Diazoxide: Pharmacologic action, Side effects and Uses

Chemical properties

White or off-white crystalline powder. Melting point 330-331 ° C. Soluble in ethanol, slightly soluble in acetone, chloroform, methanol, insoluble in water, soluble in sodium hydroxide solution. It is odorless and smells slightly bitter.

Antihypertension medication

Diazoxide is an anti-hypertensive drug having a basic structure of thiazide drug, but has no diuretic effects. It has its major effects on the arterioles directly with no significant effect on the veins. It may reduce the blood pressure by activating ATP-sensitive potassium channels; hyperpolarizing arterial smooth muscle cells; producing smooth muscle relaxation and decreasing peripheral vascular resistance with a reflex increase of heat rate and cardiac output. 

Diazoxide is a rapid-acting antihypertensive drug which can reduce the blood pressure of hypertension patients with standing and lying position, and is also used in the treatment of hypertensive emergencies. Diuretics should be used simultaneously in clinical use. It is contraindicated in severe hypertensive patients with congestive heart failure, diabetes, and renal insufficiency.

Method of production

Diazoxide is obtained by cyclization of 5-chloro-2-acetamido-N-acetylbenzenesulfonamide at a high temperature. The cyclization reaction was carried out at 250-260 ° C and stirred for 15 min. Then, cooled it down, and ground it after the material was solidified, and washed with ethanol to obtain a crude diazoxide. Then have it recrystallized with 40 times the amount of 80% ethanol to produce the finished product.

Side effects

1. Long-term use of Diazoxide may result in a lot of side effects, mainly including sodium and water retention, induced angina, palpitations, temporary atrial or ventricular arrhythmia, Headache, redness of the skin and etc induced by hyperuricemia, allergic reaction reflex causing heart excitement, and may also lead to cardiovascular diseases such as heart failure, dissection aneurysm, angina pectoris, myocardial ischemia, and myocardial infarction. Therefore, it is not recommended for long-term use.

2. Diazoxide is contraindicated in severe hypertensive patients with congestive heart failure, diabetes and renal insufficiency and breast-feeding women.

3. Diazoxide interferes with insulin release from Beta cells of the pancreas, which may cause hyperglycemia So in order to prevent blood sugar from rising, insulin or oral hypoglycemic drugs may be used to control blood sugar.

4. Transient brain or myocardial ischemia, fever, headache, nausea, insomnia, constipation, abdominal discomfort, hearing abnormalities, venous burning sensation may occur after the medication.

5. Long-term oral use of Diazoxide may lead to such adverse reactions as extrapyramidal syndrome, abnormal hair growth on the face, arms and so on.

6. Diazoxide should not be used together with other drugs and infusions.

Reference

J. Haseman, R. Melnick, L. Tomatis, and J. Huff, Carcinogenesis bioassays: study duration and biological relevance. Food Chem. Toxicol. 39(7), 739–744 (2001).
M. Soffritti, F. Belpoggi, F. Minardi, and C. Maltoni, Ramazzini Foundation cancer program: history and major projects, life-span carcinogenicity bioassay design, chemicals studied, and results. Ann. N. Y. Acad. Sci. 982, 26–45 (2002).
J. Huff, M. F. Jacobson, and D. L. Davis, The limits of twoyear bioassay exposure regimens for identifying chemical carcinogens. Environ. Health Perspect. 116(11), 1439–1442(2008).

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