Calcium

Role of calcium:

Calcium is one of the essential components for contraction of muscles. Calcium is also responsible for the excitation-secretion coupling in exocrine and endocrine glands.

Calcium channels:

Calcium got entry into cells through pores in the membrane. These particular pores are named as calcium channels.

Types of calcium channels:

Action of calcium:

The calcium influx is elevated in ischemia as a result of membrane depolarization that is caused by reduced oxygen supply. This depolarization is voltage operated and is done by L- type channels. This increase results in the rise of activity of many ATP-consuming enzymes resulting in the reduction of energy stores. This leads in increase of ischemic effects.

Sometimes channels are opened by receptors for neurotransmitters and therefore this activation is referred to as receptor operated.

Mechanism of action of calcium entry blockers:

Calcium entry blockers get stick to receptors on voltage gated calcium channels resulting in blockage of these channels and saving tissues by preventing the entry of calcium into smooth muscle cells of the systemic arterial beds and muscle cells of coronary arteries (of the heart). Thus they reduce myocardial oxygen demand by saving ATP of muscles of the heart.

Some of the calcium entry blockers cause arteriolar dilatation; resulting from the decreased oxygen demand of the heart muscles, by affecting the heart directly i.e. causes the heart to beat slowly. They are, therefore, also working as vasodilators resulting in the decrease in smooth muscle tone and vascular resistance.

Actions:

Calcium entry blockers work better when the tissue is depolarized. At therapeutic doses, these agents affect on the resistance of vascular smooth muscle and the muscles of the heart.

They also decrease blood pressure.

They have negative chronotropic and inotropic effect resulting in less oxygen demand.

The prominent effect (anti-anginal) in angina caused by exercise and unstable angina is achieved by the reduction in cardiac afterload. On the other hand, vasospastic angina is relieved by dilatation of the coronary arteries and arterioles.

Calcium plays essential role in


1. contraction of muscles of the heart
2. regulating the firmness of the smooth muscles

Calcium get entry to the muscle cells through special channels namely voltage gated calcium channels. As a result, the release of calcium from the sarcoplasmic reticulum and mitochondria is initiated. This causes an additional elevation in the level of calcium in the fluid part of the cytoplasm (cytosol).
Therapeutic Uses:
They are also used in:
1. Systemic hypertension
2. Peripheral vascular disease
3. Hypertrophic subaortic stenosis
4. Stroke
5. Migraine
6. Suppression of atherogenesis

Adverse effects:
Hypotension, Headache, flushing, dizziness (These are caused by vasodilatory effects of calcium entry blockers).
Bradycardia (This is caused by less SA automaticity).
Heart block (This may be caused by reduced AV conduction).
Congestive heart failure (may be due to reduced contraction of the heart muscle).

Constipation (may be due to gentle excitation-contraction uncoupling in GI smooth muscle).