine -anticholinergic like

symptoms
-Escitalopram
(Lexapro)

Management of patients on Antidepressants

1. Tricyclics takes 30 days or more to work
2. SSRI may take 1 to 4 weeks
3. Fluoxetine should be taken early in the day why? interfere with sleep
4. Tricyclic cause sedation and dry mouth
5. Don't mix SSRI and MAO inhibitors (St.Johns wort / SSRI & MAO) why?
Risk of Serotonin Syndrome; Fever, hypertension, hyperthermia, seizures, hyperreflexia, diarrhea
6. 2-week washout period after stopping SSRI and starting MAO inhibitor
-Antimanics -Lithium -MOA unknown -Mania -Narrow therapeutic
-MOOD STABILIZER -Bipolar (mania + index (0.8 to 1.2
-Possible MOA: depression) mEq/L)
- Inhibits inositol metabolism -SIADH -NDI leading to
- Inhibits the conversion of IP2 Hyponatremia
to IP1 -due to vomiting and
- Decreased action of diarrhea
transmitters -Tremor
-renal and thyroid
dysfunction in
children and women
(behave)
 -Carbamazepine -Agranulocytosis

-Valproic acid -rapid cycling Mood -

swings
-Olanzapine

-Lamotrigine -minimally sedating -Bipolar depression -steven Johnson

syndrome
Management of patients on Lithium
1.Therapeutic range for lithium from 0.6 to 1.2 mEq/L
2.Tolerance for lithium is high in acute mania, slow onset of action
3. Assess suicidal tendencies
4. Assess for lithium toxicity: tremors
5. Teach the patient to drink 2 L of fluid daily and maintain adequate salt intake
6. May cause hypothyroidism (measure TSH every 6 months)

-Antianxiety Drugs -Panic Disorder -Alprazolam -Drug of Choice -For acute panic attack

-TCAs, SSRIs, Beta

blockers
-Phobia -SSRI
-Benzodiazepines
-OCD -Clomipramine
-Paroxetine
-Fluvoxamine -newly FDA approved -recently approved for
OCD
-PTSD -SSRI
-Atypical Antipsychotics

-GAD -Busipirone -serotonin agonist (5-HT1A)

-Other -Zolpiden -Nonbenzodiazepine

-Hydroxyzine -Antihistamines

Toxicology
-Heavy Metal -Type -Antidote -Clinical Presentation/ MOA -Etiology -Other
1. Lead Poisoining -Acute: GI distress (lead colic),
tinnitus, encephalopathy
-Chronic: anemia (decrease
heme), wrist drop (affected radial
nerve), proteinuria, decrease
fertility
-Pica during pregnancy
lead poisoning in the
new born mental
retardation

-Succimer -A chelating agent

-Given orally and for children
-EDTA (Ethylene -EDTA: Given as IV
diamine tetraacetic -Dimercaprol: for encephalopathy
Acid) because it crosses BBB
-Dimercaprol
-Penicillamine

2. Arsenic -Dimercaprol or -Acute: Rice watery stools, garlic -Drinking water

poisoning Penicillamine breath, seizures (ground water) Most
-Chronic: stocking glove common route of
neuropathy, alopecia exposure
-Skin: "raindrop" pattern of
hyperpigmentation
- Mees lines (white lines
on the finger nails)

3. Iron Poisoning -Deferoxamine IV -Acute (children): Necrotizing

Gastroenteritis, hematemesis and
bloody diarrhea

4. Mercury -Succimer PO or -Acute: (Vapor) pneumonitis,

Poisoning Dimercaprol (IM) (Salt ingestion): Bleeding, renal
failure
-Chronic: Auditory and visual
loss, ataxia, paresthesia
 5. Copper -Wilson's disease (Kayser- -Defect in the function
Poisoning Fleischer rings) of cerulplasmin which
normally binds Cu in the
blood

-d-PENCILLAMINE -Chelates copper

-Trientine

-Substance Abuse -Type -Overdose/withdrawal -Clinical presentation/MOA -Other

Tx
1. Opiates: -Opiates receptors
Morphine, Heroin, -NE receptors: Locus ceruleus
Methadone pathway

-Naloxone -Overdose: pinpoint pupils,

respiratory depression, coma
-Clonidine -Withdrawal: Flu-like symptoms,
Lacrimation, rhinorrhea, yawning,
muscle aches.

2. Cocaine , -Dopamine receptors: Nucleus

Amphetamine & accumbens
MDMA
(Ecstasy),
mephedrone (bath
salt)
-Haloperidol -Overdose: Euphoria,
hypervigilance, paranoia
-Bromocriptine, -Withdrawal: Dysphoric mood,
Amantadine unpleasant dreams
-Cocaine (crash - first phase of
cocaine withdrawal)

3. Barbiturates -GABA receptors

and Benzo
 -Flumazenil for Benzo -Overdose: Impaired judgment,
slurred speech, incoordination,
unsteady gait, coma

-Withdrawal: Anxiety, rebound

insomnia (Benzo), Life
threatening seizures (Barb)
4. Hallucinogens -Acid
LSD (Lysergic -Serotonin receptors - 5-HT2A
acid diethylamide) -Effects: visuals, altered sense of
time and spiritual experiences
(Trips)

-Haloperidol or -Overdose: Idea of reference,

diazepam depersonalization, illusions
-Withdrawal: None

5. PCP, -Glutamate receptors leads to

(phencyclidine), prolonged depolarization
Ketamine club --Ketamine: therapeutic
drugs anesthetic

-Dark room, talk -Overdose: Vertical nystagmus,

down, Haloperidol impulsiveness, violent behavior
-Withdrawal: None

6. Cannabis: -Inhibits GABA

Marijuana & Hash -CB1: stimulation leads to
inhibition of GABA and
disinhibition of dopamine

-Abstinence and support -Overdose: Slowed time,

impaired judgement, amotivational
syndrome
-Withdrawal: None

7. Nicotine -Cholinergic agonist

-Activates dopamine receptors
 -Nicotine patch, -Overdose: Headache, increased
fluoxetine, wellbutrin depression, impotency
(Bupriopin)
-Varenicline -Partial agonist on nicotine
(CHANTIX) receptors

- Education, wellbutrin Withdrawal: Irritability,

increased appetite, anxiety,
depressed mood and decreased
heart rate

8. Caffeine - Antagonist of adenosine

receptors
- Analgesics, lower - Overdose: Restlessness,
caffeine intake agitation, insomnia
- Withdrawal: Headache,
drowsiness, nausea

9. Inhalants: Glue, - Enhance GABA receptor

paint thinner, fuel funtions
additives, - Inhalants: doesnt make you
chemical vapors: hungry and cheap thus street kids
nitrates, ketones, like it.
and aliphatic and
aromatic
hydrocarbons
- Education & - Overdose: Uncoordination,
Counselling lethargy, unsteady gait
- Withdrawal: None

OTC (Over The Counter) Medications

-Herbal Medicine
1. Saw Palmetto -5-alpha reductase inhibitor -Rx of BPH
2. St John's wort -Antidepressant -Depression -induces Cyt P450
-enhances serotonin therefore has drug
interactions
 -Serotonine
syndrome when
taken with SSRIs
3. Ginkgo - Increases superoxide dismutase -Rx of Alzheimer's
-Antioxidant -Intermittent
claudication

4. Echinacea -enhances interleukin -Rx of common cold

5. Melatonin -Serotonin effects -Rx of insomnia & jet- - decreases
lag ovulation, decreases
prolactin, LH surge
and contraindicated
in pregnancy
6. Ephedra - -Weight loss & -sympathomimetic
Congestion therefore
contraindicated for
stroke patients
7. Ginseng -mental & physical enhancer
-Antioxidant and enhancement of
memory

8. Garlic -Inhibits HMG-CoA reductase -Heart disease & cancer

-ACE inhibitors
-antiviral, antibacterial and
antifungal, lipid lowering property
9. -Androgen precursor -Anti-aging - SLE -increase risk of
Dehydroepiandrosterone -to increase body mass, memory. -Adrenal insufficiency breast cancer,
prostate cancer, heart
disease, diabetes and
stroke, BPH

10. Kava -Enhances GABA -Rx of anxiety

-Alcohol like effects due to GABA
actions therefore do not mix with
Alcohol
11. Feverfew -Decreases LTs & PGs -Rx of migraine
12. Milk thistle -sylibum marianum (hepato- -Rx of Liver disease
protector)
 -Antioxidant -Rx of mushroom
poisoning

-Serotonin (5HT) 1. Buspirone -Partial Agonist for 5HT1A -Rx of GAD

Receptors
(additional info)
2. Sumatriptan -Agonist for 5HT1D -Rx for Migraine

3. Olanzapine -Antagonist to 5HT2A -psychosis

4. Cyprohepatadine -Antagonist to 5HT2 -For treating carcinoid
-H1 Blocker syndrome
5. Ondasetron -Antagonist to 5HT3 -Rx for chemotherapy or
-Has no 2nd messenger radiation induced
vomiting
6. Tegaserod -Agonist for 5HT4 -Rx of constipation in -Causes cardio
IBD (irritable bowel problems
syndrome)

Anticancer Drugs
2 types of drugs against cancer:
1. Cell-cycle specific (acts on cell undergoing division)
In general, CCS drugs are most effective in high growth fraction tumors
2. Cell-cycle nonspecific (acts on cell during any phase)
useful in low growth fraction solid tumors as well as in high growth fraction tumors

Growth fraction: is the % of cell which are actively dividing

Generation time: Time to complete one cycle

First order kinetics : (fractional cell kill)

Cancer drugs kill a fixed percentage (proportion ) of tumor cells and not a fixed number of cells

One of the reason for use of drug combination is because of the log-cell kill hypothesis (kills in logs of 3)
-Cell Cycle
1. Non phase -Alkylating agents
specific (CCNS) -Nitrosourea
 -Decarbazine
-Cisplatin
-Antitumor
antibiotics

2. Phase Specific
(CCS)

a) G1 phase: -L-asparginase -Synthesis of cell components

-Mitomycin needed for DNA synthesis
b) S-phase: -Cytarabine -Cell cycle specific: Period of
-6-Mercaptopurine DNA synthesis
(6MP) -First three are S-phase specific
-6-Thioguanine (6TG)
-Methotrexate (MTX)
-Hydroxyurea
-Etoposide
c) G2 phase: -Bleomycin
d) M phase -Vinblastine -Mitosis
-Vincristine
-Paclitaxel

1. Alkylating -cyclophosphamide, -donate alkyl groups to guanine

Agents ifosfamide, N7 of DNA - non functional
mechrorethamine DNA
melphalan, chlorambucil -intra and interstrand
-busulphan crosslinking
-Alkylation of Guanine can
result in miscoding through
abnormal base pairing with
Thymine
-DNA destruction
-cyclophosphamide: -Active metabolites: Acrolein and -Hemorrhagic
phosphoramide mustard cystitis (acrolein
-Prevention of hemorrhagic toxic to bladder
cystitis is Mesna mucosa)
(mecarptoethane sulfonate)
which incactivates acrolein
 B. Nitrosurea -Carmustine, -Crosses the BBB -Brain tumors
-Lomustine,
-Semustine
C. Platinum 1.Cisplatin -***Most toxic anticancer agent -renal toxicity (side
agents out there effects)
-First generation -peripheral sensory
-Prevention of renal tox: IV fluid neuropathy,
and Amifostine (cytoprotectant). ototoxicity
-thiol metabolite available to
scavenge reactive cisplatin
metabolites
2.*Carboplatin -2nd generation -myelosuppression

3.Oxaliplatin -3rd generation -peripheral sensory

neuropathy

D. Others Procarbazine -Depolymerizes DNA -Hodgkins, NHL (non- -increased risk of

hodgkin lymphomas) secondary cancers -
acute myeloid
leukemia

-Dacarbazine (MM)
-Altretamine (OC)

-Busulphan -Chronic myelogenous -**causes pulmonary

leukemia fibrosis
-skin pigmentation
-acute lung injury,
chronic interstitial
fibrosis, alveolar
hemorrhage
(busulphan lung)

2. Antimetabolites

A. Purine Analog 1. 6-MercaptoPurine -Activated by HGPRT to -Leukemia

6 -Thioinosinic Monophosphate
 Active metabolite
-Inactivated by xanthine oxidase
-Reduce dose if given with
Allopurinol (by 50%)
2. 6-ThioGuanine -No dose modification with
Allopurinol

B. Pyrimidine -5- FluoroUracil (5FU) - Fluoro -deoxyUridine- -Cancer cells -nausea, mucositis,
Antagonist MonoPhosphate (FdUMP) diarrhea, hand and
-Inhibits thymidylate synthase foot syndrome
thymineless death
-FUTP (Triphos.): interferes
with RNA processing
-Flucytosine -Fungal cells

-Capecitabine -converted to 5-fluorouracil in

the tumor

-Cytarabine (Ara-C) -highly schedule dependent -Acute Myelogenous

-Inhibits DNA synthesis therefore Leukemia
S phase specific
C. Folate -Methotrexate (MTX) -It inhibits the enzyme
Antagonist DiHydroFolate Reductase
(DHFR) thereby inhibiting DNA,
RNA and protein synthesis

-Folinic acid: Antidote to

-Leucovorin rescue methotrexate toxicity
-Reduced form of folic acid thus
normal cells can have THF
D. Others: -Hydroxyurea -It inhibits Ribonucleotide -Used for CML
reductase - inhibition of DNA -in low dose used in Rx
synthesis of Sickle cell anemia
-Thus belongs to S-phase
-In sickle cell, converts HbS to
HbF
3. Antibiotics A. Doxorubicin - inhibits topoisomerase II 1. Cardiotoxicity
(Anthracyclines) (Adriamycin) - binds to DNA through because of
B. Daunorubicin intercalation semiquinone
- blockade of the synthesis of -Acute form, can be
DNA & RNA, and DNA strand reversed (ECG
scission changes)
-generation of semiquinone free -Chronic: CHF due
radicals (iron containing) to cardiomyopathy
2. Redness and
-Dexrazoxane -Antidote: (prevents CHF)- scaling of the skin in
chelating agent radiation recall
reaction
C. Bleomycin -causes DNA strand scission -Pulmonary toxicity -
pneumonitis with
cough, dyspnea

4. Mitotic A. Vinca Alkaloid -Bind to tubulin and prevent the

Inhibitors joining of and tubulin
-Block microtubular
polymerization
- Cell division is arrested in
metaphase

1. Vinblastine -bone marrow

suppression,
alopecia

2. Vincristine -**No bone marrow suppression -Peripheral

neuropathy

3. Vinorelbine -bone marrow

suppression

B. Taxanes 1. Paclitaxel (Taxol) -enhancement of tubulin -breast, lung and ovarian -Alopecia, arthralgia,
polymerization cancer peripheral
-Prevents the separation of tubulin neuropathy
dimers.
 -metabolized by cytochrome P450

2. Docetaxel -metabolized by cytochrome P450 -advanced breast cancer

5. Miscellaneous A. Topoisomerase 1. Etoposide & -Inhibit topoisomerase II -Lung cancer

inhibitors Teniposide

2. Irinotecan & -Inhibits topoisomerase I -Colorectal cancer

Topotecan

B. Enzymes 1. L-Asparginase -Catalyzes hydrolysis L- -***Pancreatitis

Aspargine to aspartic acid
-Tumor cells require L-Aspargine
for growth

-Tyrosine kinase
inhibitors
-Imatinib (GLEEVEC) -inhibitor of tyrosine kinase
domain Bcr-Abl oncoprotein
-prevents the phosphorylation of
kinase substrate by ATP
-first line therapy in
chronic phase of CML,
and blast crisis
-GIST

-Dasatinib (SPRYCEL) -used when there is resistance to

-Nilotinib (TASIGNA) imatinib

-Growth factor
receptor inhibitors

-Gefitinib (IRESSA) & -small molecule inhibitors of the -used in non-small cell
Erlotinib (TARCEVA) tyrosine kinase domain lung cancer
associated with the EGFR
(Epidermal Growth Factor
Receptor )

- Cetuximab -EGFR inhibitor -used in metastatic

(ERBITUX) colorectal cancer
 - Rituximab -Targets CD20 -used in B cell
(RITUXAN) lymphoma

- Trastuzumab -Targets HER2/neu (ErbB-2) -used in breast cancer

(HERCEPTIN)
Lapatinib (TYKERB) -can cross the BBB -Used for brain cancers

Valmurafenib -Metastatic melanoma

(Zelboraf) harboring BRAF
mutations
Chemo protocols: Hodgkins disease: ABVD regimen
doxorubicin(Adriamycin), Bleomycin Vinblastine Dacarbazine

Resistance to Chemotherapy
1. Formation of cancer drug inactivating enzymes (alkaline phosphatase for 6MP): 6-Mercaptopurine and 5-Fluorouracil
2. Decrease of binding affinity and drug sensitivity: Etoposide, methotrexate, vincristine, vinblastine
3. Decrease drug accumulation or permeability (by expulsion): Methotrexate, dactinomycin, cyclophosphamide
4. Chemical reactions inactivating chemotherapy (conjugated by glutathione and excreted in feces): Cyclophosphamide, bleomycin, cisplatin
5. Increased nucleic acid repair mechanism: Cisplatin, Cyclophosphamide
6. Reduced activation of pro-drugs: 6-Mercaptopurine, 5-Fluorouracil
7. ***Multidrug resistance:
increased expression of MDR1 gene for P-glycoprotein
overexpression of the multidrug resistance protein 1 (MRP1)

Antifungal
Opportunistic infections: cryptococcosis and aspergillosis
Hospital-associated infections: candidemia
Community-acquired infections: coccidioidomycosis (valley fever), blastomycosis, and histoplasmosis

A. Polyene 1. Amphotericin B -MOA: Binds to ergosterol -IV for serious and life -Dose dependant
Antifungal (Fungicidal) threatening infections -Nephrotoxic
-Gets inserted to membranes and -Severe fungal -Hypokalemia: renal
forms micropores pneumonia, tubular acidosis,
 -cryptococcal severe Mg+ and K+
-For the flu-like symptoms: meningitis wasting
Premedicate patients with -Disseminated -Normochromic
antipyretic, antihistaminic and infections normocytic anemia
antiemetic agents histoplasmosis,
coccidiodomycosis -Infusion dependant
-Distribution: Low penetration reactions (cause
into CSF No BBB crossing -Aspergillus fumigatus, release of
(Given intrathecally) -Candida albicans, prostaglandins)
-Cryptococcus -Flu-like symptoms
-Drug Interactions: synergistic Neoformans, -fever, nausea and
with fluocytosine -Histoplasma vomiting
capsulatum
-Resistance: Decreased ergosterol -Blastomyces
levels and decreased affinity dermatitidis
-Coccidioides immitis
-Fluconazole is often given after -Mucor
an aggressive treatment with
amphotericin B -Rx of resistant
Cryptococcus and
-Not absorbed in the GI thus given candidiasis
intravenously.

2. Nystatin -Used topically for Rx -too toxic for

of candidiasis systemic use

-B. Azole -Ketoconazole - -Block synthesis of ergosterol by -Paracoccidiomycosis

Antifungals Fluconazole inhibiting 14 alpha demethylase -Blastomycosis and
Itraconazole in the fungal P450 complex Histoplasmosis
Clotrimazole - -Inhibition of lanosterol to
Miconazole ergosterol

-Resistance: Decrease
intracellular levels of drugs due to
decreased entrance of the drugs
into the cell
 -Clotrimazole and -given topically -Rx of candida and
Miconazole dermatophytic infections

-Ketoconazole CyP inhibitor in humans thus the -Gynecomastia and

side effects and drug interaction decrease libido
-Menstrual
irregularities

-Kinetics -Fluconazole -good CSF penetration -treatment and

-high water solubility secondary prophylaxis
-high oral bioavailability of cryptococcal
-least effect on enzymes meningitis
-Candidemia
coccidioidomycosis
mucocutaneous
candidiasis
Tenia infections

-Itraconazole -No CSF penetration -Drug of choice for

-Less inhibition of CYP enzymes paracoccidiodomycosis,
chromomycosis
-Absorption increased by food
-Treatment of
dimorphic fungi:
histoplasma,
Blastomycosis,
sporothrix

-Fluconazole & -are available IV

Itraconazole

-Voriconazole -Rx for InVasive -Visual disturbances

aspergillosis

-Active against Candida

species
 -Posaconazole -Prophylaxis of fungal infections -Salvage (last resort)
during chemotherapy for leukemia therapy in invasive
aspergillosis

-Antifungal with 1. Griseofulvin -MOA: Disruption of mitotic
limited indications spindle by interfering with
microtubules
-Given orally and for a long time
because it is fungistatic
-Rx of tinea cruris - Increase effects of
(Jock itch) alcohol (disulfaram-
like action)
-Contraindicated in
intermittent porphyria
-Induces Cyt P450

2. Terbinafine -MOA: inhibits squalene -Rx of onychomycosis -Elevated liver

epoxidase (nail fungal infection) function tests
-It is fungicidal

3. Flucytosine -5 FC Fungal 5FU -Used with amphotericin -Decrease bone

Cytosine deaminase
5FdUMP
inhibiti
on of thymidylate synthetase
leading to decreases thymine
B in severe candidiasis marrow
(when resistant) -Leukopenia,
thrombocytopenia
-GI: severe
enterocolitis, hepatitis

-Cytosine deaminase is not found

in humans

-Echinocandins -capsofungin, -inhibit the synthesis of (1-3) -disseminated and

micafungin glycan mucocutaneous
candidiasis,
prophylaxis of candida
infections
-salvage therapy in pts
with invasive
aspergillosis

-esophageal candidiasis
and invasive
candidiasis
 AntiViral
-Avir: for AIDS
-Ivir: for influenza

-Amantadine 1. Inhibition of viral penetration

-Rimantadine and uncoating

-Acyclovir 2. Inhibition of Viral DNA

-Gancyclovir Polymerase
-Famcyclovir
-Valacyclovir
-Foscarnet 3. Inhibition of Viral DNA &
RNA Polymerase

-Ribavirin 4. Inhibition of viral RNA

polymerase

-Zidovudine 5. Inhibition of Viral Reverse

-Didanosine Transcriptase
-Zalcitabine
-Stavudine
-Lamivudine
-Nevirapine

-Indinavir 6. Inhibition of Viral Aspartate

-Ritonavir Protease
-Saquinavir
-Nelfinavir

-Zanamivir 7. Inhibition of viral

-Oseltamivir neuraminidase
1. Amantadine -Interfere with the attachement, -Influenza A
penetration and uncoating of the -Parkinson's disease -Livedo (bluish
viral particle by inhibiting M2 discoloration of the
(proton pump) skin) reticularis

-Anticholinergic
effects

2. Ribavirin - inhibits viral RNA polymerase -RSV (bronchiolitis -Teratogenic

-inhibits end capping (guanine) of and pneumonia in
viral mRNA children less than 2yrs)

3. Acyclovir -MOA:inhibits viral DNA -Herpes simplex -Neurotoxicity and

polymerase -Varicella zoster Crystalluria
-Activated by phosphorylation by (Shingles)
Viral Thymidilate Kinase

-Resistance: Decrease activity to

viral thymidilate kinase

-**Not effective in CMV

infections

4. Famciclovir & -MOA Similar to Acyclovir -Newly FDA approved

Valacyclovir for Herpes simplex

5. Gancyclovir -MOA: similar to Acyclovir -**Rx of CMV -Leukopenia

-Viral thymidylate kinase in (common in HIV) -thrombocytopenia
Herpes, Phosphotransferase in -Seizure in overdose
CMV -Crystalluria

6. Foscarnet -Inhibits DNA polymerase -Same As Ganciclovir -Nephrotoxicity

-Rx of CMV retinitis in
-Drug interactions: IV AIDS patients
pentamidine + Foscarnet leads to -Not retinal detachment
severe hypocalcemia
 7. Zanamivir and -Inhibits neuraminidases of -Prophylaxis to Reduce - Inhaled Zanamivir
Oseltamivir influenza A & B flu symptoms cause throat irritation
-Nausea & Vomiting

-Drugs used for Rx

of AIDS
-4 Classes of drugs

1. Nucleosides -Phosphorylated to triphosphate

Reverse that inhibit RT (Reverse
Transcriptase Transcriptase)
Inhibitors
-Resistance: Specific point
mutations in the RT gene

A. (AZT) -Zidovudine is the most effective -Bone marrow

treatment for HIV but it is also the suppression:
one with the most adverse effect Neutropenia
-Peripheral
Neuropathy
-Lactic acidosis
(Rare)

B. Didanosine (DDI) -Pancreatitis,

hyperuricemia

C. Zalcitabine (DDC) -Peripheral

Neuropathy
D. Stavudine (D4T) -Peripheral
neuropathy
E. Lamivudine (3TC) -First oral drug for Hepatitis B that -Hep B -GI distress
removes Ag from blood

F. Latest update: -FDA approved for HBV -Not approved for

Adefovir HIV due to renal
toxicity
2. NonNucleoside -Delavirdine -No bone marrow suppression as -Rash
Reverse -Nevirapine NRTI -Liver toxicity
Transcriptase -Efavirenz
Inhibitors -Given only when patients cannot
tolerate NRTI

3. Protease -Inhibit Aspartate protease by -Protease inhibitors

Inhibitors binding to dipeptide are reported to
produce:
-Resistance: Point mutation in the -Abnormal lipid and
pol encoded gene CHO metabolism
-Central adiposity
and insulin
resistance

A. Indinavir -Nephrolithiasis
-Hyperbilirubinemia
-Inhibition of p450

B. Ritonavir -Increase effects of dronabinol -GI distress

and rifampin -Inhibit p450

C. Nelfinavir -GI distress

D. Saquinavir -GI distress

4. Fusion Inhibitors -Enfuvirtide -Inhibits fusion of HIV to CD4

cells

5.Integrase -Raltegravir -used in combination with NRTI

inhibitors and good as proteases drugs

6.CCR5 -Maraviroc
Antagonists
HIV drugs are used in combinations
"Drug cocktails"
HIV cocktail: HAART; Highly Active AntiRetroviral Therapy
 Acquired Immune Deficiency Syndrome (AIDS)
Treatment is based on CD4 cell count

When you start therapy?

1. CD4 < 500 normal 600-1200
2. Viral load (PCR) > 10,000-20,000 normal <400

What's recommended?
2+1
Any 2 Nucleosides inhibitors + 1 Protease inhibitor
2 of (AZT, DDI, 3TC, D4T) + 1 of (Indinavir or Ritonavir)

When you start prophylaxis?

CD4 > 500 = No prophylaxis
**Except PPD +ve with any CD4
people with HIV often die of pneumonia thus you want to prevent tuberculosis

1. if CD4 < 200

a. Pneumocystis carinii pneumonia (PCP) propylaxis
Trimethoprim/sulpha, Dapsone or Pentamidine
**PCP is the number one killer for AIDS
b. Pneumococcal vaccine

2. If CD4 < 100

Toxoplasmosis Prophylaxis
Trimethoprim/Sulpha

3. If CD4 < 75
Mycobacterium Avium Complex (MAC) prophylaxis
Azithromycin, Clarithromycin (MACrolides for MAC)

4. If CD4 < 50
Cytomegalovirus Prophylaxis
Ganciclovir

HIV Transmission
Needle stick: 1:300
 Anal receptive: 1:50-100
Vaginal: M to F: 1:1000, F to M: 1:2000-3000
Pregnant mom to baby: 25%
Pregnant taking AZT: 8%

Clinical Cases of HIV

1. Stuck with a needle of HIV+ve patient?
2 + 1 for 4 weeks
2. Patient had sex one time with an HIV+ve?
2 + 1 for 4 weeks
3. 27y/old female CD4 >500 and PCR <400
Nothing
4. 27 y/old female pregnant CD4 >500 and PCR <200
AZT to prevent transmission
reduce risk from mom to baby: 25% to 8%
5. 27 y/old female pregnant CD4 1 and PCR 700,000
2 + 1, PCP MAC CMV prophylaxis

Drugs Affecting The Blood

(read to slide 15)
-Antiplatelets
1. Antiplatelets
that inhibit
TXA2:

-Aspirin -Irreversibly inhibits COX1 and -Prophylaxis in MI and -Gastric ulcer and
COX2 stroke bleeding
-Antiplatelets (low doses) and
Antiinflammatory

-Dipyridamole -Inhibits platelets aggregation -prevent embolization on

-In high doses inhibits prosthetic valves
phosphodiesterase

-Cilostazol (New) -selective PDE3 inhibitor -FDA approved for Rx

of intermittent
claudication (PAD)
 2. Antiplatelets that -Clopidogrel , Prasugrel -Alternatives to Aspirin in MI and -MI and Stroke -Hemorrhage,
inhibit ADP Ticlopidine stroke. Also used in combination - + Aspirin: prevents leukopenia and TTP,
receptors with aspirin for coronary stent neutropenia and
prevention of coronary stent thrombosis agranulocytosis (with
thrombosis the Ticlo)

3. Antiplatelets that -IV Abciximab -Prevent platelets aggregation by -Acute coronary disease
inhibits IIb/IIIa -Eptifibatide inhibiting fibrinogen from -Angioplasty
receptors -Tirofiban binding to IIb/IIIa receptors -PCI

Anticoagulants -Heparin IV (indirect -the LMWH: associated with less

thrombin inhibitor) hemorrhagic complications
-Warfarin Orally
-Low-Molecular-Weight
Heparin
-Dalteparin, enoxaparin
-Danaparoid: Safer in
hypersensitivity to
Heparin

-Direct Thrombin - Argatroban

Inhibitors:
- Bivalirudin -**Unstable angina
undergoing PTCA
(Angioplasty)

-Heparin -Activates the plasma -Bleeding

antithrombin III by enhancing -Thrombocytopenia
the serine protease activity -Osteoporosis

-Antithrombin III will cause

inactivation of factors: IIa, IXa,
Xa, XIa, XIIa

-Site of action: Circulating blood

 effective in vivo and in vitro

-Safe in Pregnancy: Doesn't

cross the placenta

-Antidote to Heparin: Protamine

sulfate strongly basic : binds
tightly and neutralize its
anticoagulant effect

-Affects PTT thus aPTT

monitors heparin therapy
(intrinsic pathway)

-Warfarin (Refer to -Inhibits the hepatic synthesis of -Bleeding

ppt:24) Vitamin K factors (acts on Vit K - Skin necrosis
reductase): II, VII, IX, and X (appears after 3 to
10 days) (more in
-by blocking gamma people with decrease
carboxylation of clotting factors protein C)
- Purple toe
-Site of action: liver. Only syndrome
effective in vivo (blue-tinged
discoloration of the
-Contraindicated in Pregnancy. plantar surfaces)
Why? Cross the placenta (in 3-8 weeks)
-Teratogenic: Bone
-Sorta decrease protein C too defects (Fetal
thereby disinhibiting intrinsic warfarin syndrome:
pathway thus the skin necrosis abnormal
due to dermal vascular calcification of the
thrombosis bone)

-Antidote to Warfarin:
Vit K1 (Phytonadione)

-Affects PT and INR thus used to

monitor warfarin therapy
(extrinsic pathway)
 -Low therapeutic index
-Enoxaparin -LMWH (MW=4500 daltons) -FDA approved for -Hemorrhage,
-high activity against factor X prevention of DVT thrombocytopenia,
compared to factor II local irritation
-longer t1/2 than heparin -contraindicated in
-Less thrombocytopenic prosthetic heart
-*Doesn't affect PT or PTT valves
why? high risk for
thromboembolism
(2006)

Indications for Anticoagulants

1. Thromboembolic disorders: (DVT, PE and Afib)
2. Non-Stemi, Unstable Angina, undergoing PTCA
Bivalirudin + warfarin

Contraindications
1. Hypersensitivity
2. Underlying coagulation disorder
3. Ulcer disease
4. Severe thrombocytopenia
5. Active bleeding

Adverse reactions
1. Thrombocytopenia [(HIT): 10-14 days after heparin]
2. Pain at site of injection
3. Spinal and epidural hematoma should be avoided in lumbar puncture, regional anesthetic block

Cautions with Anticoagulants

1. Heparin is given only IV or SC
2. Heparin first and then Warfarin for maintenance
3. Monitor heparin by obtaining PTT values
Goal with heparin: PTT >1.5 to 2.5 times normal.
4. Monitor warfarin by obtaining INR values
Goal with Warfarin: INR> 2.5 times normal
Normal PTT: 21-35 seconds
Normal PT 12-15s
 Normal INR: 1

-Fibrinolytics
Mechanism of Action of thrombolytics
whaActivate conversion of plasminogen to plasmin
Plasmin cause lysis of fibrin clot to degradation products
Plasmin is a serine protease and is inhibited by alpha2 antiplasmin

Indications:
Acute MI, Acute PE, DVT, superior vena caval syndrome, ascending thrombophlebitis, Acute Ischemic stroke
Has to be used btw 6hrs of acute MI (STEMI and bundle branch block)
-for ischemic stroke, has to be used within 3hrs

1. Tissue -Alteplase -Recombinant DNA

plasminogen -Reteplase -Clot specific: preferred for acute
Activator (tPA) ischemic stroke
-No Allergy or hypersensitivity
reactions

2. Streptokinase -Streptococci -Non specific -Allergic reactions

(Antigenic) -Decrease circulating fibrinogen and hypotension
and factors V and VIII
-Antibodies may decrease
activity after recent use
-Cannot be used twice in one
patient because it will be
ineffective because of presence of
antibodies against it

3. Anistreplase -Anistreplase -Prodrug, anisoylated

streptokinase
-slowly release streptokinase

4. Urokinase -Urokinase -Human kidney

-Rarely used due to high $$$

What if too much bleeding occur with Fibrinolytics?

 Use antidote to fibrinolytics
Aminocaproic Acid (EACA) we call it systemic hemostatics
- A drug used to stop bleeding during surgery

Topical hemostatic
Used during surgery to limit blood loss
Absorbable gelatin sponge ( Gelfoam)
Absorbable gelatin powder
Microfibrillar collagen hemostat (MCH)
Thrombin

Blood and Blood ComponentsF

Whole Blood: Hemorrhage, hypovolemic shock
Packed red blood cells: transfused if whole blood results in overload
Fresh Frozen plasma: Clotting deficiencies
Plasma exchange (Plasmapheresis): Immune-related disorders
Cryoprecipitate: Von Willebrand factor, VIII, fibrinogen; Hemophilia, Von Willebrand's disease

Antiprotozoal
-Metronidazole 1. Giardiasis: Giardia
Lamblia
Most common water
born disease, Back-
packer's diarrhea
2. Amebiasis:
Entamoeba Histolytica.

3. Trichomoniasis:
Trichomonas vaginalis
Gotta Rx the partner
 -Diloxanide, Iodoquinol -Asymptomatic/non-
and Paramomycin invasive intestinal
(luminal) amebiasis

-Nitazoxanide (New) -Cryptosporium-severe

diarrheas in AIDS
patients and mild in
normal
-Stibogluconate 4. Leishmaniasis:
Leishmania Brasiliensis,
American
mucocutaneous
leishmaniasis

-Nifurtimox 5. Trypanosomiasis:
Trypanosoma cruzi
-American
Trypanosomiasis
(Chagas disease)

-Suramin + Melarsoprol 5., African

trypanosomiasis
(Sleeping sickness)

-Pyrimethamine + Pyri- inhibits DHFR and Sulfa 6. Toxoplasmosis:

Sulfadiazine inhibits DHTS Toxoplasma Gondii

-Trimethoprin- 7. Pneumocystosis:
Sulphamethoxazole Pneumocystis carinii
(TMP-SMX or
Cotrimodazole)
-IV Pentamidine
-Atovaquone

-Malaria
-Chloroquine -inhibits the polymerization of 8. Malaria:
heme caused by plasmodium
 -Plasmodium
Falciparum (No relapses
or reoccurrence)
-Plasmodium Malariae

-Chloroquine + -Primaquine inhibits the dormant 8. Malaria:

Primaquine hepatic stage of malaria -Plasmodium Vivax
-Chloroquine inhibits the -Plasmodium Ovale
erythrocytes stage of malaria
Prophylaxis for chloroquine-sensitive Malaria:
Buzz word: Chloroquine +/- Primaquine
Second line: Pyrimethamine-sulfadoxine, Hydroxychloroquine

Prophylaxis for Chloroquine-Resistant Malaria:

Buzz word: Mefloquine
Second line: Atovaquone-proquanil, Doxycycline (effective against all forms of malaria)

Rx for Chloroquine-Resistant Malaria

Buzz word: Quinine +/- Doxycycline

Rx for Multidrug-Resistant Malaria

Artesenate and Artemether (New)

Adverse effects of -Chloroquine -Has high volume thus deposits in -First sign: Tinitus
antimalatial drugs organs. Pruritis, ocular
(****Look the dysfunction,
tables in ppt) hemolysis
-Avoid in psoriasis

-Mefloquine -Syncope,
extrasystoles.
-Avoid in seizure and
cardiac arrhythmias

-Primaquine -Neutropenia,
hemolysis
-Avoid in pregnancy,
G6PD deficiency.
 -Quinine -Cinchonism, CNS
defects, hemolysis,
black water fever
-Avoid in pregnancy

-Drugs for -Mebendazole, -MOA: Decrease glucose uptake

intestinal Albendazole and microtubular structure
nematodes
(worms)
-Pyrantel pamoate Route of infection:
EAT: Enterobius,
Ascaris, Trichinella

SAND: Strongyloides,
Ancylostoma, Necator

Tissue Nematode -Ivermectin

-Praziquantel -MOA: Increase Ca++ influx -Cestodes (Tapeworms)

& Trematodes (Flukes)

FYI: Thiabendazole: inhibits fumarate reductase

Dibucaine: inhibits Na+ permeability
Piperazine: Inhibits acetylcholine leading to muscle paralysis
-Leprostatic Drugs -Dapsone -Rx of leprosy and
dermatitis herpitiformis
-Thalidomide: -FDA pregnancy category X -FDA approved for Rx -Why? Risk of
-Physicians should alert male and of Erythema nodosum phocomelia (absent
female patients in effective leprosum arms and legs)
methods of birth control

Autonomic Nervous System Drugs

-Glaucoma drugs
1. Direct acting -Carbachol, -Activation of M receptors
Cholinomimetic -Pilocarpine Contraction of ciliary muscle
 Increase flow through the canal of
Schlemm

2. Acetylcholine -Ecothiophate -Increases the outflow

esterase inhibitors

3. Beta Blockers -Betaxolol, -Block NE at ciliary epithelium

- Timolol decrease aqueous humor
formation

4. -Apraclonidine (alpha 2 -Decrease NE release

Sympathomimetic agonist) prejunctional aqueous
humor
-Epinephrine -Increase outflow

5. Carbonic -Acetazolamide, -decrease HCO3 leads to decrease

anhydrase inhibitor -dorzolamide aqueous formation

6. Prostaglandin -Latanoprost -Increase the outflow through the

PGF2 alpha analog meshwork

Cholinergic pharmacology
Muscuranic receptors: M2 found in the heart, M1 GIT glands and M3 everywhere else
Effects of the activation of the receptors:
Eye: Miosis and accommodation
Heart: Bradycardia, decreases HR(SA node) and conduction velocity (AV node) (M2)
Lungs: Bronchospasm and secretion
GIT: Increases motility, secretion (M1), contraction-diarrhea
Bladder: Contraction (detrusor), sphincter relaxation, voiding, urinary incontinency
Sphincters: Relaxation except for the LES (contraction)
Glands: Salivation and secretion and lacrimation
Blood Vessels: Dilation via NO

M1 and M3 via Gq: Increase phospholipase C leading to increase IP3, DAG, Ca++
M2 via Gi: decrease adenylyl cyclase leading to decrease cAMP
Nn and Nm: No 2nd messenger. Activated by opening Na/K channels
-Muscarinic
Agonists (Direct
acting)

1. Acetylcholine -has a short half life. No clinical

use
2. Bethanechol -Rx of ileus (lack of
peristalsis) and urinary
retention
3. Methacholine -Diagnostic of Bronchial
hyperactivity (Methacholine
challenge test for asthma)

4. Pilocarpine -Rx of glaucoma

(topical) and xerostomia
(dryness of the mouth)
-
Acetylcholinesterase
inhibitors (Indirect
acting)
1. Edrophonium -Short acting -Diagnosis of
Myasthenia gravis: used
to diff btw MG and
cholinergic crisis
2. Physostigmine -tertiary amines (enter CNS) -Rx of glaucoma,
-Antidote in overdose
of atropine

3. Neostigmine, -quarternary amines (No CNS) -Rx of Myasthenia

pyridostigmine gravis, ileus, urinary
retention
-Reversal of
nondepolarizing NM
blockers

4. Donepezil, tacrine, -Lipid-soluble (CNS entry) -Rx of Alzheimer's

Rivastigmine, disease
Memantine
 5. Organophosphates -Lipid-soluble, irreversible -Rx of gluacoma
Like Ecothiophate inhibitors
Insecticides Toxicity:
Malathion and Parathion
Biotansformed by insect P450 to form acetylcholine esterase inhibitors
In humans this biotransformation occurs more slowly
Symptoms of acetylcholine esterase inhibitors toxicity:
Parasympathetic EFFECTS + Muscle fasciculations and paralysis (Nicotinic receptors) + CNS stimulation
Rx Buzz word: Atropine and pralidoxime (2-PAM)

-Anticholinergics -Muscarinic receptors antagonists

(parasympatholytics -Used to treat asthma

-ATROPINE -opposite side effects of

(prototype) cholinergics

-Physostigmine used in overdose

-Clinically used 1. Atropine -Block bradycardia during -Antispasmodic, -cardiotoxicity,
Anticholinergics anesthesia antidiarrheal, Rx of convulsions and
cholinergic toxicity coma
2. Tropicamide -mydriasis and cycloplegia -ophthamological
(recovery in 2 hours) (topical)
3. Ipratropium -Rx of asthma and
COPD. No change in
mucus
4. Scopolamine -Rx of motion sickness -sedation and short
(Hyoscine) term memory block
-Hyoscyamine -for abdominal
cramp/spasm
-Oxybutynin -for urinary incontinence

5. Glycopyrrolate -Rx of peptic ulcers,

antispasmodic
6. Benzatropine, -Rx of Parkinson
trihexphenidyl -Rx of antipsychotics
induced
extrapyramidal effects.
-Nicotinic blocking -Ganglion -Hexamethonium and -Competitive inhibitors at
agents Blockers Mecamylamine Nicotinic Nn receptors in
autonomic ganglia
-They block both parasympathetic
and sympathetic effects
-***look for the predominant
tone and reverse it (reduce the
predominant autonomic tone)
-Parasympathetic is dominant in
dual innervation:
-Heart, pupil, GI, GU and
sphincters, salivary gland
-Sympathetic is dominant in:
-Blood vessels and sweat
glands

-***Ganglion blockers block

Autonomic reflexes but not
direct actions of muscuranic
agonists

-Neuromuscular -Block acetylcholine at the

Blockers (Skeletal nicotinic receptors of the skeletal
muscle relaxants) muscles
-Muscle relaxation in anesthesia
-Endotracheal intubation

1. Non depolarizing -Nicotinic receptors antagonists

(Competitive) A -Competitive means can be
reversed by increasing
Acetylcholine
-MOA: Block acetylcholine
causing paralysis of eyes and face
then progress to the limbs and
respiratory muscles
-No effect on cardiac or smooth
muscles or consciousness (CNS)
 -Antidote: Neostigmine; An
acetylcholine esterase inhibitor

- D-Tubocurarine -the prototype

- Pancuronium

- Atracurium -Rapid recovery -Laudanosine can

-Safe in hepatic and renal cause seizures
impairment
-Spontaneous inactivation to
Lausanosine
-Mivacurium -very short duration of action
-metabolized by plasma
pseudocholine esterase
2. Depolarizing -Succinylcholine -Nicotinic Receptors Agonist -Hyperkalemia
(Non competitive) -Non Competitive means cannot -Malignant
be reversed by giving hyperthermia: Rare
acetylcholine but life threatening
-MOA in 2 phases: increase in
-Phase I: fasciculation which gets temperature as much
worse if neostigmine is given as 1.8 F every 5
Phase II: Desensitization minutes (highest
With adding Succinylcholine, the reported 109.4 F) +
membrane is desensitized muscle rigidity,
becomes unresponsive to hyperthermia,
Acetylcholine for some time hypertension,
acidosis, and
-Succinylcholine is metabolized hyperkalemia
by plasma pseudocholine
esterase Cause:
and has a short duration of action Pharmacogenetics =
drug + genetic
-There is NO antidote so careful
administration is essential -Reported with
succinylcholine and
d-tubocurarine
 -Treat Malignant hyperthermia Also with
with Dantrolene inhalational
anesthetics

-Rx: Dantrolene

-Spasmolytics -Skeletal muscle relaxants that act

(Centrally acting in the CNS, the spinal cord
Skeletal Muscle or directly on the muscle itself
Relaxants)
1. Benzodiazepines -BZ potentiates GABA actions at
GABAa receptors
-They reduce the tone of spinal
motorneurons

2. Baclofen (not -Direct agonist at GABAb

addictive) receptors in the spinal cord
-As good as diazepam with less
sedation

3. Dantrolene -Acts directly on the skeletal -Malignant

muscle to decrease contractility hyperthermia (due to
-How? By blocking Ca++ release excessive calcium
from the sarcoplasmic reticulum release)

Adrenergic Pharmacology
Refer to ppt for some information
3. NE metabolism (Termination of action)
a. Uptake through NE transporter system
b. activation of alpha 2 receptors inhibit release of NE
c. MAO metabolizes NE at prejunctional levels.
2 Forms of MAO:
MAO type A: Buzz word: metabolizes NE, 5HT, and tyramine
e.g.: Phenelzine and tranylcypromine (inhibitors) - Rx of depression
MAO type B: Buzz word: metabolizes Dopamine
e.g.: Selegiline (inhibitors)- Rx of Parkinson's disease
d. Catechol-O-Methyl transferase (COMT) metabolizes NE postjunctional at target cells
 Buzz word on drugs affecting NE:
1. Interference with Synthesis: methyl-p-tyrosine
2. Displacement of Mobile Pool (indirect acting sympathomimetic): Amphetamine and ephedrine
3. Blockade of Reuptake of NE (indirect acting sympathomimetic): Cocaine and Tricyclic antidepressants
4. MAO inhibitors: inhibit metabolism of NE; Phenelzine, Tranylcypromine and Selegiline
5. Blockade of granular uptake: Reserpine used in Hypertension
6. Blockade of release from granules: Guanethedine used in Hypertension
7. Presynaptic alpha 2 agonists: Clonidine, methyldopa: used in Hypertension

Adrenergic Receptors (Refer to Kaplan Notes)

Alpha 1: Blood vessels (vasoconstriction), eyes and male sex organs (ejaculation)
Alpha 2: decrease sympathetic outflow
B1: Heart
B2: Bronchioles, Blood vessels (vasodilation), Uterus (relaxation)-tocolytics
D1: Peripheral; Renal (Vasodilation)

Insulin is stimulated by B2 and inhibited by alpha 2

Renin is stimulated by B1 and inhibited by alpha 1

Beta receptors are more sensitive to stimulation than alpha receptors

What happens to a drug that stimulate both alpha and beta?
At low doses Beta predominates
At high doses alpha predominates
Example: Epinephrine

G-Proteins and adrenergic receptors

Alpha1 via Gq: Increase phospholipase C leading to increase IP3, DAG, Ca++
Alpha2 via Gi: inhibits adenylyl cyclase leading to decreased cAMP
B1, B2, D1 via Gs: stimulates adenylyl cyclase leading to increased cAMP

-Alpha 1 Agonists 1. Phenylephrine - Nasal Decongestant -Nasal congestion

- Mydriasis without cycloplegia
(ophthalmologic use)

2. Methoxamine -Used for PAT

(paroxymal atrial
 tachycardia) bcos of
reflex bradycardia
-Alpha 2 Agonists -Decrease sympathetic

1. Clonidine -Central alpha 2 effects cause -Rx of mild to moderate -Rebound

decrease in BP hypertension "overshoot"
hypertension when
discontinued

2. Alpha-methyl dopa -a prodrug: metabolized into the

active form
-B Agonists -B1: Increase HR, SV, CO
-B2: Vasodilator: decrease TPR

1. Dobutamine -B1>B2 -Rx of acute

decompensated CHF

2. Isoproterenol -B1 = B2 -Rx of bronchospasm, -Flushing,

heart block and arrhythmias, angina
bradycardia

3. Selective B2
agonists

a. Albuterol -Rx of acute asthma

b. Metaproterenol -Bronchodilator
c. Salmetrol -long acting bronchodilator -(Asthma prophylaxis)

d. Terbutaline -Bronchodilator and Tocolytics -Premature uterine

-e. Ritodrine: Tocolytics: prevent contraction
premature labor (calcium channel
blockers are alternatives

****REFER TO PPT #11 and 12 (ANS 3ppt)

-Indirect acting 1. Tyramine -hypertensive crisis
agonists with MAO
inhibitors
 2. Amphetamine -CNS effects include release of -Clinical use: ADHD,
(Methylphenidate) both NE and DA, 5HT Weight loss, and
Narcolepsy

3. Ephedrine -decongestant -Cold Medication

4. Cocaine -Block reuptake of NE, DA, and
5HT
-Block Na++ channels and used as
Local anesthetic

5.Dopamine -Dose dependant

-Low dose (D1): Increase RBF
and GFR
-Medium dose (D1, B1): increase
CO
-Large dose (B1 and alpha 1):
Vasoconstriction

Adrenergic -Alpha Blockers 1. Phentolamine -Blocks alpha 1, alpha 2

Antagonists -Competitive (reversible)
-alpha 1 blokade leads to decrease
TPR BP Reflex
Tachycardia

-2. Phenoxybenzamine -Blocks alpha 1, alpha 2 -Short term use (drug of -reflex tachycardia,
-non competitive (irreversible) choice) in miosis, inhibition of
-makes covalent bond with alpha 1 pheochromocytoma ejaculation
receptors

-Selective alpha 1 -Prazocin - Doxazocin -Less reflex tachycardia because -Rx of Hypertension and -Elderly get syncope
blockers Terazocin (not used of NE feedback by alpha 2 is BPH
much anymore) intact

-Tamsulosin -Selective alpha 1 blocker -Only for BPH

 -Alpha 2 blockers: -Yohimbine -Rx of postural
hypotension and
impotence
-Mirtazapine - Rx of depression +
anorexia
-Beta blockers -Drugs ending in "olol"

-Propranolol -is the first beta blocker and is non -Increase LDL and
selective TGs
3. CNS depression (cross BBB)

-Acebutolol - 1. Cardio-selective (B1

Metoprolol - Atenolol blockade)

-Acebutolol - Pindolol 2. ISA (Intrinsic Symphathetic

Activity)
-They are partial agonists
producing less bradycardia

-Atenolol - Nadolol 4. No CNS entry:

-CarvedIlol - LabetAlol 5. Combined alpha and beta

blockers

***Refer to slide #17 ANS 3

Cardio and Renal Pharmacology

Antihypertensive drugs
(Ppt1 Slides #1-#14)

1. Diuretics

1. Thiazides -Chlorothiazide - Inhibit Na/Cl cotransport in the -Hyponatremia,

diuretics -Hydrochlorothiazide DCT hypokalemia,
-Chlorthalidone -Increase excretion: Na+, K+, Cl-, hypomagnesia,
-Indapamide Mg++, HCO3 Metabolic Alkalosis
 -Metolazone -decrease excretion: Ca++, uric (because k+ and H+
acid kinda move
-Crossallergy with sulfa drugs together)
-Drug interaction with Digoxin Hypercalcemia,
(electrolyte inbalance) hyperuricemia
-Avoid in patients with DM
-HyperGLUC:
glycemia, lipidemia,
Uricemia and
calcemia

-Increase plasma
cholesterol and TGs
(except indapamide)

2. Loop Diuretics -Furosemide -Inhibit the Na+/K+ dichloride -Indicated for -Hyponatremia,
-Bumetanide (2Cl-) cotransport system hyperalcemia (myeloid hypokalemia,
-Torsemide -Increase excretion: Na+, K+, leukemia) hypomagnesia,
-Ethacrynic acid Mg++, Cl, HCO3, Ca++ Metabolic alkalosis,
-Crossallergy to sulfa drugs Hypocalcemia
EXCEPT for Ethacrynic acid -Ototoxicity (EA
-loop diuretic + Antibiotic >furo)
(aminoglycosides): Increased
risk for Ototoxicity

3. Osmotic -Mannitol -Increase the osmotic pressure in -Rx of Increase -Acute hypovolemia
Diuretics -Urea the proximal tubule leading to intracranial and
inhibition of reabsorption of water intraocular pressure
and electrolytes -Acute renal failure

4. Carbonic -Acetazolamide -increase excretion of Na+, K+, -Rx of Glaucoma -Hyperchloremic

anhydrase -Dorzolamide and HCO3 -Rx of overdose of metabolic acidosis,
inhibitors acidic drugs hypokalemia, renal
-Metabolic alkalosis stones, sulfonamide
-Acute Mountain hypersensitivity,
sickness (the pul. edema paresthesia
and the resp. alkalosis
that ensues)
 -ACIDazolamide
causes ACIDosis
5. K+ Sparing -Spironolactone and -K+ STAys: Act on the Collecting -Spironolactone + ACE -Hyperkalemia,
Diuretics eplerenone (Aldosterone duct inhibitors increased metabolic acidosis
Antagonist) -S is a competitive inhibitor of survival in heart -decrease libido
aldosterone failure (spironolactone)-
-Rx of Hirsutism breast enlargement

-Triamterene -They block Na+ channels -Amiloride used for Rx -Nephrolithiasis

-Amiloride of Nephrogenic DI (triamterene)
caused by lithium - Hyperkalemia,
metabolic acidosis
2. ACE inhibitors -Angiotensin Converting Enzyme -Rx Hypertension in DM -Dry cough because
Inhibitors of the lack of
MOA:ppt 24 inactivation of
-Drugs that end in pril bradykinin
-Hyperkalemia
-Why? Diabetic patients tend to -Acute Renal Failure
get nephropathy and ACE in renal artery
inhibitors slow down renal stenosis
damage
-ACE inhibitors are
contraindicated in
2nd and 3rd
trimester (Class D)
fetopathy

-Oligohydramnios,
IUGR,
hypocalvaria, Renal
failure.
- Captopril -Captopril
- Lisinopril associated with
angioedema
- Enalapril - IV for hypertensive
emergency
 - Fosinopril -no dose adjustment in renal
failure

3. ARB -Losartan -Drugs ending in ".sartan" -Acute renal failure

(Angiotensin II -Valsartan -No dry cough in renal artery
Receptors Blockers) -Candesartan -They block angiotensin II stenosis (same as that
-Irbesartan receptor (type 1) reduce of ACEIs)
vasoconstriction -Contraindicated in
Pregnancy

4. BB (Beta -drugs ending in ".olol" 1. Coronary artery -Contraindications:

blockers) -White respond better than
African American
-Safe in pregnancy
disease Asthma, heart block
2. Tachyarrhythmia -Bronchospasm,
3. Migraine headaches fatigue, glucose
4. Anxiety (stage fright) intolerance
-Cautions:
1. Mask signs of
hypoglycemia (in
diabetics)
2. Abrupt withdrawal
can cause
hypertension
Due to Upregulation
of # of receptors

-Propranolol -The prototype -tachycardia in

thyrotoxicosis
-Stage fright

-Atenolol, Pindolol

-Labetalol -Hypertensive
emergency/crisis
(BP>180 and
symptomatic)
-Carvedilol -for compensated heart
failure
5. CCB (Calcium -Drugs ending in ".dipine" -Angina pectoris,
Channel Blockers) except for Diltiazem and peripheral vascular
Verapamil disease,
-block the L-type Ca++ channels tachyarrhythmia.
-African American and elderly
respond well

-Amlodipine -Amlodipine is most commonly -Reflex tachycardia

-Nifedipine (Prototype) prescribed flushing, ankle edema
-Isradipine -Dihydropyridines (vascular
tissues)

-Diltiazem -Nonhydropyridines (heart) -decrease cardiac

-Verapamil contractility
-possible AV block

-Nimodipine -is approved for acute

subarachnoid
hemorrhage - prevents
post hgic vasospasm

6. Alpha 2 agonist -Clonidine -patches cause less side effects -Mild to moderate -Edema, rebound
Hypertension hypertension after
sudden withdrawal
-Alpha methyl dopa ****Safe in pregnancy and renal -Mild to moderate -+ve Coombs test:
dysfunction hypertension hemolytic anemia
(due to hapten
formation)
7. Adrenergic -Guanethidine -Binds to storage vesicles and -Fluid retention
Neurononal inhibit release of NE -Contraindicated
Blocking Drugs with
Antidepressants

-Reserpine -Binds to storage vesicles and -Psychotic depression

destroys them and suicide
-It causes depletion of NE, DA
and serotonin
8. Alpha blockers -Prazocin - Doxazocin - -Lower blood pressure -First dose
Terazocin and used for BPH "Syncope",
orthostatic
hypotension
-Incontinence in
women when
coughing, sneezing or
trying to lift a weight
Why? alpha blockade
effect on the bladder
and sphincter

9. Direct acting -Hydralazine -Relaxes arteriolar smooth muscle -moderate to severe -Reflex tachycardia,
Vasodilators -Safe in Pregnancy hypertension palpitations (use a
BB)
-SLE like syndrome
and hemolytic
anemia
-***Sodium -Dilate both resistance and -Drug of choice for Rx -accumulation of
Nitroprusside capacitance vessels of hypertensive crisis cyanide and
-Administer with nitrites and (IV) thiocyanate
thiosulfate to chelate CN-
-Minoxidil -A prodrug which after sulfation -Rogaine (Topically) for -Hypertrichosis
appears to activate ATP dpt K+ baldness (excessive hair
channels growth)

-Diazoxide -Activates ATP dpt K+ -IV Rx of hypertensive -Hyperglycemia

channels causing relaxation of
smooth muscle
emergencies (decrease insulin
-Used to Rx insulinoma release from B cells)
- Sulfonylureas (oral -Hypertrichosis
hypoglycemic): work on
the same type of K+
channel but close them

Antiarrhythmic Drugs
(ppt 2 Slide #1 - #7)
4 Classes
 Class 1: Na+ Channels Blockers
Class 2: Beta Blockers
Class 3: K+ Channels Blockers
Class 4: Calcium Channels Blockers
-Class 1 and 3 are the BIG GUNS: for life threatening arrhythmia

Class 1: Na+
Channel Blockers

-Class 1A -Block Activated Na+ Channel

- Vmax, and prolong APD
(Action Potential Duration)

-Quinidine - APD & ERP in atria, -GI: NVD (Nausea,

ventricles and purkinje fibers of vomiting and
His diarrhea)
-Anticholinergic effect: Increase -CV: increase QT
heart rate and conduction interval (Torsades de
-Alpha Blocking effect: pointes)
vasodilation & reflex tachycardia -Thrombocytopenia
-Cinchonism:
-Drugs Interactions: tinnitus, loss of
-Antacids increase quinidine hearing, GI upset,
absorption diplopia
-Quinidine displaces digoxin
from tissue binding sites

-Procainamide -Less anticholinergic -Agranulocytosis

-No alpha blocking activity -SLE like syndrome
-Metabolized by N - with slow
acetyltransferase into Active acetylators
metabolite NAPA (N-Acetyl
Procainamide)

-Disopyramide -The most anticholinergic

 -Class 1B -Inactivated Na+ Channel -Preference for
-No effect on Vmax, but ischemic tissues
decrease APD (partially depolarized)
-Increase threshold of V fib
-Slow conduction in hypoxic and
ischemic tissue

-Lidocaine -Least Cardiotoxic of the -Rx VTac after MI, or

conventional anti-arrhythmic digitalis toxicity
drugs
-IV because of first pass
metabolism

-Mexiletine and -Given Orally

Tocainide
-Class 1C -Both Na+ Channels
-Marked decrease of Vmax, but
no effect on APD

-Flecainide and -Pro-Arrhythmic

Moricizine effects: can worsen
existing arrhythmia
-Increase in sudden
death and cardiac
arrest after MI

Class 2: Beta -Propranolol, - SA & AV nodal conduction -Used as propylaxis

Blockers Acebutolol, Esmolol -Decrease the slope of phase 4 Post-MI and to Rx SVTs
depolarization

-Esmolol -has a t1/2 of 8 minutes -Given IV for

emergency Rx of SVT

Class 3: K+ Channel -Bretylium, - APD & ERP

Blockers Amiodarone, Sotalol -Prolong Repolarization and
lengthen phase 2
 -Bretylium -Rx of life threatening V -Releases
arrhythmia not catecholamines and
controlled by IA or IB may worsen or cause
arrhythmia
-Cause orthostatic
hypotension and
reflex tachycardia

-Amiodarone -Mimics class 1, 2, 3, and 4 -Severe Nausea and

-Binds to Na+ channel vomiting
(Inactivated) -Pulmonary fibrosis
-Blocks k+ & Ca++ Channels -Hepatotoxicity
-Non-competitive inhibitor of B -Smurf skin (Bluish
receptors pigmentation of skin)
-t1/2: 25-60 days -Thyroid
-Amiodarone: is #1 drug used for dysfunction
pharmacological cardioversion Hypothyroidism 5%
- #2 Dofetilide & hyperthyroidism
- #3 Ibutilide 2%
-May cause torsades
de pointes

-Dronaderone -like amiodarone but less effective

and has less side effect
-Sotalol -Beta blockers & K+ channel -Rx of life threatening V -Headache,
blocker Arrhythmia depression and
-Class 2: Decrease heart rate and impotence
AV conduction -Careful with
-Class 3: prolongs APD & ERP asthmatic

Class 4: Calcium -Verapamil & Diltiazem - SA & AV nodal conduction and -Rx of PSVT due to AV -Contraindicated in
channel Blockers slope of phase 4 nodal re-entry atrial tachycardia due
to WPW (tissue
problem)

Unclassified -Adenosine -Vasodilation causing bradycardia -Rx of PSVT

Reflex tachycardia
 Antagonist: Theophylline

Torsades de pointes
Management
Discontinue the drug prolonging the QT
K+ channel blockers, thioridazine, TCAs
Correct hypokalemia & Hypomagnesemia
Magnesium is indicated

Drugs for Coronary Artery Disease

(PPT #3 1-5)
ANTIANGINAL 1. Nitrates 1. Increase blood/oxygen supply
DRUGS 2. Beta Blockers By decreasing vasospasm
2. Decrease blood/oxygen demand
By decreasing TPR, CO, or both

1. Nitrates -Activation of Nitric Oxide (NO) -Used in Cyanide -Headache, flushing,

-eNOS (Endothelial nitric oxide poisoning as antidote: and syncope
synthase) can be activated by: Amyl nitrate -Reflex tachycardia
Acetylcholine, histamine, - Cyanide ions inhibit and edema
bradykinin, and serotonin complex IV of the -Tachyphylaxis that
NO electron transport chain require rest of >12
GTP cGMP relaxation -Amyl nitrate forms hours
Guanylyl cyclase methemoglobin that -
-How? Dephosphorylation of binds to CN- ions to Methemoglobinemia
myosin light-chain prevention form was reported with
of its interaction with actin cyanomethemoglobin amyl nitrate
relaxation vasodilation - antidote: Methylene
Cyanomethemoglobin is blue
-How Nitrates decrease cardiac reconverted to -
oxygen demand? Dilation of large methemoglobin by Rx Cyanomethemoglobi
veins lead to decrease preload and with Na+ thiosulfate n antidote: Na+
decrease cardiac work (decrease thiocyanate ion (less thiosulfate
oxygen demand) toxic)

- How Nitrates increase cardiac -Drug Interactions:

oxygen supply? At high doses, -Always ask the patient
nitrates cause arteriolar dilation at the ER if they are
 (Aorta) causing decrease of taking Sildenafil
afterload (increase oxygen supply) (Viagra). It is a deadly
combination due to
- Other actions of Nitrates: severe hypotension
1. Improve collateral blood flow
2. Decrease coronary vasospasm
3. Inhibit platelets aggregation

1. Nitroglycerin -Sublingual, PO, transdermal, and

IV forms

2. Isosorbide PO, and extended release

2. Beta Blockers -Atenolol -Act directly on the heart. No -Cautions with

direct effect on Blood vessels Prinzmetal's
- Decrease force of contraction, Angina: Beta
HR and CO decrease in O2 blockers keep alpha1
demand open causing
vasospasm

-Carvedilol -The only Beta blocker that has

shown similar effect to Nitrate
Why? it is an alpha and beta
blocker

3. Ca++ Channel -Dihydroperidine:

Blockers Amlodipine
-Nonhydroperidine:
Verapamil and
Diltiazem

-Bepridil -An FDA approved CCB for -If Bepridil blocks

angina Why? it dilates coronary K+ channel???
arteries -May cause
-Blocks Na+ and K+ channels Torsades De pointes

Myocardial Infarction
Goal of Treatment
 Relieve chest pain, Stabilize the heart rhythm, Reduce cardiac workload
ER Management of Myocardial Infarction
1. Oxygen
2. Morphine for pain and anxiety
3. Nitroglycerin sublingually
4. Aspirin to chew on (prevents platelets aggregation)
5. Beta blockers to decrease cardiac rhythm
6. ACE inhibitors to reduce preload and afterload
7. Buzz word: Thrombolytics to dissolve blood clots

Heart Failure
Goal of treatment of Heart failure
1. Drugs that increase contractility
2. Drugs that decrease preload
3. Drugs that decrease afterload
4. Drugs that reduce edema

1. Drugs that -Digitalis -Also known as Cardiac -CV: PVCs,

increase glycosides tachyarrhythmias,
contractility -Digitalis inhibit Na+/K+ AV block, sinus
ATPase pump bradycardia
1. Direct effect: Inhibits Na+/K+ -GI: ANV & diarrhea
ATPase pump leading to increase -CNS: Headache,
intracellular Na+ increased visual halos,
Ca++ increased force of hallucinations
contraction -EKG: Decrease QT
-AV node: decrease conduction interval, T wave
velocity inversion
-Ventricles and Purkinje:
decrease APD & ERP -Hypokalemia
2. Indirect effect:
a. Cholinergic effect through -Drugs causing
vagal stimulation digitalis toxicity
Atria: decrease SA nodal rate Diuretics - Quinidine
AV node: Increase ERP, decrease Verapamil -
velocity NSAIDs -
Ventricles and purkinje: no Amiodarone -
effect erythromycin
 b. sympathomimetic effect (B1)
Atria: increase SA rate
AV node: Decrease refractory
period
Ventricles and Purkinje:
Increase conduction velocity
abnormal automaticity

-Antidote: DigiFab (digibind)

(DIGOXIN) -Most commonly prescribed

digitalis
-+ve inotropic
--ve chronotropic
-t1/2: 20-40 hours
- Clearance: Renal
-Protein binding: 25%
- Vd: 6.3L/kg
-Digoxin should be avoided in
WPW (does not act on the
accessory pathway [bundle of
kent])

-Bipyridines: Amrinone -drugs ending in "rinone" -short term Rx of HF -Hypotension

- Inamrinone - Milrinone - inhibit PDE causing increase -Inamrinone:
cAMP positive inotropy Thrombocytopenia
- inhibition of PDE also cause -Milrinone:
increase in cGMP vasodilation Decreases survival in
HF
ER treatment of Heart Failure
1. Sympathomimetic: Dobutamine
indicated in acute heart failure to increase contractility
2. Diuretics: Loop and thiazides
FReduction of congestion and edema in acute failure
Spironolactone reduced mortality when combined with ACE inhibitors
3. ACE inhibitors: Lisinopril
4. CCBs: Amlodipine and Verapamil
5. BB: Carvedilol has proven to decrease mortality
 Metoprolol survival benefits in latest study
6. Nesiritide (New): Recombinant B type natriuretic peptide
rh BNP increase cGMP leading to smooth muscle relaxation
Indicated to relieve dyspnea at rest in severe CHF

Antihyperlipidemic Drugs
Cholesterol lowering drugs
(PPT #4 16-17)
1. Statin -Atorvastatin -(drugs ending in "Statin") -Hyperlipoproteinemia -Myopathy: From
Simvastatin, Pravastatin -(HMG-CoA reductase -Hypercholesterolemia muscle ache,
Inhibitors) -Hypertriglyceridemia myalgia, myositis to
-(3-Hydroxy-3-MethylGlutaryl Statin are used for 2ry rhabdomyolysis
CoA reductase inhibitors) prevention of heart (break down of
-Statin inhibit the rate limiting disease skeletal muscle)
step in cholesterol biosynthesis renal failure
-Statin reduce LDL, cholesterol,
and triglycerides
-Statin increase HDL (Good
Cholesterol)
-Statin increase NO and decrease
mRNA for endothelin-1
vasodilation

2. Bile acid -Cholestyramine -Bind bile acids in the GI form
Sequestrants Cholestipol an insoluble complex that is
excreted in the feces. So
cholesterol is used to make more
bile acid thus lowering LDL (bad
cholesterol)
-Special indication for -Not used in
Cholestyramine : Rx of hypertriglyceridemia
pruritis due to biliary because they increase
obstruction. How? In VLDL and TG
biliary obstruction the -Constipation
liver can't eliminate bile -Malabsorption of Fat
soluble vitamins
(ADEK)
-Malabsorption of
digoxin, thiazide, and
warfarin

3. Nicotinic Acid -Inhibits VLDL synthesis. -Flushing and

Activates lipoprotein lipase pruritis,
hyperuricemia
 4. Gemfibrozil & -PPAR alpha agonist -Flu-like muscle
Clofibrate (peroxisome proliferator activating aches, gallstones
receptor)
-Activates lipoprotein lipase.
Decrease VLDL, TG, and LDL

5. Probucol -Increases level of cholesterol -Increase QT interval,

ester transport protein arthralgia

6. Ezetimibe (Vytorin) -Inhibits cholesterol absorption in -Sinusitis and

the small intestine pharyngitis
-Most effective when used with a
statin drug
Simvastatin + Ezetimibe

Gastrointestinal Dysfunction Drugs

Peptic Ulcer Drugs 1.Histamine (H2) -cimetidine, ranitidine -Block H2 receptors -Duodenal ulcer -CNS effects :
antagonists (Zantac), famotidine -Reduce basal acid output - -Gastric ulcer confusion, agitation
inhibit 6070% of total 24-hour -Stress ulcers hallucinations,
acid secretion -GERD -Antiandrogenic
-More effective at inhibiting action: Cimetidine
nocturnal and fasting acid (prevents the binding
secretion of DHT to its
-Partially inhibits vegal and receptor and can
gastrin stimulation of ECL cells increase prolactin
(gastric mast cells) level thus
impotence/gynacom
astia in males and
galactorrhea in
females)
-Elevation of liver
enzymes
-Drug interactions:
Cimetide (inhibits
Cyt P450)
warfarin and
phenytoin toxicity
2.Proton pump -omeprazole (Prilosec), -the ..prazole drugs -Peptic ulcer -reduction in oral
inhibitors (PPIs) pantoprazole (Protonix), -Irreversibly inhibits H+ K+ -H Pylori associated cyanocobalamin
rabeprazole (Aciphex), ATPase Ulcers: direct absorption
esomeprozazole -inhibit 9098% of 24-hour acid antimicrobial properties megaloblastic anemia
(Nexium) secretion and by raising -hypergastrinemia
-inhibit both fasting and meal- intragastric pH due to disinhibition
stimulated secretion -NSAID associated of gastrin
Ulcers atrophic gastritis
-Prevention of -osteoporosis due to
rebleeding from peptic decreased
ulcers reabsorption of
-GERD: most effective calcium
agents -respiratory and
-Prevention of stress enteric infections
related mucosal bleeding
- omeprazole (FDA
approved)
-Zollinger-Ellison
syndrome

3.Prostaglandin -Misoprostol (Cytotec) -(PGE1) analog -prevention of NSAID -diarrhea, abdominal

analogs -Promote mucus & HCO3 associated ulcers cramps, uterine
secretion -Medically abortificient bleeding
-Increase mucosal blood flow and
modest acid inhibition

4.Antacids: -Na HCO3 (Alka- -Neutralize gastic acid -intermittent heartburn - Drug interactions
Selzter), Al(OH)3 , -Raise the antral pH > 4 and dyspepsia (form complexes with
Mg(OH)2 , Ca CO3 -may also promote mucosal -GERD tetracyclines and
(Tums) defense mechanisms fluoroquinolones
and makes them
unabsorpable)

-Sodium bicarbonate -Belching and gastric

(Na HCO3) distention, metabolic
alkalosis, fluid
retention
 -Calcium carbonate: Ca -Gastric distention
CO3 (Tums) and belching
-can increase HCl
production,
constipation

-magnesium hydroxide -Diarrhea

(Mg(OH)2 )
-Aluminum hydroxide - constipation,
(Al(OH)3) hypophosphatemia,
osteomalacia

-antacid - Maalox , Mylanta - Mg & Al hydroxide

combination - Al salts Ca salts

5.Ulcer protectives: -sucralfate, bismuth

subcitrate (Pepto
Bismol)

-Sucralfate: Polymerizes at pH < 5 -prevention of stress-

-Forms protective gel like coating related bleeding
of ulcer beds -Increases healing and
-Augments PG synthesis decreases ulcer
recurrence
-Colloidal Bismuth -Increased production of mucus -used as part of triple -blackening of tongue
compounds: bismuth and HCO3 therapy (BMT regimen) -Diarrhea
subsalicylate -Forms a complex which coats -nonspecific treatment of
ulcers dyspepsia and acute
-Detaches and kills H.pylori diarrhea, travelers
diarrhea

***H-Pylori Triple therapy: Drugs: amoxicillin, clarithromycin, tetracycline and metronidazole + PPIs (2 antibiotics +1PPI): triple therapy
(metronidazole if allergic to penicillin)

Antiemetics -Anticholinergics -Hyoscine - MOA: block cholinergic -Rx of motion sickness -high incidence of
(Scopalamine) pathway - vestibular apparatus (kinetosis) anticholinergic
-Dicyclomine effects
-H1 -Promethazine -Motion sickness, chemo -highly sedative
Antihistaminics (Phenargan) induced vomiting
-Diphenhydramine
(Benadryl)
-Cyclizine
-Cinnarazine

-5HT3 antagonists -Ondansetron (Zofran) -the ..setron drugs -chemotherapy-induced

-Granisetron -Central: 5-HT3-receptor nausea and vomiting
-Dolasetron blockade in the vomiting center -postoperative and post-
and CTZ (chemoreceptor trigger radiation nausea and
zone) vomiting
- Peripheral: blockade of 5-HT3 -More prophylactic than
receptors on extrinsic intestinal curative (30mins before
vagal and spinal afferent nerves chemotherapy)
-Dopamine -Phenothiazines: -Block D2 in the CTZ - postoperative nausea And Prokinetics:
antagonists prochlorperazine, and vomiting -Extrapyramidal
promethazine -drug induced vomiting effects (dystonias,
- Butyrophenones: -disease induced akathisia,
droperidol vomiting parkinsonian
features)
-Galactorrhea,
gynecomastia,
impotence, and
menstrual disorders
(tuberoinfundibular
pathway
disruption).
-Prokinetics -Metoclopramide - Centrally: inhibit dopamine - Prevention of nausea
(D2) in the CTZ and vomiting
-Peripherally: inhibit dopamine -gastro esophageal
(D2) reverse the motility of reflux disease (GERD)-
the vomiting reflex Increase tightens the LES
lower esophageal sphincter -Impaired gastric
pressure, and enhance gastric emptying - delayed
emptying (increase downward gastric emptying due to
peristalsis and closes the lower postsurgical disorders
esophageal sphincter) (vagotomy, antrectomy)
 and diabetic
gastroparesis.
-nonulcer dyspepsia
-Corticosteroids -Dexamethasone
(IV) -Methylprednisolone

-Neurokinin -Aprepitant -NK1 receptor blocker - used in combination

receptor antagonists with 5-HT3-receptor
antagonists and
corticosteroids for the
prevention of acute and
delayed nausea and
vomiting from highly
emetogenic
chemotherapeutic
regimens
-CANNABINOIDS -Dronabinol -tetrahydrocanabinol (THC) - used in combination
-Nabilone with phenothiazines in
chemotherapy. Also as
appetite stimulant and to
improve weight

Drugs for -Bulk-forming -psyllium

constipation laxatives -methylcellulose
(Laxatives) (overnight)

-Stool surfactant -Docusate (Colace) -Given orally or emema

agents (softeners)

-glycerin suppository - Given suppository

(fleet)
-Osmotic laxative -Magnesium oxide
-Sorbitol

-Stimulant -Aloe -Stimulate peristalsis

laxatives -Senna
(cathartics) -Bisacodyl (Dulcolax)
 -Miscellaneous - magnesium citrate and - purgatives (immediate in action)
sodium phosphate
- Balanced - used for bowel cleansing before
Polyethylene Glycol colonoscopy
(GoLYTELY)
- Lactulose - used to decrease ammonia in -Hepatic encephalopathy
patients (Rifaximin)
- Lactulose converts ammonia to
ammonium which can be
excreted in the urine
Antidiarrheal agents -Opioid agonists - agonists
- Loperamide -does not cross the BBB thus no
risk of addiction
- Diphenoxylate and -Crosses the BBB in high doses
atropine (opioid + Anticholinergic) to
prevent addiction

-Colloidal bismuth -bismuth subsalicylate

compounds

- Bile saltbinding - cholestyramine or - diarrhea caused by

resins colestipol excess fecal bile acids
- Octreotide -somatostatin analog -used in chronic
secretory diarrhea
Drugs used in the -Serotonin 5-HT3- -Alosetron -IBS + Constipation
treatment of receptor only in female patients
irritable bowel antagonists
syndrome (IBS)

Drugs used to treat -Aminosalicylates - 5-ASA bound by an azo (N=N) -Ulcerative colitis and
Inflammatory bond to an inert compound or to Crohn's disease
Bowel Disease another 5-ASA molecule
(IBD) - 5-ASA drugs induce and
maintain remission in ulcerative
colitis
-first-line agents for treatment of
mild to moderate active ulcerative
colitis.
 -Crohn's disease - first-line
therapy for mild to moderate
disease involving the colon or
distal ileum.
-Sulfasalazine - 5-ASA + Sulfapyridine
[trasporter to deliver ASA to the
colon, to prevent destruction in the
upper GIT]
-olsalazine
-balsalazide

-TNF inhibitors -Infiximab -Monoclonal antibody

-Blocks TNF alpha

- Glucocorticoids - prednisone and -moderate to severe

prednisolone active inflammatory
bowel disease
- Hydrocortisone
enemas, foam, or
suppositories
- Budesonide

Bile acid therapy for -Ursodiol -Ursodiol decreases the cholesterol - Ursodiol is used for
gallstones content of bile by reducing hepatic dissolution of small
cholesterol secretion cholesterol gallstones in
patients with
symptomatic gallbladder
disease who refuse
cholecystectomy or who
are poor surgical
candidates

Drugs for Achalasia - Nitrates

cardia -Calcium channel
blockers
-Botulimium toxin