Diuretic (Carbonic Anhydrase Inhibitor)
- Used for metabolic alkalosis or glaucoma (open angle glaucoma) in small animals and hyperkalemic periodic paralysis (HYPP) in horses.
- Contraindicated in patients with significant hepatic, renal, pulmonary, or adrenocortical insufficiency, hyponatremia, hypokalemia, hyperchloremic acidosis, trouble breathing, nausea, vomiting or electrolyte imbalance.
- Give oral doses with food if GI upset occurs.
- Electrolytes and acid/base status should be monitored with chronic or high dose therapy. 1
- In the event of a missed dosed, the literature advises to skip the missed dose rather than running the risk of GI complications.
Acetazolamide has been used principally in veterinary medicine for its diuretic action and its effects on aqueous humor production in the treatment of glaucoma and metabolic alkalosis. It may be useful as an adjunctive treatment for syringomyelia in dogs. 1
In humans, acetazolamide (an inhibitor of carbonic anhydrase which catalyzes hydration/dehydration of carbon dioxide) has been used for correction of metabolic, alkalosis in patients with chronic obstructive pulmonary disease (COPD). It is also used to prevent and reduce the symptoms of exposure to high altitude (altitude sickness).
Acetazolamide is a diuretic used primarily to treat hyperkalemic periodic paralysis (HYPP), a genetic disease of the neuromuscular system in horses. HYPP is a muscular disease that affects horses, causing muscle weakness and tremors, sweating and difficulty breathing. Acetazolamide is also used to decrease intraocular pressure in the treatment of glaucoma in dogs and cats.
Acetazolamide is a prescription drug primarily used to treat dogs, cats and horses. Acetazolamide’s use in small animals is complicated by a relatively high occurrence of adverse effects. 1
As a carbonic anhydrase inhibitor, acetazolamide acts through a noncompetitive, reversible inhibition of the enzyme, carbonic anhydrase. This reduces the formation of hydrogen and bicarbonate ions from carbonic acid, thereby reducing the availability of these ions for active transport into body secretions.
Drug information on acetazolamide indicates that the pharmacologic effects of carbonic anhydrase inhibitors include decreased formation of aqueous humor, thus reducing intraocular pressure, increased renal tubular secretion of sodium and potassium and, to a greater extent, bicarbonate, leading to increased urine alkalinity and volume. Acetazolamide has some anticonvulsant activity, which is independent of its diuretic effects (mechanism is not fully understood, but may be due to carbonic anhydrase or a metabolic acidosis effect).
In anesthetized cats, methazolamide did not, but acetazolamide did, reduce the hypoxic ventilatory response. The authors believe this is not a result of carbonic anhydrase inhibition but is instead due to acetazolamide’s effects on carotid bodies or type I cells. 2
One study concluded that after a dosage of 22 mg/kg (2-5 times standard dosage), the onset of action for acetazolamide is 30 minutes; maximal effects occur in 2 to 4 hours; duration of action is about 4 to 6 hours in small animals. 3 In horses, IV administration of acetazolamide results in a high mean clearance rate (4.5 mL/kg/min) and a short mean residence time (1.71 h). Immediate release formulations show a low oral bioavailability (25%) with maximum concentrations of 1.9 micrograms/mL. 4
Acetazolamide has been detected in the milk of lactating dogs and it crosses the placenta (in unknown quantities). Within 24 hours of oral tablet administration, an average of 90% of the drug is excreted unchanged into the urine by tubular secretion and passive reabsorption processes. 1
Contraindications / Precautions:
Carbonic anhydrase inhibitors are contraindicated in patients with significant hepatic disease (in patients with liver disease, acetazolamide may precipitate hepatic coma), renal or adrenocortical insufficiency (kidney disease), irregular heartbeat, hyponatremia, hypokalemia, hyperchloremic acidosis, or other electrolyte imbalances. This class of drugs should not be used in patients with severe pulmonary obstruction that are unable to increase alveolar ventilation or in those who are hypersensitive to them. Long-term use of carbonic anhydrase inhibitors is contraindicated in patients with chronic, noncongestive, angle-closure glaucoma as further angle closure may occur and the drug may mask the condition by lowering intraocular pressures. 1
Acetazolamide should be used with caution in patients with severe respiratory acidosis or those with preexisting hematologic abnormalities. Decreased exercise capacity, hypercapnia, and respiratory acidosis may occur in healthy horses during exercise with chronic, high dose administration. 5 Use of acetazolamide with antibacterial sulfonamides or furosemide may cause cross sensitivities. 1
Potential adverse effects that may be encountered include GI disturbances, CNS effects (eg, sedation, depression, weakness, excitement), hematologic effects (eg, bone marrow depression), renal effects (eg, crystalluria, dysuria, renal colic, polyuria), hypokalemia, hyperchloremia, hyperglycemia, hyponatremia, hyperuricemia, hepatic insufficiency, dermatologic effects (eg, rash), and hypersensitivity reactions.
These effects may be exacerbated in smaller animals.1 At the dosages used for HYPP in horses, adverse effects are reportedly uncommon.
The following drug interactions with acetazolamide have either been reported or are theoretical and may be of significance in veterinary patients.
- ALKALINE URINE: Drugs where acetazolamide induced alkaline urine may affect their excretion rate: Decreased urinary excretion of quinidine, procainamide, and tricyclic antidepressants may result in toxicity. Increased urinary excretion of salicylates and phenobarbital may compromise efficacy.
- ASPIRIN (or other salicylates): Increased risk of acetazolamide accumulation and toxicity; increased risk for metabolic acidosis.
- CYCLOSPORINE: Acetazolamide may increase levels.
- DIGOXIN: As acetazolamide may cause hypokalemia, increased risk for digoxin toxicity.
- INSULIN: Rarely, carbonic anhydrase inhibitors interfere with the hypoglycemic effects of insulin.
- METHENAMINE COMPOUNDS: Acetazolamide may negate methenamine effects in the urine.
- DRUGS AFFECTING POTASSIUM (eg, corticosteroids, amphotericin B, corticotropin, or other diuretics): Concomitant use may exacerbate potassium depletion. 1
Acetazolamide has been implicated in fetal abnormalities in mice and rats when used at 10 times the recommended dose. Fetal toxicity has been noted when the drug has been used in pregnant humans. In humans, the FDA categorizes this drug as category C for use during pregnancy. 1
A physician (veterinarian) should be consulted immediately in the event of the occurrence of rash; red, swollen, blistered, or peeling skin; red or irritated eyes; sores in the mouth, throat, nose, or eyes; fever, chills, or sore throat; weakness, bruising or bleeding; signs of liver problems like dark urine, lethargy, loss of appetite, GI upset or light-colored stools.
In the event of human exposure, call your doctor for medical advice about side effects.
Dogs: Adjunctive therapy of glaucoma, hydrocephalus, or metabolic acidosis (extra-label): 4 – 10 mg/kg PO every 8-12 hours; or IV once.
Cats: Adjunctive therapy of glaucoma (extra-label): 6 – 8 mg/kg PO every 8-12 hours. 1
Horses (NOTE: ARCI UCGFS CLASS 4 DRUG): Prevention or adjunctive therapy of hyperkalemic periodic paralysis (HYPP) episodes (extra-label): 2 – 3 mg/kg PO every 8-12 hours when diet or environmental adjustments do not control episodes. 6
1Plumb's Veterinary Drugs.
2Teppema LJ, et al. The carbonic anhydrase inhibitors methazolamide and acetazolamide have different effects on the hypoxic ventilatory response in the anaesthetized cat. Journal of Physiology-London. 2006;574(2):565-572.
3Roberts, SE. Assessment and management of the ophthalmic emergency. Comp CE. 1985;7(9):739-752.
4Alberts MK, et al. Pharmacokinetics of acetazolamide after intravenous and oral administration in horses. Am J Vet Res. 2000;61(8):965-968.
5Vengust M, et al. Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses. Equine Vet J. 2010;42:40-50
6Valberg, S. Muscle Tremors in Horses. Proceedings: Western Veterinary Conference 2008. 2008. Veterinary Information Network