Pharmacodynamics of nitroglycerin

Mechanism of action and main effects

The primary pharmacodynamic effect of nitroglycerin is associated with pronounced vasodilation. Like other nitrate-like compounds (e.g., molsidomine), it exerts its effect through a mechanism involving the release of nitric oxide (NO). Blood vessel dilation effectively relieves pain in coronary artery disease. The drug acts very rapidly, especially in spray form, which surpasses traditional sublingual tablets in speed of onset. In acute heart failure, the intravenous solution works as a powerful systemic vasodilator.

Indications for use

Due to its vasodilating properties, the drug is used in various acute and chronic clinical situations:

• Stable exertional angina: for emergency relief of attacks, as well as their targeted prevention. The drug is taken a few minutes before expected physical exertion that typically triggers an attack.
• Vasospastic angina (also known as Prinzmetal angina) and unstable angina.
• Myocardial infarction: continuous intravenous infusion is used in the acute phase.
• Acute heart failure: used as a solution from ampoules to reduce myocardial workload.

Side effects and tolerance development

The pharmacodynamics of the drug causes a number of characteristic adverse reactions directly related to systemic vasodilation:

• Headache (resulting from pronounced meningeal vessel vasodilation).
• Facial flushing (hyperemia).
• Arterial hypotension and orthostatic reactions, which can lead to syncope upon sudden postural changes.
• Reflex tachycardia, occurring as a compensatory response to lowered blood pressure.

With prolonged and regular use, tolerance to nitrates develops. Cross-tolerance with other drugs of this group (e.g., isosorbide dinitrate) is also possible. To maintain therapy efficacy and prevent habituation, nitrate-free intervals must be strictly observed in scheduled treatment regimens.

Strict contraindications

The drug is strictly contraindicated in conditions where further blood pressure drop or vasodilation is critically life-threatening:

• Pronounced arterial hypotension, collapse, and severe hypovolemia.
• Cardiogenic shock (permitted only with appropriate hemodynamic support).
• Elevated intracranial pressure.
• Closed-angle glaucoma accompanied by high intraocular pressure.
• Known hypersensitivity to organic nitrates.

Of particular danger is co-administration with phosphodiesterase-5 inhibitors (e.g., sildenafil and its analogs) within the preceding 24–48 hours. This combination leads to a sharp, uncontrolled, and extremely dangerous drop in blood pressure.

Place in the classification of antianginal drugs

Nitroglycerin is a short-acting organic nitrate. For a longer duration of effect (up to 12 hours), prolonged-release forms of other nitrates are used, such as isosorbide dinitrate or its active metabolite isosorbide mononitrate. Notably, nitrates are the drugs of choice specifically for acute attack relief. For baseline therapy of stable exertional angina, first-line drugs are β-blockers, while calcium channel blockers show high efficacy in the vasospastic form.

Class and exam questions

What else to study on this topic

• Pharmacokinetics and metabolism of isosorbide dinitrate and mononitrate.
• Mechanism of action of molsidomine and the formation of the active metabolite SIN-1.
• Use of β-blockers as first-line drugs in stable angina.
• Role of calcium channel blockers (verapamil, diltiazem) in the treatment of vasospastic angina.
• Ivabradine as a second-line drug in case of β-blocker intolerance.

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