Antianginal Drugs: Nitrates, Beta-Blockers, and More

Antianginal Drugs: Overview

• Antianginal drugs relieve chest pain (angina pectoris) caused by reduced blood flow to the heart muscle (ischemia).
• Angina pectoris occurs due to an imbalance between myocardial oxygen supply and demand.
• The main determinants of myocardial oxygen demand are heart rate, myocardial contractility (wall tension), and ventricular wall stress (preload and afterload).
• Antianginal drugs either increase myocardial oxygen supply or decrease myocardial oxygen demand.

Classification of Antianginal Drugs

• The main classes of antianginal drugs include nitrates, beta-blockers, and calcium channel blockers.
• Other drugs like ranolazine, ivabradine and trimetazidine are also used.

Nitrates

• Nitrates, like glyceryl trinitrate (GTN, nitroglycerin) and isosorbide dinitrate/mononitrate, are prodrugs that release nitric oxide (NO).
• NO activates guanylate cyclase, increasing cGMP levels in smooth muscle cells, leading to vasodilation.
• Nitrates primarily cause venodilation, reducing preload and decreasing myocardial oxygen demand.
• They also dilate coronary arteries, improving myocardial oxygen supply, especially in cases of vasospasm.
• GTN is used sublingually for acute angina attacks because of its rapid onset of action.
• Isosorbide dinitrate and mononitrate have longer durations of action and are used prophylactically.
• Common side effects include headache (due to meningeal artery vasodilation), flushing, and reflex tachycardia.
• Tolerance can develop with prolonged use, requiring nitrate-free intervals to maintain efficacy.

Beta-Adrenergic Blockers (Beta-Blockers)

• Beta-blockers, such as propranolol, metoprolol, and atenolol, block beta-adrenergic receptors in the heart.
• They decrease heart rate and contractility, reducing myocardial oxygen demand.
• Beta-blockers are effective in chronic stable angina.
• They are contraindicated in vasospastic angina (Prinzmetal's angina) because they can worsen vasospasm.
• Beta-blockers should be avoided in patients with asthma, severe bradycardia, or heart block.
• Common side effects include bradycardia, fatigue, and bronchospasm.

Calcium Channel Blockers (CCBs)

• Calcium channel blockers, such as verapamil, diltiazem, and nifedipine, block calcium channels in vascular smooth muscle and cardiac muscle.
• They cause vasodilation, reducing afterload and decreasing myocardial oxygen demand.
• Some CCBs (verapamil and diltiazem) also decrease heart rate and contractility.
• CCBs are effective in both stable and vasospastic angina.
• Dihydropyridines (e.g., nifedipine, amlodipine) are more selective for vascular smooth muscle and cause more vasodilation.
• Verapamil and diltiazem can cause bradycardia and should be used cautiously in patients with heart failure.
• Common side effects include headache, flushing, and peripheral edema (more common with dihydropyridines).

Ranolazine

• Ranolazine reduces angina symptoms by inhibiting the late sodium current (INa) in cardiac myocytes.
• This reduces intracellular sodium and calcium overload, improving myocardial relaxation and decreasing diastolic wall tension.
• Ranolazine does not significantly affect heart rate or blood pressure.
• It can prolong the QT interval and should be used with caution in patients with pre-existing QT prolongation.

Ivabradine

• Ivabradine selectively inhibits the If (funny current) channel in the sinoatrial (SA) node, reducing heart rate without affecting contractility or blood pressure.
• It is used in patients with stable angina who are unable to tolerate beta-blockers or when beta-blockers are contraindicated.
• Ivabradine is contraindicated in patients with severe hepatic impairment, sick sinus syndrome, or heart block.
• Common side effects include bradycardia and visual disturbances (phosphenes).

Trimetazidine

• Trimetazidine inhibits fatty acid oxidation, shifting myocardial metabolism towards glucose oxidation.
• This improves the efficiency of ATP production and reduces myocardial ischemia.
• It does not significantly affect heart rate or blood pressure.
• Trimetazidine is used as an add-on therapy in patients with stable angina who are not adequately controlled with other antianginal drugs.
• Common side effects are rare but can include gastrointestinal disturbances and extrapyramidal symptoms.

Combination Therapy

• Combination therapy with different classes of antianginal drugs may be necessary to control angina symptoms in some patients.
• Common combinations include nitrates with beta-blockers or calcium channel blockers.
• Careful monitoring is required to avoid excessive hypotension or bradycardia.

Choice of Antianginal Drug

• The choice of antianginal drug depends on the type of angina, patient comorbidities, and potential side effects.
• Beta-blockers are often the first-line therapy for chronic stable angina.
• Nitrates are useful for both acute relief and prophylaxis of angina.
• Calcium channel blockers are effective in both stable and vasospastic angina.
• Ranolazine, ivabradine, and trimetazidine are used as add-on therapies or when other drugs are contraindicated or not tolerated.

Management of Acute Angina Attack

• Sublingual GTN is the drug of choice for acute angina attacks.
• The patient should rest and take one tablet sublingually.
• If the pain persists after 5 minutes, another tablet can be taken.
• If the pain is not relieved after 3 tablets, medical attention should be sought immediately.