DIAZOXIDE

DIAZOXIDE (dye-az-ox'ide) Hyperstat I.V., Proglycem Classifications: antihypertensive; vasodilator; sulfonylurea; antidiabetic agent; Therapeutic: antihypertensive; antidiabetic agent Prototype: Hydralazine Pregnancy Category: C

Availability

50 mg capsules; 50 mg/mL suspension; 15 mg/mL injection

Action

Rapid-acting thiazide nondiuretic hypotensive and hyperglycemic agent. In contrast to thiazide diuretics, causes sodium and water retention thus decreasing urinary output. This is probably due to its increase of proximal tubular reabsorption of sodium and decrease of glomerular filtration rate. Hypotensive effect may be accompanied by marked reflex increase in heart rate, cardiac output, and stroke volume; thus cerebral and coronary blood flows are usually maintained.

Therapeutic Effect

Reduces peripheral vascular resistance and BP by direct vasodilatory effect on peripheral arteriolar smooth muscles, perhaps by direct competition for calcium receptor sites.

Uses

Intravenously for emergency lowering of BP in hospitalized patients with malignant hypertension, particularly when associated with renal impairment. Not effective in pheochromocytoma. Commonly used with a diuretic such as furosemide (Lasix) to counteract diazoxide-induced sodium and water retention. Orally in treatment of various diagnosed hypoglycemic states due to hyperinsulinism when other medical treatment or surgical management has been unsuccessful or is not feasible.

Contraindications

Hypersensitivity to diazoxide; cerebral bleeding, eclampsia; aortic coarctation; AV shunt, significant coronary artery disease; pheochromocytoma; pregnancy (category C), lactation. Use of oral diazoxide for functional hypoglycemia or in presence of increased bilirubin in newborns.

Cautious Use

Diabetes mellitus; impaired cerebral or cardiac circulation; impaired renal function; patients taking corticosteroids or estrogen–progestogen combinations; hyperuricemia, history of gout, uremia; thiazide diuretic hypersensitivity.

Route & Dosage

Severe Hypertension Adult/Child: IV 1–3 mg/kg up to 150 mg, repeat at 5–15 min intervals if necessary Hypoglycemia Adult/Child: PO 3–8 mg/kg/d divided q8–12h Neonate/Infant: PO 8–15 mg/kg/d divided q8–12h

Administration

Intravenous Note: Give any prescribed diuretic 30–60 min prior to IV diazoxide. Keep patient recumbent 8–10 h because of possible additive hypotensive effect. PREPARE: Direct: Give undiluted.   ADMINISTER: Direct: Give IV by rapid direct injection over 10–30 sec. Keep patient recumbent while receiving IV and for at least 30 min following administration.   Check IV injection site frequently. Solution is strongly alkaline. Extravasation of medication into tissues can cause severe inflammatory reaction. Administer drug by peripheral vein ONLY. INCOMPATIBILITIES Y-site: Hydralazine, lidocaine, propranolol.

• Do not give darkened solutions. Store capsules, oral suspension, and injectables at 2°–30° C (36°–86° F) unless otherwise directed. Protect from light, heat, and freezing.

Adverse Effects (≥1%)

CNS: Headache, weakness, malaise, dizziness, polyneuritis, sleepiness, insomnia, euphoria, anxiety, extrapyramidal signs. CV: Palpitations, atrial and ventricular arrhythmias, flushing, shock; orthostatic hypotension, CHF, transient hypertension. Special Senses: Tinnitus, momentary hearing loss; blurred vision, transient cataracts, subconjunctival hemorrhage, ring scotoma, diplopia, lacrimation, papilledema. GI: Nausea, vomiting, abdominal discomfort, diarrhea, constipation, ileus, anorexia, transient loss of taste, impaired hepatic function. Hematologic: Transient neutropenia, eosinophilia, decreased Hgb/Hct, decreased IgG. Body as a Whole: Hypersensitivity (rash, fever, leukopenia); chest and back pain, muscle cramps. Urogenital: Decreased urinary output, nephrotic syndrome (reversible), hematuria, increased nocturia, proteinuria, azotemia; inhibition of labor. Skin: Pruritus, flushing, monilial dermatitis, herpes, hirsutism; loss of scalp hair, sweating, sensation of warmth, burning, or itching. Endocrine: Advance in bone age (children), hyperglycemia, sodium and water retention, edema, hyperuricemia, glycosuria, enlargement of breast lump, galactorrhea; decreased immunoglobulinemia, hirsutism.

Diagnostic Test Interference

Diazoxide can cause false-negative response to glucagon.

Interactions

Drug: sulfonylureas antagonize effects; thiazide diuretics may intensify hyperglycemia and antihypertensive effects; phenytoin increases risk of hyperglycemia, and diazoxide may increase phenytoin metabolism, causing loss of seizure control.

Pharmacokinetics

Onset: 30–60 s IV; 1 h PO. Peak: 5 min IV. Duration: 2–12 or more h IV; 8 h PO. Distribution: Crosses blood–brain barrier and placenta. Metabolism: Partially metabolized in the liver. Elimination: In urine. Half-Life: 21–45 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for therapeutic effectiveness. Discontinue if not effective in 2 or 3 wk.
• Lab tests: Initial blood glucose, serum electrolytes, and CBC and at regular intervals in patients receiving multiple doses.
• Monitor BP q5min for the first 15–30 min or until stabilized, then hourly for balance of drug effect.
• Notify physician immediately if BP continues to fall 30 min or more after IV drug administration. Cause other than drug effect is probable.
• Monitor pulse: Tachycardia has occurred immediately following IV; palpitation and bradycardia have also been reported.
• Report promptly any change in I&O ratio.
• Observe patient closely for S&S of CHF (see Appendix F).
• Monitor diabetics carefully for loss of glycemic control.
• Evaluate serum electrolyte levels at regular intervals, particularly in patients with impaired renal function; hypokalemia potentiates hyperglycemic effect of diazoxide.
• Note: In contrast to IV diazoxide, oral administration usually does not produce marked effects on BP. However, do make periodic measurements of BP and vital signs.
• Monitor S&S for up to 7 d for both oral and parenteral forms; essential because of long half-life of diazoxide.

Patient & Family Education

• Note: Drug may cause hyperglycemia and glycosuria in diabetic and diabetic-prone individuals. Closely monitor blood and urine glucose; report any abnormalities to physician.
• Report palpitations, chest pain, dizziness, fainting, or severe headache.
• Note: Lanugo-type hirsutism occurs frequently, commonly in children and women. It is reversible with discontinuation of drug.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug