Antianginal drugs

Angina Pectoris - Chest's Cry for Help

Myocardial ischemia from an oxygen supply/demand mismatch.

• Stable Angina: Due to fixed coronary stenosis (>70%). Predictable, exertional chest pain relieved by rest or nitroglycerin.
• Unstable Angina: Plaque rupture with a non-occlusive thrombus. New, worsening, or rest pain. High risk for MI.
• Prinzmetal's (Variant) Angina: Focal coronary artery vasospasm. Transient, occurs at rest, often at night.

⭐ Prinzmetal's angina is associated with transient ST-segment elevation on ECG, unlike stable or unstable angina which typically show ST-segment depression.

Nitrates - Vessels on Vacation

• Drugs: Nitroglycerin, Isosorbide Dinitrate, Isosorbide Mononitrate.
• Mechanism: Primarily venodilators. They release nitric oxide, causing $NO \rightarrow \uparrow cGMP \rightarrow Venodilation$, which leads to a ↓ in preload (left ventricular end-diastolic pressure).

• Adverse Effects: Reflex tachycardia, hypotension, flushing, and headaches.
• 📌 Tachyphylaxis: Tolerance develops rapidly. A daily "nitrate-free" interval (8-10 hours, typically overnight) is required to restore sensitivity.

⭐ Workers in dynamite factories (exposed to nitrates) would develop tolerance. After a weekend off, re-exposure caused tachycardia, dizziness, and headache, known as "Monday disease."

Beta-Blockers - Heart's Chill Pill

• Mechanism: Act as negative chronotropes and inotropes → ↓ heart rate & ↓ contractility. This reduces cardiac workload and overall myocardial oxygen demand ($↓ MVO_2$).

• Types & Selectivity:

  • Cardioselective (β1): Metoprolol, Atenolol, Bisoprolol. Preferred in patients with pulmonary issues.
  • Non-selective (β1 + β2): Propranolol. Use with caution in asthma/COPD due to bronchoconstriction risk.

⭐ Beta-blockers are proven to reduce mortality post-myocardial infarction.

📌 Mnemonic: "BAM" for β1-selective blockers: Bisoprolol, Atenolol, Metoprolol.

Calcium Channel Blockers - Calcium's Gate Crashers

• Mechanism: Block L-type Ca²⁺ channels → ↓ intracellular Ca²⁺ → coronary vasodilation & ↓ systemic vascular resistance (afterload).

⭐ Exam Favorite: Can cause gingival hyperplasia (esp. Nifedipine, Verapamil) and peripheral edema (esp. Dihydropyridines).

Newer Agents - The Modern Arsenal

• Ranolazine: Inhibits the late $I_{Na}$ current, reducing intracellular Ca²⁺ overload and diastolic wall tension. Has minimal effect on heart rate or blood pressure.
• Ivabradine: Selectively inhibits the $I_f$ (“funny”) current in the SA node, slowing the heart rate without affecting contractility or blood pressure.

⭐ Ranolazine can prolong the QT interval.

High‑Yield Points - ⚡ Biggest Takeaways

• Nitrates cause potent venodilation, reducing preload. They are key for acute angina relief but require a nitrate-free interval to prevent tachyphylaxis.
• Beta-blockers are first-line for chronic stable angina, decreasing myocardial O2 demand by lowering heart rate and contractility.
• Calcium channel blockers are the treatment of choice for vasospastic (Prinzmetal) angina.
• Ranolazine treats refractory angina by inhibiting the late sodium current, but carries a risk of QT prolongation.
• Avoid combining non-dihydropyridine CCBs with beta-blockers due to the additive risk of severe bradycardia and AV block.