Nitrates

Nitrates

Nitrates are the drugs of choice for relieving acute angina. Ni-trates commonly prescribed to treat angina include:

·                 amyl nitrite

·                 isosorbide dinitrate

·                 isosorbide mononitrate

·                 nitroglycerin.

Pharmacokinetics

Nitrates can be administered in a variety of ways.

All absorbed…

Nitrates given sublingually (under the tongue), buccally (in the pocket of the cheek), as chewable tablets, as lingual aerosols (sprayed onto or under the tongue), or by inhalation (amyl nitrite) are absorbed almost completely because the mucous membranes of the mouth have a rich blood supply.

…Half-absorbed…

Swallowed nitrate capsules are absorbed through the mucous membranes of the GI tract, and only about one-half of the dose en-ters circulation.

Transdermal nitrates (a patch or ointment placed on the skin) are absorbed slowly and in varying amounts, depending on the quantity of drug applied, the location of its application, the sur-face area of skin used, and circulation to the skin.

…Or no absorption required

I.V. nitroglycerin, which doesn’t need to be absorbed, goes directly into circulation.

Pharmacodynamics

Nitrates cause the smooth muscle of the veins and, to a lesser ex-tent, the arteries to relax and dilate. This is what happens:

·                 When the veins dilate, less blood returns to the heart.

·                 This, in turn, reduces the amount of blood in the ventricles at the end of diastole, when the ventricles are full. (The volume of blood in the ventricles just before contraction is called preload.)

·                 By reducing preload, nitrates reduce ventricular size and ven-tricular wall tension (the left ventricle doesn’t have to stretch as much to pump blood). This, in turn, reduces the oxygen requirements of the heart.

Don’t fight it

The arterioles provide the most resistance to the blood pumped by the left ventricle (called peripheral vascular re-sistance). Nitrates decrease af-terload by dilating the arteri-oles, reducing resistance, eas-ing the heart’s workload, and easing the demand for oxygen.

Pharmacotherapeutics

Nitrates are used to relieve and prevent angina.

For speedy relief…

The rapidly absorbed nitrates, such as nitroglycerin, are the drugs of choice for relief of acute angina because:

·                 they have a rapid onset of action

·                 they’re easy to take

·                 they’re inexpensive.

…Or prevention

Longer-acting nitrates, such as the daily nitroglycerin transdermal patch, are convenient and can be used to prevent chronic angina. Oral nitrates are also used because they seldom produce serious adverse reactions.

Drug interactions

§    Severe hypotension can result when nitrates interact with alco-hol.

§    Erectile dysfunction drugs shouldn’t be taken within 24 hours of nitrate administration because of possible enhanced hypotensive effects.

§    Absorption of sublingual nitrates may be delayed when taken with an anticholinergic drug.

§    Marked orthostatic hypotension (a drop in blood pressure when a person stands up) with light-headedness, fainting, or blurred vi-sion may occur when calcium channel blockers, antihyperten-sives, beta-adrenergic blockers, or phenothiazines and nitrates are used together. (See Adverse reactions to nitrates.)