nitrate
A nitrate relieves the chest pain of angina by giving veins and arteries a chemical signal to relax. When the heart muscle is starved of oxygen because its supply cannot meet demand, a nitrate widens the plumbing so the heart has less work to do and gets a little more blood. A tablet melted under the tongue can ease an angina attack within minutes.
Organic nitrates such as glyceryl trinitrate (nitroglycerin), isosorbide mononitrate and isosorbide dinitrate are converted in the body to nitric oxide. Nitric oxide stimulates the enzyme guanylyl cyclase to make cyclic GMP in vascular smooth muscle, which relaxes the muscle and dilates vessels. Veins dilate most, reducing the volume of blood returning to the heart (preload) and thus the heart's oxygen demand; larger doses also dilate arteries.
Common effects are throbbing headache, flushing and a drop in blood pressure that can cause dizziness. With continuous exposure the body develops tolerance, the response fading within a day or so, so regimens build in a daily nitrate-free interval to restore sensitivity. Crucially, nitrates must never be combined with phosphodiesterase-5 inhibitors such as sildenafil, because the two together can cause a catastrophic fall in blood pressure.
A patient with stable angina places a glyceryl trinitrate tablet under the tongue at the first twinge of chest tightness; within two to three minutes the vessels dilate and the pain settles.
Sublingual nitrate is both the rescue treatment and a quick diagnostic clue for angina.
Sublingual glyceryl trinitrate bypasses the gut and the liver's first-pass metabolism, which is why it works so fast and why the swallowed form is far less effective for an acute attack.