Antianginal drugs 1 Angina pectoris is characterized by

Antianginal drugs 1

• Angina pectoris is characterized by sudden severe pressing chest pain or heaviness radiating to the neck, jaw, back and arms. • • It is often associated with diaphoresis, tachypnea and nausea. • • Angina is caused by coronary flow that is insufficient to meet oxygen demands of the myocardium. • 3. There are three types of Angina : • 1. Stable Angina • 2. Unstable Angina • 3. Prinzmetal (variant) angina 2

Stable Angina • • Attacks are provoked by exercise, emotion etc. It lasts for several seconds and subsides on rest. • • “Stable” indicates the reproducible nature of the angina; the same activity at the same intensity produces symptoms. 3

Unstable Angina • The unstable angina is characterized by recurrent attacks of angina. • It occurs with minimal exertion. • It is precipitated due to combination of athero scleroti-plaque, platelet aggregation at ruptured plaque and vasospasm. 4

Prinzmetal (Variant) Angina • This is a relatively uncommon usually occurring at rest or during sleep and often in young individuals. • It is induced by coronary artery vasospasm. • it generally responds promptly to vasodilators. 5

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Nitroglycerin , Isosorbide mononitrate Isosorbide dinitrate Nitrates release nitric oxide which is a powerful vascular smooth muscle relaxant. more effective on veins than arteries 7

Preload reduction • Nitroglycerin dilates veins more than dilation of arteries, resulting in peripheral pooling of blood & decreased venous return. decreased preload Afterload reduction • Nitrates also produce some arteriolar dilatation Decrease peripheral resistance Reduction of afterload Redistribution of coronary flow • Dilatation of coronary arteries Increase blood supply to the myocardium. Oter effects • Relax the bronchi, biliary tracts & esophagus muscles. • Also dilates cutaneous & meningeal vessels. 8

Pharmacokinetics • Absorbed through buccal mucosa (SL), skin & GIT • All except Isosorbide Mononitrate undergo extensive first pass metabolism • SL route produces rapid onset 2 -5 Min, but shorter duration • Absorption through skin is slow Adverse effects • Headache • Postural hypotension • Tachycardia, palpitations • Weakness • Flushing • Tolerance on prolonged use • Overdosage may cause methemoglobinemia 9

Uses of Nitrates • Angina: – Sublingual NTG drug of choice for acute anginal attacks. Oral nitrates can be used for prophylaxis of angina • Myocardial Infarction • Congestive heart failure • Biliary colic • Cyanide poisoning (Nitrates form methemoglobin which has an affinity for binding cyanide forming cyanmethemoglobin, a less toxic form of cyanide. ) • Esophageal spasm 10

Calcium channel blockers • Block Voltage sensitive L-type of Ca 2+ channels. • Prevent entry of calcium into the cell. • No excitation contraction coupling in the heart and vascular smooth muscles. • ↓ Myocardial contractility • ↓ Cardiac work & oxygen consumption • Coronary vasodilation • Relaxation of Vascular smooth muscles ↓ PVR & After Load 11

Calcium channel blockers Verapamil & Diltiazem • Have more effect on heart than in vascular smooth muscle. • Causes decrease automaticity of heart, decrease conduction velocity, decrease contractility. • Useful for arrhythmia & angina (due to cardiac depressant action. ) • Therapeutic uses of verapamil & Diltiazem • 1. Exertional angina , Unstable angina , Angina due to coronary spasm (Prinzmetal angina or variant angina) 2. Systemic Hypertension • 3. Atrial fibrillation, flutter , Paroxysmal supraventricular tachycardia. 12

Nifedipine, amlodipine – significantly more arteriolar vasodilation, little effect on cardiac tissue. More used in systemic hypertension. Nifedipine has more vasodilation effect which can even lead to reflex tachycardia • Amlodipine is more useful antihypertensive agent. Therapeutic uses 1. Exertional angina , Unstable angina , Coronary spasm 2. 2. Hypertension 3. 3. Raynaud’s phenomenon 13

Adverse effects (Extension of pharmacological actions). Nifedipine: Flushing, tachycardia Verapamil : Constipation excessive smooth muscle relaxation in GI smooth muscle Bradycardia, atrioventricular block, heart failure 14

Beta blockers • Reduce frequency and severity of anginal attacks of exertional angina • Used for long term prophylaxis of classical angina, may be combined with nitrates MOA: ↓ oxygen consumption by ↓contractility & HR • Selective Beta blockers are preferred 15

Others ►ACEI. ►Anticoagulants and/or Thrombolytic Therapy. ►Cholesterol Lowering Agents. ►Angioplasty ►Surgery. 16