Calcium entry blockers

Much of the calcium entry blockers are dihydropyridines.

Clacium entry blockers include Amlodipine, Bepridil, Diltiazim, Felodipine, Isradipine, Nicardipine, Nifedipine, Nimodipine, Nisoldipine, Nitrendipine, Verapamil

Mechanism of action:

They get bind to receptors present on L-type calcium channels (voltage gated calcium channels) resulting in the blockage of calcium channels in the heart and in the smooth muscles of the coronary and peripheral vessels. This causes inhibition of calcium inflow to the cardiac and smooth muscle cells resulting in relaxation of muscles.

Actions:

Calcium channel blockers cause relaxation of the arterioles and veins but relaxation is more pronounced in arterioles than in the veins.

Calcium channel blockers causes dilatation of the coronary arterioles and coronary arteries and reduction of coronary artery spasm. This results in elevated oxygen supply to the muscles of the heart in patients with variant angina.

On the other hand, dilatation of the peripheral arterioles causes a decrease in total peripheral vascular resistance leading to decreased blood pressure. This affect is mainly caused by nifedipine. This causes a decrease in oxygen requirement of the muscles of the heart.

All of these factors are responsible for less oxygen requirement in patients with angina:

1. Reduced generation of impulses in SA node and reduced conduction in AV node

2. Reduced cardiac contractility and output

Verapamil and diltiazim show more pronounced effects on the heart.

Verapamil blocks release of insulin.

Verapamil blocks sodium channels less effectively, so that is why it has slight local anesthetic activity.

Pharmacokinetics:
They have a half life of about 2.5-8 hours, when used orally.

Therapeutic uses:
In hypertension when accompanied by angina, diabetes and/or asthma.

They are also used for angina pectoris, hypertrophic cardiomyopathy, migraine and atherosclerosis.

Verapamil is used to treat migraine, angina and supraventricular tachyarrhythmias.

Adverse effects:
They may cause dizziness, bradycardia, cardiac arrest, hypotension, nausea, constipation (in about 10% of patients), flushing and headache.

Contraindications:
These are contraindicated in patients with
1. cardiogenic shock
2. severe hypotension

Classification of Anti-Anginal Drugs

Classification according to differences in agents/groups:

Organic nitrites and nitrates:
Nitrites:
Amylnitrite,

Nitrates:
Erythrityl tetranitrate, Isosorbide dinitrate, isosorbide mononitrate, nitroglycerin, Pentaerythritol tetranitrate

β adrenoceptor blockers:
Nonselective β adrenoceptor blockers:
        Propranolol, Timolol, Nadolol
Selective β1 adrenoceptor blocker:
        Acebutolol, Atenolol, Metoprolol, Esmolol

Ca2+ entry blockers:
Amlodipine, Bepridil, Diltiazim, Felodipine, Isradipine, Nicardipine, Nifedipine, Nimodipine, Nisoldipine, Nitrendipine, Verapamil

Other vasodilator agents:
Dipyridamole, Nylidrin

Miscellaneous agents:
Camphotamide, Prenylamine

Plant products:
Papaverine

Classification according to types of angina pectoris:
Stable angina:
Nitroglycerin,

Variant angina:
Nitroglycerin, calcium entry blockers

Angina

It refers to a severe type of pain from any cause usually angina pectoris is considered.

Angina pectoris:
It is type of condition in which heart lacks blood supply resulting in severe constricting pains in the chest. The pain of angina pectoris often develops and spreads from the precordium of the heart to a shoulder (usually left) and down in the arm (of left side).

Cause of angina:
It may be due to ischemia of the myocardium usually produced as a result of coronary heart disease.

Types of angina:
It may be of different types:

1. Classical angina:
This is also referred to as angina of effort or exercise induced or stable angina or typical angina.
Symptoms:
It is marked by feeling of squeezed chest as well as burning in the chest.
Mechanism:
It may be due to blockage of the large coronary vessels leading to reduced coronary perfusion. This blockage may be caused by lipid deposits in the vessels.

2. Variant angina:

It is also called as vasospastic or prinzmetal’s angina. This often occurs at rest.

Mechanism:
1. It is caused by coronary artery spasm.
2. It also occurs as a result of less flow of blood to the muscles of the heart.

3. Unstable angina:

It occurs fewer than other types of angina and its cause is not among other causes of angina. It is in between stable angina and myocardial infarction. This often occurs at night in bed.

Stable Angina ---------- Unstable Angina ----------- Myocardial Infarction

Treatment of angina:

Angina is treated by any/both of the following mechanisms:
1. Promote perfusion of the muscles of the heart
2. Less metabolic demand of the muscles of the heart

Less requirement of oxygen in patients with angina is done by one of the following mechanisms:
1. Less generation of impulses in SA node
2. Reduced conduction velocity in AV node and Purkinje cells
3. Reduced contractions of the heart muscles
4. Reduced cardiac output.

Classification of Anti-Anginal Drugs

Transferrin

Transferrin: A protein in the serum which gets bound with the iron and helps in its transportation to the bone marrow.