|Systematic (IUPAC) name|
|oral or intravenous|
|PDB ligand ID||AZM (, )|
|Melting point||258 to 259 °C (496 to 498 °F)|
|(what is this?)|
Acetazolamide, usually sold under the trade name Diamox in some countries, is a carbonic anhydrase inhibitor that is used for the medical treatment of glaucoma, epileptic seizure, idiopathic intracranial hypertension, altitude sickness, cystinuria, periodic paralysis, central sleep apnea, and dural ectasia. Acetazolamide is a diuretic, and it is available as a generic drug in the United States. Diamox is now available as Diamox Sequels in the United States since the original product is no longer made or sold there.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
It is used in the treatment of glaucoma, drug-induced edema, heart failure-induced edema, centrencephalic epilepsy and in reducing intraocular pressure after surgery. It has also been used in the treatment of mountain sickness, Ménière's disease, increased intracranial pressure and neuromuscular disorders.
In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an adjunct in refractory epilepsy. It has been demonstrated in drug trials to relieve symptoms associated with dural ectasia in individuals with Marfan's Syndrome. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea. In the treatment of mountain sickness, acetazolamide forces the kidneys to excrete bicarbonate, the conjugate base of carbonic acid. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. As the body equates acidity of the blood to its CO2 concentration, artificially acidifying the blood fools the body into thinking it has an excess of CO2, and it excretes this imaginary excess CO2 by deeper and faster breathing, which in turn increases the amount of oxygen in the blood. Acetazolamide is not an immediate cure for acute mountain sickness; rather, it speeds up part of the acclimatization process which in turn helps to relieve symptoms.
Pregnancy and lactation
Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs. Despite this there is insufficient evidence from studies in humans to either support or discount this evidence. It is also excreted in breast milk and hence breastfeeding is advised against in mothers taking this drug.
Common adverse effects of acetazolamide include: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black feces, polyuria, kidney stones, metabolic acidosis and electrolyte changes (hypokalemia, hyponatremia). Whereas less common adverse effects include: stevens-johnson syndrome, anaphylaxis and blood dyscrasias.
- Hyperchloremic acidosis
- Hypokalemia (low blood potassium)
- Hyponatremia (low blood sodium)
- Suprarenal gland failure
- Impaired kidney function
- Hypersensitivity to acetazolamide or other sulfonamides.
- Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.
It is possible that it might interact with:
- Amphetamines, due to the fact it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines.
- Other carbonic anhydrase inhibitors - potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity.
- Ciclosporin, may increase plasma levels of ciclosporin.
- Antifolates such as trimethoprim, methotrexate, pemetrexed and raltitrexed.
- Hypoglycemics, acetazolamide can both increase or decrease blood glucose levels.
- Lithium, increases excretion, hence reducing therapeutic effect.
- Methenamine compounds, reduces the urinary secretion of methenamines.
- Phenytoin, reduces phenytoin secretion, hence increasing the potential for toxicity.
- Primidone, reduces plasma levels of primidone. Hence reducing anticonvulsant effect.
- Quinidine, reduces urinary secretion of quinidine, hence increasing the potential for toxicity.
- Salicylates, potential for severe toxicity.
- Sodium bicarbonate, potential for kidney stone formation.
- Anticoagulants, cardiac glycosides, may have their effects potentiated by acetazolamide.
Mechanism of action
hence lowering blood pH, by means of the following reaction that carbonic acid undergoes:
which has a pKa of 6.3.
The mechanism of diuresis involves the proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation, increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.
The tablets are made with acetazolamide in its original form, whereas the injection is in the sodium salt form. Its free form is fairly insoluble in water and alcohol. Its free form is white-faintly yellow, in colour. It also degrades upon contact with light.
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