Antianginal Medications

## Overview

Angina pectoris results from myocardial oxygen demand exceeding supply, typically due to coronary artery disease. Antianginal drugs work by reducing oxygen demand, increasing oxygen supply, or both. Three classical drug classes form the foundation of therapy.

## Nitrates

Nitroglycerin (sublingual, transdermal, IV) and isosorbide mononitrate release nitric oxide, which activates guanylyl cyclase and produces vascular smooth muscle relaxation. Venodilation reduces preload (the primary antianginal mechanism), while arterial dilation at higher doses reduces afterload and dilates coronary arteries. Sublingual nitroglycerin acts within 1-3 minutes for acute relief. Nitrate tolerance develops with continuous exposure due to depletion of sulfhydryl groups and neurohormonal counter-regulation. A nitrate-free interval of 10-12 hours daily is required to maintain efficacy.

## Beta-Blockers

Beta-blockers reduce heart rate, contractility, and systolic blood pressure, decreasing myocardial oxygen demand at rest and during exercise. They are first-line for chronic stable angina. Heart rate targets of 55-60 bpm correlate with symptom relief. Abrupt withdrawal can cause rebound angina due to beta-receptor upregulation.

## Calcium Channel Blockers

Dihydropyridines (amlodipine) reduce afterload and dilate coronary arteries. Non-dihydropyridines (verapamil, diltiazem) additionally reduce heart rate and contractility. Verapamil and diltiazem are alternatives when beta-blockers are contraindicated. Short-acting nifedipine is avoided as monotherapy due to reflex tachycardia.

## Ranolazine

Ranolazine inhibits the late sodium current (INa-late), reducing intracellular sodium and calcium overload during ischemia. It does not significantly affect heart rate or blood pressure, making it useful as add-on therapy. It prolongs QTc modestly and is contraindicated with strong CYP3A4 inhibitors.

## Antianginal Strategy

First-line therapy combines a beta-blocker with sublingual nitroglycerin for acute episodes. A calcium channel blocker is added or substituted if beta-blockers are insufficient or contraindicated. Ranolazine is reserved for refractory symptoms. Aspirin and statins address the underlying atherosclerosis but are not antianginal per se.

## Vasospastic Angina

Prinzmetal angina (coronary vasospasm) responds best to calcium channel blockers and nitrates. Beta-blockers may worsen vasospasm by leaving alpha-mediated coronary constriction unopposed and are generally avoided in pure vasospastic angina.

## Key Takeaways

- Nitrates reduce preload; a nitrate-free interval prevents tolerance
- Beta-blockers are first-line for chronic stable angina
- Non-dihydropyridine CCBs provide rate control plus vasodilation
- Ranolazine offers add-on relief without hemodynamic effects