Antianginal drugs

Antianginal Drugs : Antianginal Drugs Dr. Feras Darwish El-Hajji

Introduction : Introduction Angina: Coronary artery disease (CAD) or ischemic heart disease (IHD)

Introduction : Introduction Symptoms of angina: Sudden severe pressing chest pain radiating to the neck, jaw, back and arms Chronic ischemia may lead to deterioration of cardiac function  heart failure, arrhythmias and sudden death Management of angina: 1- Lifestyle modification 2- Risk factor prevention 3- Drugs 4- Surgery

Types of angina : Types of angina A. Stable angina (classic or effort induced): Most common type of angina Symptoms: short-lasting burning, heavy or squeezing feeling in the chest Causes: physical activity, emotional excitement or any other cause of increased cardiac workload Relief: rest or nitroglycerin

Types of angina : Types of angina B. Unstable angina: Stable angina  unstable angina  MI Symptoms: increased frequency, duration and intensity of angina symptoms How to decide: Rest angina for > 20 min New onset of angina Increasing symptoms, appearing shortness of breath Not responding to nitroglycerin Action: hospital admission

Types of angina : Types of angina

Types of angina : Types of angina C. Prinzmetal angina: Variant, vasospastic or rest-angina Mainly due to coronary artery vasospasm Unrelated to physical activity Relief: coronary vasodilators such as nitroglycerin and calcium-channel blockers

Acute coronary syndrome : Acute coronary syndrome Can be: Unstable angina ST-segment Elevation MI (STEMI) Non-ST-segment Elevation MI (NSTEMI) Acute coronary syndrome ST-segment elevation Biomarkers (e.g. Troponin and CK) Unstable angina X X STEMI √ √ NSTEMI X √

Organic nitrates : Organic nitrates They cause a rapid relief of symptoms of angina by a rapid reduction in myocardial oxygen demand Effective in stable, unstable and variant ( Prinzmetal ) angina Differ in their volatility: Isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN): solids at room temp. Nitroglycerin ( glyceryl trinitrate ): moderately volatile Amyl nitrite: extremely volatile

Organic nitrates : Organic nitrates MOA: 1- Coronary vasodilation  ↑ myocardial perfusion 2- Venodilation  ↓ preload and myocardial O 2 consumption

Short-acting organic nitrates : Short-acting organic nitrates Nitroglycerin For prompt relief of an ongoing attack of angina (due to physical or emotional stress) Route of administration: sublingual, oral or transdermal Dosage forms: tablet, spray or patches If angina attack symptoms were relieved within 5 min  stable angina If symptoms persist for 20 – 30 min  unstable angina

Short-acting organic nitrates : Short-acting organic nitrates Time to onset of action = 1 min Significant 1 st pass metabolism in the liver Side effects: headache, orthostatic hypotension, flushing and tachycardia Contraindication: with phosphodiesterase 5 inhibitors e.g. Sildenafil , ta dalafil and vardenafil

Short-acting organic nitrates : Short-acting organic nitrates Time to onset of action = 1 min Significant 1 st pass metabolism in the liver Side effects: headache, orthostatic hypotension, flushing and tachycardia Contraindication: with phosphodiesterase 5 inhibitors e.g. Sildenafil , tadalafil and vardenafil

Long-acting organic nitrates : Long-acting organic nitrates ISDN and ISMN Route of administration: oral and transdermal Dosage form: tablet and patches Low dose of ISDN can be taken as sublingual Onset of action: longer than nitroglycerin

Long-acting organic nitrates : Long-acting organic nitrates ISDN is more susceptible to liver enzyme metabolism  giving two mononitrates ISMN has LONGER duration of action than ISDN Side effects and contraindications: the same as nitroglycerin

Nitrates : Nitrates

Tolerance to nitrates : Tolerance to nitrates Desensitisation to vasodilatory effect of the nitrates Develops rapidly Solution: nitrate-free interval for 10 to 12 hours  to restore sensitisation Nitrate-free interval is usually at night, unless angina happens at early morning  make it afternoon Transdermal patches: for 12 hours, then remove for another 12 hours

β-blockers : β -blockers Metoprolol , atenolol , carvedilol and propranolol Drug of choice to control effort-induced angina ↓ O 2 consumption by having negative inotropic and chronotropic effect Reduce the frequency and severity of angina attacks Avoid β -blockers with intrinsic sympathomimetic activity

Calcium channel blocker : Calcium channel blocker

Calcium channel blocker : Calcium channel blocker Not preferred with β -blockers Verapamil and diltiazem are contraindicated with β -blockers Main site of action Drug Group Myocardium Verapamil Nondihydropyridine Intermediate (myocardium and vasculature) Diltiazem Vasculature Nifedipine Dihydropyridine Amlodipine Felodipine Nicardipine

Calcium channel blocker : Calcium channel blocker Verapamil : Slows cardiac AV conduction  ↓ HR, ↓ contractility, ↓ BP and ↓ O 2 demand Greater – ive inotropic effect than other calcium channel blockers Weaker as a vasodilator Adjust the dose in liver dysfunction Causes constipation

Calcium channel blocker : Calcium channel blocker Diltiazem : Has almost the same cardiovascular effect as verapamil ↓ HR but to a lesser extent than verapamil Relieves coronary artery spasm  good for Prinzmetal (variant) angina Well tolerated

Calcium channel blocker : Calcium channel blocker Nifedipine : Short acting dihydropyridine Arteriolar vasodilator (minimal effect on cardiac conduction or HR) Oral extended-release tablets S.E: flushing, headache, hypotension, peripheral oedema and constipation Vasodilatory effect may cause reflex tachycardia

Ranolazine : Ranolazine Antagonises sodium current  improves diastolic function For chronic management of angina (not acute attacks) Usually in combination with other drugs