Medchem Exam 4

Function & Types of Cardiac Agents
Glycoside & Nonglycoside
Increase contractility in CHF
Glycosides
Digitoxin & Digoxin (12-hydroxy digitoxin)
Adjunct CHF Therapy
Diuretics (Loop & Niseritide) & Vasodilators (captopril)
Nonglycosides
PDE-3i (Inamrinone IV, milrinone IV) & B1 Ag (dobutamine IV)
Digoxin
Lanoxin
MOA: inhibits Na/K Pump -> Na gradient is inhibited -> Less Ca is pumped out -> increased Ca in cell -> increased contractility
A: less than digitoxin
D: PPB less than digitoxin
M: kidney
E: urine
K t1/2: shorter than digitoxin
Inamrinone
Inocor IV
MOA: inhibits PDE-3 -> longer CAMP residence -> increased Ca influx -> increased contractility
M: directly phase II
K t1/2: short
Milrinone
Primacor IV
MOA: inhibits PDE-3 -> longer CAMP residence -> increased Ca influx -> increased contractility
M: phase I -> phase II
K t1/2: longer
Digitoxin
MOA: inhibits Na/K Pump -> Na gradient is inhibited -> Less Ca is pumped out -> increased Ca in cell -> increased contractility
A: more than digoxin
D: PPB more than digoxin
M: liver
E: bile -> recycled
K t1/2: longer than digitoxin
Dobutamine
Dobutrex
MOA: bind B1 stimulating contractility
M: COMT & PhaseII
Anti-Arrhythmic Drug Classes
Class I: Phase 0: Na Channel Blockers
Class II: Phase 2: Beta Blockers
Class III: Phase 3: K Channel Blockers
Class IV: CCBs
Class IA Drugs
Quinidine, Procainamide, Diisopyramide
MOA: decrease upstroke height; slows rate of depol -> prolonged axn potential
ADRs: anticholinergic effects
Class IB Drugs
Lidocaine, Tocainamide, Mexilitene, Phenytoin
MOA: decrease upstroke height; increases rate of depol -> shortened axn potential
ADRs: anticholingergic effects
Quinidine
Quinalan PO/IM
Class IA Antiarrhythmic
ADR: cinchonism
M: O-demethylation
Procainamide
Pronestyl PO
Class IA Antiarrhythmic
M: amidases (benzaldehyde amide) long k t1/2, N-deethylation, PHASE II ACETYLATION*
Diisopyramide
Norpace PO
Class IA Antiarrhythmic
M: aromatic hydroxylation
Lidocaine
Xylocaine PO
Class IB Antiarrhythmic
M: amidases (anilino amide)
short k t1/2
Tocainide
Tonocard IV/PO
Class IB Antiarrhythmic
M: amidases (anilino amide) but sterically hindered
long k t1/2
Mexilitene
Mexitil IV/PO
M: long k t1/2
No anticholinergic ADRs
Phenytoin
Dilantin IV/PO
Class IB Antiarrhythmic
*only acidic antiarrhythmic (imide)
used in seizures
M: aromatic hydroxylation
Class IC Drugs
Propaphenone, Moracizine, Fleicanide, Encainide
MOA: decrease upstroke height; no effect on length of axn potential
moracizine
Ethmozine PO
K Channel Affin: basic N heterocycle
ADR: anticholindergic
propaphenone
Rhythmol PO
K Channel Affin: aromatic ketone
flecainide
Tambocor PO
K Channel Affin: aromatic ketone
ADR: anticholinergic
encainide
Enkaid PO
K Channel Affin: aromatic ketone
Class II Drugs
sotalol
MOA: block autonomic NS stimulation @ B1 (phase 2)
sotalol
Betapace IV/PO
Class II & Class III antiarrhythmic
*also blocks Na
*conatins methyl sulfonamino group for CIII
Class III Drugs
sotalol, ibutilide, dofetilide, amiodarone, dronedarone, bretylium tosylate
MOA: inhibit K efflux (phase 3) -> longer axn potential
ibutilide
Corvert IV
Class III antiarrhythmic
*contains necessary methyl sulfonamino
*also blocks Na
dofetilide
Tikosyn PO
Class III antiarrhythmic
*contains two methyl sulfonamino
amiodarone
Cordarone IV/PO
Class III antiarrythmic
*contains aromatic ketone for K channel affin
ADR: decreased TH production (due to 2 iodine)
dronaderone
Multaq PO
Class III antiarrhythmic
very selective: contains aromatic ketone & methyl sulfonamido
bretylium tosylate
IV
ADR: severe hypotension
Class IV Drugs
Diltiazem, Verapamil
Coagulation Cascade
Injury
Epithelium releases thromboplastin
*synthesis of prothrombin is coupled with oxidation of reduced vitamin K
Prothrombin -> thrombin
Fibrinogen -> fibrin
Fibrin binds GPIIb&IIIa
Conformation Change -> P2Y12 receptor available
ADP Binds P2Y12 -> platelet becomes sticky
Termination: AT3 binds thrombin to inactivate; accelerated by heparin binding
8 Anticoagulant Drug Classes
Heparin & d/dx
Vit K Reductase Inhibs
Thrombin Antags
Ab for Platelets
Fibrinogen Antags
PDEis
Proteolytic Enz Inhibs
Prostaglandins
Heparin
IV
MOA: increase deactivation of thrombin via binding AT3 & thrombin -> decrease fibrin
OOA: Fast acting
Chem: gluconic acid & glucosamine repeating units
antidote: protamine sulfate
Vitamin K Reductase Inhibitors
PO
MOA: blocks reduction of oxidized Vitamin K -> prothrombin not made
OOA: slow acting
A: lipophilic -> good
D: strong PPB
M: aromatic hydroxylase (cyp)
antidote: vitamin K (slow acting)
Warfarin
Coumadin
Vit K Reductase Inhib
acenocoumarol
Sintrom
Vit K Reductase Inhib
phenprocoumon
Marcumar
Vit K Reductase Inhib
bishydroxycoumarin
Vit K Reductase Inhib
dicoumarol
Vit K Reductase Inhib
dimer
Thrombin Inhibitors
IV
“Rudins”
MOA: bind & inhibit thrombin (resemble AT3 structure)
Antibody Against Platelets
MOA: Antibody against GPIIb/IIIa; antagonist to fibrinogen
Abciximab
Repopro IV
Antibody against platelets
Fibrinogen Antagonists
1)Polypeptides IV
MOA: similar to fibrinogen; defebrutide
2)Nonpeptides PO
a)MOA: bind GPIIb/IIIa directly
b)MOA: bind purinergic P2Y12 receptor (inhibit ADP)
Aspirin/ASA
Advil, Motrin PO
Nonpeptide fibrinogen antagonist
MOA: acetylates GPIIb/IIIa irreversibly
tirofiban
Aggrostat IV
Nonpeptide fibrinogen antagonist
MOA: binds GPIIb/IIIa receptor
contains tryptophan
clopridogrel
Plavix PO
P2Y12 fibrinogen antagonist
k t1/2: shorter than ticlopidine
b t1/2: longer than ticlopidine (active metabolites)
ticlopidine
Ticlid PO
P2Y12 fibrinogen antagonist
k t1/2: longer than clopridogrel
b t1/2: shorter than clopridogrel
Proteolytic Enzyme Inhibitors
MOA: Inhibits thrombin’s cleavage of fibrinogen (-> fibrin)
Defibrotide
Peptide Fibrinogen Antagonist
Nafamostat
HCl Salt IV
Proteolytic Enz Inhib
Uses: during hemodialysis
M: Esterases (must be continuously infused)
Prostaglandin (PG) Synth
Arachidonic Acid (20C w/4pi bonds) cleaved from PL memb via phospholipase -> enters cytosol -> COX -> 5-memb ring + 2 pi bonds (PGE2, PGF2)
PGE2 Uses
*smooth muscle dilation
anti-HTN for PAH
anti-ulcer -> mucin secretion
induce labor -> relax circular cervix muscle
induce menstruation
induce abortion (RU486)
anti-asthma nasal spray
PGF2 Uses
*smooth muscle contraction
post-partum bleeding -> vasoconstriction
induce labor -> contract uterus & contract radial cervix
PGI2 (Prostacyclin) Uses
Open heart surgery -> inhibit blood clotting & dilate vessels
TXA Uses
after surgery -> induce platelet aggregation to stop bleeding
PGE2 Structure
cyclopentane w/ketone + 7C A chain ([email protected],6) + 8C B chain ([email protected],14)
PGF2 Structure
cyclopentane w/chiral OH + 7C A chain (same direction as OH) ([email protected],6) + 8C B Chain ([email protected],14)
PGI2 Structure
cyclopentane+furan + 5C A chain ([email protected],6) + 8C B chain ([email protected],14)
TXA2 Structure
Pyran Backbone + 7C A chain ([email protected],6) + 8C B chain ([email protected],14)
Montelukast
Singulair PO
Leukotriene Antagonist
Bronchodilation
Antipyretic Analgesic Drug Classes
Salicylates & Anilines
aspirin
Salicylate Antipyretic Analgesic
diflunisal
Dolobid
Salicylate Antipyretic Analgesic
methylsalicylate
Bengay
Salicylate Antipyretic Analgesic
acetaminophen
Tylenol
Aniline Antipyretic Analgesic
M: oxidized to NAPQI -> reactive with any -SH (glutathione) -> toxicity
Antidote: Mesna releases glutathiones
NSAID structure
similar to arachidonic acid:
lipophilic tail + acidic head
NSAID Drug Classes
fenamates, acetic acid d/dx, propionic acid d/dx, enoic acid d/dx, misc 🙂
mefenamic acid
Ponstel
fenamate NSAID
meclofenamic acid
Meclomen
fenamate NSAID
indometacin
Indocin
acetic acid NSAID
ADR: serious HA/dizzy due to CNS affinity
sulindac
Clinoril — PRODRUG
acetic acid NSAID
contains sulfoxide (too polar) -> sulfide (lipo)
long t 1/2
zomeprac
Zomax
acetic acid NSAID
etodolac
Lodine
acetic acid NSAID
NSAID ADME & ADR
A: good oral absorption
D: high PPB
M: Phase 1 -> inactive metabolite (too polar to bind COX)
E: Phase II glucoronide in urine
ADR: ulcerogenic bc acid & mucin inhibition
ibuprofen
Motrin, Advil
Propionic acid NSAID
naproxen
Naprosyn/Aleve
propionic acid NSAID
long t 1/2
peroxicam
Feldene
enoic acid NSAID
*contains sulfonamide -> directly Phase II
*longest t 1/2 🙂
nabumetone
Relafen — PRODRUG
miscellaneous NSAID
ketone -> acid
*avoids stomach irritation 🙂
celecoxib
Celebrex
miscellaneous NSAID — Cox2 Selective
*minimized ulcer risk
*contains sulfonamide -> longest t 1/2
Anti-Gout Drug Classes
Inhibitors of WBC Maturation; Xanthine Oxidase Inhibitors; Uricosuric Agents
cochicine
Colcrys
WBC Maturation Inhibitor
allopurinol
Zyloprim
XO Inhibitor
Nitrogens are simply closer together
probenacid
Probalan
Uricosuric
MOA: prevent proximal tubule reabsorp of uric acid
*contains sulfonamide -> goes directly to SOA
sulfinpyrazone
Anturane
Uricosuric
MOA: prevent proximal tubule reabsorp of uric acid
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