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  1. Pharmacology

    1. Diazoxide, a nondiuretic thiazide, is a direct arterial vasodilator that formerly was used to treat severe hypertension. Heart rate and cardiac output increase owing to a reflex response to decreased peripheral vascular resistance. The duration of the hypotensive effect ranges from 3 to 12 hours, although the elimination half-life is 20–40 hours.

    2. Diazoxide has been used in the treatment of oral hypoglycemic overdose because it increases serum glucose by inhibiting insulin secretion, diminishing peripheral glucose utilization, and enhancing hepatic glucose release. However, octreotide (See Octreotide) has become the preferred agent because of its safety and efficacy.

  2. Indications

    1. Management of an acute hypertensive crisis, although other antihypertensive agents are preferred (see “Phentolamine,” “Nitroprusside,” and “Labetalol,”).

    2. Oral hypoglycemic overdose when serum glucose concentrations cannot be maintained adequately by intravenous 5% dextrose infusions and the preferred agent, octreotide, is unavailable or the patient cannot tolerate it (known hypersensitivity).

  3. Contraindications

    1. Hypertension associated with aortic stenosis, aortic coarctation, hypertrophic cardiomyopathy, or arteriovenous shunt.

    2. Known hypersensitivity to thiazides or other sulfonamide derivatives.

  4. Adverse effects

    1. Hypotension or excessive blood pressure reduction must be avoided in patients with compromised cerebral or cardiac circulation.

    2. Fluid retention from prolonged therapy may compromise the condition of patients with congestive heart failure.

    3. Hyperglycemia may occur, particularly in patients with diabetes or hepatic dysfunction.

    4. Parenteral product is highly alkaline and intended only for IV administration.

    5. Use in pregnancy. FDA Category C (indeterminate). This drug has caused skeletal, cardiac, and pancreatic abnormalities in animals, but no adequate human data exist. Use of this drug near term may cause hyperbilirubinemia and altered carbohydrate metabolism in a fetus or neonate, and intravenous administration during labor may cause cessation of uterine contractions. These cautions, however, do not necessarily preclude acute, short-term use of the drug for a seriously symptomatic patient (See Introduction in Section III).

  5. Drug or laboratory interactions

    1. The hypotensive effect is potentiated by concomitant therapy with diuretics or beta-adrenergic blockers.

    2. Diazoxide displaces warfarin from protein-binding sites and may transiently potentiate its anticoagulant effects.

    3. Diazoxide can increase phenytoin metabolism.

  6. Dosage and method of administration (adults and children)

    1. For oral hypoglycemic–induced hypoglycemia

      1. Give an infusion of 0.1–2 mg/kg/h; initiate at a lower infusion rate and titrate up as needed. Hypotension is minimized by keeping the patient supine and increasing the infusion rate slowly. Duration of therapy has ranged from 22 to 60 hours.

      2. An oral dosing regimen of 3–8 mg/kg/d divided into two to three doses is recommended for children and adults. If the condition is refractory, higher doses of up to 10–15 mg/kg/d may be required (200 mg every 4 hours has been used).

    2. For hypertensive crisis, give 1–3 mg/kg IV (maximum, 150 mg) or 50–100 mg total every 5–15 minutes as needed. Note: The use of a 300-mg rapid bolus is no longer recommended.

  7. Formulations

    1. Parenteral. Diazoxide (Hyperstat, others), 15 mg/mL in 10- and 20-mL ampules.

    2. Oral. Diazoxide (Proglycem, others), 50-mg/mL oral suspension (with alcohol and parabens); 50- and 100-mg capsules.

    3. Suggested minimum stocking ...

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