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.)