Antianginal Agents

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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). Myocardial oxygen supply-demand imbalance
  • 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. Nitric oxide pathway and vasodilation mechanism
  • 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. Effects of Beta-Blockers and Pharmacokinetic Data

⭐ 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).

Calcium Channel Blockers: Types and Sites of Action

FeatureDihydropyridines (DHPs)Non-Dihydropyridines (Non-DHPs)
ExamplesAmlodipine, NifedipineVerapamil, Diltiazem
Primary SitePeripheral arterioles (vasodilation)Myocardium (SA/AV nodes, contractility)
Cardiac EffectsPotent vasodilation; reflex tachycardia (some)↓HR, ↓contractility, ↓AV conduction (Verapamil > Diltiazem)
Key Side EffectsAnkle edema, headache, flushing, gingival hyperplasiaConstipation (Verapamil), bradycardia, AV block, gingival hyperplasia

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_._

Practice Questions: Antianginal Agents

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The following smooth muscle relaxants act by affecting calcium release except:

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Flashcards: Antianginal Agents

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_____ is a neprilysin and ACE inhibitor developed for heart failure

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_____ is a neprilysin and ACE inhibitor developed for heart failure

Omapatrilat

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