Antianginal Agents

Angina Pectoris - The Squeezing Truth

• Symptom complex: Chest pain/discomfort due to transient myocardial ischemia.
• Pathophysiology: Imbalance between myocardial oxygen supply (coronary flow) and demand (HR, contractility, wall tension).
• Key Types:
  • Stable (Typical/Effort): Atherosclerotic obstruction; triggered by exertion, relieved by rest/nitrates.
  • Unstable: Rupture of atherosclerotic plaque; occurs at rest or minimal exertion.
  • Variant (Prinzmetal): Coronary artery spasm; often at rest.
• Therapeutic Goals: ↓ Myocardial O₂ demand, ↑ O₂ supply.

⭐ Unstable angina is a medical emergency requiring immediate attention.

Nitrates - Vasodilation Victory

• Mechanism: Release NO → ↑cGMP → vasodilation (venous > arterial). ↓Preload, ↓O2 demand. Coronary dilation.
• Key Drugs & Uses:
  • Glyceryl Trinitrate (GTN): Acute angina (SL 0.3-0.6 mg), IV for MI, LVF.
  • Isosorbide dinitrate (ISDN), Isosorbide mononitrate (ISMN): Prophylaxis.
• Adverse Effects: Headache (common), postural hypotension, reflex tachycardia, flushing.
  • Tolerance: Develops rapidly. Prevent with 8-12 hr nitrate-free interval daily. 📌 "Nitrate-free nights prevent tolerance plight."
• Contraindications: Hypotension, HOCM, RV infarction, ↑ICP.

⭐ Co-administration with PDE-5 inhibitors (e.g., sildenafil) is strictly contraindicated due to risk of profound hypotension.

Beta-Blockers - Calming the Pump

• Mechanism: ↓ Myocardial O₂ demand by ↓Heart Rate, ↓Contractility, ↓Blood Pressure.
  • Improves diastolic filling time, enhancing coronary perfusion.
• Types & Examples:
  • Cardioselective (β₁): Metoprolol, Atenolol, Bisoprolol (📌 BAM). Safer in mild asthma.
  • Non-selective (β₁, β₂): Propranolol.
  • Intrinsic Sympathomimetic Activity (ISA): Pindolol (less ↓HR at rest).
  • Combined α & β blockade: Carvedilol, Labetalol (additional vasodilation).
• Key Uses: Chronic stable angina, post-MI protection, hypertension, heart failure.
• Side Effects: Bradycardia, fatigue, bronchospasm (esp. non-selective), masks hypoglycemia symptoms.

⭐ Beta-blockers are generally contraindicated in Prinzmetal's (variant) angina as they may worsen coronary vasospasm due to unopposed alpha-receptor activity.

Calcium Channel Blockers - Easing the Squeeze

Mechanism: Block L-type Ca²⁺ channels in cardiac & smooth muscle → vasodilation (↓afterload), ↓contractility, ↓HR, ↓myocardial O₂ demand. Uses: Angina (stable, variant), hypertension. Non-DHPs also for arrhythmias (e.g., SVT).

Other Antianginals - Niche Players

• Ranolazine: Inhibits late $Na^+$ current (late $I_{Na}$). Minimal effect on HR/BP.

  ⭐ Ranolazine exerts its antianginal effect by inhibiting the late sodium current, without significantly affecting heart rate or blood pressure.

• Ivabradine: Selective $I_f$ (funny current) inhibitor in SA node. ↓ HR. For stable angina if β-blockers C/I or intolerant.
• Trimetazidine: Metabolic modulator (pFOX inhibitor). Shifts cardiac metabolism from fatty acids to glucose.
• Nicorandil: K+ channel opener & NO donor. Dual mechanism: arterial & venous dilation; cardioprotective preconditioning effect.

High‑Yield Points - ⚡ Biggest Takeaways

• Nitrates (GTN, ISDN): Venodilation (↓preload) via NO release. S/E: headache, tolerance. Avoid with sildenafil.
• Beta-blockers: First-line for chronic stable angina (↓O2 demand). C/I: variant angina, asthma.
• CCBs (Verapamil, Diltiazem, Amlodipine): Effective for variant angina. Verapamil: constipation.
• Nicorandil: K+ channel opener & NO donor. S/E: aphthous ulcers.
• Ranolazine: Late Na+ current inhibitor. No significant HR/BP effect.
• Ivabradine: Selective If channel inhibitor in SA node, purely ↓HR_._