Products
Isosorbide dinitrate is commercially available in many countries in the form of tablets, sustained-release tablets, sustained-release capsules, as an infusion concentrate, and as a spray (Isoket). The drug first came on the market in the 1940s.
Structure and properties
Isosorbide dinitrate (C6H8N2O8, Mr = 236.14 g/mol) exists as a white, fine, crystalline and odorless powder that is very sparingly soluble in water. It is an organic nitrate (dinitrated isosorbide). Isosorbide dinitrate, like nitroglycerin, can explode on impact or at high heat. Therefore, the pharmacopoeia defines isosorbide dinitrate diluted with lactose monohydrate and mannitol.
Effects
Isosorbide dinitrate (ATC C01DA08) has vasodilatory and antianginal properties. The effects are due to the release of nitric oxide (NO), which relaxes smooth muscle. NO stimulates guanylate cyclase and increases the intracellular concentration of cyclic guanosine monophosphate (cGMP). Isosorbide dinitrate is active on both veins and arteries and mediates the following effects, among others:
- Decrease in preload, reduction in blood return to the heart.
- Reduction of oxygen consumption of the heart muscle.
- Reduction of aortic pressure and peripheral resistance (reduction of afterload).
Isosorbide dinitrate has a short half-life of 30 to 40 minutes. However, it has active metabolites with a longer half-life of up to 5 hours ( isosorbide mononitrate).
Indications
For prevention and treatment of angina pectoris attacks, long-term treatment of coronary artery disease. Other indications:
- Post-treatment of myocardial infarction.
- Arterial pulmonary hypertension
- Treatment of chronic heart failure in combination with cardiac glycosides and/or diuretics.
- Fresh myocardial infarction with left heart failure.
Dosage
According to the professional information. The application depends on the preparation. The drugs, which are intended for ingestion, are usually administered once or twice daily. Isosorbide dinitrate has marked first-pass metabolism and therefore is also administered sublingually (buccally) for seizure treatment. The onset of action is achieved more rapidly when absorbed via the oral mucosa. A spray is available for this purpose on the one hand and a deep-dose, non-retarded tablet on the other. Tolerance may develop with continuous treatment. If multiple doses are taken, a therapy-free interval of at least 8 hours per day should be observed.
Contraindications
- Hypersensitivity
- Acute circulatory failure, cardiogenic shock
- Hypertrophic obstructive cardiomyopathy
- Constrictive pericarditis
- Cardiac tamponade
- Marked hypotension, severe hypovolemia, severe anemia.
- Combination with phosphodiesterase-5 inhibitors such as sildenafil, tadalafil and vardenafil.
- Combination with riociguat
For complete precautions, see the drug label.
Interactions
Antihypertensive agents may potentiate the antihypertensive effect of isosorbide dinitrate. This also applies to phosphodiesterase-5 inhibitors and riociguat (contraindicated). Other drug-drug interactions have been described with dihydroergotamine and sapropterin.
Adverse effects
The most common possible adverse effects include headache (“nitrate headache”), dizziness, drowsiness, weakness, rapid heartbeat, and low blood pressure. These side effects are largely due to vasodilation caused by isosorbide dinitrate.
