The Parkinsn's List Drug Database
acetazolamide, DiamoxTM
PARENTERAL CARBONICANHYDRASE INHIBITOR
Altitude sickness,Glaucoma
Description: Acetazolamide is an oral and parenteral carbonic anhydrase inhibitor. Other members of this class include methazolamide and dichlorphenamide.Acetazolamide is used for the prophylaxis and treatment of altitude sickness, and as an adjunct treatment for glaucoma andepilepsy. Acetazolamide has been used as a diuretic for edema due to congestive heart failure, but it has been replaced by thiazide and loop diuretics because it rapidly loses its diuretic effect and is less potent than other classes of diuretics. Carbonicanhydrase inhibitors other than acetazolamide are not effective anticonvulsant agents. Acetazolamide was approved by the FDA in 1953.
Mechanism of action: Carbonicanhydrase is an enzyme responsible for forming hydrogen and bicarbonate ions from carbon dioxide and water. By inhibiting this reaction, acetazolamide reduces the availability of these ions for active transport. Hydrogen ion concentrations in the renal tubule lumen are reduced by acetazolamide, leading to analkaline urine and an increased excretion of bicarbonate, sodium,potassium, and water. A reduction in plasma bicarbonate results in metabolic acidosis, which rapidly reverses the diuretic effect. Reduced intraocular pressure (IOP) is the result of a 50-60% reduction in aqueous humor production by acetazolamide and is likely due to decreased bicarbonate ion concentrations inocular fluid.
The anticonvulsant activity of acetazolamide may depend on a direct inhibition of carbonic anhydrase in theCNS, which increases carbon dioxide tension and inhibits neuronal transmission. The successful treatment of altitude sickness involves production of respiratory and metabolic acidosis, which increases ventilation and binding of oxygen to hemoglobin. This occurs because the drug decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension.
Pharmacokinetics:Acetazolamide is available for oral, intravenous, and intramuscular administration. Acetazolamide is rapidly absorbedfrom the GI tract, and peak serum concentrations for the tablets and extended-release capsules are achieved in 2-4 hours and 8-12hours, respectively. When used for glaucoma, the onset of action for the tablets is about 1.5-2 hours, and the peak effect on IOP is achieved within 2-12 hours, depending on the formulation used.The onset of action following IV administration is about 2minutes, reaching a peak effect in 15 minutes and lasting 4-5 hours. Acetazolamide is approximately 90% bound to plasma proteins and is widely distributed. The half- life of the tablets is 10-15 hours. Acetazolamide is eliminated renally. Following administration of the tablet or IV preparation, 90-100% of a dose is excreted within 24 hours. Approximately 47% of an extended-release dose is eliminated renally within 24 hours.
CONTRAINDICATIONS/PRECAUTIONS: Acetazolamide is classified as pregnancy category C. This drug has not been linked to congenital defects in humans. Because there have been reports of teratogenic effects in animals, however, acetazolamide is not recommended for use during pregnancy, especially during the first trimester, unless the benefits of treatment outweigh the risks to the fetus. The safe use of acetazolamide during breast-feeding has not been established. This drug should be used only when clearly needed.
Acetazolamide should be avoided in patientswith hepatic disease. These patients are more susceptible to electrolyte imbalances. In addition, patients with hepatic disease, especially cirrhosis, are at an increased risk for hepatic encephalopathy.
Acetazolamide should not be given to patients with hyponatremia, hypokalemia, adrenal insufficiency, hyperchloremic metabolic acidosis, or renal disease. Plasma chloride levels and excretion of sodium and potassium are altered during treatment, and these conditions can be exacerbated by the renal and metabolic effects of the drug.
Patients with pulmonary disease, including those with pulmonary infection, obstruction, emphysema, or respiratory acidosis, should be monitored closely during treatment with acetazolamide because of the potential for respiratory acidosis.
Acetazolamide can induce bone marrow depression, so patients with a hematological disease should have periodic hematologic evaluations.
DRUG INTERACTIONS:Acetazolamide can decrease excretion of dextroamphetamine, anticholinergics, mecamylamine, ephedrine, mexiletine, or quinidine because carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of nonionized drug available for renal tubular reabsorption. The effects of these drugs can be prolonged or enhanced. Increased urine alkalinity also can inhibit the conversion of methenamine to formaldehyde, which is the active bacteriostatic form.Concurrent use of methenamine and acetazolamide is not recommended.
Acetazolamide produces alkaline urine and can increase the rate of excretion of weakly acidic drugs including barbiturates and salicylates. Acetazolamide can potentiate salicylate toxicity by causing metabolic acidosis and enhancing the penetration of the salicylate into tissues. In addition, salicylates decrease the elimination of acetazolamide, whichcould result in CNS toxicity.
Acetazolamide can induce osteomalacia in patients being concomitantly treated with carbamazepine, primidone, or phenytoin. Potential mechanisms for this interaction include an acetazolamide-induced increase in the urinary excretion of calcium and effects resulting from metabolicacidosis.
Acetazolamide can enhance the effect of other diuretics, such as thiazides, when used concurrently. The hypokalemic and hyperuricemic effects, however, also can be potentiated.
Acetazolamide can potentiate the hypokalemia caused by corticosteroids, amphotericin B, or corticotropin, ACTH. In addition, patients receiving digoxin and acetazolamide concurrently are at an increased risk for digoxin toxicity if hypokalemia develops during treatment. A large proportion of ciprofloxacin is normally excreted unchanged in the urine. If acetazolamide is used concomitantly, the solubility of ciprofloxacin can be decreased because of alkaline urine.Patients should be monitored for crystalluria and nephrotoxicity.
ADVERSE REACTIONS: The inhibition of carbonic anhydrase affects excretion of electrolytes. Hyperchloremia and/or metabolic acidosis can result from an increase in plasma chloride concentrations. Acetazolamide increases the excretion of bicarbonate and sodium, decreasing the extracellular fluid concentration of bicarbonate and causing metabolic acidosis. Increased excretion of potassium is most likely to occur during the use of high dosages or during concurrent use of other potassium-depleting agents, and can result in hypokalemia. Carbonic anhydrase inhibitors are sulfonamide derivatives and have caused crystalluria and sulfonamide-like nephrotoxicity characterized by renal intratubular obstruction, hematuria, dysuria, and oliguria. An increase in calcium excretion can cause nephrolithiasis. Patients with preexisting hypercalemia develop renal calculi most frequently.
Acetazolamide has caused aplastic anemia, pancytopenia, thrombocytopenia, agranulocytosis, hemolysis(producing hemolytic anemia), and leukopenia. In rare instances, fatalities have occurred.
Discovery of the central nervous system side effects of acetazolamide was the first indication that the drug had activity in the CNS. Adverse CNS effects, such as drowsiness, seizures, irritability, libido decrease, vertigo, confusion, and paresthesias, can develop. Paresthesias occur frequently and are manifested as numbness, tingling, or burning in the hands, fingers, feet, toes, mouth, tongue, lips, or anus.
Adverse GI effects that have been reported with acetazolamide include nausea/vomiting, diarrhea, xerostomia, excessive thirst, and anorexia. Symptoms such as nausea/vomiting, xerostomia, and increased thirst may indicate hypokalemia.
Acetazolamide has rarely caused hyperglycemiaand glycosuria in patients with diabetes mellitus. Hyperglycemia may be due to the acetazolamide-induced hypokalemia.
In patients with hepatic disease, especially cirrhosis, hepatic encephalopathy can occur as a result of hypokalemia and elevations in serum ammonia concentrations. Disorientation also has been observed in these patients, possibly due to elevated ammonia concentrations.
Hyperuricemia can develop during treatment with acetazolamide. Gout can be exacerbated in susceptible patients.Alterations in serum uric acid levels are reversible following discontinuation of the drug.
PATIENT INFORMATION:
What do acetazolamide tablets do?
Acetazolamide (DiamoxTM ) helps to treatglaucoma, certain types of epilepsy or seizure disorders. It can also help mountain climbers who get altitude or mountainsickness. Generic acetazolamide tablets are available.
What should my doctor, dentist, or pharmacist know before I take acetazolamide?
They need to know if you have any of theseconditions:
How should I take this medicine?
Take acetazolamide tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take acetazolamide with food if it upsets your stomach. Take your doses at regular intervals. Do not take your medicine more often than directed. If you are taking acetazolamide for mountain sickness, take the first dose 24 to 48 hours before you start the climb. Continue to take it while at high altitude.
If you are unable to swallow the tablets, a liquid can be made by softening (or crushing) a tablet in 2 teaspoonfuls of water and adding 2 teaspoonfuls of honey or syrup. This liquid should be made just before the dose is taken.
Special precautions foruse in children:
This medicine is not for general use inchildren, but in certain circumstances may be prescribed by the doctor.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact withacetazolamide?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking acetazolamide?
Serious side effects with acetazolamide include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with acetazolamideinclude:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take acetazolamide?
Ask your doctor about your potassium level. It is important not to have too little or too much potassium. You may need to take a potassium supplement or eat foods that are high in potassium if acetazolamide is making your body lose too much potassium.
Do not stop taking acetazolamide suddenly if you are taking it to prevent seizures. Your doctor may want you to reduce your dose gradually.
You may get drowsy; until you know how acetazolamide affects you, do not drive, use machinery, or do anything that needs mental alertness.
Drink several glasses of water a day. This will help to reduce possible kidney problems.
If you are diabetic, monitor blood and urine sugar and ketones regularly. Acetazolamide can increase sugar levels. Check with your doctor if you notice any changes.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C(50 and 86F). Throw away any unused medicine after the expiration date.
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