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Routes of Drug Administration
Types of Orally Administered Drugs
Percutaneous Drug Administration
Other Topicals
Parenteral Drug Administration
Oral
Topical (Percutaneous)
Rectal or Vaginal
Pulmonal
Parenteral
Pills (single dose)
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
Pulmonary Formulations
Suppositories
Ampules
Vials
Cartridge Ampules
Infusions
Advantage: 100% Absorption,
enters circulation without hepatic
elim, better bioavailability of
hydrophilic drugs
Types of Barriers for Drug
Distribution/Absorption
Drug Distribution
Bioavailability
Volume of Distribution
Rate of Elimination
External Absorption Barriers:
(epithelial layer on skin, lung,
intestine—Lipophilic barrier)
Internal Blood-Tissue Barriers:
Cardiac muscle, endocrine glands,
gut, liver, CNS
Passive Diffusion
Active Transport
Receptor-mediated Endocytosis
[DRUG] IS A FUNCTION OF
ABSORBTION AND
ELIMINATION!
The AUC of the administered drug
divided by the AUC of the
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
liver (metabolism)
Usually first order kinetics
3 drugs have zero-order kinetics
Rate of Elim/[Drug]
Clearance
Rate of Elim= k*Cp*Vd
K= ln2/T ½
CL= K*Vd
Phase I Reactions
Phase II Reactions
MFO
Mixed Function Oxidases
P450 Enzymes
Conjugation Reactions
Convert parent compound into more
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)
Conjugation with gucoronide,
sulfate, acetate, amino acid
Require reducing agent and
molecular oxygen
Two enzymes: 1) Flavoprotein,
NADPH-cytochrome c reductase
2) Cytochrome P450 (electron
acceptor); CYP
PPAR ligands, CYP1, CYP2E,
CYP2B
Polymorphisms cause changes in
drug metab: CYP2C19, CYP2B,
CYP2D6
Induction of P450
enzymes=metabolize drug
Glucoronidation
Sulfation
Acetylation
Amino acid Conj
Glutathione Conj
Fatty acid Conj
Condensation Reaction
Monoamine Oxidases (MAO)
Therapeutic Index
Agonist
Antagonist
Four major drug targets
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
Doesn’t take into account variability
btw indivs
LD50/ED50
Can be drugs or endogenous ligands
for the receptor
Increasing [agonist] will produce
increase in biological response
Full:evokes 100% max possible effect
Partial: not 100%
Block or reverse effect of agonist
No effect on their own
Competitive, Non-competitive,
inverse agonist (triggers neg
response)
Receptor
Enzyme
Ion Channel
Transporter
Ca++ as a Second Messenger
Ca Channels
G-Protein-coupled Receptors
G-Proteins
PKA
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
Sesnsors: Annexins, EF-hand
proteins, Calmodulin, ProponinC
Target of many drugs!
GPCR: transmembrane
Bind GTP and GDP
GAPS, GEFS, RGSs important in
this regulation
Main Targets: Phospholipase C,
Adenylate cyclase
G-Proteins: Guanine nucleotide
binding proteins
2 groups:
Small GTP binding
Heterotrimeric G proteins
Target of cAMP
Four subunits (2 reg, 2 catalytic)
Phosphorylates transcription factors
ex: CREB
Regulation of Receptors
Nuclear Receptors
GC, Mineralcorticoids, Retinoids
PPARs
Phospholipids
Phospholipases
Heterologous desensitization
(Incoming signal from different
receptor)
Homologous desensitization (only
occurs on receptor which has already
been stimulated)
Lipid soluble ligands that penetrate
cell membrane, Receptors contain
DNA-binding domains
(transcriptional
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),
PLC (Beta: Reg through GPCR,
Gamma: EGFR or TCR, activated
through tyrosine phosphorylation
Phospholipases…
DAG: membrane bound, acts as a
substrate for PLA2
IP3: Ca++ regulated
Arachidonic Acid Metabolism
Eicosanoids: derivative of
arachadonice acid
Rapidly metab by COX into PG and
LTs
1st reaction: cyclic ring structure
(COX), 2nd reaction: oxidation
(Peroxidase)
Function of PGs
Leukotrienes
Nervous System
Cholinergic Receptors
Cholinomimetics=
Parasympathomimetics
Vascular tone (relaxation,
constriction)
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)
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
Autonomous
Auto: Sypmathetic and
Parasympathetic
Muscarinic Receptors:
Heterotrimeric G protein coupled,
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)
Inderect Parasympathometics:
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!
Carbamate
Quaternary Alcohols
Horny Goat Weed
Ogranophosphates
Nerve Gasses
Achestease Inhibitors, raise Ach
Physiostigmine (topical only)
Neostigmine
Edrophonium (diagnose Myasthenia
Gravis)
AcCh-ase inhib
Acts as AcCh-ase inhib but active
ingredient unkown
Indirect stimulation of M3 receptor
(vascular), triggers NO
production=vasodilation
Action similar to Viagra (dangerous)
AcCh-ase inhibitors (irreversible)
No medical application
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
Adrenergic Receptors
Tranylcypromine
Moclobemide
Ephedrine
Amphetamines
Methylphenidate
Fenfluramine
Metamphetamine
Epinephrine
Norepinephrine
Alpha1 (vasc smooth muscle)
Alpha 2 (presynaptic)
Beta 1 (Heart)
Beta 2 (repiratory, uterine SM cells)
Beta 3 (Adipocytes)
MAO-Inhibitors
Indirect Sympathicomimetics
Inhib of MAO causes increase in free
Nor-Ep, in CNS NAO metab
dopamine and serotonin
(inhib=increase in happy hormones)
Indirect Sympathicomimetics
Displace nor-E in storage
vesicles=forced release of NorE
Dietary Supplements
Indirect Sympathomimetics
Displace norE in storage vesicles,
forced release, inhib NorE re-uptake
and deg by MAO (TRIPPLE
ACTION), Meth=ADD,
Fen=Appetite suppressant,
Meta=more lipophilic, depletes NorE
Non-selective Agonists
Sympathomimetics
Ep: Activates alpha and beta rec
Blood pressure increase, dilates
bronchii, vasopressor, Treat
anaphylactic shock
NorE: alph receptors, increase BP,
potent vasopressor
Methoxamine
Phenylephrine
Naphazoline
Oxymetazoline
Xylometazoline
Clonidine
Guanfacine
Alpha1 selective agonist
Sympathomimetics
Methoxamine: treatment of
hypotensive state
Phen: Local vasoconstrictor, nasal
decongestant
Zoline=alpha 1
Alpha 2 selective agonist
Produce sympatholytic effect, but
sympathomimetics! Actviate
presynaptic a-2 rec in cardiovascular
control in the CNS
BP decrease
Dobutamine
B1-selective agonist, stimulate heart
Strgon inotropic effect, little
chronotropic effect, short term
treatment of impaired cardiac
function
Metaproterenol
Albuterol
Formoterol
B2 selective agonist
Treat asthma, non-selective
sympathomimetics
Differ in speed and onset, duration of
action
Non-selective Blockers
Phentolamine
Indicated for pheocromocytoma.
Blocking α1 causes vasodilation;
reducing BP
Blocking α2 removes inhibition,
increasing NE action on β receptors
 increasing HR and cardiac output
Prazosin, Terazosin, etc
Yohimibine
Propranolol
Metoprolol, Atenolol…
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)
Potential targets of Antihypertensive
Heart: decrease cardiac output
drugs
Veins: Dilate, decrease preload
Arterioles: dilate, decrease afterload
Kidneys: increase diuresis
Dihydropyridines:
Nifedipine, Nicardipine,
Nimodipine…
Minoxidil
Nitroprusside
Captopril
Enalapril
Benazepril
Lisinopril
Losartan
Candesartan
etc…
Calcium channel blockers
(antagonist)
Inhibit Ca entry into cells of arteries
Targets specifically L-type channels
on VSMC, no cardiac effect
Can cause peripheral edema
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)
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
converted into the active peptide
(ATII), no aldosterone & ADH
release  no fluid retention
-no sympathomimetic effects
-no vasoconstriction
Side effect – causes coughing
Angiotensin II (ATII) Receptor
Blocker
Inhibits the effect of AT II by
blocking the receptor
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
Variant Angina
Chest pain almost always occurs at rest. Due to
coronary artery spasm. Treatment: Calcium channel
blockers (Nifedipine, etc…)
Nitroglycerine
Isosorbide-dinitrate
(ISDN)
Nitroprusside
Arrythmia Treatment
Class I
Arrythmia Treatment
Class II
Treats angina pectoris. Reduces cardiac
workload (and its oxygen demand) by
reducing venous return. Causes
vasodilation primarily in veins. Oral,
sublingual, IV, Buccal and Transdermal
ROA
Do not combine w/ other vasodilators
(Viagra)
More stable than nitroglycerine
Tolerance can occur, give lowest dose
Do NOT combine w/ other vasodilators
Promotes peripheral vasodilation.
IV only; rapid onset and short duration –
allows for titration
Sodium Channel Blockers
Slows depolarization phase of AP.
Procainamide – used for atrial & ventricular
arrhythmias
Lidocaine – used for acute ventricular
arrhythmias
Flecainide – used for chronic treatment of
ventricular arrhythmias
β-Blockers
Propranolol
used for tachycardia
Arrythmia Treatment
Class III:
Potassium Channel Blockers
Prolongs repolarization by blocking potassium
efflux.
Bretylium & Amiodarone
used for intractable ventricular arrhythmias
Class IV:
Calcium Channel Blockers
Prolongs repolarization by blocking calcium
influx
Verapamil – blocks both L & T Type calcium
channels!
Blocking T Type channels  slows conduction
(Blocking L Type channels  coronary +
arterial vasodilation)
Other Cardiac Arrythmia Drugs
Adenosine – for paroxysmal supraventricular
tachycardia
Digoxin – atrial fibrillation
Epinephrine - bradycardia
Congestive Heart Failure
Cardiac Glycosides
(Digoxin)
ACE inhibitors &
ATII antagonists
Inadequate contractility; ventricles unable to
expel blood  rise in venous blood pressure.
Caused by blocked coronary arteries, viral
infections, hypertension, leaky heart vavles,
myocardial infarction
Right sided failure – lower limb edema, Left
sided failure – pulmonary edema & respiratory
distress
Slows heart rate and increases
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
vasoconstriction, inhibits sodium/fluid
retention, inhibits NE release
Captopril & Losartan
Vasodilators
Nitrates: Nitroglycerine, etc. (review
Nitrates notes)
Carbonic Anhydrase Inhibitors
Azetazolamide
Dorzolamide
Inhibits conversion of CO2  (H+) +
(HCO3-), blocking reabsorption of Na+
-Usually indicated for Glaucoma
Causes metabolic acidosis (lower HCO3-)
Loop Diuretics (high ceiling)
Furosemide
Torasemide
Thiazide Diuretics
Hydrochlorothiazide
Benzthiazide
Potassium-Sparring Diuretics
Spironolactone
Amiloride
Osmotic Diuretics
Mannitol
Uricosuric Agents
Probenecid
Inhibits Na+/K+/2Cl- symporter at
ascending limb in the Loop of Henle;
blocking Na, K, Cl reabsorption
most potent diuretic
for severe/moderate hypertension &
edema
Causes hypokalemia
Inhibits Na+/Cl- symporter at distal
convoluted tube
Used for moderate hypertension & heart
failure (edema)
Causes hypokalemia
Acts as distal portion of distal tube;
enhances Na excretion & reduces K
excretion
Spironolactone – aldosterone receptor
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
water excretion w/ little Na excretion),
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 inhibits reabsorption of uric acid
Sub-therapeutic dose: inhibits both
excretion and reabsorption
Strongly inhibits penicillin excretion
which is good if need long lasting
penicillin performance
Weak Bases:
Aluminum Hydroxide
Magnesium Hydroxide
PeptoBismol, Tums
H2 Receptor Blockers:
Cimetidine
Ranitidine
Proton Pump Inhibitors:
Omeprazole
Lansoprazole
Esomeprazole
Rabeprazole
Mucosal Protective Agents:
Misoprostol
Sucralfate
Antiemetic Drugs:
Potential Treatment Options
Neutralizes stomach acid.
Magnesium Hydroxide – causes diarrhea
Aluminum hydroxide – causes
constipation
Often combined to reduce side effects of
each
Competitively inhibits binding of
histamine to H2 receptors on parietal
cells; reduces histamine stimulated
gastric acid production
Irreversible inhibition of H+/K+ ATPase
in parietal cells
Only active at low pH (activity restricted
to stomach)
Inhibits acid production for 1-2days
Does not neutralize acid in stomach, only
prevents production
Misoprostol: PGE analog; stimulates
mucus and HCO3 production
Combined w/ NSAIDS
Sucralfate: stabilizes mucus to inhibit H+
diffusion, not absorbed
H1 Antagonists
Muscarinic receptor antagonists
Benzodiazepines
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:
Metoclopramide
Domperidone
Cannabinoids
Competitively blocks C2 receptors in the
CTZ
Increases gastric emptying
Contraindicated in patients w/
Parkinson’s disease
Synthetic cannabinoids: Nabilone,
Dronabinol
Acts as agonist at cannabinoid receptors
in the CNS
Bulk Laxatives
Increases bowel content volume
triggering stretch receptors
Carbohydrate Based
Vegetable Fibers, Bran
Insoluble, expands with water
May cause constipation if not enough
water
Osmotically Active
Epsom salt
Glauber’s salt
Irritants:
Ricinoleic acid (Castor Oil)
Anthraquinones
Diphenolmethanes
Bisacodyl
Sodium picosulfate
partially soluble/non-absrobable
potent and fast acting
Castor oil converted to ricinoleic acid
works in the small intestine
Works in the large intestine
Laxative Abuse
Longer interval needed to refill colon,
most common cause of constipation
Loss of water/salt in gut leads to
aldosterone release
Causes excretion of K+
Antidiarrheal:
Loperamide
(Imodium)
Opiod derivative that selectively acts in
the GI tract (w/no CNS activity)
Acts on the intestinal muscles reducing
motility=increase in water and electrolyte
reabsorption
Dimethicone: anti-gas agent that is often
combined with anti-diarrheal drugs
Insulin (unmodified)
Insulin Lispro (Humalog)
short acting
only insulin that can be administered
thru iv
rapid onset and short acting
Insulin Lente
SC injection only, insulin + zinc  microprecipitates delayed absorption
long lasting, UltraLente = longest lasting
Insulin Lente
SC injection only, insulin + zinc  microprecipitates delayed absorption
long lasting, UltraLente = longest lasting
NPH Insulin
insulin + protamine delayed absorption
long lasting
Insulin Glargine
Lantus
Synthetic insulin that is soluble at low
pH, but becomes insoluble and forms
precipitates at neutral pH after SC
administration
long lasting (similar to Lente)
Sulfonylureas
Tolbutamide (1st gen.)
Glimepiridide
Glipizide
Stimulates insulin release; useful for
diabetes caused by low insulin levels
where β- pancreatic cells are still present
Glitazones
Rosiglitazone
Pioglitazone
Increases insulin sensitivity at target cells
Acts as a nuclear hormone receptor
(PPARγ agonist) increasing transcription
of insulin receptor signaling components
and glucose transporters
Biguanides
Metformin
Statins
Lovastatin
Atorvastatin (Lipitor)
Fibrates
Clofibrate
Benzafibrate
Unknown mechanism
Increases glucose uptake & inhibits
gluconeogenesis
Lowers LDL and VLDL
Suppresses appetite
No hypoglycemic effects
Reversible HMG-CoA Reductase
inhibitors. HMG-CoA reductase is the
rate-limiting enzyme in the production of
cholesterol. Inhibition effectively reduces
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
Promotes lipoprotein lipase activity
Lowers VLDL (minor effect on LDL)
Increases HDL levels
Resins
Cholestyramine
Colestipol
Glucorticoids (GCs)
Bile acid binding resins prevent
reabsorption of bile acids in
enterohepatic circulation, Increases
cholesterol synthesis to make more bile
acid-plasma 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
(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
Hydrocortison
Prednisone
=Cortisol, main GC in humans
Used for adrenal insufficiency (Addison’s
Disease)
mostly topical application
Binds with mineralcorticoid receptors
Have Na retaining effects
Pro-drug; converted to active form
(prednisolone)
Prednisolone
Drug of choice for systemic
administration
Lower Na retaining effects
Triamcinoline
Halogenated GC
Estrogens:
Stronger anti-inflammatory than cortisol
No Na retaining effect
Betamethasone, Dexamethasone: 30x
more potent than cortisol, no water or Na
retaining effects
Estrone
Produced from andgrogen precursors
Estradiol=primary estrogen in human,
breast devel, bone density, growth of
uterus, increase HDL, etc., no oral admin
(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
Estradiol
Tamoxifene
(antiestrogen)
Indicated for breast cancer
anti-estrogenic effect on breast tissue
weak effect on bone and lipid metabolism
Progesterones:
Progesterone
Inhibits rhythmic contractions of
myometrium, not for oral admin (1st pass
elim)
Hydroxyprogesterone
Stable derivatives
Medroxyprogesterone
Progesterone
Norethindrone
Norgestrel
Desogestrel
Anti-Progesterones
Mifepristone
Testosterone
Nandrolone
(banned)
Testosterone derivatives with
progesterone activity
1980s French company, found that it
blocks progesterone receptors, induces
abortion
Addition of small doses of prostaglandin
analogue few days later stimulates uterine
contractions=very efficacious for
termination of pregnancy
Responsible for both anabolic and
androgenic effects
Rapidly metabolized by the liver.
-ester derivatives increases its
half-life
Strong anabolic effects, Injection only
Stanozolol
(banned)
Strong anabolic effects (Not a β blocker!)
Oral admin
DHEA
Flutamide
Finasteride
Danazol
Synthetic GnRH
-Gonadorelin
-Buserelin
Dehydroepiandrosterone. Marketed as
an anabolic steroid
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.
Used to treat prostate cancer
Competitive androgen receptor
antagonist
Blocks testosterone stimulating effects
Treats prostate gland enlargement and
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
endometrium outside of the uterus)
Inhibits GnRH release, no LH/FSH
production=no steroid production
Given in pulses (s.c.), induced ovulation
(stimulates LH/FSH)
Given continuously, medical castration
(desensitize GnRH receptors)
Resins
Cholestyramine
Colestipol
Glucorticoids (GCs)
Bile acid binding resins prevent
reabsorption of bile acids in
enterohepatic circulation, Increases
cholesterol synthesis to make more bile
acid-plasma 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
(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
Hydrocortison
Prednisone
=Cortisol, main GC in humans
Used for adrenal insufficiency (Addison’s
Disease)
mostly topical application
Binds with mineralcorticoid receptors
Have Na retaining effects
Pro-drug; converted to active form
(prednisolone)
Prednisolone
Drug of choice for systemic
administration
Lower Na retaining effects
Triamcinoline
Halogenated GC
Estrogens:
Stronger anti-inflammatory than cortisol
No Na retaining effect
Betamethasone, Dexamethasone: 30x
more potent than cortisol, no water or Na
retaining effects
Estrone
Produced from andgrogen precursors
Estradiol=primary estrogen in human,
breast devel, bone density, growth of
uterus, increase HDL, etc., no oral admin
(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
Estradiol
Tamoxifene
(antiestrogen)
Indicated for breast cancer
anti-estrogenic effect on breast tissue
weak effect on bone and lipid metabolism
Progesterones:
Progesterone
Inhibits rhythmic contractions of
myometrium, not for oral admin (1st pass
elim)
Hydroxyprogesterone
Stable derivatives
Medroxyprogesterone
Progesterone
Norethindrone
Norgestrel
Desogestrel
Anti-Progesterones
Mifepristone
Testosterone
Nandrolone
(banned)
Testosterone derivatives with
progesterone activity
1980s French company, found that it
blocks progesterone receptors, induces
abortion
Addition of small doses of prostaglandin
analogue few days later stimulates uterine
contractions=very efficacious for
termination of pregnancy
Responsible for both anabolic and
androgenic effects
Rapidly metabolized by the liver.
-ester derivatives increases its
half-life
Strong anabolic effects, Injection only
Stanozolol
(banned)
Strong anabolic effects (Not a β blocker!)
Oral admin
Combination Pills
Mini Pill
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)
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
Levonorgestrel
High dose of progesterone
Must be taken within 72 hours of sexual
intercourse
Dephenhydramine
(Benadryl)
H1 antagonists (antihistamine), 1st
generation
Indicated for seasonal and skin allergies
Dimenhydrinate
(Dramamine)
Anti-emetic
Also blocks mAChRs
Doxyamine
(Nyquil)
H1 antagonist, 1st generation
Most potent OTC sedative (better than
barbiturates)
Same efficacy as diphenhydramine in
terms of anti-allergies
Clemastine
Chlorpheniramine
1st generation H1 antagonist
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
Nedocromil
Montelukast (Singulair)
Mast cell stabilizer
Prevents asthma, does not stop attack
Prevents mediator release from mast cells
Inhalation or eye drops
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
Triazolam
side effects than barb., anterograde
amnesia
MAO Inhibitors as Antidepressants
Tranylcypromine
Phenelzine
Increase norepinephrine, serotonin, and
dopamine (prevents metab)
Side effects high
Food-drug interaction: cheese
SSRIs
Fluoxetine
Paroxetine
Sertraline
Clotalopram
Increase serotonin levels by preventing
neuronal reuptake
Same efficacies as TCAs, fewer side
effects
Inhib sexual climax, can cause aggression
Tricyclic Antidepressants
Imipramine
Desipramine
Clomipramine…
Increase norepinephrine and serotonin by
preventing neuronal reuptake, strong
interaction with alcohol. Sedation=side
effect
Phenothiazines
Treat Schizophrenia
1st gen: neuroleptic
Block dopamine receptor on post synaptic
vesicle, Cause acute dystoni, akathesia,
tardive dyskinesia, sedation, dry mouth,
lactation, interaction with alcohol
Butyrophenones
Clozapine
Olanzapine
L-dopa (Levodopa)
Carbidopa
Atypical Neuroleptics (2nd gen)
Inhibit 5-HT and D2 receptors, act mostly
on limbic system, not in striatum (fewer
side effects)
Treat Parkinsons Disease
Metabolic precursor of dopamine, often
combined with Carbidopa (LDOPA
decarboxylase inhib). Increases amt of LDopa that reaches the brain
Bromcriptine
Pergolide
Dopamine Agonists
Similar to L-dopa
D2 agonists, treat Parkinsons
Pramipexole
Selegiline
Atropine
Inhib of MAOb, extends half-life of
dopamine, Indirect dopamine agonists,
Treats Parkinsons, also antidepressant
Muscarinic acetylcholine receptor
antagonist.
Reduces cholinergic signals in the CNS
(responsible for stimulating GABA
output suppressing the thalamus)
No longer used for Parkinson’s disease
Phenytoin
Ethosuximide
Blocks voltage gated Na channels that are
in the inactivated state, preferentially
blocks high frequency discharges. (usedependent 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,
Etho=blocks T-type channels, drug of
choice for absence seizures
Valproate
Val=mech unclear, good for convulsive
and absence seizures
Hepatotoxic
Disulfuram
Naltrexone
Thiopental
(barbiturate)
Propofol
Ketamine
Treats alcholoism
inhibits aldehyde dehydrogenase; leading
to acetylaldehyde accumulation causing
“hang-over”
-also blocks the conversion of dopamine
to NE, rise in dopamine levels causes
schizophrenic symptoms
Treats Alcoholism
opiod receptor antagonist; inhibiting the
reward response that normally results for
alcohol consumption
IV anesthetic
Rapid onset with high lipid solubility
(accumulates in fat); slow recovery
Narrow therapeutic range
No analgesic effect
IV anesthetic
Rapidly metabolized for quick recovery.
Used for same-day surgery
IV anesthetic
Phencyclidine (PCP) analogue; may cause
hallucinations during recovery
Have both anesthetic and analgesic
properties
-often used in veterinarian medicine and
in tranqulizers
Midazolam
Ether
Nitrous Oxide
Haloethanes
Enfluran
Isofluran
Desfluran
IV anesthetic
Benzodiazepine. Very short-acting.
Have all benzodiazepine properties, often
used for anesthesia induction
Obsolete
Slow onset and recovery
Post operative nausea, vomiting
Low potency (must be combined with
other agents to achieve anesthesia)
Rapid induction and recovery
Both anesthetic and analgesic properties
High potency anesthetic; combined w/
N2O
No analgesic properties.
Some hepatic metabolism occurs;
repeated use causes hepatoxicity
Also causes hypotension (thru
vasodilation and cardiac suppression)
High potency anesthetic; similar to
haloethanes
Fewer side effects because less
metabolized by liver.
Morphine
Codeine
Dextromethrophan
Heroin
CNS – sedation, nausea, and cough
suppression
Respiratory System – reducing frequency
and depth of breathing
GI Tract – increases segmentation and
decreases peristalsis (constipation)
Eyes – papillary constriction (due to
parasympathetic activation)
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
not act thru opioid receptors.
Same efficacy as codeine
No GI or analgesic effect
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
Oxycodone
Meperidine
Indicated for chronic pain.
Addicts chew thru the slow release
formulation to obtain immediate release
to mimic heroin rush
Similar to morphine, but shorter
duration.
Used during labor.
Similar to morphine, but much longer
duration.
Used to treat morphine/heroin addiction
Methadone
Fentanyl
Naloxone
High potency. Can be used
transdermally.
Short-lasting. Used in anesthesia and
patient controlled infusions.
Opiate Antagonist
Short-acting competitive antagonist used
to rapidly reverse opioid induced
analgesia and respiratory suppression
Naltrexone
Opiate Antagonist
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
Antibiotics
Cell wall synth inhib
Protein synth inhib
Folate antagonists
Quinolones
Penicillins
Cephalosporins
Carbapenems
Monbactams
Vancomycin, Bacitracin
All Beta-Lactam Antibiotics
Benzylpenicillin
Phenoxymethylpenicillin
Penicillins, cell wall synth inhib
Inhibit transpeptidase, cant make cell
wall
Beta-lactamase sensitive
Narrow spectrum
Phenoxy has better oral avail
G+ bacteria
Methicillin
Oxacillin
Cloxacillin
Dicloxacillin
Narrow spectrum, b-lactamase resistant
Cell wall synth inhib
G+ bacteria
Methicillin=poor oral avail
Oxacillin=good oral avail
Ampicillin
Broad spectrum, penicillinase sensitive
Cell wall synth inhib
Amp=good oral avail, G+ and G-, entero
Amox=excellent oral avail
Amoxicillin
Carbenicillin
Ticarcillin
Mezlocillin
Pipercillin
Cefazolin
Cephalexin
Extended spectrum, b=lactamase
sensitive, cell wall synth inhib
Carb=poor oral avail, G+ and G-,
pseudomonas, Klebsiella
B-lactamase sensitive
Cell wall synth inhib
st
1 generation cephalorsporins
Cross allergies with pen.
G+ bacteria
Cefaclor
Cefamandole
2nd generation Cephalosporins
B-lactamase sensitive
Cell wall synth inhib
Some G-, mostly G+
Cefoxitin
Clavulanic Acid
Sulbactam
Vancomycin
Bacitracin
Aminoglycosides
Tetracyclins
Macrolides
Chloramphenicol
Clindamycin
Gentamicin
Tobramycin
Streptomycin
Neomycin
Kanamycin
Amikacin
B-lactamase inhib, cell wall synth inhib
Irreversible inhib, good oral absorption
Often combined with amoxicillin or
ticarcillin
Cell wall syth inhib
Vanc=only effective against G+, poor oral
absorption, used to treat GI infections
Bacitracin=mixture of polypeptides,
serious nephrotoxicity
Protein synth inhib
Inhibit either 30s or 50s ribosomal unit
Drugs need to enter bacteria (point of
resistance)
Aminoglycosides (protein synth
inhibitors)
Tetracycline
Oxytetracycline
Minocycline
Doxycycline
Erythromycin
Azithromycin
Clarithromycin
Chloramphenicol
Clindamycin
Tetracyclines, energy dependent
transport, oral absorption impaired by
food (antacids, Ca)
Incorp into teeth and bones=staining,
causes photosensitivity
Broad spectrum antibiotics
Macrolides
Narrow spectrum, good alternative for
patients with allergy to pen, few side
effects
Azi=long T ½ , convenient 6 pills regimen
Clarith=used for H. pylori infection
Protein synth inhib
Chlor=broad spectrum, severe side
effects, reserved for life threatening
situations
Clind=medium broad spectrum, treat pen
resistant cocci
Side effect=collitis
Sulfonamides
Sulfadiazine
Sulfadimidine
Sulfamethoxazole
Trimethroprim
Folate antagonist, blocks folate
synth=blocked replication
Structural analogues of PABA
Competes with folates fro Dihydrofolatereductase (folate antag), Similar to
sulfonamides, combined with
Sulfomethoxazole
Treat UTIs
Quinolones
Nalidixic acid
Ciprofloxacin
…floxacin
Inhibit DNA-Gyrase (Topoisomerase II),
very broad spectrum, bactericidal,
usually fluorinated
(Fluoroquinolones)