Eudaxen

• Hypoglycemia

Diazoxide tablets are used orally in the treatment of intractable hypoglycemia.Hypoglycaemia: Diazoxide administered orally is indicated for the treatment of intractable hypoglycaemia with severe symptoms from a variety of causes including idiopathic hypoglycaemia in infancy, leucine-sensitive ... Read moreDiazoxide tablets are used orally in the treatment of intractable hypoglycemia.Hypoglycaemia: Diazoxide administered orally is indicated for the treatment of intractable hypoglycaemia with severe symptoms from a variety of causes including idiopathic hypoglycaemia in infancy, leucine-sensitive or unclassified; functional islet cell tumours both malignant and benign if inoperable, extra-pancreatic neoplasms producing hypoglycaemia; glycogen storage disease; hypoglycaemia of unknown origin. Diazoxide also causes salt and water retention.

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In the treatment of hypoglycaemia, Diazoxide is contraindicated in all cases which are amenable to surgery or other specific therapy. Hypersensitivity to any component of the preparation or other thiazides

As a diuretic, Diazoxide inhibits active chloride reabsorption at the early distal tubule via the Na-CI cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like Diazoxide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of Diazoxide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. As a antihypoglycemic, Diazoxide inhibits insulin release from the pancreas, probably by opening potassium channels in the beta cell membrane.Pharmacodynamics: Diazoxide is a potassium channel activator. Its mechanism of action revolves around enhancing cell membrane permeability to potassium ions. This action consequently elicits the relaxation of local smooth muscles. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential.

Drugs potentiated by Diazoxide therapy include: oral diuretics, antihypertensive agents and anticoagulants. Phenytoin levels should be monitored as increased dosage may be needed if administered concurrently with diazoxide. The risk of hyperglycaemia may be increased by concurrent administration of corticosteroids or oestrogen-progestogen combinations.

The adverse reactions are thrombocytopenia, pancreatitis, hypotension, diarrhea, heart failure etc.

Excessive dosage of Diazoxide can result in hyperglycaemia. Severe hyperglycaemia may be corrected by giving insulin and less severe hyperglycaemia may respond to oral hypoglycaemics. Hypotension may be managed with intravenous fluids and in severe cases may require sympathomimetics.

Pregnancy: Reproduction studies using the oral preparation in rats have revealed increased fetal resorptions and delayed parturition, as well as fetal skeletal anomalies; evidence of skeletal and cardiac teratogenic effects in rabbits has been noted with intravenous administration. The drug has also been demonstrated to cross the placental barrier in animals and to cause degeneration of the fetal pancreatic beta cells. Since there are no adequate data on fetal effects of this drug when given to pregnant women, safety in pregnancy has not been established. When the use of Diazoxide is considered, the indications should be limited to those specified above for adults, and the potential benefits to the mother must be weighed against possible harmful effects to the fetus. Diazoxide Tablets are only to be used in pregnant women when the indicated condition is deemed to put the mother's life at risk. Prolonged oral therapy of Diazoxide during pregnancy has been reported to cause alopecia in the newborn.Nursing mothers: Information is not available concerning the passage of Diazoxide in breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions from Diazoxide in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

In the treatment of hypoglycaemia it is necessary that the blood pressure be monitored regularly. Retention of sodium and water is likely to necessitate therapy with an oral diuretic such as frusemide or ethacrynic acid The dosage of either of the diuretics mentioned may be up to 1g daily. It must be appreciated that if diuretics are employed then both the hypotensive and hyperglycaemic activities of Diazoxide will be potentiated and it is likely that the dosage of Diazoxide will require adjustment downwards. In patients with severe renal failure it is desirable to maintain, with diuretic therapy, urinary volumes in excess of 1 litre daily. Hypokalaemia should be avoided by adequate potassium replacement.Diazoxide should be used with caution in patients with cardiac failure or impaired cardiac reserve in whom sodium and water retention may worsen or precipitate congestive heart failure. A direct effect on myocardium and cardiac function cannot be excluded.Diazoxide should be used with care in patients with impaired cardiac or cerebral circulation and in patients with aortic coarctation, aortic stenosis, arteriovenous shunt, heart failure or other cardiovascular disorders in which an increase in cardiac output could be detrimental.Diazoxide should be administered with caution to patients with hyperuricaemia or a history of gout, and it is advisable to monitor serum uric acid concentration. Whenever Diazoxide is given over a prolonged period regular haematological examinations are indicated to exclude changes in white blood cell and platelet counts.Also in children there should be regular assessment of growth, bone and psychological maturation.The very rapid, almost complete protein binding of Diazoxide requires cautious dosage to be used in patients whose plasma proteins may be lower than normal