isosorbide

Isosorbide is a class of nitrate esters derived from sorbitol and used as vasodilators in cardiovascular disease. The two main pharmaceutical forms are isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN). ISDN is a di-nitrate; ISMN is a mono-nitrate that can be administered directly, while ISDN is largely metabolized in the body to ISMN and other products. Both forms release nitric oxide, which activates soluble guanylate cyclase and increases cyclic GMP, leading to smooth muscle relaxation. The resulting effect is predominant venodilation, which lowers preload and myocardial oxygen demand; at higher doses, arterial dilation reduces afterload.

Uses: ISDN is used for short-term relief of angina and for prophylaxis of anginal attacks; ISMN is used mainly for long-acting prevention of angina. Nitrates may also be used in certain chronic heart failure regimens as part of combination therapy.

Administration and pharmacokinetics: ISDN undergoes substantial first-pass metabolism, making it suitable for sublingual or parenteral use; ISMN has good oral bioavailability and a longer duration of action. Common regimens include sublingual tablets for acute relief and extended-release oral tablets or transdermal patches for maintenance. To prevent tolerance, a nitrate-free interval of about 8–12 hours daily is recommended.

Adverse effects and interactions: common adverse effects include headache, dizziness, flushing, hypotension, and reflex tachycardia. Tolerance can develop with continuous use. Nitrates are contraindicated with phosphodiesterase type 5 inhibitors (for example, sildenafil) due to the risk of severe hypotension, and should be used with caution with other vasodilators.