Description
Acetazolamide Pharmacodynamics
Acetazolamide is a systemic inhibitor of carbo-anhydrase with weak diuretic activity. Carboanhydrase (CA) is an enzyme involved in the process of carbon dioxide hydration and carbonic acid dehydration. Inhibition of carboanhydrase reduces the formation of bicarbonate ions with a consequent decrease in sodium transport inside the cells. The effects of acetazolamide preparations are due to the point of application of the molecule: the vascular plexuses of the brain, the proximal nephron, the ciliary body of the eye, and erythrocytes.
Acetazolamide is used for treatment of liquorodynamic disorders and intracranial hypertension by reducing the excessive production of cerebrospinal fluid at the level of cerebral vascular plexuses. Inhibition of carboanhydrase in the ependymocytes of the vascular plexus decreases the excess negative charge in the ependymal cells and reduces the gradient plasma filtration into the brain ventricular cavity.
Acetazolamide is used in the therapy of edema syndrome due to its weak diuretic effect. As a result of inhibition of carboanhydrase activity in proximal part of nephron, carbonic acid formation decreases and reabsorption of bicarbonate and sodium ions by tubule epithelium decreases, which significantly increases water excretion. Acetazolamide increases the excretion of bicarbonates, which may lead to metabolic acidosis. Acetazolamide causes renal excretion of phosphate, magnesium, calcium, which may also lead to metabolic disorders. During the next three days of therapy reabsorption of sodium ions in the distal nephron is compensatorily activated, reducing the diuretic effect of acetazolamide.
After 3 days from the start of use acetazolamide loses its diuretic properties. After a break in treatment for several days, newly prescribed acetazolamide resumes its diuretic effect due to restoration of normal proximal nephron carboanhydrase activity.
Acetazolamide is used to treat glaucoma. During ocular aqueous humor formation, bicarbonate ions (HCO3-) are actively transported to the posterior chamber from the cytoplasm of nonpigmented cells to compensate for the gradient of positive ions caused by active transport of sodium ions. CA inhibitors block the formation of carbonic acid, thus reducing the production of HCO3′ ions. In the absence of sufficient amounts of HCO3’ions, the positive ionic gradient increases, causing a decrease in aqueous humor secretion. Inhibition of carboanhydrase of the ciliary body reduces the secretion of aqueous humor of the anterior chamber of the eye, which reduces intraocular pressure. Tolerance to this effect does not develop. Ophthalmotonus when receiving acetazolamide-d begins to decrease after 40-60 minutes, the maximum effect is seen after 3-5 hours, the intraocular pressure remains below the initial level for 6-12 hours. On average, intraocular pressure decreases by 40-60% of the initial level. Acetazolamide is used as an adjunctive agent in the treatment of epilepsy, because inhibition of carboenhydrase in nerve cells of the brain inhibits pathological excitability.
Indications
– Edematous syndrome (mild to moderate, in combination with alkalosis);
– Cure of an acute attack of glaucoma, preoperative preparation of patients, persistent cases of glaucoma (in complex therapy);
– In epilepsy as an additional therapy to antiepileptic drugs;
– Acute “altitude” sickness (the drug reduces the acclimatization time);
– Lykovodynamicheskie violations, intracranial hypertension (benign intracranial hypertension, intracranial hypertension after ventricular bypass) in the treatment.
Contraindications
– Hypersensitivity to acetazole amide, other sulfonamides and/or drug components;
– acute renal failure;
– Severe chronic renal failure (creatinine clearance less than 10 ml/min);
– uremia;
– hepatic insufficiency (risk of encephalopathy);
– refractory hypokalemia;
– refractory hyponatremia;
– metabolic acidosis;
– hypocorticism;
– Addison’s disease;
– decompensated diabetes mellitus;
– long-term use in chronic closed-angle glaucoma, as decreased intraocular pressure may mask worsening glaucoma and allow organic angle closure to develop;
– pregnancy (first trimester);
– Breastfeeding period;
– children under 3 years of age.
With caution
– Edema of hepatic and renal genesis;
– concomitant use with acetylsalicylic acid (doses over 300 mg/day);
– Pulmonary embolism and pulmonary emphysema (risk of acidosis);
– Pregnancy (II and III trimester);
– advanced age;
– Water-electrolyte imbalance;
– liver function abnormality;
– in patients with risk of urinary tract obstruction;
– diabetes mellitus.
Administration during pregnancy and lactation
Well controlled clinical trials of the drug use in pregnant women have not been conducted. Therefore during pregnancy the drug is contraindicated in I trimester and in II and III trimesters it is used with caution and only in cases when the potential benefit for a mother exceeds the potential risk for a fetus.
Acetazolamide is excreted in small amounts with breast milk, therefore, if it is necessary to use the drug Acetazolamide, breast-feeding should be stopped.
Dosage and administration method
- The drug is taken orally, strictly as prescribed by the physician.
- If the drug is skipped, do not increase the dose at the next dose.
- Edematous syndrome
- At the beginning of treatment, 250 mg in the morning. To achieve the maximum diuretic effect, Acetazolamide should be taken once a day every other day or two days in a row with a one-day break. Increasing the dose does not increase the diuretic effect.
If the previously achieved response to acetazolamide therapy decreases, the drug should be withdrawn for 24 hours (to restore renal carboenhydrase activity). The use of acetazolamide does not cancel the need for the use of other drugs, bed rest and restriction of sodium chloride intake. - Gpaucoma .
- Acetazolamide should be taken as part of complex therapy.
- In adults with open-angle glaucoma, the drug is prescribed in a dose of 250 mg 1-4 times a day. Doses in excess of 1000 mg do not increase the therapeutic effect. In secondary glaucoma, the drug is prescribed in a dose of 250 mg every 4 hours during the day. In some patients, the therapeutic effect appears after a short-term administration of the drug in a dose of 250 mg 2 times a day.
- In acute attacks of glaucoma; the drug is prescribed in a dose of 250 mg 4 times a day.
In children aged over 3 years old in glaucoma attacks
the drug is prescribed in a dose of 10-15 mg/kg of body weight daily in 3-4 doses.
After 5 days of dosing a break is made for 2 days. During long-term treatment it is necessary to prescribe potassium preparations, potassium-saving diet. - In preparation for surgery, 250-500 mg is prescribed in the morning before and on the day of surgery.
- Epilepsy
- Doses for adults: 250-500 mg/day in one dose for 3 days, on the 4th day there is a break. In concomitant use of Acetazolamide with other anticonvulsants, 250 mg once daily is used at the beginning of treatment, gradually increasing the dose if necessary. The maximum daily dose in adults is 1000 mg.
- Doses for children over 3 years of age: 8-30 mg/kg per day, divided into 1-4 doses. The maximum daily dose is 750 m g.
- Acute “altitude” sickness.
- The use of the drug in a dose of 500-1000 mg per day is recommended.
In case of rapid ascent -1000 mg per day. The drug should be used 24-48 hours before ascent. In case of occurrence of disease symptoms the treatment is continued for the next 48 hours or longer, if necessary. - Livorodynamic disorders, intracranial hypertension
It is recommended to use the drug in a dose of 250 mg per day or 125-250 mg every 8-12 hours. The maximum therapeutic effect is achieved with a dose of 750 mg per day. To achieve optimal effect, a daily, intermittent administration of the drug may be required.
