Carbonic anhydrase diuretics include 

Acetozolamide, Dichlorophenamide, Methazolamide

Refer- Acetozolamide

Interacting drugs - summary

 Acetazolamide +

 Cyclosporine

 increased cyclosporine levels with possible nephrotoxicity and neurotoxicity occur

Primidone

 primidone and urine concentrations decreased.

 Carbonic anhydrase Inhibitors (CAI ) +

 Salicylates

 concurrent use result in accumulation and toxicity of the CAI, including Salicylates

+ CAI

 CNS depression and metabolic acidosis. Also CAI-induced acidosis may allow increased penetration by salicylates

 + CAI

 Difunisal

concurrent use result in a significant decrease intraocular pressure, the effect less pronounced with methazolamide. Increased side effects also occur.

+ Folic acid

May potentiate effect of Folic acid antagonists,oral hypoglycaemic agents and oral anticoagulants.

Aids penetration of weakly acidic substances like sulphonamide across blood/CSF barrier.

Potentiates effect of mercurial diuretics.

May inhibit renal excreation of basic drugs.

May increase salicylate toxicity (acidosis).

Hypokalaema with corticisteroids,potassium wasting diuretics.

May diminsh effect of lithium.primidone.

May cause osteomalasia with phenytoin.

Epilepsy

Carbonic anhydrase diuretics include - Acetozolamide, Dichlorophenamide, Methazolamide

Refer- Acetozolamide

Sulfonamide -type adverse reactions may occur

GI- malena, anorexia, nausea, vomiting, constipation,taste alteration, diarrhea.

Renal- hematuria, glycosuria, urinary frequency, renal colic, renal calculi, crystalluria, polyuria, phosphaturia.

CNS- convusions, weakness, malaise, fatigue, nervousness, drowsiness, depression, dizziness, disorientation, confusion, artaxia,tremor, tinnutus, headache, lassitude, facial paralysis, parethesia of the extremities

Hematologic- bone marrow depression, thrombocytopenia, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, agranulocytosis

Dermatologic- urtocaria, pruritus, skin eruption( including eryhema multiforme , Stevens-Johnson Syndrome, toxic epidermal necrolysis), photosentivity

Miscellaneous- weight loss, fever, acidosis, (usually corrected with bicarbonate) decreased/absent libido) impotence, electrolye imbalance, hepatic insufficiency, transcient myopia.

Renal hypercholaemic acidosis.

Addisons disease,sensitivity to sulphonamides.

Special precautions:

Potassium supplements may be reqd.

Elderly with reduced renal functions.

Monitoring- monitor for hematologic reactions common to sulfonamides. Obtain baseline CBC and platelet counts before therapy at regular intervals during therapy. Hpokalemia may develop when severe cirrohis is present during comcomittant use of steroids or ACTH and with inteference with adequate oral electrolyte intake.

Dose decreases- increasing the dose of acetaozolamide does not increase diuresis and may increase drowsiness or paresthesia, it often results in decreased diuresis.

Pulmonary conditions-use dichlorphenamide with caution in patients with severe degrees of respiratory acidosis. Use with caution in patients with pulmonary obstruction or emphysema when aveolar ventilation may be improved.

Cross sensitivity- between antibacterial sufonamides and sufonamide derivative diuretics including acetazolamide and various acetaozalomide and various thiazides has been reported.

Warnings

Hepatic function impairment- use of methazolamide in this condition could precipitate hepatic coma.

Pregnancy- do not use during pregnancy especialy in first trimester, unless the potentail benefits outweigh the potential hazards.

Lactation- safety for use in nursing mother has not been established. Children- safety and efficacy for use in children have not been established.

Indications:

Centreencephalic epilepsies (prtit mal, localised seizures), edema due to congestive heart failure and drug induced edema, glaucoma. For prevention or amelioration of acute mountain sickness in climbers attempting rapid accent.

Dosage:

Take with food

Epilepsies- 8 to 30mg/kg/day in divided doses.

Optimum range 375 to 1000mg daily..

Parentral - Direct IV admin preferred because IM admin is painful.

Storage:

Reconstituted solutions retain potency for 1 week if refrigerated. However since product does not normally contain a preservative, use within 24 hours of reconstitution.

Overdosage

Symptoms -

Drowsiness, anorexia, nausea, vomiting,dizziness paresthesias, ataxia, tremor, tinnitus

Treatment

1. Induce emesis or perform gastric lavage.

2.The electrolyte disturbance most likely to be encountered from overdosage is hyperchloremic acidosis that may respond to bicarbonate administration.

3. Potassium supplementtation may be required.

4. Observe carefully give supportive treatment

Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Renal tubular acidosis- 

 Drugs causing adverse reactions- 

1. Degraded tetracycline

2. Amphotericin B

3. Acetazolamide

Calculi

 Drugs causing adverse reactions- 

 1. Acetazolamide

2. Vitamin D

Carbonic anhydrase diuretics include

Acetozolamide, Dichlorophenamide, Methazolamide

Refer- Acetozolamide

1. It GI upset occurs, take with food.

2. Avoid prolonged exposure to sunlight or sunlamps, may cause photosensitivity

3. May cause drowsiness, observe caution while driving or performing other tasks requiring alertness, coordination or physical dexterity

4. Notify physician if sore throat, fever, unusual bleeding or bruising, tingling ortremors in the hands or feet, flank or loin pain or skin rashes occurs

5. Allergies- tell your doctor if you have ever had any allergic reaction to carbonic anhydrase inhibitors, sulfonamide, or thiazidediuretics . also tell your doctor if you are allergic to any other substances such as foods, preservatives or dyes.

6. Pregancy- not studied in pregnant woman. Before taking this medicine make sure that your doctor knows that you are pregnant orif you may become pregnant.

7. Breast feeding- may pass into breast milk- It may be necessary for you to either use other medicine or to stop breast feeding during treatment.

8. Children- these medicines are not expected to cause different side effects or problems in children than they do in adults.

9. Elderly- these medicines are not expected to cause different side effects or problems in elderly than in younger adults.

10. Other medicines- Tell your doctor if you are using any other medicines e.g. - Amphetamines or Mecamylamine or Quinidine - use of carbonic anhydrase inhibitors may increase the chance of side efects. Methenamine - use of carbonic anhydrase inhibitors may decrease the effectiveness of methenamine

11. Other medical problems- tell your doctor if you have any other medical problems- Diabetes mellitus - use may increase the patients blood and urine sugar concentrations Emphysema or other chronic ling disease- use may increase the risk of acidosis

 12. Missed dose- if you miss a dose of this medcine take it as soon as possible. However, if it is time for the next dose,skip the missed dose and go back to the normal dose schedule Do not double doses.

Pharmacology:

Acetazolamide has been used as an adjuvant in the treatment of certain CNS dysfunctions.eg epilepsy. Inhibition of carbonic anhydrease in this area appears to retard abnormal .paraoxymal , excessive discharge from CNS neurons

The mechanism of anticonvulsant action is not fully understood. Beneficial effects may be related to direct inhibition of carbonic anhydrase, or due to acidosis produced by therapy

Take with food

Pregnancy

Do not use during pregnancy especialy in first trimester, unless the potentail benefits outweigh the potentail hazards

Lactation-

Safety for use in nursing mother has not beenestablished.

Children-

Safety and efficacy for use in children have not been established.