Antihypertensives Part 4 – Nitrates

Welcome to today’s episode, where we’re diving into the world of nitrate medications—one of the cornerstone therapies in cardiovascular care. Whether you’re a pharmacist, nurse, med student, or just curious about how medications keep the heart happy, nitrates are fascinating because of their unique mechanism and versatile clinical uses.

Nitrates work by releasing nitric oxide, a powerful molecule that relaxes smooth muscle and dilates blood vessels. This vasodilation primarily reduces venous return to the heart, lowering preload and myocardial oxygen demand, and at higher doses, can also decrease afterload. For patients with angina, this means less chest pain, improved exercise tolerance, and better quality of life.

In this episode, we’ll cover the most commonly used nitrates—from sublingual nitroglycerin for rapid relief of acute angina, to isosorbide dinitrate and mononitrate for chronic management. We’ll discuss how their formulations, onset, and duration of action affect clinical use, and why concepts like tolerance and nitrate-free intervals are critical to understand.

We’ll also explore important drug interactions, including why combining nitrates with PDE5 inhibitors can be dangerous, and highlight practical tips for patient counseling and monitoring. By the end of this episode, you’ll have a clear picture of how and when nitrates are used, and the key pearls every clinician should know to maximize benefit while minimizing risk.

So whether you’re reviewing for boards, prepping for clinical rotations, or just brushing up on cardiovascular pharmacology, stay tuned—we’re about to break down nitrates in a way that’s simple, practical, and memorable.

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Nifedipine Pharmacology

Nifedipine is a dihydropyridine calcium channel blocker that selectively inhibits L-type calcium channels in vascular smooth muscle, leading to vasodilation and reduced peripheral vascular resistance.

The extended-release formulation of nifedipine provides more stable plasma concentrations and is preferred for chronic management of hypertension and angina.

Common adverse effects include headache, flushing, peripheral edema, and dizziness, all related to its vasodilatory action.

Nifedipine undergoes extensive first-pass metabolism in the liver, primarily via CYP3A4 enzymes, which significantly influences its bioavailability and potential drug interactions.

CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, grapefruit juice) can increase plasma levels of nifedipine, raising the risk of hypotension and adverse effects.

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Isosorbide Mononitrate Pharmacology Podcast

On this episode, I discuss isosorbide mononitrate pharmacology, adverse effects, and important drug interactions.

Isosorbide mononitrate is a vasodilator that works by relaxing and widening the blood vessels (primarily veins) through nitric oxide action. This reduces the preload and oxygen demand on the heart.

The primary use for isosorbide mononitrate is angina prevention. It is important to remember that it is NOT meant for acute relief of chest pain.

Headache is a major adverse effect of isosorbide mononitrate and can be very bothersome for patients. Vasodilation is primarily responsible for this adverse effect.

PDE-5 inhibitors are notorious for causing drug interactions with any nitrate medication. I discuss management strategies in this podcast episode.

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Ranolazine (Ranexa) Pharmacology Podcast

Ranolazine is primarily used for chronic angina management. I discuss pharmacology, drug interactions, adverse effects, and more in this podcast episode.

Ranolazine is well known to have drug interactions. CYP3A4 is of major importance but there are other subtle drug interactions that are important.

QTc prolongation has been reported with ranolazine so it is important to recognize risk factors and other medications that may contribute to this concern.

Enzyme inducers like carbamazepine, phenytoin, and St. John’s wort are all associated with reducing the concentrations of ranolazine.

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