Adenosine

It is one of the naturally occurring nucleoside.
Action:
It causes a reduction in conduction velocity. It causes an increased refractory period and reduces automaticity in the AV node.

Pharmacokinetics:
Its duration of action is short. Its half life is approximately 10 seconds.

Therapeutic uses:
Acute supraventricular tachycardia (IV administration)

Adverse effects:
Flushing, chest pain, dyspnea, hypotension

Digoxin

Action:
It causes a decrease in refractory period in atrial and ventricular cells of heart muscles. It causes an increase in effective refractory period and decreasing conduction velocity in AV node.

Therapeutic uses:
Atrial fibrillation and flutter (while controlling ventricular response rate).

Adverse effects:
It may cause ventricular beats originating from abnormal place. These beats may cause ventricular tachycardia and fibrillation. (treated with lidocaine or phenytoin)

Verapamil and Diltiazem

Verapamil has major affect on heart muscles than on vascular smooth muscles. has major affect on heart muscles than on vascular smooth muscles.

Nifedipine has major affect on vascular smooth muscles than on heart. So, used to treat hypertension.
Diltiazem has medium affect.

Actions:
Calcium enters the cells through two channels:
1. Voltage sensitive channels
2. Receptor operated channels

The entry of calcium is controlled by the binding of agonists like catecholamines to the receptors.

Calcium entry blockers have pronounced effect on voltage sensitive channels leading to the slow influx of calcium resulting in contraction of cardiac muscles.

Verapamil and diltiazem gets bind to open, depolarized channels only, thus blocking the repolarization till the drug is dissociated from the channel.

They are therefore helpful only when there is rapid heart beat. (Normally, the calcium channels takes time for the repolarization until then the bound drug gets detached from the channel).

By reducing the inward flow, verapamil and diltiazem:
1. Decreases the conduction and
2. Increases the effective refractory period in AV node.

Therapeutic uses:
1. Atrial and ventricular arrhythmias
2. Reentrant supraventricular tachycardia
3. Decreases the ventricular rate in atrial flutter and fibrillation
4. Hypertension
5. Angina

Pharmacokinetics:
They are absorbed orally. Verapamil is extensively metabolized in the liver.

Adverse effects:
1. Negative inotropism
2. Reduces blood pressure (due to peripheral vasodilation. This effect is helpful in hypertension.)

Class IV Antiarrhythmic Drugs

These are calcium entry blockers. Its major effect is seen in vascular smooth muscle and the heart.


Action:
It reduces the influx of calcium leading to reduced rate of Phase 4 (spontaneous depolarization).

It also causes a reduction of conduction in those tissues which are dependent on calcium flow i.e. AV node.

Dofetilide

Pharmacokinetics:
Its half life is about 10 hours. It is excreted in urine.

Therapeutic uses:
1. First line agent in sustained atrial fibrillation. Alongwith, amiodarone and β-blocking agents it is mostly used for atrial fibrillation.
2. In coronary disease of artery when left ventricular function is disturbed.

Sotalol

It also has a potent non-selective β-blocking agent.

As indicative of β-blocking agents, it also has the ability of decreasing mortality from acute myocardial infarction.

Actions:
It causes the inhibition of potassium outflow (also referred to as delayed rectifier). This inhibition increases both
1. Repolarization and
2. Action potential duration

And have the ability of prolonging the effective refractory period.

It has the ability of suppressing the ectopic beats and decreases myocardial oxygen demand. In the case of myocardial ischemia, it has prominent anti-fibrillatory affect.

Therapeutic uses:
1. Myocardial Ischemia
2. Sustained ventricular tachycardia

Adverse effects:
Prolonging the QT interval leading to torsade de pointes syndrome.

Class III Antiarrhythmic Drugs

These are potassium channel blockers.


Actions:
They reduce the outward flow of potassium during repolarization phase of cardiac cells.

They have the ability of increasing the duration of action potential without changing Phase 0 of depolarization or the resting membrane potential.

They also have the ability of prolonging the effective refractory period.

Class III antiarrhythmic agents have the potential of induction of arrhythmias.