Antianginal drugs Antidysrrhytmic drugs Anton Kohút P.J. Šafárik University Faculty of Medicine Department of Pharmacology Košice Ladies and gentlemen, I would like to present, in couple of minutes, our preliminary results of recent project . Impact……

DRUGS INFLUENCING THE HEART a. Blod flow (supply by O2) 1. Antianginal drugs b. Rhytm and rate 2. Antidysrhytmic drugs c. Contraction (used to treat cardiac failure) 3. Cardiotonics

Antianginal drugs

Angina pectoris

Angina pectoris occurs when where is an imbalance between the oxygen suply and oxygen demands .

Cellular changes after ischemia

Causes of O2 imbalance Supply decreased by : Coronary artery disease Decrease of vessel calibre Compression of intramyocardial vessels Anaemia Demands are increased by:  Exercise  Tachycardia  Hypertension (increased preripheral resistance - afterload)  Filling pressure ) preload)

Therapeutic strategy To increase supply To reduce demands Dilatation of the coronary artery Decrease of ventricular wall tension To reduce demands Decrease of myocardial contraction Decrease of heart rate  Decrease of preload  Decrease of afterload

Vasodilators (dilate arteries and veins) -  calcium-channel blockers - nitrodilators Cardioinhibitory drugs (reduce heart rate and contractility) -  beta blockers -  calcium-channel blockers Ranolizine (blocker of late sodium currents) Trimezatidine Anti-thrombotic drugs (prevent thrombus formation) -  anticoagulants -  anti-platelet drugs

Antianginal drugs

Nitrates and nitrites

Mechanism of action of nitrates

Organic nitrates History - Nitroglycerin was first synthesized in 1846 - Hering, in 1847, developed the sublingual dosage form. Chemistry - Organic nitrates - esters of nitric acid, - Organic nitrites - esters of nitrous acid are capable of denitration to release nitric oxide (NO) Effects - Relaxation most of smooth muscle - Dilatation of the veins predominates over that of arterioles - Decrease of preload - Systemic arterial pressure may fall slightly, and heart rate is unchanged or slightly increased reflexly. Other Effects The nitrovasodilators act on almost all smooth muscle.

Beta antagonists

Beta antagonists and cardiac rhytm

Classification of beta blockers

Calcium-channel blockers

Actions Therapeutic uses Hypertension Angina pectoris Cardiac failure Dysrhytmias

Grops of calcium channels blockers

Therapeutic uses of calcium channel blockers  angina pectoris (verapamil, diltiazem),  cardiac failure (verapamil, diltiazem, amlodipine, nisoldipine),  dysrrythmias (verapamil, diltiazem),  hypertensions (dihydropyridines),  migraine (verapamil),  stroke (nimodipine). Side effects - tachykardia (nifedipine) - ortostatic hypotension

Ranolazine Ranolazine represents a new class of antianginal drugs. By blocking late inward sodium currents, calcium overload and diastolic wall stress are reduced, leading to improved coronary blood flow. Partial fatty oxidation inhibitor This agent is likely to become standard therapy for chronic stable angina and may play a future role in the management of acute coronary syndromes.

Antidysrhytmic drugs

Therapeutic indications of antiarrhythmic agents