ANTIARRHYTHMIC DRUGS

Classification (Vaughan Williams)

▪ I. Sodium channel blockers
o I. A prolong repolarization : 
QUINIDINE
PROCAINAMIDE
DISOPYRAMIDE
o I. B shorten repolarization:
LIDOCAINE MEXILETINE
TOCAINIDE PHENYTOIN
o I.C little effect on repolarization:
FLECAINIDE
PROPAFENONE
MORICIZINE
▪ II. Beta blockers
PROPRANOLOL METOPROLOL
ESMOLOL ATENOLOL
▪ III. Potassium channel blockers
AMIODARONE BRETYLIUM
SOTALOL (also β- IBUTILIDE
blocker) DOFETILIDE
▪ IV. Calcium channel blockers
VERAPAMIL
DILTIAZEM
▪ V. Antiarrhythmics that work by other or unknown mechanism
ADENOSINE
DIGOXIN

Mechanism of action
 CLASS I A ANTIARRHYTHMICS

Mechanism of action
▪ they block the voltagedependent sodium channels in their open or refractory state.
Their effects are to slow phase 0 (increasing the effective refractory period) and
phase 4 (reducing automaticity), and to prolong action potential duration.
Indications
▪ ventricular arrhythmias;
▪ prevention of paroxysmal recurrent atrial fibrillation;
▪ Wolff-Parkinson-White syndrome (Procainamide).
Contraindications
▪ heart block;
▪ sinus node dysfunction;
▪ cardiogenic shock;
▪ severe uncompensated heart failure;
▪ systemic lupus erythematosus (Procainamide).
Adverse effects
▪ arrhythmias: A-V block, torsades de pointes;
▪ cinchonism: nausea, vomiting, diarrhea, tinnitus, headache, vertigo, auditory and
visual disturbances;
▪ hypersensitivity, thrombocytopenia, agranulocytosis;
▪ lupus-like syndrome (Procainamide): arthralgia, arthritis, pleuritis, pericarditis,
parenchymal pulmonary disease;
▪ hypotension (Disopyramide).

CLASS I B ANTIARRHYTHMICS

Mechanism of action
▪ they block the voltage-dependent sodium channels in their refractory state, decrease
action potential duration and increase the effective refractory period.
Indications
▪ treatment and prevention during and immediately after MI, though this practice is
now discouraged given the increased risk of asystole;
▪ ventricular tachycardia;
▪ epilepsy (Phenytoin).
Contraindications
▪ sinoatrial disorders;
▪ total A-V block;
▪ epilepsy or history of convulsions;
▪ porphyria.
Adverse effects
▪ hypotension;
▪ bradycardia;
▪ drowsiness, sedation, confusion, convulsions, paresthesia;
▪ dizziness, respiratory depression, severe hepatic failure (Lidocaine);
 ▪ nausea, vomiting, constipation, arrhythmias, bone marrow suppression, hepatitis
(Mexiletine);
▪ nausea, vomiting, peripheral neuropathy (Phenytoin).

CLASS I C ANTIARRHYTHMICS

Mechanism of action
▪ they are the most potent sodium channel blockers with little effect on repolarization.
Indications
▪ prevents paroxysmal atrial fibrillation;
▪ ventricular tachyarrhythmias.
Contraindications
▪ heart failure;
▪ history of MI.
Adverse effects
▪ anorexia, nausea, vomiting, constipation;
▪ dizziness;
▪ visual disturbances;
▪ arrhythmias.

CLASS II ANTIARRHYTHMICS
(BETA BLOCKERS)

Indications
▪ decrease MI mortality;
▪ prevent recurrence of tachyarrhythmias.

CLASS III ANTIARRHYTHMICS

(POTASSIUM CHANNEL BLOCKERS)

Mechanism of action
▪ they are potassium-channel blockers that prolong cardiac action potential duration
and the effective refractory period;
▪ Amiodarone also blocks sodium and calcium channels;
▪ Sotalol is a β-blocker with class III activity.
Pharmacokinetics
▪ For Sotalol: rapid and complete absorbed after oral administration, the t 1/2 is 12
hours;
▪ For Amiodarone: the t1/2 is 20-100 days, which means slow onset of activity, slow
stabilization of blood levels and long Cl of the drug from blood if toxicity occurs.
Interactions
▪ Amiodarone increases the level of Digoxin and the effects of Warfarin or
Procainamide.
Indications
▪ supraventricular arrhythmias: atrial fibrillation and flutter;
▪ ventricular tachycardias.
Contraindications
 ▪ pheochromocytoma (Bretylium);
▪ A-V block, sinus bradycardia or thyroid dysfunction (Amiodarone);
▪ contraindications of β-blockers.
Adverse effects
▪ arrhythmias (torsades de pointes);
▪ hypotension, nausea and vomiting (Bretylium);
▪ thyroid dysfunction, liver damage, pulmonary disorders, photosensitivity and
neuropathy (Amiodarone);
▪ reduced ventricular function, bradycardia, bronchoconstriction, peripheral vascular
insufficiency, hypoglycemia and withdrawal symptoms (Sotalol).
Therapeutic notes
▪ Bretylium is administered IV while Amiodarone and Sotalol are administered orally or
IV.

CLASS IV ANTIARRHYTHMICS
(CALCIUM CHANNEL BLOCKERS)

Mechanism of action
▪ they are calcium antagonists that shorten phase 2 of the action potential, thus
decreasing action potential duration;
▪ they are particularly effective in nodal cells, where calcium spikes initiate conduction.
Indications
▪ prevent recurrence of paroxysmal supraventricular tachycardia;
▪ reduce ventricular rate in patients with atrial fibrillation or flutter.
Contraindications
▪ heart block;
▪ heart failure;
▪ WPW syndrome.

OTHER ANTIARRHYTHMICS

❖ ADENOSINE

Mechanism of action
▪ Adenosine causes myocyte hyperpolarization and delay in conduction.
Pharmacokinetics
▪ Biotransformation and elimination: it has an extremely rapid metabolism: the t 1/2 is
10 seconds.
Indications
▪ supraventricular arrhythmias.
Contraindications
▪ heart block;
▪ sick sinus syndrome.
Adverse effects (lasting less than 30 seconds)
▪ facial flushing;
▪ chest pain;
▪ dyspnea.
Therapeutic notes
▪ it is administered IV.
 ANTIANGINAL DRUGS

ORGANIC NITRATES

Classification
▪ Short acting nitrates
GLYCERYL TRINITRATE (GTN) – NITROGLYCERINE (sublingual administration)
ISOSORBIDE DINITRATE (ISDN) (sublingual administration)
▪ Long acting nitrates
GLYCERYL TRINITRATE (GTN) – NITROGLYCERINE (local administration)
ISOSORBIDE DINITRATE (ISDN) (oral administration)
ISOSORBIDE MONONITRATE (ISMN) (oral administration)
PENTAERYTHRITYL TETRANITRATE (oral administration)
Mechanism of action
▪ most nitrates are prodrugs, denitrated to produce nitric oxide (“NO”), which activates
guanylyl cyclase, thereby increasing the concentrations of cyclic guanosine 3’,5’-
monophosphate (cGMP), dephosphorilation of the light chain of myosin which results
in smooth muscle relaxation and vasodilation;
▪ venodilation decreases preload and thus the oxygen demand of the heart, while
dilation of the coronary arteries increases blood flow and oxygen delivery to the
myocardium.
Pharmacokinetics
▪ Absorption: ISDN is completely absorbed after oral administration, but only 20%
enters into the systemic circulation as intact drug, the rest being converted to ISMN;
▪ Biotransformation: Hepatic first pass metabolism is high and oral bioavailability is
very low for GTN and ISDN. The t1/2 is 3 minutes for GTN, 10 minutes for ISDN and 280
minutes for ISMN.
Indications
▪ prophylaxis and treatment of angina;
▪ left ventricular failure.
Contraindications
▪ hypersensitivity to nitrates;
▪ hypotension;
▪ hypovolemia.
Adverse effects
▪ postural hypotension;
▪ tachycardia (reflex mediated);
▪ headache (dilation of menningeal arterial vessels), flushing and dizziness;
▪ drug rash (after pentaerythrityl tetranitrate).
Therapeutic notes
▪ the sublingual route of administration is rapid (onset of action 1-3 minutes) and
effective in acute attacks of angina;
▪ the oral (modified release) and transdermal routes of administration are used to
provide prolonged prophylaxis against angina attacks (3-10 hours);
▪ GTN can be given by IV infusion in emergencies, because of the rapid onset of action;
▪ to avoid nitrate tolerance, a drug-free period of approximately 8 hours is needed.
 BETA BLOCKERS
(see antihypertensive drugs)

CALCIUM CHANNEL BLOCKERS

Mechanism of action
▪ they block L-type calcium channels in the heart and in the vascular smooth muscle,
thereby reducing calcium entry into cardiac and vascular cells, reducing cardiac
contractility and causing vasodilation, which results in: reduced preload and
afterload, increased coronary blood flow, reduced cardiac contractility (reduced
myocardial oxygen consumption) and a decreased heart rate;
▪ dihydropyridines blocks L-type calcium channels in vascular cells;
▪ they do not affect cardiac contractility or conduction.
Indications
▪ prophylaxis and treatment of angina;
▪ HBP.
Contraindications
▪ heart block (Verapamil, Diltiazem);
▪ heart failure (Verapamil, Diltiazem);
▪ WPW syndrome;
▪ cardiogenic shock;
▪ advanced aortic stenosis (dihydropiridines).
Adverse effects
▪ hypotension;
▪ rash;
▪ bradycardia, heart block (Verapamil, Diltiazem);
▪ tachycardia (dihydropiridines)
▪ constipation (Verapamil, Diltiazem);
▪ peripheral edema (dihydropiridines);
▪ flushing, dizziness (dihydropiridines).
Therapeutic notes
▪ dihydropyridines are especially useful in angina associated with coronary vasospasm.

POTASSIUM CHANNEL ACTIVATORS

❖ NICORANDIL

Mechanism of action
▪ Nicorandil activates the potassium channels of the vascular smooth muscle and
potassium flows out of the cells, inhibiting the influx of calcium, and the contraction
(vasodilation).
Indications
▪ prophylaxis of angina.
Contraindications
▪ cardiogenic shock;
▪ left ventricular failure;
▪ hypotension.
Adverse effects
▪ headache;
▪ cutaneous vasodilation;
▪ nausea, vomiting.