Nitrate-containing drugs: mechanism of action, effect, and precautions!

Nitrates are widely used as antianginal agents for various forms of coronary heart disease (angina pectoris, myocardial infarction, etc.). They are very effective but are incompatible with some drugs, such as sildenafil 20 mg (Revatio).

Mechanism of action

The therapeutic effect of nitrates (nitrovasodilators) is based on the ability to increase the content of nitric oxide, which is an endothelial relaxing factor. This factor stimulates guanylate cyclase, increases the content of cyclic guanosine monophosphate inside the cell and, as a result, causes vasodilation.

Types of nitrates

Nitrovasodilators include organic nitrates, as well as sydnone imines (molsidominum) and other donators of nitric oxide (amyl nitrite). In clinical practice the most common are organic nitrates (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate). Recently, not only new compounds and dosage forms of organic nitrates (including those of prolonged action) have been developed, but also indications for their use, in particular, for heart failure, have been clarified and expanded. Objective methods for assessing their effectiveness and ways for overcoming tolerance have been developed. Medicinal forms of nitrates ensure the penetration of the active substance into the bloodstream through the oral mucosa (tablets, aerosols), after ingestion (tablets, capsules for ingestion), transdermally, i.e. when applied to the skin (ointments, patches, disks), or after being used as injection.

Effect of nitrates

The antianginal effect of nitrates is caused by the restructuring of hemodynamics associated with the overall vascular action of the drugs, and relaxation of smooth muscles of peripheral vessels. Under the influence of nitroglycerin, the venous blood flow to the heart decreases, the pressure in the right atrium and in the pulmonary artery system goes down, and peripheral vascular resistance declines. As a result, the myocardium is unloaded, its tension to overcome the resistance to blood ejection is reduced, energy consumption and the need for oxygen are reduced.

The occurring decrease in cardiac tension and thrombolytic action contribute to the restoration of blood flow through the small vessels of the myocardium, and to the improvement of blood flow in the coronary arteries. Along with the reduction of ischemia, the pain impulse from the ischemic focus disappears and pain syndrome ceases. The action of nitrates is not limited to affecting the coronary vessels. They cause the expansion of other blood vessels (cerebral vessels, peripheral vessels, vessels of the abdominal cavity). Nitrate intake can improve fibrinolysis (a process that prevents blood clots’ growing) by changing in the plasma the ratio between the two major components of this system: the tissue activator of plasminogen and its inhibitor, which may be due to a change in hemodynamics, or the result of the inhibitory effect of NO on platelet aggregation.

Precautionary measures

Nitrates should never be used in combination with PDE5 inhibitors, such as Revatio and Viagra. Let’s consider why. How does Viagra work? It relaxes the blood vessels and can slightly lower the pressure. Nitrates also lower the pressure, so a combination of these groups of drugs can cause a significant blood pressure reduction. Nitrates & Viagra side effects in such a case may be very severe.