Treatment of T Angina reatment of By Ali Alalawi

Transcription

1 Treatment of Angina By Ali Alalawi

2 Determinants of Oxygen Demand Need to improve ratio of: Coronary blood flow / cardiac work Or Cardiac O2 Supply / Cardiac Requirement

3 Coronary Circulation vs Other Circulation Most tissues can increase O2 extraction with demand Heart extracts near maximal amount of O2 at rest. Therefore can only increase O2 delivery by increasing coronary blood flow

4 Goals of Treatment Antianginal drugs may relieve attacks of acute myo- cardial ischemia by: 1. Increasing myocardial oxygen supply or 2. Decreasing myocardial oxygen demand or 3. Both.

5 Three groups of pharmacological agents have been shown to be effective in reducing the frequency, severity, or both of primary or secondary angina. These agents include : 1. The nitrates. 2. B-adrenoceptor antagonists. 3. Calcium entry blockers.

6 Improving supply/demand ratio 1. Relaxation of resistance vessels (small arteries and arterioles) TPR BP Afterload (Nitrates, calcium channel blockers and beta-blockers) 2. Relaxation of capacitance vessels (veins and venules) Venous return, heart size, Preload (Nitrates and calcium channel blockers) 3. Blockade or attenuation of sympathetic influence on the heart demand Contactility, HR, O2 (Beta-blockers) 4. Coronary Dilation - Important mechanism for relieving vasospastic angina O2 supply (Nitrates)

7 The Nitrates: Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol which lead to activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), Lead to producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation.

8 N I T R A T E S

9 Nitrates Common Available Agents Isorbide dinitrate Isorbide mononitrate Long-acting transdermal patches Nitroglycerin sl

10 Nitrates Side Effects Headache Flushing Palpitations Tolerance

11 Nitrates Reducing Tolerance Smaller doses Less frequent dosing Avoidance of long-acting formulations unless a prolonged nitrate-free interval is provided Build-in a nitrate-free interval 8-12 hours

12 B-adrenoceptor antagonists. Common Available Agents : Propranolol Atenolol Metoprolol Nadolol Timolol

13 Mechanism of action of ß-blockers Activation of ß adrenoceptors on heart Cardiac Output Peripheral resistance B 1BLOCKERS Decrease in blood pressure Angiotension II Renin aldosterone Sodium, water retention Blood volume

14 ß-blockers

15 ß-blockers: Decrease myocardial oxygen consumption Blunt exercise response Beta-one drugs have theoretical advantage Try to avoid drugs with intrinsic sympathomimetic activity First line therapy in all patients with angina if possible

16 Side effects: Bronchospasm Diminished exercise capacity Negative inotropy Sexual dysfunction Bradyarrhythmia Masking of hypoglycemia

17 Calcium entry blockers. Mechanism of action: 1. They block voltage-dependent L-type calcium channels relaxation of smooth muscle vasodilation reduce peripheral vascular resistance reduction of BP. 2. Block platelet aggregation. Uses: particularly effective in the prophylaxis of coronary vasospasm or variant angina. These compounds are used in the chronic treatment of secondary angina. Two members of this group: verapamil Diltiazem Also have been approved for use in the therapy of certain supraventricular tachyarrhythmias

18 alcium blockers. Ca

19 Side Effects: Palpitations Headache Ankle edema Gingival hyperplasia

20 Drug Choices in Angina A. Effort: nitrates, calcium blockers, beta blockers B. Variant: nitrates, calcium blockers, beta blockers, aspirin, anticoagulants, thrombolytics Aims in the use of antianginal drugs: a. Treatment of acute attack - nitroglycerin very effective (i.e., sublingual, oral spray) b. Short term prophylaxis - taking nitroglycerin prior to anticipated physical or emotional stress may prevent attack c. Long term prophylaxis - objective is to reduce frequency of anginal attacks. Many options are now availabile i.e. Ca blockers, ß- blockers, aspirin, anticoagulants, thrombolytics

21 Qustions

22