Carbonic Anhydrase Inhibitors: Acetazolamide
Indication
Acetazolamide is used to reduce intraocular pressure in glaucoma and as a diuretic. Acetazolamide may also be used in the treatment of hydrocephalus, refractory seizures, epilepsy, and altitude sickness. It is also use to treat secondary metabolic alkalosis.
Mechanism of Action
As a diuretic, acetazolamide initiates competitive, reversible inhibition of carbonic anhydrase, which results in increased renal excretion of sodium, potassium, bicarbonate, and water. Acetazolamide also inhibits carbonic anhydrase in the central nervous system, thus, reducing discharges from central nervous system neurons.
Dosing
Children:
Edema:
Oral,I.V.: 5mg/kg/dose or 150mg/m2/dose once everyday
Secondary metabolic alkalosis:
Oral, I.V.: 3 to 5mg/kg/dose every 6 hours for four doses
Adults:
Edema:
Oral, I.V.: 250 to 375mg once daily
Urine alkalinization:
Oral: 5 mg/kg/dose repeated two to three times over 24 hours
In patients with renal impairment:
Clcr 10 to 50mL/min: administer every 12 hours
CLcr less than 10 mL/min: avoid use
Pharmacokinetics
Acetazolamide has an onset of action of 2 minutes after I.V. injection, 1 to 2 hours after tablet ingestion, and 2 hours after extended-release capsule administration. The duration of action of the drug is 4 to 5 hours if administered I.V., 8 to 12 hours after a tablet, and 18 to 24 hours after an extended-release capsule. Absorption of acetazolamide is dose dependent, and acetazolamide distributes into erythro-cytes and the kidneys. The half-life ranges from 2.4 to 5.8 hours, with 70 to 100% of the I.V. or tablet dose eliminated unchanged in the urine within 1 day.
Monitoring parameters: CBC, platelets, serum electrolytes
Contraindications: allergy to sulfonamides,hyperchloremic acidosis, severe renal disease, hepatic insufficiency, low serum sodium or potassium
Precautions/Adverse Effects
Warning: sulfonamides have caused fatalities caused by toxic epidermal necrol-ysis, Stevens-Johnson syndrome, hepatic necrosis, aplastic anemia, and other blood dyscrasias. Discontinue use at the first sign of rash or adverse reaction.
Use with caution in patients with chronic obstructive pulmonary disease, respiratory acidosis, gout, and diabetes mellitus; reduce dosage in patients with renal dysfunction.
Common side effects of acetazolamide include cyanosis, drowsiness, fever, seizures, dizziness, depression, rash, photosensitivity, vertigo, hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, nausea, vomiting, black stools, polyuria, muscle weakness, anorexia, cholestatic jaundice, hepatic insufficiency, and hyperpnea.
Poisoning Information
Symptoms of acetazolamide overdose include drowsiness, nausea, vomiting, confusion, tachycardia, sweating, dizziness, convulsions, tingling of lips and tongue, and low blood sugar. Treat hypoglycemia with dextrose I.V. if necessary.
Drug-Drug Interactions
Acetazolamide may decrease the rate of excretion of other drugs, such as procainamide, flecainide, quinidine, and tricyclic antidepressants; and it may increase the excretion of salicylates and phenobarbital. Acetazolamide use may increase toxicity with propofol (cardiorespiratory instability); may increase cyclosporine levels; and may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital. Concomitant topiramate use may increase the risk of nephrolithiasis and paresthesia; and concomitant salicylates increase acetazolamide serum levels, resulting in central nervous system toxicity. Acetazolamide increases lithium excretion.
Compatible Diluents/Administration
Reconstituted injectable formulation at 100 mg/mL concentration is stable for 1 week refrigerated. It maybe diluted further in D5W or normal saline for I.V. infusion, with a stability of 5 days at room temperature and 44 days refrigerated.
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