ACETAMOX TABLETS

Indications

• Glaucoma
• Ocular hypertension
• Epilepsy
• Reduction of intraocular pressure

Dosage

Children: For children 1 month to 11 years, the initial dose is 2.5 mg/kg 2-3 times a day, with a maximum of 750 mg per day. For children 12-17 years, the dose is 250 mg 2-4 times a day.

Adults: Initial dose for adults is typically 250 mg 2-4 times a day, adjusted according to response; maximum 1000 mg per day.

Mechanism of action

Acetazolamide inhibits the enzyme carbonic anhydrase, which is involved in the production of bicarbonate ions. This inhibition leads to a decrease in bicarbonate concentration, resulting in reduced aqueous humor production and lower intraocular pressure.

Pharmacodynamics

The drug has a diuretic effect, leading to increased urinary bicarbonate, sodium, and water excretion. It also affects the acid-base balance, potentially causing metabolic acidosis.

Pharmacokinetics

Acetazolamide is absorbed orally, with peak plasma concentrations occurring within 2-4 hours. It is widely distributed in body tissues and has a half-life of approximately 10 hours. The drug is primarily excreted unchanged in the urine.

Contra-indications

• Adrenocortical insufficiency
• Hyperchloraemic acidosis
• Hypokalaemia
• Hyponatraemia

Adverse effects

• Dizziness
• Nausea
• Hearing impairment
• Electrolyte imbalance
• Depression
• Bone marrow disorders
• Renal colic
• Tinnitus
• Urinary tract discomfort
• Skin reactions
• Severe cutaneous adverse reactions (SCARs)
• Thrombocytopenia
• Angioedema
• Raised intracranial pressure
• Sensation abnormal

Interactions

• Acetazolamide + methenamine: Severe (decreases efficacy)
• Acetazolamide + antiepileptics: Unknown (increases risk of overheating and dehydration)
• Acetazolamide + zonisamide: Unknown (increases risk of overheating and dehydration)
• Acetazolamide + lithium: Unknown (affects concentration)

Precautions

• Consider cautions listed for systemically administered beta blockers
• Avoid extravasation at injection site (risk of necrosis)
• Diabetes mellitus
• Impaired alveolar ventilation

Pregnancy

Manufacturer advises avoidance.

Breast-feeding

Manufacturer advises avoidance.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Eye drops: 2.5 mg/ml
• Ophthalmic gel-forming solution: 2.5 ml
• Injectable solution: 250 mg per 5 ml

Mechanism of action

The anticonvulsant activity of Acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension. The diuretic effect depends on the inhibition of carbonic anhydrase, causing a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen. This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water. Carbonic anhydrase inhibitors potently inhibit (IC50 for acetazolamide is 10 nM) both the membrane bound and cytoplasmic forms of carbonic anhydrase, resulting in nearly complete abolition of NaHCO3 reabsorption in the proximal tubule. /Carbonic Anhydrase Inhibitors/ Although the proximal tubule is the major site of action of carbonic anhydrase inhibitors, carbonic anhydrase also is involved in secretion of titratable acid in the collecting duct system (a process which involves a proton pump), and therefore the collecting duct system is a secondary site of action for this class of drugs. /Carbonic Anhydrase Inhibitors/ Acetazolamide frequently causes paresthesias and somnolence, suggesting an action of carbonic anhydrase inhibitors in the CNS. The efficacy of acetazolamide in epilepsy is in part due to the production of metabolic acidosis; however, direct actions of acetazolamide in the CNS also contribute to its anticonvulsant action. ... Inhibition of carbonic anhydrase decreases the rate of formation of aqueous humor and consequently reduce intraocular pressure. /Carbonic Anhydrase Inhibitors/ For more Mechanism of Action (Complete) data for ACETAZOLAMIDE (6 total), please visit the HSDB record page.

Pharmacodynamics

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion, in the treatment of certain convulsive disorders and in the promotion of diuresis in instances of abnormal fluid retention. Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.