Acetazolamide dosing

In the treatment of all types of glaucoma, acetazolamide is the most widely used orally administered CAI. Acetazolamide is commercially arailable as 125- and 250-mg tablets, 500-mg sustained-release capsules (Diamox Sequels), and a 500-mg vial formulated for parenteral administration. In glaucoma therapy in adults, acetazolamide is usually administered in doses of 250 mg every 6 hours or a single 500-mg sustained-release capsule twice daily. The recommended acetazolamide dose for children is 5 to 10 mg/kg body weight, administered every 4 to 6 hours. 

A study in 3 men found that 72 hours after they started taking acetazolamide (dose not stated) their trough serum eielosporin levels rose by more than sixfold, from a range of 54 to 270 nanograms/mL up to 517 to 1827 nanograms/mL. Another man with a heart transplant had a fivefold increase in his serum eielosporin levels, marked renal impairment, and neurotoxicity when he was given oral aeetazolamide for raised intra-ocu-... 

Treatment is largely symptomatic, and the prognosis ranges from dismal to guarded. Thiamine, lipoic acid, ketogenic diet and physostigmine have been tried in different concentrations and doses with equivocal results. Some patients with periodic ataxia resulting from PDHC deficiency may respond to acetazolamide. 

Dose increases Increasing the dose of acetazolamide does not increase diuresis and may increase drowsiness or paresthesia it often results in decreased diuresis. However, very large doses have been given with other diuretics to promote diuresis in complete refractory failure. 

Drowsiness and paresthesias are common following large doses of acetazolamide. Carbonic anhydrase inhibitors may accumulate in patients with renal failure, leading to nervous system toxicity. Hypersensitivity reactions (fever, rashes, bone marrow suppression, and interstitial nephritis) may also occur. 

In 1940 sulfanilamide was shown to inhibit carbonic anhydrase. It was not useful as a diuretic because the doses required to produce diuresis were excessive. Investigation of some heterocyclic sulfonamides produced some clinically effective diuretics, for example ethoxzolamide (188), but the first really useful sulfonamide diuretic was acetazolamide (189). This compound also has anticonvulsant activity which is probably related to the presence of carbonic anhydrase in the CNS. Acetazolamide had the disadvantage of producing a metabolic acidosis through the excretion of HCO3- rather than Cl and it was found that some 1,3-disulfonamidobenzenes gave a more balanced diuresis. 

Procainamide (Pronestyl, Pronestyl SR, Procanbid) [Antiarrhythmic] WARNING Only use in life-treating arrhythmias hematologic tox can be severe Uses Supraventricular/ventricular arrhythmias Action Class 1A antiarrhythmic (Table VI-7) Dose Adults. Recurrent VF/pulseless VT 20 mg/min slow IV inf to a max of 17 mg/kg or until QRS T by 50% or dysrhythmia resolves Maint inf 4 mg/min (mix 1 gm in 250 mL NS to make 4 mg/mL use 60 gtt set—60 gtt/min = 4 mg) Peds. Loading dose 15-50 mg/kg IV/IO Caution [C, +] Contra Complete heart block, 2nd- or 3rd-degree heart block w/o pacemaker, torsades de pointes, SLE Disp Tabs caps 250, 500 mg SR tabs 500, 750, 1000 mg inj 100, 500 mg/mL SE 1 BP, lupus-like synd, GI upset, taste perversion, arrhythmias, tach, heart block, angioneurotic edema, blood dyscrasias Interactions T Effects W/ acetazolamide, amiodarone, cimetidine, ranitidine, trimethoprim T effects OF anticholinergics, antihypertensives i effects W/ procaine, EtOH EMS Monitor BP and ECG use caution to prevent rapid... 

Acetazolamide can cause a metabolic acidosis in 50% of elderly patients (SEDA-11,199) occasionally (particularly if salicylates are being given or renal function is poor) the acidosis can be severe. It does this by inhibiting renal bicarbonate reabsorption. This effect is of particular use in treating patients with chronic respiratory acidosis with superimposed metabolic alkalosis. Life-threatening metabolic acidosis is rarely observed in the absence of renal insufficiency and/or diabetes mellitus. In three patients with central nervous system pathology alone conventional doses of acetazolamide resulted in severe metabolic acidosis (34). After withdrawal it took up to 48 hours for the metabolic acidosis and accompanying hyperventilation to resolve. 

Children with heart disease often require high-dose diuretic therapy, which can lead to hypochloremic metabolic alkalosis. There are limited data on the safety of acetazolamide in the treatment of hypochloremic metabolic alkalosis in children. In 28 patients, median age 2 (range 0.3-20) months who took acetazolamide 5 mg/kg for 3 days, there were no adverse events (36). There was no significant difference in any electrolyte concentration, except for serum HC03, which fell from 36 to 31 mmol/1, and serum chloride, which rose from 91 to 95 mmol/1. There was no change in urine output. Acetazolamide appears to be safe in very young patients when given for 3 consecutive days. 

Salicylates Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. Salicylates may displace drugs from plasma protein binding sites. Carbonic anhydrase inhibitors [NE] Increased acetazolamide serum concentrations increased salicylate toxicity due to decreased blood pH. 

Dahl A, Russell D, Rootwelt KC et al (1995). Cerebral vasoreactivity assessed with transcranial Doppler and regional cerebral blood flow measurements dose serum concentration and time course of the response to acetazolamide. Stroke 26 2302-2306... 

Disposition in the Body. Readily absorbed after oral administration. Acetazolamide binds tightly to carbonic anhydrase and will accumulate in tissues in which this enzyme is present, particularly in red blood cells and the renal cortex. About 70 to 90% of a dose is excreted in the urine as unchanged drug in 24 hours but the renal clearance is increased if the urine is alkaline small amounts of unchanged drug are excreted in the bile. 

Acetazolamide is readily absorbed from the gastrointestinal tract after oral administration. After ingestion of acetazolamide tablets, the drug attains peak plasma levels within 2 to 4 hours. Peak levels are maintained for 4 to 6 hours. Drug levels are higher after acetazolamide tablets are ingested than after an equivalent dose of the sustained-release formulation. The time-release capsules produce maximum drug levels in 3 to 4 hours, and levels of 10 mg/ml are maintained for approximately 10 hours. 

Systemic Effects. Although acetazolamide is effective as an ocular hypotensive agent, a significant number of side effects limit its clinical usefulness (Box 10-5). Maximal doses of CAIs produce intolerable effects in 30% to 80% of patients. The incidence of side effects varies with the dose and the fitrmulation however, when all side effects are considered, the incidence probably approaches 100% in patients taking either acetazolamide tablets or the 500-mg sustained-release capsules. One study demonstrated that only 26% of patients could tolerate acetazolamide tablets beyond 6 weeks, whereas 58% of patients could tolerate prolonged use of the sustained-release formulation. 

Acetazolamide should be avoided in patients with severe COPD. These patients may be unable to increase their alveolar ventilation enough to compensate for the acid-base alterations induced by acetazolamide. In some patients, especially those with severe pulmonary disease, increased CO2 gradients or acidosis may lead to acute respiratory failure. Acetazolamide should be used cautiously in such patients, and the practitioner should use the lowest effective dose to reduce lOP... 

Only 55% of methazolamide binds to plasma proteins, compared with 90% to 95% of acetazolamide. Becanse only the imboimd portion of the drug dose is pharmacologically active, methazolamide can be given at lower doses than acetazolamide to achieve comparable effects. 

Methazolamide is one of the best-tolerated oral CAIs, especially at low doses. However, administration of this drug poses the same general risk as administration of acetazolamide, and the side effects associated with methazolamide use are essentially the same as those associated with acetazolamide. Compared with acetazolamide, methazolamide generally produces less acidosis and has less effect on urinary citrate levels.Thus, patients who are intolerant of acetazolamide may tolerate methazolamide therapy without difficulty. 

Skin eruptions can also occur. Methazolamide should be used cautiously in patients of Japanese or Korean descent. Reports of severe Stevens-Johnson syndrome have been documented, with one case occurring after a single dose. Although Stevens-Johnson syndrome has been reported after use of acetazolamide in patients with various ethnic backgrounds, methazolamide-induced Stevens-Johnson syndrome has been encountered only in the Japanese. 

Dorzolamide has been compared with acetazolamide for the prevention of lOP spikes after YAG laser capsulo-tomy. One drop of topical dorzolamide 2% and one 125-mg dose of acetazolamide 1 hour before capsulotomy are comparable in preventing elevations of lOP. Dorzolamide is also effective in preventing lOP spikes after argon laser trabeculoplasty or laser iridotomy... 

Larsson L, Ahn A. Aqueous humor flow in human eyes treated with dorzolamide and different doses of acetazolamide.Arch Ophthalmol 1998 116 19-24. 

Adverse effects. High doses of acetazolamide may cause drowsiness and fever, rashes and paraesthesiae may occur, and blood disorders have been reported. Renal calculi may develop, because the urine calcium is in less soluble form owing to low citrate content of the urine, a consequence of metabolic acidosis. 

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