Chapter 17: Antiarrhythmic Drugs Flashcards
What are class I (Na+ channel blockers)? (7)
Disopyramide (IA) Procainamide (IA) Quinidine (IA) Lidocaine (IB) Mexiletine (IB) Flecainidine (IC) Propafenone (IC)
What are class II (B-adrenoreceptor blockers)? (3)
Esmolol
Metoprolol
Propranolol
What are class III (K+ channel blockers)? (4)
Amiodarone
Dofetilide
Dronedarone
Sotalol
What are class IV ( Ca2+ channel blockers)?
Diltiazem
Verapamil
What are other anti-arrhythmic drugs?
Adenosine
Digoxin
What are causes of arrhythmias?
- Abnormal automaticity: cardiac sites other than the SA node showing enchanced automaticity generating competing stimuli; also damaged cardiomyocytes which may remain depolarized during diastole and reach the firing threshold earlier than normal SA cells
Effects of drugs on automaticity: suppress automaticity by blocking Na+ or Ca2+ channels to reduce ratio of these ions to K+, this decreases slope of phase 4 depolarization and lowers the threshold to a less negative voltage
2. Abnormalities in impulse conduction: reentry can occur if unidirectional block caused by myocardial injury to prolonged refractory period results in abnormal confuction; most common cause of arrhythmias Effects of drugs on conduction abnormalities: prevent reentry by slowing conduction (class I) or increasing the refractory period (class III), converting the unidirectional block into a bidirectional block
What is the mechanism of class I antiarrhythmic drugs?
-block voltage sensitive sodium channels via the same mechanism as local anesthetics, decrease rate of entry of Na+ slows rate of rise of Phase 0 of the action potential
What is the use dependence of class I drugs? IA, IB, IC
Class I drugs bind to open or inactivated Na+ channels than to channels that are fully repolarized; these drugs show more effect in tissues that are rapidly repolarzing
-these drugs are use dependent: they blocks cells that are discharging at an abnormally high frequency without interfering with the normal low frequency beating of the heart
Class IA: slow rate of rise of action potentian and prolong action potential, increase ventricular refractory period
Class IB: little effect on rate of depolarization; they decrease duration of action potential by shortening repolarization; rapidly interact with Na+ channels
Class IC: depress rate of rise of the action potential; they cause slowing of confuction but have little effect on duration of membrane action potential
What is the use dependence of class I drugs? IA, IB, IC
Class I drugs bind to open or inactivated Na+ channels than to channels that are fully repolarized; these drugs show more effect in tissues that are rapidly repolarzing
-these drugs are use dependent: they blocks cells that are discharging at an abnormally high frequency without interfering with the normal low frequency beating of the heart
Class IA: slow rate of rise of action potentian and prolong action potential, increase ventricular refractory period
Class IB: little effect on rate of depolarization; they decrease duration of action potential by shortening repolarization; rapidly interact with Na+ channels
Class IC: depress rate of rise of the action potential; they cause slowing of confuction but have little effect on duration of membrane action potential or ventricular effective refractory period; bind slowly to Na+ channels
What is the MOA, indications, pharmokinetics, and adverse effects of quinidine?
MOA: binds to open and inactivated Na+ channels and prevents Na+ influx (slows upstroke of phase 0); also decreases slope of phase 4 and inhibits K+ channels
indications: atrial, AV junctional and ventricular tachyarrhythmias
pharmokinetics: oral administration, hepatic cytochrome P450 enzymes
adverse effects: development of an arrhythamia
What is the MOA, indications, pharmokinetics, and adverse effects of quinidine?
MOA: binds to open and inactivated Na+ channels and prevents Na+ influx (slows upstroke of phase 0); also decreases slope of phase 4 and inhibits K+ channels
indications: atrial, AV junctional and ventricular tachyarrhythmias
pharmokinetics: oral administration, hepatic cytochrome P450 enzymes
adverse effects: development of an arrhythmia
What is the MOA, indications, pharmokinetics, and adverse effects of procainamide?
MOA: class IA drug, derivative of local anesthetic procaine, shows actions simliar to quinidine
pharmokinetics: oral; prolongs duration of the action potential, eliminated renally
adverse effects: high incidence (with chronic use) of reversible lupus syndrome
CNS side effects: depression, hallucination, psychosis
What is the MOA, indications, pharmokinetics, and adverse effects of disopyramide?
MOA: actions similar to quinidine, produces negative inotropic effect, causes peripheral vasoconstriction
indications: treatment of ventricular arrhythmias as an alternate to procainamide or quinidine
pharmokinetics: excreted renally and liver
adverse effects: may produce important decrease in myocardial contractility in patients with preexisting impairment of left ventricular function; anticholinergic activity
What is the MOA, indications, pharmokinetics, and adverse effects of lidocaine? IB drug (IB drugs rapidly associate and dissociate from sodium channels)
MOA: shortens phase 3 repolarization in ventricular muscle and decreases duration of action potential; work when cardiac cell is depolarzied and firing rapidly
indications: ventricular arrhythamias (in emergency situation) in MI
pharmokinetics: IV
adverse effects: wide toxic-to-therapeutic ratio
What are indications of mexiletine and tocainide?
Class IB drugs with similar action to lidocaine
Mexiletine: chronic treatment of ventricular arrhythmias associated with previous MI
Tocainide: treatment of ventricular tachyarrhythmias; has pulmonary toxicity which may lead to pulmonary fibrosis
What is the MOA, indications, pharmokinetics, and adverse effects of lidocaine? IB drug (IB drugs rapidly associate and dissociate from sodium channels)
MOA: shortens phase 3 repolarization in ventricular muscle and decreases duration of action potential; work when cardiac cell is depolarzied and firing rapidly
indications: ventricular arrhythamias (in emergency situation) in MI
pharmokinetics: IV
adverse effects: wide toxic-to-therapeutic ratio
What is the MOA, indications, pharmokinetics, and adverse effects of flecainide? IC drug
MOA: IC drug-slowly dissociate from resting Na+ channels; suppresses phase 0 upstroke in Purkinje and myocardial fibres which causes slowing of conduction in all cardiac tissue
indications: treatment of refractory ventricular arrhythmias; partially useful in suppressing premature ventricular contraction
What is the MOA, indications, pharmokinetics, and adverse effects of flecainide? IC drug
MOA: IC drug-slowly dissociate from resting Na+ channels; suppresses phase 0 upstroke in Purkinje and myocardial fibres which causes slowing of conduction in all cardiac tissue
indications: treatment of refractory ventricular arrhythmias; partially useful in suppressing premature ventricular contraction
pharmokinetics: absorbed orally
adverse effects: like all other class IC drugs, can aggrevate preexisting arrhythmias or induce life threatening ventricular tachycardia that is resistant to treatment
What is the MOA, indications, pharmokinetics, and adverse effects of Class II antiarrhythmic drugs?
ex: propanolol, metoprolol, esmolol
MOA: these drugs are B adrenergic antagonists; diminish phase 4 depolarization which depresses automaticity, prolongs AV conduction, decreases HR and contractility
indications: treatment of tachyarrhythmias caused by increased sympathetic activity
What is the MOA, indications, pharmokinetics, and adverse effects of Class II antiarrhythmic drugs?
ex: propanolol, metoprolol, esmolol
MOA: these drugs are B adrenergic antagonists; diminish phase 4 depolarization which depresses automaticity, prolongs AV conduction, decreases HR and contractility
indications: treatment of tachyarrhythmias caused by increased sympathetic activity; useful in atrial flutter and fibrillation
Ex: Propanolol- reduces sudden arrhythmic death after MI by preventing ventricular arrhythmias
Metaprolol- widely used to treat cardiac arrhythmias; reduces risk of bronchospasm
Esmolol- very short acting used in acute arrhythmias that occur after surgery or during an emergency
What is the mechanism of Class III antiarrhythmic drugs? ex: Aminodarone, Dronedarone, Sotalol, Dofetilide
- block K+ channels which diminishes the outward K+ current during repolarization of cardiac cells
- prolong the effective refractory period
- all class III drugs have the potential to induce arrhythmias
What is the MOA, indications, pharmokinetics, and adverse effects of amiodarone?
MOA: prolongation of action potential duration and refractory period; antianginal and antiarrhythmic activity
indications: treatment of severe refractory supraventricular and ventricular tachyarrhythmias; main treatment of atrial fibrillation; effective in maintaining sinus rhythm
pharmokinetics: oral administration, prolonged halflife of several weeks and distributes in adipose tissue
adverse effects: high doses cause interstitial pulmonary fibrosis, GI intolerance, liver toxicity and blue skin discolouration
-iodine moieties responsible for thyroid dysfunction
What is the MOA, indications, pharmokinetics, and adverse effects of dronedarone?
- simliar to amiodarone but less toxic since it doesn’t have the iodine moiety
- less effective than amiodarone in decreasing AF recurrance
What is the MOA, indications, pharmokinetics, and adverse effects of sotalol?
MOA: potent class III drug that also has nonselective B-blocker activity; blocks rapid outward K+ current which prolongs repolarization and duration of action potential which prolongs the refractory period
What is the MOA, indications, pharmokinetics, and adverse effects of sotalol?
MOA: potent class III drug that also has nonselective B-blocker activity; blocks rapid outward K+ current which prolongs repolarization and duration of action potential which prolongs the refractory period
indications: long term therapy to decrease rate of death in patients after a MI; suppress ectopic beats and reduce myocardial O2 demand; more effective in preventing arrhythmias than imipramine, mexiletine, procainamide, propafenone, and quinidine in patients with sustained ventricular tachycardia
adverse effects: prolong QT interval; torsades de pointes is a serious potential adverse effect
What is the MOA, indications, pharmokinetics, and adverse effects of sotalol?
MOA: potent class III drug that also has nonselective B-blocker activity; blocks rapid outward K+ current which prolongs repolarization and duration of action potential which prolongs the refractory period
indications: long term therapy to decrease rate of death in patients after a MI; suppress ectopic beats and reduce myocardial O2 demand; more effective in preventing arrhythmias than imipramine, mexiletine, procainamide, propafenone, and quinidine in patients with sustained ventricular tachycardia
adverse effects: prolong QT interval; torsades de pointes is a serious potential adverse effect
What is the MOA, indications, pharmokinetics, and adverse effects of dofetilide?
-can be used as first line antiarrhythmic drug in persistent AF and HF in patients with CAD with impaired left ventricular function
What is the MOA, indications, pharmokinetics, and adverse effects of dofetilide?
MOA: class III antiarrhythmic drug; prolongs phase 3 repolarization in ventricular muscle fibres
indications: can be used as first line antiarrhythmic drug in persistent AF and HF in patients with CAD with impaired left ventricular function
pharmokinetics: renally excreted
adverse effects: risk of proarrhythmia
What is the mechanism of class IV antiarrhythmic drugs? Ex: Verapamil, Nifedipine, Diltiazem
- Ca2+ channel blockers; decrease inward Ca2+ current resulting in decrease rate of phase 4 spontaneous depolarization; slow conduction in tissues dependent on Ca2+ currents
- Verapamil has greater action on the heart than on vascular smooth muscle; Nifedipine(used to treat HT) has stronger effect on vascular smooth muscle than the heart; Diltiazem is intermediate in action
Verapamil, Diltiazem
MOA: effective against voltage sensitive channels causing a decrease in slow inward current that triggers cardiac contraction; prevent repolarization until drug dissociates from channel; slow conduction and prolong refractory period
indications: atrial arrhythmias; reentrant supraventricular tachycardia and reduce ventricular rate in atrial flutter and fibrillation; treat HT and angina
pharmokinetics: oral administration and metabolized by the liver
adverse effects:negative inotropic properties so contraindicated in patients with preexisting depressed cardiac function; both drugs can decrease BP because of peripheral vasodilation (beneficial in treating HT)
What are the other antiarrhythmic drugs and their mechanisms?
Digoxin: shortens refractory period in atrial and ventricular myocardial cells while prolonging effective refractory period and diminishing conduction velocity in the AV node
- used to control response rate in atrial fibrillation and flutter
- at toxic concentrations: causes ectopic ventricular beats that may result in ventricular tachycardia and fibrillation
Adenosine: at high doses it decreases conduction velocity, prolongs refractory period and decreases automaticity in the AV node
-IV is drug of choice for abolishing acute supraventricular tachycardia
