Antiarrhythmic Agents Flashcards
(20 cards)
Antiarrhythmic Drugs
Medications that correct abnormal heart rhythms (arrhythmias).
Treats: Conditions like atrial fibrillation, ventricular tachycardia, and premature heartbeats.
Class I: Sodium channel blockers (e.g., lidocaine)
Class II: Beta-blockers (e.g., propranolol)
Class III: Potassium channel blockers (e.g., amiodarone)
Class IV: Calcium channel blockers (e.g., verapamil)
What are arrhythmias?
Types of arrhythmias according to:
1) Heart rate
2) Etiology
What are the risk factors for arrhythmias?
abnormal heart beats.
1) Bradycardia (slow) and tachycardia (fast)
2) delayed after depolarization, heart block, abnormal pacemaker (ectopic foci) and reentry circus movement.
caffeine, alcohol, tobacco, stress, digitalis overdose, hypertension, CAD, heart muscle damage after MI
What causes cardiac arrhythmias?
What are ANTIARRHYTHMIC DRUGS?
How antiarrhythmics act/ work?
disturbance in conduction of impulse through myocardial tissue or by disorders of impulse formation.
Drugs that are used for the treatment of cardiac arrhythmias.
They affect impulse conduction by altering conduction velocity and the duration of the refractory period of heart muscle tissue.
Explain the cardiac muscle action potential.
Voltage-gated fast Na+ channels open causing rapid depolarization.
Some K⁺ leaves decreasing voltage a little. (early repolarization)
Voltage gated slow Ca²⁺ channel opens and some K⁺ channels close creating a balance /plateau/ maintained depolarization that keeps the heart muscle squeezing long enough to pump blood.
Voltage gated K+ channels open and Ca closes causing repolarisation.
What are the Classes of Antiarrhythmic Drug?
remember this is based on mechanism o faction or pattern of electrophysiological effects on heart tissue.
CLASS I - MEMBRANE-DEPRESSANT DRUGS
CLASS II - ADRENERGIC BLOCKING AGENTS
CLASS III - REPOLARIZATION PROLONGATORS
CLASS IV - CALCIUM CHANNEL BLOCKERS
What are the characteristics of
CLASS I - MEMBRANE-DEPRESSANT DRUGS
Remember they are subdivided based on the relative ease with which they dissociate from the Na+ ion channel.
What are the characteristics of these subtypes?
- membrane stabilizing properties (shift to more negative potentials).
- act on the fast Na+ channels.
- interfere with process by which depolarizing charge is transferred across the membrane.
-proarrhythmic in MI patients.
IC: dissociates slowly, does not shift action potential most potent sodium channel–blocking agents
IB: dissociate rapidly, shortens AP by shifting to left, lowest potency as sodium channel blockers
IA: intermediate rate, lengthens AP by shirting to right
Examples and MOA of Class I Drugs.
IA: quinidine, procainamide, disopyramide
lengthens refractory period.
IB: lidocaine, phenytoin, tocainide, mexiletine
shortens duration of action potential
IC: encainide, flecainide. larcainide, moricizine, propafenone
slows conduction
Antiarrhythmic drugs have low affinity for R (rested) channels
but relatively high affinity for the A (activated) or I (inactivated) channels or both.
T/F
True
What are the characteristics of
CLASS II -ADRENERGIC BLOCKING AGENTS
Give an example and its MOA.
- inhibition of adrenergic stimulation to heart
- electrophysiological property is reduction of phase 4 slope of potential sinus or ectopic pacemaker cells (HR decreases and ectopic tachycardias are either slowed or converted to sinus rhythm.
e.g propranolol : slows AV conduction time.
What are the characteristics of
CLASS III -REPOLARIZATION PROLONGATORS
Give examples and MOA.
- prolong AP
- increases effective refractory period of the membrane AP without altering depolarization or resting potential
e.g amiodarone, bretylium, sotalol
prolong refractoriness
Sotalol K+ channel blocker and has some beta-adrenergic blocking properties.
Amiodarone and bretylium, also have Na+ channel–blocking properties.
What are the characteristics of
CLASS IV -CALCIUM CHANNEL BLOCKERS
Remember this mechanism: Blocks the slow inward Ca channel
- verapamil and diltiazem only block Ca2+ during phase 2 of the AP in cardiac cells.
- verapamil selectively blocks entry of Ca2+ into the myocardial cell.
- acts on slow-response fibers in sinus and AV node.
- slowing conduction velocity and increasing refractoriness in the AV node.
Points to note in the metabolism of lidocaine.
Hepatic metabolism via First-Pass Effect
Metabolic Pathway: N-deethylation
Key Metabolites:
1) Monoethylglycinexylidine (MEGX) – an active metabolite with antiarrhythmic properties. However, rapid hydrolysis by microsomal amidases prevents its clinical use in humans.
Glycyl-2,6-xylidine (GX) – a further breakdown product.
Points to note in the metabolism of CCB diltiazem.
primary pharmacologically active metabolite is deacetyldiltiazem which has 40-50% activity of the potency of parent compound
Points to note in the metabolism of Beta Blocker Propranolol.
Metabolites
1) Naphthoxylactic Acid
Formed through N-dealkylation, deamination, and oxidation of the aldehyde.
Major metabolite after a single oral dose.
2) 4-Hydroxypropranolol formed via aromatic hydroxylation is an active metabolite.
Points to note in the metabolism of Beta Blocker Metoprolol
Metabolic Pathways:
1) Benzylic Hydroxylation forms Active Metabolite α-Hydroxymetoprolol
2) O-Demethylation
Metabolism & Stereochemical Aspects
of procainamide.
1)enzymatic metabolism of procainamide hydrochloride forms N-acetylprocainamide (NAPA). It has 25% activity of parent compound. Due to its amide structure, procainamide hydrochloride is more stable in water than procaine.
Metabolism & Stereochemical Aspects of
propafenone.
1) R and S enantiomers of Propafenone have similar Na+ channel blocking effects. But S also acts as beta blocker so 40-fold more potent.
2) Propafenone undergoes hydroxylation to form 5-hydroxypropafenone. These 5-hydroxy metabolites (from both enantiomers) are just as potent at blocking Na channels as parent compound.
Metabolism & Stereochemical Aspects of
propafenone of Amiodarone.
Drug-drug Interactions
Contains iodine in its structure, which can affect thyroid hormone metabolism.
potent inhibitor of multiple cytochrome P450 enzymes.
It impairs the metabolism of digoxin, theophylline, and warfarin so dose must be adjustmented.
Metabolism & Stereochemical Aspects of
propafenone of Sotalol.
L(-) enantiomer → Has both beta-blocking (Class II) and potassium channel-blocking (Class III) effects.
D(+) enantiomer → Also has Class III effects, but its beta-blocking activity is 30-60 times weaker than the L(-) enantiomer.
Drug-drug Interactions of Quinidine
inhibits the metabolism of Digoxin, Tricyclic antidepressants and Codeine
Cimetidine, Azole antifungals and Calcium channel blockers can inhibit its metabolism
