What is the bradykinin antagonist?

Icatibant has recently become available as a bradykinin antagonist for the treatment of hereditary angioedema. This synthetic agent can be injected under the skin in a dissolved form with a syringe during an acute attack and leads to an improvement of symptoms after 1-2 hours. At the molecular level, the antagonist binds to and blocks the B2 receptor located in blood vessels, thus preventing the binding of bradykinin and activation of the receptor.

This principle is called competitive inhibition. This prevents vasodilatation and an increase in the permeability of the vessel wall and prevents the outflow of fluid. As a result, there is no swelling of the affected area that would otherwise occur.

The same mechanism could make Icatibant an effective drug for the treatment of ascites, a condition that is often associated with severe liver damage. This disease is characterized by increased water leakage into the abdominal cavity due to reduced liver function and the resulting decrease in oncotic pressure in the blood vessels, which may be prevented by Icatibant. Icatibant may also be used in a number of other diseases, especially as an anti-inflammatory agent in chronic inflammatory or vascular diseases.

What role does bradykinin play in angioedema?

Angioedema is a temporary painless swelling of the skin and subcutaneous fatty tissue. It can occur all over the body and in most cases remains symptom-free. Angioedema in the intestinal area can be problematic, as it can cause severe pain and restrict digestion.

Angioedema in the respiratory tract is particularly dangerous as it can block the airways. In this case, emergency medical help is sometimes necessary. The development of angioedema can have very different causes, from allergic reactions to drug intolerance.

One particular form of angioedema is hereditary angioedema (HAE), which is characterized by a congenital deficiency of C1 esterase inhibitor. As a result, the hormone bradykinin can no longer be broken down as effectively. As a result, bradykinin-induced fluid outflow from blood vessels increases, thus increasing the risk of angioedema.

Patients with HAE have a 50% chance of developing dangerous angioedema at least once in their lives. A bradykinin antagonist in syringe form is available to treat HAE. When taking ACE inhibitors (drugs used mainly to treat high blood pressure), dry irritable cough may occur.

The reason for this is that the hormone bradykinin is broken down by ACE (angiotensin converting enzymes), among other things, and therefore when this enzyme is inhibited it is present in the body in greater quantities and for longer periods. At the bronchial tubes, bradykinin causes contraction of the smooth muscles and thus a narrowing of the airways, which in some cases can lead to an unpleasant, dry cough. This may mean that therapy with ACE inhibitors must be discontinued.