Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

ACETAZOLAMIDE SODIUM

Chemistry - A carbonic anhydrase inhibitor, acetazolamide occurs as a white to faintly yellowish-white, odorless, crystalline powder with pKas of 7.4 and 9.1. It is very slightly soluble in water andsparingly soluble in hot water (90-100°C), and sparingly soluble in alcohol. Acetozolamide sodiumoccurs as a white lyophilized solid and is freely soluble in water. The injection has a pH of 9.2 afterreconstitution with Sterile Water for Injection.

Storage, Stability, Compatibility

Acetazolamide products should be stored at room tempera-ture. After reconstitution, the injection is stable for one week when refrigerated, but as it contains nopreservatives, it should be used within 24 hours.
Acetazolamide sodium for injection is reportedly physically compatible with all commonly used IV solutions and cimetidine HCl for injection.

Pharmacology - ACETAZOLAMIDE SODIUM

The carbonic anhydrase inhibitors act by a noncompetitive, reversible inhibition ofthe enzyme carbonic anhydrase. This reduces the formation of hydrogen and bicarbonate ions fromcarbon dioxide and reduces the availability of these ions for active transport into body secretions.
Pharmacologic effects of the carbonic anhydrase inhibitors include decreased formation ofaqueous humor, thereby reducing intraocular pressure; increased renal tubular secretion of sodiumand potassium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume;anticonvulsant activity, which is independent of its diuretic effects (mechanism not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis effect).

Uses, Indications

Acetazolamide is used principally in veterinary medicine for its effects onaqueous humor production in the treatment of glaucoma. It has also been used for its diuretic actionand in the treatment of metabolic alkalosis. In humans, the drug has been used as adjunctive therapyfor epilepsy and for acute high-altitude sickness.

Pharmacokinetics - ACETAZOLAMIDE SODIUM

The pharmacokinetics of this agent have apparently not been studied in domestic animals. One report (Roberts 1985) states that after a dose of 22 mg/kg, the onset of actionis 30 minutes; maximal effects occur in 2-4 hours; duration of action of 4-6 hours in small animals.
In humans, the drug is well absorbed after oral administration with peak levels occurring within 1 - 3 hours. It is distributed throughout the body with highest levels found in the kidneys, plasma anderythrocytes. Acetazolamide has been detected in the milk of lactating dogs and it crosses theplacenta (unknown quantities). Within 24 hours of administration, an average of 90% of the drug isexcreted unchanged into the urine by tubular secretion and passive reabsorption processes.
Contraindications/Precautions - Carbonic anhydrase inhibitors are contraindicated in patientswith significant hepatic disease (may precipitate hepatic coma), renal or adrenocortical insufficiency, hyponatremia, hypokalemia, hyperchloremic acidosis or electrolyte imbalance. They should not beused in patients with severe pulmonary obstruction unable to increase alveolar ventilation or thosewho are hypersensitive to them. Long term use of carbonic anhydrase inhibitors are contraindicatedin patients with chronic, noncongestive, angle-closure glaucoma as angle closure may occur and thedrug may mask the condition by lowering intra-ocular pressures.
Acetazolamide should be used with caution in patients with severe respiratory acidosis or whohave preexisting hematologic abnormalities. Cross sensitivity between acetazolamide and antibacterial sulfonamides may occur.

Adverse Effects, Warnings

Potential adverse effects that may be encountered include GI disturbances, CNS effects (sedation, depression, excitement, etc.), hematologic effects (bone marrowdepression), renal effects (crystalluria, dysuria, renal colic, polyuria), hypokalemia, hyperglycemia, hyponatremia, hyperuricosemia, hepatic insufficiency, dermatologic effects (rash, etc.), andhypersensitivity reactions.
Overdosage - Information regarding overdosage of this drug is not readily available. It is suggested to monitor serum electrolytes, blood gases, volume status, and CNS status during an acuteoverdose. Treat symptomatically and supportively.

Drug Interactions

Oral acetozolamide can inhibit primidone absorption. Primidone or phenytoin, used with acetazolamide, may cause severe osteomalacia.
Because acetozolamide alkalinizes the urine, the excretion rates of many drugs (e.g., quinidine, procainamide, phenobarbital, methotrexate, etc.) may be affected. It may also negate the effects of methenamine compounds in the urine.
Concomitant use with corticosteroids, amphotericin B, corticotropin, or other diuretics mayexacerbate potassium depletion; this may be especially significant in patients receiving digitalis preparations.
Rarely, carbonic anhydrase inhibitors interfere with the hypoglycemic effects of insulin.
Laboratory Interactions - By alkalinizing the urine, carbonic anhydrase inhibitors may causefalse positive results in determining urine protein using bromphenol blue reagent (Albustix®,
Albutest®, Labstix®), sulfosalicylic acid (Bumintest®, Exton's Test Reagent), nitric acid ring test, or heat and acetic acid test methods.
Carbonic anhydrase inhibitors may decrease iodine uptake by the thyroid gland in hyperthyroid or euthyroid patients.
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