- Major symptom – Chest pain.
- Due to imbalance between oxygen supply & demand.
- Due to fixed atherosclerotic narrowing of coronary arteries.
Aim of management:
- Two major strategies for treatment & prevention of angina:
- Decreasing oxygen requirement.
- Increasing blood supply to ischemic region.
- New strategy: By making efficient utilization of substrates by heart.
- Nitrates (GTN, isosorbide dinitrate), beta-blockers, CCB’s, fatty acid oxidation inhibitors, potassium channel opener (Nicorandil), metabolic modifiers (Trimetazidine) & newer drugs.
Classification of drugs:
- To abort or terminate attack: GTN,lsosorbide dinitrate (sublingually).
- For chronic prophylaxis: All other drugs.
- For chronic resistant angina: Ranolazine (LC-3 KAT inhibitor & metabolic modifier-spares fatty acid oxidation).
Important drugs & description:
- Mainstay therapy for immediate angina relief.
- MOA: Reduces preload & lowers end diastolic pressure.
- Short acting: Glyceryl trinitrate (GTN, Nitroglycerine).
- Long acting: Isosorbide dinitrate (short acting by sublingual route), Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritot tetranitrate
2. Calcium channel blockers & β-blockers:
- For prophylaxis
- Phenyl alkylamine: Verapamil
- Benzothiazepine: Diltiazem
- Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine, Lacidipine, Lercanidipine, Benidipine.
- By vasodilation.
- By decreasing heart rate & contractility.
- Uses: Indicated only for unresponsive coronary spasm to nitrates.
- Only anti-anginal drugs decreasing mortality in CAD patients (Post-MI).
- Drugs: Propranolol, Metoprolol & Atenolol.
- By reducing myocardial oxygen demand –
- Due to negative chronotropic effect (particularly during exercise), negative inotropic effect, & reduced arterial blood pressure (particularly systolic pressure) during exercise.
- Decreased heart rate & contractility → Increases systolic ejection period & left ventricular end-diastolic volume → Increases O2 consumption.
- Long-term β-blocker therapy – Total amount of “ischemic time”/day reduced.
- Contra-indications: Variant angina.
4. Fatty acid oxidation inhibitors:
- MOA: Alters myocardial metabolism.
5. Potassium channel opener:
- By coronary dilation – By activating myocardial ATP sensitive K+ channels.
- Possess NO releasing property without tolerance property.
6. Metabolic modifier:
- MOA: Improves cellular tolerance to ischemia.
- No effect on HR/BP.
- Cause reversible parkinsonism.
7. Newer drugs:
- 1st new antianginal drug approved by FDA.
- Approved as first-line agent for chronic angina.
- Congener of trimetazidine.
- LC3-KAT inhibitor.
- Spares fatty acid oxidation & inhibits late INa+ current in myocardium indirectly facilitating Ca2+ entry.
- Chronic angina.
- Erectile dysfunction.
- QT prolongation.
- Small decrease in HbA1C.
- Treatment of acute anginal episodes.
- Liver & kidney disease.
- New drug.
- A bradycardiac agent – Decreases heart rate without affecting conduction or contractility).
- Acts by blocking hyperpolarization activated sodium channel (carries funny current).
- Visual disturbances (most important)
- Selective Rho A/Rho kinase (ROCK) inhibitor.
- ROCK – An enzyme involved in vasoconstriction & cardiac remodeling.
- ROCK enzyme inhibition –> Causes vasodilation.
- Used in angina & cerebral vasospasm.
8. Other antianginal drugs:
- Dipyridamole: Failure drug due to coronary steal phenomenon
- Two major strategies for treatment & prevention of angina are decreasing oxygen requirement & increasing blood supply to ischemic region.
- New strategy for development of anti-angina drug is by making efficient utilization of substrates by heart.
- Anti-angina drugs include nitrates (GTN, isosorbide dinitrate), beta-blockers, CCB’s, fatty acid oxidation inhibitors, potassium channel opener (Nicorandil), metabolic modifiers (Trimetazidine) & newer drugs.
- GTN, isosorbide dinitrate (sublingually) aborts or terminate acute anginal attack.
- Ranolazine (LC-3 KAT inhibitor & metabolic modifier-spares fatty acid oxidation) is used for chronic resistant angina.
- Glyceryl trinitrate (GTN, Nitroglycerine) are short-acting nitrates.
- Isosorbide dinitrate (short-acting by sublingual route), Isosorbide mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate are all long-acting nitrates.
- Nitrates are mainstay therapy for immediate angina relief.
- Nitrates reduce preload & lowers end diastolic pressure.
- CCB’s are indicated only for unresponsive coronary spasm to nitrates.
- β-Blockers are only anti-anginal drugs decreasing mortality in CAD patients (Post-MI).
- β-Blockers acts by reducing myocardial oxygen demand.
- β-Blockers are contraindicated in variant angina.
- Fatty acid oxidation inhibitors act by altering myocardial metabolism.
- Nicorandil is a potassium channel opener.
- Nicorandil acts by coronary dilation, by activating myocardial ATP sensitive K+ channels.
- Trimetazidine is a metabolic modifier.
- Ranolazine is a 1st new antianginal drug approved by FDA, approved as first-line agent for chronic angina.
- Ranolazine is a congener of trimetazidine.
- Ranolazine is LC3-KAT inhibitor, spares fatty acid oxidation & inhibits late INa+ current in myocardium indirectly facilitating Ca2+ entry.
- Ivabradine is a bradycardiac agent.
- Fasudil is a selective Rho A/Rho kinase (ROCK) inhibitor.
- Fasudil is used in angina & cerebral vasospasm.
- Dipyridamole is a failure drug due to coronary steal phenomenon.
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