Anti-Anginal Drugs

Pathophysiology:

• 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.

Anti-angina drugs:

• 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:

1. Nitrates:

• Mainstay therapy for immediate angina relief.
• MOA: Reduces preload & lowers end diastolic pressure.
• Drugs:
  • 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
• CCB’s:
  • Phenyl alkylamine: Verapamil
  • Benzothiazepine: Diltiazem
  • Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine, Lacidipine, Lercanidipine, Benidipine.
• MOA:
  • By vasodilation.
  • By decreasing heart rate & contractility.
• Uses: Indicated only for unresponsive coronary spasm to nitrates.

3. β-Blockers:

• Only anti-anginal drugs decreasing mortality in CAD patients (Post-MI).
• Drugs: Propranolol, Metoprolol & Atenolol.
• MOA: 
  • 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:

• Nicorandil.
• MOA:
  • By coronary dilation – By activating myocardial ATP sensitive K+ channels.
  • Possess NO releasing property without tolerance property.

6. Metabolic modifier:

• Trimetazidine:
  • MOA: Improves cellular tolerance to ischemia.
  • No effect on HR/BP.
  • Cause reversible parkinsonism.

7. Newer drugs:

7a. Ranolazine:

• • 1^st new antianginal drug approved by FDA.
  • Approved as first-line agent for chronic angina.
  • Congener of trimetazidine.
• MOA: 
  • LC3-KAT inhibitor.
  • Spares fatty acid oxidation & inhibits late I_Na+ current in myocardium indirectly facilitating Ca²⁺ entry.
• Uses:
  • Chronic angina.
  • Erectile dysfunction.
• Adverse effects:
  • QT prolongation.
  • Small decrease in HbA1C.
• Contraindications:
  • Treatment of acute anginal episodes.
  • Liver & kidney disease.

7b. Ivabradine:

• New drug.
• A bradycardiac agent – Decreases heart rate without affecting conduction or contractility).
• MOA: 
  • Acts by blocking hyperpolarization activated sodium channel (carries funny current).
• Adverse effect:
  • Visual disturbances (most important)

7c. Fasudil:

• 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
• Oxyphedrine.

Don’t Forget to Solve all the previous Year Question asked on ANTI-ANGINAL DRUGS