Acetazolamide

Acetazolamide (molecular formula C4H6N4O3S2), a diuretic from the substance class of sulfonamides, is the prototypical representative of the competitive carbonic anhydrase inhibitors (see also brinzolamis, dorzolamide). Carboanhydrase inhibitors are glomerularly filtered and tubularly secreted and exert their effect on the luminal side of the tubule cells. Acetazolamide inhibits very effectively the reabsorption of NaHCO3 especially in the proximal tubule.

In the proximal tubule, the interaction of the Na+-H+ antitransporter and the carbonic anhydrases ensures the reabsorption of NaHCO3. Carboanhydrase inhibitors interfere with this process, increase renal HCO3- excretion (mainly in the form of KCO3) and thus cause metabolic alkalosis. Furthermore, renal phosphate excretion is also increased. The effect on the kidney is accompanied by increased potassium consumption, which may need to be compensated.

Acetazolamide can reduce intraocular pressure (therapeutic indication: glaucoma), intracranial pressure (Supuran CT 2015) and blood pressure.

In the pancreas, it decreases the secretion of pancreatic secretion rich in bicarbonate.

The antiepileptic effects of acetazolamide have not been adequately studied. However, neurotropic effects on excitatory conduction are considered likely.

Acetazolamide leads to increased excretion of potassium in the urine, so that an increased intake of potassium with food must be taken into account with long-term use.

The active ingredient acetazolamide is currently used primarily in ophthalmology to reduce elevated intraocular pressure in glaucoma.

Edema of various origins (including pseudotumor cerebri or cystoid macular edema).

Respiratory failure with respiratory alkalosis (Adamson R et al 2017).

Pancreatitis or pancreatic fistulas, and in epilepsy or Meniere's disease. Acetazolamide is also approved for the preventive treatment of altitude sickness.

Preventive treatment of epilepsy.

Certain forms of myotonia congenita (not approved for this indication).

Acetazolamide is used in brain perfusion scintigraphy (off-label use) to distinguish areas with normal reserve capacity from areas whose vessels are already maximally dilated to compensate for upstream vasoconstriction.

Glaucoma: In acute cases ½-2 ampoules or 1-4 tablets (250-1000 mg) during 24 hours, depending on the case in divided doses, e.g. ½ ampoule or 1 tablet every 4 hours or 2 × daily. Possibly also apply 1 ampoule or 2 tablets (500 mg) initially and ¼-½ ampoule every 4 hours.

Continuous medication: ¼-1 ampoule (125-500 mg) or ½-1 tablet (125-250 mg) daily.

Oedema: Initially ½-¾ ampoule (5 mg/kg Kpgw.) i.v. or 1-1½ tablets (5 mg/kg Kpgw.) daily in the morning for 2-3 days, then ½-¾ ampoule i.v. or 1-1½ tablets 2× weekly.

Respiratory failure with respiratory acidosis: Continuous daily administration of 1-1½ ampoules or 2-3 tablets (500-750 mg) of Diamox for prolonged periods.

Epilepsy: ½-2 ampoules or 1-4 tablets (250-1000 mg) daily in divided doses. Initiation of therapy or a switch to Diamox must be gradual. In combination with other antiepileptic drugs, the initial dose is 250 mg daily. For status epilepticus, 500 mg daily (2× ½ ampoule) i.v.

Acute pancreatitis, pancreatic fistulas: 2-5 ampoules (1000-2500 mg) daily slowly i.v. or as continuous drip infusion.

For prophylaxis of altitude sickness: 1 tablet (250 mg) 2× daily or 1 sustet (500 mg) every 24 hours for at least 4 days, beginning 1 day before exposure.

When used intravenously, dizziness, tinnitus, paraesthesia around the mouth, nausea and drop in blood pressure occur. The symptoms are usually mild and subside on their own.

An acidotic state may occasionally occur during long-term therapy, which can usually be corrected by administration of bicarbonate.

Transient myopia has been reported. These disturbances disappear when the dose is reduced or the drug is discontinued.

Other occasional adverse reactions include urticaria, melena, hematuria, glucosuria, hepatic insufficiency, flaccid paralysis, and convulsions.

Dermatologic UAWs: Because acetazolamide is a sulfonamide derivative, typical sulfonamide side effects may include exanthema

• erythema multiforme
• Stevens-Johnson syndrome
• toxic epidermal necrolysis

Fever, crystalluria, kidney stones, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis.

Contraindications are allergies to sulfonamides and subacute stage of stroke.

Decreased serum sodium and potassium levels.

Hyperchloremic acidosis

Severe renal and hepatic disease

Gout

Adrenal insufficiency

Hypercalciuria

Nephrocalcinosis

Long-term treatment of chronic, non-congestive glaucoma with a closed chamber angle

Pregnancy: risk of malformation of the embryo (Al-Saleem AI et al 2016).

Acemit® (D),Diamox® (A, CH), Glaupax® (D, CH)

Originally, the active substance was used as a diuretic. However, acetazolamide is now rarely used as a diuretic (Kassamali R et al. 2011).

1. Adamson R et al (2017) Acetazolamide Use in Severe Chronic Obstructive Pulmonary Disease. Pros and cons. Ann Am Thorac Soc 14:1086-1093.
2. Al-Saleem AI et al. (2016) Possible association between acetazolamide administration during pregnancy and multiple congenital malformations. Drug Des Devel Ther 10:1471-1476.
3. Kassamali R et al (2011) Acetazolamide: a forgotten diuretic agent. Cardiol Rev 19:276-278.
4. Reinelt CD (2016) Diploma thesis: diuretics - merits and dangers Diploma thesis at the Medical University of Graz.
5. Supuran CT (2015) Acetazolamide for the treatment of idiopathic intracranial hypertension. Expert Rev Neurother 15:851-856.
6. Van Berkel MA et al (2018) Evaluating off-label uses of acetazolamide. Am J Health Syst Pharm 75:524-531.