Oral

Topical (Percutaneous)
Routes of Drug Administration Rectal or Vaginal
Pulmonal
Parenteral

Pills (single dose)

Types of Orally Administered Drugs
Percutaneous Drug Administration
Tablets
Coated Tablets (shell)
Matrix Tablets (carrier meshwork)
Capsules (gelatin shell)
Troches/Lozenges
Solutions
Ointment + Lipophilic cream
Paste
Lotion
Gels
Can be single or multilayer, or
contained in a reservoir

Eye Drops
Nose Drops
Other Topicals Pulmonary Formulations
Suppositories

Ampules
Vials
Cartridge Ampules
Parenteral Drug Administration Infusions
Advantage: 100% Absorption,
enters circulation without hepatic
elim, better bioavailability of
hydrophilic drugs
 External Absorption Barriers:
(epithelial layer on skin, lung,
Types of Barriers for Drug intestine—Lipophilic barrier)
Distribution/Absorption Internal Blood-Tissue Barriers:
Cardiac muscle, endocrine glands,
gut, liver, CNS

Passive Diffusion
Active Transport
Drug Distribution Receptor-mediated Endocytosis
[DRUG] IS A FUNCTION OF
ABSORBTION AND
ELIMINATION!

The AUC of the administered drug

divided by the AUC of the
Bioavailability intraveneously administered drug
IV>TD>IM=SC>Rectal>Oral=Inhal

Vd=Amt of drug in the mody/[drug]

R of E: Via kidney (filtration) or
Volume of Distribution liver (metabolism)
Rate of Elimination Usually first order kinetics
3 drugs have zero-order kinetics

Rate of Elim/[Drug]

Rate of Elim= k*Cp*Vd

Clearance K= ln2/T ½

CL= K*Vd
 Convert parent compound into more
Phase I Reactions polar metabolite
Add/unmask functional group:
OH, SH, NH2, COOH, etc
Oxidation, Reduction, hydrolytic
cleavage, Alkylation, Dealkylation,
etc…

Conjugation with endogenous

substrate (increase aq solubility)
Phase II Reactions Conjugation with gucoronide,
sulfate, acetate, amino acid

Require reducing agent and

molecular oxygen
Two enzymes: 1) Flavoprotein,
MFO NADPH-cytochrome c reductase
Mixed Function Oxidases 2) Cytochrome P450 (electron
acceptor); CYP

PPAR ligands, CYP1, CYP2E,

CYP2B
P450 Enzymes Polymorphisms cause changes in
drug metab: CYP2C19, CYP2B,
CYP2D6
Induction of P450
enzymes=metabolize drug
Glucoronidation
Sulfation
Conjugation Reactions Acetylation
Amino acid Conj
Glutathione Conj
Fatty acid Conj
Condensation Reaction

Monoamine Oxidases (MAO)
Therapeutic Index Doesn’t take into account variability
Catalyze oxidative deamination of
endogenous catecholamines
(epinephrine)
Lacated in never terminals and
peripheral tissues
Many drug/food interactions!
(cheese, wine)
Inhib by MAO inhib
Maximum non-toxic dose/Min
effective dose
btw indivs
LD50/ED50

Can be drugs or endogenous ligands

for the receptor
Increasing [agonist] will produce
Agonist increase in biological response
Full:evokes 100% max possible effect
Partial: not 100%

Block or reverse effect of agonist

No effect on their own
Antagonist Competitive, Non-competitive,
inverse agonist (triggers neg
response)

Receptor
Four major drug targets Enzyme
Ion Channel
Transporter

Ca++ as a Second Messenger
Regulates many cellular and phys.
Responses
Gradient btw extracellular and
intracellular (high:low) creates many
opportunities for regulation
Stored in ER and other

Voltage mediated: L, N, T
Ligand gated
Store operated
Ca Channels Sesnsors: Annexins, EF-hand
proteins, Calmodulin, ProponinC
Target of many drugs!

GPCR: transmembrane
Bind GTP and GDP
GAPS, GEFS, RGSs important in
G-Protein-coupled Receptors this regulation
Main Targets: Phospholipase C,
Adenylate cyclase

G-Proteins: Guanine nucleotide

binding proteins
2 groups:
G-Proteins Small GTP binding
Heterotrimeric G proteins

Target of cAMP
Four subunits (2 reg, 2 catalytic)
PKA Phosphorylates transcription factors
ex: CREB
 Heterologous desensitization
(Incoming signal from different
Regulation of Receptors receptor)
Homologous desensitization (only
occurs on receptor which has already
been stimulated)

Lipid soluble ligands that penetrate

cell membrane, Receptors contain
Nuclear Receptors DNA-binding domains
GC, Mineralcorticoids, Retinoids (transcriptional
PPARs activators/suppressors)
Takes longer to act—requires
penetration and protein synth first
Common fatty acid chain+glycerol
backbone+phosphor-residue
PLA2 (reg through Ca++ and phos),
Phospholipids PLC (Beta: Reg through GPCR,
Phospholipases Gamma: EGFR or TCR, activated
through tyrosine phosphorylation

DAG: membrane bound, acts as a

Phospholipases… substrate for PLA2
IP3: Ca++ regulated

Eicosanoids: derivative of
arachadonice acid
Rapidly metab by COX into PG and
Arachidonic Acid Metabolism LTs
st
1 reaction: cyclic ring structure
(COX), 2nd reaction: oxidation
(Peroxidase)
 Vascular tone (relaxation,
constriction)
Function of PGs Platelet agg (Inc and Dec)
Uterus tone (Inc)
Bronchial Muscle (Contriction,
relaxation)
Gastric secretion (Inib), temp/pain
LTC4, D4 and E4 mediate allergic
rxn (SRS-A)
Leukotrienes Mediate anaphylactic shock, 10,000
more postent than histamine
Constricts bronchi, dilates bv
LTB4 strong chemattractant for
macrophage
Divided into CNS and PNS
PNS div into Somatic and
Nervous System Autonomous
Auto: Sypmathetic and
Parasympathetic

Muscarinic Receptors:
Heterotrimeric G protein coupled,
Cholinergic Receptors CNS, gastric mucosa M1
Cardiac=M2, Glandular=M3
Nicotinic Receptors: Ion channel
coupled Muscle type, Ganglion type,
CNS type
Direct Parasympathomimetics:
Affinity for M or N receptors (mimic
Ach)
Cholinomimetics= Inderect Parasympathometics:
Parasympathomimetics Inhibit activity of Achesterase (Ach
increased)
 1. Mimic Input
2. Block Input
To affect Paraympathetic…

To Treat associated diseases…. 3. Promote Parasymp

4. Block Symp

Pilocarpine Muscarinic Parasymp, does not

activate N rec, treates glaucoma
(local! Eyedrops)

Muscarine Muscarine has no therapeutic

application!

Achestease Inhibitors, raise Ach

Carbamate Physiostigmine (topical only)
Neostigmine

Quaternary Alcohols Edrophonium (diagnose Myasthenia

Gravis)

AcCh-ase inhib
Acts as AcCh-ase inhib but active
ingredient unkown
Horny Goat Weed Indirect stimulation of M3 receptor
(vascular), triggers NO
production=vasodilation
Action similar to Viagra (dangerous)

Ogranophosphates AcCh-ase inhibitors (irreversible)

No medical application
Nerve Gasses

Atropine
Hyoscine
Nicotinic Parasympatholytics
Succinocholine/Suxamethonium
Transmitters in the Autonomic
Nervous System
Termination of (Nor)epinephrine
action
Muscarinic Parasympathomimetic
Atropine (antagonist of cholinergic
system): CNS stimulant, before
anesth. Prevent hypersecretion of
bronchial mucus, treats bradycardy..
Hyoscine=CNS depressant,
antiemetic,
Competitive Antagonists: Compete
with AcCh for N rec, prevent
depolarization, reversible
Agonists: Depolarizing blockers,
AcCh mimetics not hydrolyzed by
AcCh-ase, trigger a sustained
depolarization, irreversible
Dimeric AcCh, Acts as agonist like
AcCh, not hydrolyzed by AcCh-ase
(only plasma esterase)
Depolarization triggers muscle
twitching initially,
Used for brief procedures
AcCh: Preganglionic, parasyathetic
post ganglionic neurons
Norepinephrine: Most symp. Post
ganglionic neurons (except sweat
glands and renal arteries)
Epinephrine (adrenalin): Adrenal
medulla--symp impulses (no gang)
Reuptake into presynaptic nerve
ending
Catechol-O-methyltransferase
MAO
Presynaptic alpha 2 receptors
 Alpha1 (vasc smooth muscle)
Alpha 2 (presynaptic)
Adrenergic Receptors Beta 1 (Heart)
Beta 2 (repiratory, uterine SM cells)
Beta 3 (Adipocytes)

MAO-Inhibitors
Indirect Sympathicomimetics
Inhib of MAO causes increase in free
Tranylcypromine Nor-Ep, in CNS NAO metab
Moclobemide dopamine and serotonin
(inhib=increase in happy hormones)

Indirect Sympathicomimetics
Displace nor-E in storage
Ephedrine vesicles=forced release of NorE
Dietary Supplements

Indirect Sympathomimetics
Amphetamines Displace norE in storage vesicles,
Methylphenidate forced release, inhib NorE re-uptake
Fenfluramine and deg by MAO (TRIPPLE
Metamphetamine ACTION), Meth=ADD,
Fen=Appetite suppressant,
Meta=more lipophilic, depletes NorE
Non-selective Agonists
Epinephrine Sympathomimetics
Ep: Activates alpha and beta rec
Norepinephrine Blood pressure increase, dilates
bronchii, vasopressor, Treat
anaphylactic shock
NorE: alph receptors, increase BP,
potent vasopressor
 Alpha1 selective agonist
Methoxamine Sympathomimetics
Phenylephrine Methoxamine: treatment of
Naphazoline hypotensive state
Oxymetazoline Phen: Local vasoconstrictor, nasal
Xylometazoline decongestant
Zoline=alpha 1
Alpha 2 selective agonist
Produce sympatholytic effect, but
sympathomimetics! Actviate
Clonidine presynaptic a-2 rec in cardiovascular
Guanfacine control in the CNS
BP decrease

B1-selective agonist, stimulate heart

Strgon inotropic effect, little
Dobutamine chronotropic effect, short term
treatment of impaired cardiac
function

B2 selective agonist
Metaproterenol Treat asthma, non-selective
Albuterol sympathomimetics
Formoterol Differ in speed and onset, duration of
action

Indicated for pheocromocytoma.

Blocking α1 causes vasodilation;
Non-selective Blockers reducing BP
Phentolamine Blocking α2 removes inhibition,
increasing NE action on β receptors
 increasing HR and cardiac output

Prazosin, Terazosin, etc
Yohimibine
Propranolol
Metoprolol, Atenolol…
Potential targets of Antihypertensive
drugs
Selective α1 Blocker
Indicated for hypertension and
urinary retention.
Side effects: Reflex tachycardia and
postural hypotension
Selective α2 Blocker
(sympathomimetic!)
Increases sympathetic outpout. Used
for male sexual dysfunction and as a
weight loss drug
Noncardioselective β blockers
1st gen. drug, cross reaction w/ β2
causes bronchoconstriction
Labetalol also blocks α1 receptors
(strong antihypertensive drug)
same indications as cardioselective
blockers
Cardioselective β blockers
Newer drugs are more β1 selective.
Indicated for angina pectoris,
hypertension, cardiac dysrhythmias,
myocardial infarction, heart failure,
and stage fright (anxiolytic).
CNS/ANS (decrease symp. tone)
Heart: decrease cardiac output
Veins: Dilate, decrease preload
Arterioles: dilate, decrease afterload
Kidneys: increase diuresis
 Calcium channel blockers
Dihydropyridines: (antagonist)
Nifedipine, Nicardipine, Inhibit Ca entry into cells of arteries
Nimodipine… Targets specifically L-type channels
on VSMC, no cardiac effect
Can cause peripheral edema

Minoxidil Potassium Channel Agonists

Increases membrane permeability to
K+, K+ efflux causes membrane
hyperpolarization, inhibiting voltage
gated Ca2+ channels  relaxation of
smooth muscles  vasodilation 
reduces BP
Side effect: hair growth (Rogaine)
Nitroprusside Vasodilator
Delivered thru iv only and is
metabolized into NO which directly
activates cGMP production 
vasodilation, Rapid action!
(Caffeine & Viagra)
Hypertensive Emergencies!
ACE-Inhibitors, angiotensin I not
Captopril converted into the active peptide
Enalapril (ATII), no aldosterone & ADH
Benazepril release  no fluid retention
Lisinopril -no sympathomimetic effects
-no vasoconstriction
Side effect – causes coughing
Angiotensin II (ATII) Receptor
Blocker
Losartan Inhibits the effect of AT II by
Candesartan blocking the receptor
etc… usually used if patient cannot
tolerate the cough caused by ACE
inhibitors
 Stable Angina Predictable episodes; usually during/after physical
exertion or stress. Treatment: Nitrates & β-Blockers
(Propranolol, etc.)

Unstable Angina Chest pain unexpected and usually occurs at rest

Treatment: Nitrates

Chest pain almost always occurs at rest. Due to

Variant Angina coronary artery spasm. Treatment: Calcium channel
blockers (Nifedipine, etc…)
Treats angina pectoris. Reduces cardiac
workload (and its oxygen demand) by
reducing venous return. Causes
Nitroglycerine vasodilation primarily in veins. Oral,
sublingual, IV, Buccal and Transdermal
ROA
Do not combine w/ other vasodilators
(Viagra)
Isosorbide-dinitrate More stable than nitroglycerine
(ISDN) Tolerance can occur, give lowest dose
Do NOT combine w/ other vasodilators

Promotes peripheral vasodilation.

Nitroprusside IV only; rapid onset and short duration –
allows for titration
Sodium Channel Blockers
Slows depolarization phase of AP.
Arrythmia Treatment Procainamide – used for atrial & ventricular
Class I arrhythmias
Lidocaine – used for acute ventricular
arrhythmias
Flecainide – used for chronic treatment of
ventricular arrhythmias

Arrythmia Treatment β-Blockers

Class II Propranolol
used for tachycardia
 Arrythmia Treatment Potassium Channel Blockers
Class III: Prolongs repolarization by blocking potassium
efflux.
Bretylium & Amiodarone
used for intractable ventricular arrhythmias

Class IV: Prolongs repolarization by blocking calcium

Calcium Channel Blockers influx
Verapamil – blocks both L & T Type calcium
channels!
Blocking T Type channels  slows conduction
(Blocking L Type channels  coronary +
arterial vasodilation)

Adenosine – for paroxysmal supraventricular

tachycardia
Other Cardiac Arrythmia Drugs Digoxin – atrial fibrillation
Epinephrine - bradycardia

Inadequate contractility; ventricles unable to

expel blood  rise in venous blood pressure.
Caused by blocked coronary arteries, viral
Congestive Heart Failure infections, hypertension, leaky heart vavles,
myocardial infarction
Right sided failure – lower limb edema, Left
sided failure – pulmonary edema & respiratory
distress
 Cardiac Glycosides Slows heart rate and increases
(Digoxin) contractility.
Inhibits Na/K ATPase, leading to an
increase intracellular Na+, Increased Na+
slows Na/Ca exchanger, leading to an
increase intracellular Ca++. Low
therapeutic index.
Potassium competes with digoxin in
binding to Na/K ATPase

Reduces cardiac workload, inhibits

ACE inhibitors & vasoconstriction, inhibits sodium/fluid
ATII antagonists retention, inhibits NE release

Captopril & Losartan

Vasodilators Nitrates: Nitroglycerine, etc. (review

Nitrates notes)

Carbonic Anhydrase Inhibitors Inhibits conversion of CO2  (H+) +

Azetazolamide (HCO3-), blocking reabsorption of Na+
Dorzolamide -Usually indicated for Glaucoma
Causes metabolic acidosis (lower HCO3-)
 Inhibits Na+/K+/2Cl- symporter at
ascending limb in the Loop of Henle;
Loop Diuretics (high ceiling) blocking Na, K, Cl reabsorption
Furosemide most potent diuretic
Torasemide for severe/moderate hypertension &
edema
Causes hypokalemia

Inhibits Na+/Cl- symporter at distal

convoluted tube
Thiazide Diuretics Used for moderate hypertension & heart
Hydrochlorothiazide failure (edema)
Benzthiazide Causes hypokalemia

Acts as distal portion of distal tube;

enhances Na excretion & reduces K
Potassium-Sparring Diuretics excretion
Spironolactone Spironolactone – aldosterone receptor
Amiloride antagonist (slow)
Amiloride – directly blocks Na/K channel
(fast)
Used in combo w/ other diurectics
Non-reabsorbable molecules that inhibit
passive reabsorption of water (promoting
Osmotic Diuretics water excretion w/ little Na excretion),
Mannitol does not cross blood-brain barrier, so
water goes from brain to blood, Used to
reduce intracranial pressure, IV only

Indicated for kidney stones and gouts.

Therapeutic dose: promotes excretion and
Uricosuric Agents inhibits reabsorption of uric acid
Probenecid Sub-therapeutic dose: inhibits both
excretion and reabsorption
Strongly inhibits penicillin excretion
which is good if need long lasting
penicillin performance
 Neutralizes stomach acid.
Weak Bases: Magnesium Hydroxide – causes diarrhea
Aluminum Hydroxide Aluminum hydroxide – causes
Magnesium Hydroxide constipation
PeptoBismol, Tums Often combined to reduce side effects of
each

Competitively inhibits binding of

histamine to H2 receptors on parietal
H2 Receptor Blockers: cells; reduces histamine stimulated gastric
Cimetidine acid production
Ranitidine

Irreversible inhibition of H+/K+ ATPase

Proton Pump Inhibitors: in parietal cells
Omeprazole Only active at low pH (activity restricted
Lansoprazole to stomach)
Esomeprazole Inhibits acid production for 1-2days
Rabeprazole Does not neutralize acid in stomach, only
prevents production

Mucosal Protective Agents: Misoprostol: PGE analog; stimulates

Misoprostol mucus and HCO3 production
Sucralfate Combined w/ NSAIDS
Sucralfate: stabilizes mucus to inhibit H+
diffusion, not absorbed

H1 Antagonists
Muscarinic receptor antagonists
Antiemetic Drugs: Benzodiazepines
Potential Treatment Options D2 antagonists
Cannabinoids
H1 Antagonists Diphenhydramine, Meclizine, etc
Blocks H1 (histamine) receptors
competitively

Muscarinic Receptor Antagonists Scopolamine (anticholernergic)

Benzodiazepines Lorazempam; potentiates effects of

GABA in CNS

D2 (dopamine) Antagonists: Competitively blocks C2 receptors in the

Metoclopramide CTZ
Domperidone Increases gastric emptying
Contraindicated in patients w/
Parkinson’s disease

Synthetic cannabinoids: Nabilone,

Cannabinoids Dronabinol

Acts as agonist at cannabinoid receptors

in the CNS
Bulk Laxatives Increases bowel content volume
triggering stretch receptors

Carbohydrate Based Insoluble, expands with water

Vegetable Fibers, Bran May cause constipation if not enough
water
Osmotically Active
Epsom salt partially soluble/non-absrobable
Glauber’s salt potent and fast acting
Irritants:
Ricinoleic acid (Castor Oil) Castor oil converted to ricinoleic acid
works in the small intestine

Anthraquinones
Diphenolmethanes Works in the large intestine
Bisacodyl
Sodium picosulfate
 Longer interval needed to refill colon,
most common cause of constipation
Laxative Abuse Loss of water/salt in gut leads to
aldosterone release
Causes excretion of K+

Opiod derivative that selectively acts in

the GI tract (w/no CNS activity)
Antidiarrheal: Acts on the intestinal muscles reducing
Loperamide motility=increase in water and electrolyte
(Imodium) reabsorption
Dimethicone: anti-gas agent that is often
combined with anti-diarrheal drugs

Insulin (unmodified) short acting

only insulin that can be administered thru
iv

Insulin Lispro (Humalog) rapid onset and short acting

SC injection only, insulin + zinc  micro-

Insulin Lente precipitates delayed absorption
long lasting, UltraLente = longest lasting

SC injection only, insulin + zinc  micro-

Insulin Lente precipitates delayed absorption
long lasting, UltraLente = longest lasting

NPH Insulin insulin + protamine delayed absorption

long lasting

Synthetic insulin that is soluble at low pH,

but becomes insoluble and forms
Insulin Glargine precipitates at neutral pH after SC
Lantus administration
long lasting (similar to Lente)
 Sulfonylureas Stimulates insulin release; useful for
Tolbutamide (1st gen.) diabetes caused by low insulin levels
Glimepiridide where β- pancreatic cells are still present
Glipizide

Glitazones Increases insulin sensitivity at target cells

Rosiglitazone Acts as a nuclear hormone receptor
Pioglitazone (PPARγ agonist) increasing transcription
of insulin receptor signaling components
and glucose transporters

Unknown mechanism
Increases glucose uptake & inhibits
Biguanides gluconeogenesis
Metformin Lowers LDL and VLDL
Suppresses appetite
No hypoglycemic effects

Reversible HMG-CoA Reductase

inhibitors. HMG-CoA reductase is the
Statins rate-limiting enzyme in the production of
Lovastatin cholesterol. Inhibition effectively reduces
Atorvastatin (Lipitor) de novo synthesis of cholesterol
precursors.
Lower cholesterol levels upregulates LDL
receptors in liver removing LDL from the
bloodstream
PPARα agonists – stimulates β-oxidation
of fatty acids
Fibrates Promotes lipoprotein lipase activity
Clofibrate Lowers VLDL (minor effect on LDL)
Benzafibrate Increases HDL levels
 Bile acid binding resins prevent
reabsorption of bile acids in enterohepatic
Resins circulation, Increases cholesterol
Cholestyramine synthesis to make more bile acid-plasma
Colestipol cholesterol levels remain unchanged. The
liver also upregulates LDL receptors to
increase hepatic uptake of LDL (reducing
plasma LDL)

Inhibit all phases of inflammation,

inhibits NFκB, upregulates lipocortin
Glucorticoids (GCs) (lipocortin inhibits PLA2, =no PT or LT
synthesis, promotes fetal lung
development by increasing surfactant

Addison’s Disease Adrenal cortex failure, Lack of GC

production

Cushing Syndrome Adrenal cortex tumors, GC

overproduction

=Cortisol, main GC in humans

Used for adrenal insufficiency (Addison’s
Hydrocortison Disease)
mostly topical application
Binds with mineralcorticoid receptors
Have Na retaining effects

Prednisone Pro-drug; converted to active form

(prednisolone)
Prednisolone
Drug of choice for systemic
administration
Lower Na retaining effects
 Stronger anti-inflammatory than cortisol
Triamcinoline No Na retaining effect

Betamethasone, Dexamethasone: 30x

Halogenated GC more potent than cortisol, no water or Na
retaining effects

Estrogens: Produced from andgrogen precursors

Estradiol=primary estrogen in human,
Estradiol breast devel, bone density, growth of
uterus, increase HDL, etc., no oral admin
Estrone (1st pass hepatic elim)

Estriol Estriol only during pregnancy

Ethinylestradiol Most widely used
Induce expression of progesterone
receptors, Progesterone inhib expression
of estrogen receptors

Diethyl-Stilbestrol Oral contraceptive

Raloxifene Indicated for postmenopausal

osteoporosis, Selective estrogen receptor
modifier (SERM), Anti-estrogenic effect
on breast and endometrium, Estrogenic
effect on bone and lipid metabolism

Mestranol Oral contraceptives, prodrug

Tamoxifene
(antiestrogen) Indicated for breast cancer
anti-estrogenic effect on breast tissue
weak effect on bone and lipid metabolism
 Progesterones: Inhibits rhythmic contractions of
myometrium, not for oral admin (1st pass
Progesterone elim)

Hydroxyprogesterone
Stable derivatives
Medroxyprogesterone

Progesterone
Testosterone derivatives with
Norethindrone progesterone activity
Norgestrel
Desogestrel

1980s French company, found that it

Anti-Progesterones blocks progesterone receptors, induces
Mifepristone abortion
Addition of small doses of prostaglandin
analogue few days later stimulates uterine
contractions=very efficacious for
termination of pregnancy
Testosterone Responsible for both anabolic and
androgenic effects
Rapidly metabolized by the liver.
-ester derivatives increases its half-
Nandrolone life
(banned)
Strong anabolic effects, Injection only

Stanozolol Strong anabolic effects (Not a β blocker!)

(banned) Oral admin
 Dehydroepiandrosterone. Marketed as
an anabolic steroid
DHEA Misleading b/c it’s a precursor for both
testosterone and estrogen.
High levels of DHEA may lead to elevated
levels of testosterone and estrogen.

Flutamide Used to treat prostate cancer

Competitive androgen receptor
antagonist
Blocks testosterone stimulating effects

Treats prostate gland enlargement and

Finasteride baldness, blocks the conversion of
testosterone to DHT (testosterone
metabolite that is much more potent)
Bald men have elevated levels of DHT

Treats endometriosis (growth of

Danazol endometrium outside of the uterus)
Inhibits GnRH release, no LH/FSH
production=no steroid production

Synthetic GnRH Given in pulses (s.c.), induced ovulation

-Gonadorelin (stimulates LH/FSH)
-Buserelin Given continuously, medical castration
(desensitize GnRH receptors)
 Bile acid binding resins prevent
reabsorption of bile acids in enterohepatic
Resins circulation, Increases cholesterol
Cholestyramine synthesis to make more bile acid-plasma
Colestipol cholesterol levels remain unchanged. The
liver also upregulates LDL receptors to
increase hepatic uptake of LDL (reducing
plasma LDL)

Inhibit all phases of inflammation,

inhibits NFκB, upregulates lipocortin
Glucorticoids (GCs) (lipocortin inhibits PLA2, =no PT or LT
synthesis, promotes fetal lung
development by increasing surfactant

Addison’s Disease Adrenal cortex failure, Lack of GC

production

Cushing Syndrome Adrenal cortex tumors, GC

overproduction

=Cortisol, main GC in humans

Used for adrenal insufficiency (Addison’s
Hydrocortison Disease)
mostly topical application
Binds with mineralcorticoid receptors
Have Na retaining effects

Prednisone Pro-drug; converted to active form

(prednisolone)
Prednisolone
Drug of choice for systemic
administration
Lower Na retaining effects
 Stronger anti-inflammatory than cortisol
Triamcinoline No Na retaining effect

Betamethasone, Dexamethasone: 30x

Halogenated GC more potent than cortisol, no water or Na
retaining effects

Estrogens: Produced from andgrogen precursors

Estradiol=primary estrogen in human,
Estradiol breast devel, bone density, growth of
uterus, increase HDL, etc., no oral admin
Estrone (1st pass hepatic elim)

Estriol Estriol only during pregnancy

Ethinylestradiol Most widely used
Induce expression of progesterone
receptors, Progesterone inhib expression
of estrogen receptors

Diethyl-Stilbestrol Oral contraceptive

Raloxifene Indicated for postmenopausal

osteoporosis, Selective estrogen receptor
modifier (SERM), Anti-estrogenic effect
on breast and endometrium, Estrogenic
effect on bone and lipid metabolism

Mestranol Oral contraceptives, prodrug

Tamoxifene
(antiestrogen) Indicated for breast cancer
anti-estrogenic effect on breast tissue
weak effect on bone and lipid metabolism
 Progesterones: Inhibits rhythmic contractions of
myometrium, not for oral admin (1st pass
Progesterone elim)

Hydroxyprogesterone
Stable derivatives
Medroxyprogesterone

Progesterone
Testosterone derivatives with
Norethindrone progesterone activity
Norgestrel
Desogestrel

1980s French company, found that it

Anti-Progesterones blocks progesterone receptors, induces
Mifepristone abortion
Addition of small doses of prostaglandin
analogue few days later stimulates uterine
contractions=very efficacious for
termination of pregnancy
Testosterone Responsible for both anabolic and
androgenic effects
Rapidly metabolized by the liver.
-ester derivatives increases its half-
Nandrolone life
(banned)
Strong anabolic effects, Injection only

Stanozolol Strong anabolic effects (Not a β blocker!)

(banned) Oral admin
Combination Pills Highly effective, Estrogen component:
Ethinylestradiol, Progesterone component
varies
Biphasic preparation – includes
progesterone break after 7 day break
Monophasic preparation – no
progesterone break (but [progesterone]
varies throughout cycle)
Mini Pill Less reliable than combination pills
Contains only progesterone, used when
estrogen is contraindicated
Contraception mechanism relies mainly
on increased mucus viscosity.
-mucolytic agents (cough medications)
may cause contraception failure

Morning After Pill High dose of progesterone

Levonorgestrel Must be taken within 72 hours of sexual
intercourse

Dephenhydramine H1 antagonists (antihistamine), 1st

(Benadryl) generation
Indicated for seasonal and skin allergies

Dimenhydrinate Anti-emetic
(Dramamine) Also blocks mAChRs

Doxyamine H1 antagonist, 1st generation

(Nyquil) Most potent OTC sedative (better than
barbiturates)
Same efficacy as diphenhydramine in
terms of anti-allergies
Clemastine
 1st generation H1 antagonist
Chlorpheniramine Also anti-depressant (inhib serotonin
uptake)

Meclizine Antiemetic (less drowsiness)

Hydroxyzine Antihistamine due to metabolite

Cetrizine 2nd generation H1 antagonist

Loratadine No entry to CNS, no drowsiness T ½=8 hr

Desloratadine Longer T ½

Fexofenadine Highly selective for H1 receptor

Cromolyn
Mast cell stabilizer
Prevents asthma, does not stop attack
Nedocromil Prevents mediator release from mast cells
Inhalation or eye drops

Montelukast (Singulair) Leukotriene Receptor Blockers

Prevents exercise and aspirin-induced

asthma
Antagonist of LTD4 at cysteinyl LT
receptor

Zileuton (Zyflo) 5-Lipoxygenase Inhibitor

Prevents production of all leukotrienes

Not useful for treatment of attacks
 Barbiturates General inhibition of the CNS w/
sedative-hypnotic actions Augments
GABA responses (by potentiating GABA
signal) and mimics GABA (by opening
Cl-channels in the absence of GABA).
Keeps Cl channels open longer,
hyperpolarizing the cell preventing
further excitation. Alsoblocks excitatory
glutamate receptors

phenobarbital Barbituates
epilepsy (phenobarbital) and anesthesia
thiopental induction (thiopental)
Side effects/Risks:
Amobarbital high risk of dependence (severe/lethal
Pentobarbital withdrawal symptoms)
Secobarbital may lead to cardio-respiratory depression
potent inducers of P450 enzymes; drug
interactions (contraceptives,
etc.)
Benzodiazepines Seven-membered ring fused to aromatic
ring, Selective activates GABA receptor
Chlordiazepoxide, Diazepam, operated Cl channels, Increase affinity of
Lorazepam, Flunitrazepam, Alprazolam, GABA for rec., Treat Anxieties, fewer side
Triazolam effects than barb., anterograde amnesia

MAO Inhibitors as Antidepressants Increase norepinephrine, serotonin, and

Tranylcypromine dopamine (prevents metab)
Phenelzine Side effects high
Food-drug interaction: cheese
 SSRIs Increase serotonin levels by preventing
neuronal reuptake
Fluoxetine Same efficacies as TCAs, fewer side
Paroxetine effects
Sertraline Inhib sexual climax, can cause aggression
Clotalopram

Tricyclic Antidepressants Increase norepinephrine and serotonin by

Imipramine preventing neuronal reuptake, strong
Desipramine interaction with alcohol. Sedation=side
Clomipramine… effect

Phenothiazines Treat Schizophrenia

1st gen: neuroleptic
Butyrophenones Block dopamine receptor on post synaptic
vesicle, Cause acute dystoni, akathesia,
tardive dyskinesia, sedation, dry mouth,
lactation, interaction with alcohol

Clozapine Atypical Neuroleptics (2nd gen)

Inhibit 5-HT and D2 receptors, act mostly
Olanzapine on limbic system, not in striatum (fewer
side effects)

L-dopa (Levodopa) Treat Parkinsons Disease

Metabolic precursor of dopamine, often
Carbidopa combined with Carbidopa (LDOPA
decarboxylase inhib). Increases amt of L-
Dopa that reaches the brain
Bromcriptine Dopamine Agonists
Similar to L-dopa
Pergolide D2 agonists, treat Parkinsons

Pramipexole

Inhib of MAOb, extends half-life of

dopamine, Indirect dopamine agonists,
Selegiline Treats Parkinsons, also antidepressant

Muscarinic acetylcholine receptor

antagonist.
Atropine Reduces cholinergic signals in the CNS
(responsible for stimulating GABA output
suppressing the thalamus)

No longer used for Parkinson’s disease

Blocks voltage gated Na channels that are
in the inactivated state, preferentially
blocks high frequency discharges. (use-
Phenytoin dependent inhibition)
(does not elevate seizure threshold, limits
the propagation and spread of seizure),
Zero order kinetics, Indicated for
convulsive seizures, Side Effect:
hyperplasia
Treats Epilepsy, inhib of ca channels,
Ethosuximide Etho=blocks T-type channels, drug of
choice for absence seizures
Valproate
Val=mech unclear, good for convulsive
and absence seizures
Hepatotoxic
 Treats alcholoism
inhibits aldehyde dehydrogenase; leading
to acetylaldehyde accumulation causing
Disulfuram “hang-over”
-also blocks the conversion of dopamine
to NE, rise in dopamine levels causes
schizophrenic symptoms

Naltrexone Treats Alcoholism

opiod receptor antagonist; inhibiting the
reward response that normally results for
alcohol consumption

IV anesthetic
Rapid onset with high lipid solubility
Thiopental (accumulates in fat); slow recovery
(barbiturate) Narrow therapeutic range
No analgesic effect

IV anesthetic
Rapidly metabolized for quick recovery.
Propofol Used for same-day surgery

IV anesthetic
Phencyclidine (PCP) analogue; may cause
Ketamine hallucinations during recovery
Have both anesthetic and analgesic
properties
-often used in veterinarian medicine and
in tranqulizers
 IV anesthetic
Benzodiazepine. Very short-acting.
Midazolam Have all benzodiazepine properties, often
used for anesthesia induction

Ether Obsolete
Slow onset and recovery
Post operative nausea, vomiting

Low potency (must be combined with

Nitrous Oxide other agents to achieve anesthesia)
Rapid induction and recovery
Both anesthetic and analgesic properties

High potency anesthetic; combined w/

N2O
Haloethanes No analgesic properties.
Some hepatic metabolism occurs;
repeated use causes hepatoxicity
Also causes hypotension (thru
vasodilation and cardiac suppression)

High potency anesthetic; similar to

Enfluran haloethanes
Isofluran Fewer side effects because less
Desfluran metabolized by liver.
 CNS – sedation, nausea, and cough
Morphine suppression
Respiratory System – reducing frequency
and depth of breathing
GI Tract – increases segmentation and
decreases peristalsis (constipation)
Eyes – papillary constriction (due to
parasympathetic activation)

Codeine Pro-drug, that is converted into morphine

by CYP2D6.
CYP2D6 inhibitors may reduce codeine
efficacy, Genetic polymorphism may also
explain codeine resistance
Little euphoric effect, so low risk for
addiction.Used as an anti-tussive (cough
suppressant)

Synthetic morphine derivative that does

Dextromethrophan not act thru opioid receptors.
Same efficacy as codeine
No GI or analgesic effect

Heroin Diamorphine; diacylated-morphine is

more lipophilic than morphine so it
crosses the blood-brain barrier more
rapidly producing a greater rush.
2x more potent than morphine

Hydrocodone

Vicodin; often combined w/ NSAIDs for

synergistic effect
 Indicated for chronic pain.
Oxycodone Addicts chew thru the slow release
formulation to obtain immediate release
to mimic heroin rush

Similar to morphine, but shorter

Meperidine duration.
Used during labor.

Similar to morphine, but much longer

duration.
Used to treat morphine/heroin addiction
Methadone

High potency. Can be used

transdermally.
Short-lasting. Used in anesthesia and
Fentanyl patient controlled infusions.

Opiate Antagonist
Naloxone Short-acting competitive antagonist used
to rapidly reverse opioid induced
analgesia and respiratory suppression
 Opiate Antagonist
Naltrexone Long-acting competitive antagonist
Used to protect detoxified addicts from
relapsing

Cocaine -contains ester bond; rapidly metabolized

by non-specific esterases in the plasma
-cocaine’s CNS effects are independent
from its analgesic effect
(blocks reuptake of DA, 5-HT, NE)

Lidocaine -contains amide bond; longer acting

compared to local anesthetics w/ ester
bonds

Classification of Cell wall synth inhib

Antibiotics
Protein synth inhib

Folate antagonists

Quinolones
Penicillins
Cephalosporins
Carbapenems All Beta-Lactam Antibiotics
Monbactams
Vancomycin, Bacitracin
 Penicillins, cell wall synth inhib
Benzylpenicillin Inhibit transpeptidase, cant make cell
wall
Phenoxymethylpenicillin Beta-lactamase sensitive
Narrow spectrum
Phenoxy has better oral avail
G+ bacteria

Methicillin Narrow spectrum, b-lactamase resistant

Oxacillin Cell wall synth inhib
Cloxacillin G+ bacteria
Dicloxacillin Methicillin=poor oral avail
Oxacillin=good oral avail

Ampicillin Broad spectrum, penicillinase sensitive

Cell wall synth inhib
Amoxicillin Amp=good oral avail, G+ and G-, entero
Amox=excellent oral avail

Carbenicillin Extended spectrum, b=lactamase

Ticarcillin sensitive, cell wall synth inhib
Mezlocillin Carb=poor oral avail, G+ and G-,
Pipercillin pseudomonas, Klebsiella

B-lactamase sensitive
Cefazolin Cell wall synth inhib
Cephalexin 1st generation cephalorsporins
Cross allergies with pen.
G+ bacteria
 Cefaclor 2nd generation Cephalosporins
B-lactamase sensitive
Cefamandole Cell wall synth inhib
Some G-, mostly G+
Cefoxitin

Clavulanic Acid B-lactamase inhib, cell wall synth inhib

Irreversible inhib, good oral absorption
Sulbactam Often combined with amoxicillin or
ticarcillin

Vancomycin Cell wall syth inhib

Vanc=only effective against G+, poor oral
Bacitracin absorption, used to treat GI infections
Bacitracin=mixture of polypeptides,
serious nephrotoxicity

Aminoglycosides Protein synth inhib

Tetracyclins Inhibit either 30s or 50s ribosomal unit
Macrolides Drugs need to enter bacteria (point of
Chloramphenicol resistance)
Clindamycin

Gentamicin
Tobramycin Aminoglycosides (protein synth
Streptomycin inhibitors)
Neomycin
Kanamycin
Amikacin
 Tetracyclines, energy dependent
transport, oral absorption impaired by
Tetracycline food (antacids, Ca)
Oxytetracycline Incorp into teeth and bones=staining,
Minocycline causes photosensitivity
Doxycycline Broad spectrum antibiotics

Macrolides
Erythromycin Narrow spectrum, good alternative for
Azithromycin patients with allergy to pen, few side
Clarithromycin effects
Azi=long T ½ , convenient 6 pills regimen
Clarith=used for H. pylori infection

Protein synth inhib

Chloramphenicol Chlor=broad spectrum, severe side
effects, reserved for life threatening
Clindamycin situations
Clind=medium broad spectrum, treat pen
resistant cocci
Side effect=collitis
Sulfonamides
Folate antagonist, blocks folate
Sulfadiazine synth=blocked replication
Sulfadimidine Structural analogues of PABA
Sulfamethoxazole

Trimethroprim Competes with folates fro Dihydrofolate-

reductase (folate antag), Similar to
sulfonamides, combined with
Sulfomethoxazole
Treat UTIs
 Quinolones Inhibit DNA-Gyrase (Topoisomerase II),
Nalidixic acid very broad spectrum, bactericidal,
Ciprofloxacin usually fluorinated
…floxacin (Fluoroquinolones)