Dihydralazine is an antihypertensive agent used to treat arterial hypertension. The exact molecular mode of action is not known. A major use is for blood pressure regulation in severe preeclampsia.
What is dihydralazine?
Dihydralazine is a blood pressure-lowering agent used for the treatment of arterial hypertension. Dihydralazine is a pharmacologic agent that has applications against high arterial blood pressure. The active ingredient provides dilation of arteries and arterioles in smooth muscles, lowering peripheral resistance to blood flow. Dihydralazine is a solid substance consisting of orange needles. It is available in Germany under the trade names Nepresol and Depressan. Nepresol and Depressan are drugs for lowering blood pressure and are used especially in a severe course of hypertension. Main indication is preeclampsia in patients with pregnancy characterized by severe hypertension and edema. Dihydralazine consists of an aromatic benzene ring connected to a hetero ring of carbon and nitrogen atoms. Two hydrazine groups are still attached to this hetero ring in opposite positions. The mechanism of action of dihydralazine is not yet known.
Pharmacological action
The pharmacologic significance of dihydralazine is dilation of the arteries. The resulting reduction in arterial resistance to blood flow lowers blood pressure. The processes at the molecular level cannot yet be understood. In the organism, dihydralazine undergoes metabolization in the liver. The active substance is absorbed in the form of tablets or as a solution. Dihydralazine can also be administered intravenously. In this case, the effect occurs about 15 minutes after infusion. The half-life in the body is 2.2 to 2.6 hours. The drug has a bioavailability of about 30 to 55 percent, which means that only 30 to 55 percent of the original drug can develop its effectiveness. This is due to the fact that the active ingredient dihydralazine is subject to a strong first-pass effect during its first liver passage. During this first liver passage, a large part of the active ingredient is acetylated. In this process, a hydrogen atom on a functional group or a C-H bond is replaced by an acyl group. The acylated molecules are excreted through the urine. Depending on the duration of the acetylation process, the effect of the drug lasts for about three to four hours. Because different people acetylate at different rates or slower, the breakdown of the drug varies from person to person.
Medical application and use
Because of its blood pressure-lowering properties, dihydralazine is one of the antihypertensives. The term antihypertensives represents a collective term for all blood pressure-lowering drugs. Its largest area of application is blood pressure regulation in pregnancy-related blood pressure elevation. The increase in blood pressure, known as pre-eclampsia, can lead to kidney damage. However, under the influence of dihydralazine, as already mentioned, the arteries are dilated, improving blood flow. As a result, blood pressure drops. Especially in pre-eclampsia, it is the drug of first choice, since the active substance does not affect the blood flow of the uterus and placenta. However, no child should be breastfed after the start of treatment, as the active ingredient also passes into breast milk. Because the liver of the newborn is not yet fully mature, the active ingredient can be poorly broken down there, causing dihydralazine to accumulate in the organism. In addition to its use to regulate blood pressure in pregnant women and young mothers, dihydralazine is also used generally to lower blood pressure. In this context, it is often used together with other blood pressure-lowering drugs.
Risks and side effects
In principle, long-term oral therapy with dihydralazine would be possible. However, because of the many side effects, the drug is not suitable for such therapy. There are many contraindications, contraindications, and side effects for dihydralazine. These include sudden drop in blood pressure, flushing of the skin, gastrointestinal disorders, nausea, diarrhea, constipation, or edema. In rare cases, depression, skin rashes with itching, blood count changes, or allergic reactions occur.Even rarer are tingling or numbness in the limbs, muscle cramps or liver dysfunction. Patients who are slow acetylators may experience rheumatoid joint symptoms, lymph gland swelling, conjunctivitis, hepatitis, or urinary bladder infections. Dihydralazine is contraindicated in hypersensitivity, lupus erythematosus (butterfly lichen), aortic aneurysm, or severe heart failure. In other heart conditions, dihydralazine should never be taken alone, but in combination with beta-blockers. Dihydralazine must be used very cautiously in renal insufficiency, liver disease, or circulatory disorders in the brain. During the first trimester of pregnancy, use of dihydralazine should be avoided. There are also interactions with other medications, which can lead to both weakening and strengthening of the effect. During treatment with dihydralazine, constant medical checks are necessary to quickly detect any deviations. Reactivity may also be impaired for up to several hours after taking the drug.
