Organic nitrates
Vasodilators that release nitric oxide and relax mainly the veins, easing the heart's work in angina. Never combined with sildenafil-type drugs.
What they are
Glyceryl trinitrate (nitroglycerin), isosorbide dinitrate and isosorbide mononitrate. Sublingual or spray glyceryl trinitrate relieves an angina attack in minutes; the isosorbides and patches prevent attacks; intravenous glyceryl trinitrate is used in acute coronary syndromes, acute heart failure and perioperative hypertension. Isosorbide dinitrate with hydralazine is used in heart failure.
Mechanism of action
Nitrates are converted in the vessel wall into nitric oxide, which activates soluble guanylate cyclase in smooth muscle. More cGMP leads to dephosphorylation of myosin light chains and relaxation. Low doses dilate veins (less preload and wall tension), higher doses also dilate arteries and the epicardial coronary arteries, so the heart needs less oxygen and spasm is relieved.
Target: Soluble guanylate cyclase (through nitric oxide)
Drugs in this class
- Glyceryl trinitrateThe classic nitrate: under the tongue it relieves an angina attack in minutes; as an infusion it treats acute coronary…Soluble guanylate cyclase (activated by the nitric oxide released from the drug)
- Isosorbide dinitrateAn oral nitrate that prevents angina attacks; it is too slow to stop an attack. With hydralazine it is also used in…Soluble guanylate cyclase (activated by nitric oxide)
- Isosorbide mononitrateThe active metabolite of isosorbide dinitrate, given by mouth to prevent angina. It has no first-pass loss, so its…Soluble guanylate cyclase (activated by nitric oxide)
Others in the class
- Pentaerythritol tetranitrate
- Nicorandil (nitrate plus potassium channel opener)
Test yourself
Think of the answer, then tap the question to see it.
Why are nitrates contraindicated with sildenafil?
Both raise cGMP in vascular smooth muscle (nitrates make more, PDE5 inhibitors break down less), so the combined vasodilation can cause severe hypotension.
Which vascular bed do low doses of nitrates dilate most, and why does this help angina?
The veins: less venous return lowers preload and ventricular wall tension, so myocardial oxygen demand falls.
How is nitrate tolerance prevented with long-acting nitrates?
By leaving a daily nitrate-free interval (for example, removing the patch at night or dosing asymmetrically).
Which second messenger mediates nitrate-induced smooth muscle relaxation?
Cyclic GMP, produced by soluble guanylate cyclase activated by nitric oxide.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - NITROGLYCERIN tablet (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - NITROGLYCERIN injection, solution (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - ISOSORBIDE DINITRATE tablet (DailyMed (U.S. National Library of Medicine), 2026).
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Representative model, for educational purposes only.