Non competitive inhibitor of carbonic anhydrase-
Ans. is 'b' i.e., Acetazolamide o Carbonic anhydrase inhibitors act by a non-competitive, reversible inhibition of the enzyme carbonic anhydrase.Carbonic anhvdrase inhibitors (acetazolamide)o Carbonic anhydrase (CAse) is an enzyme which catalyzes the reversible reaction H2O + CO2 - H2CO3 - H++HCO3-.o The enzyme is present in renal tubular cells (especially PT), gastric mucosa, exocrine pancrease, ciliary body of eye, brain and RBC.o Carbonic anhydrase inhibitors inhibit intracellular CAse in PT cells resulting in slowing of hydration of CO2 -decreased availability of H+ to exchange with luminal Na+ through Na+-H+ antiport,o Inhibition of brush border CAse retards dehydration of H2CO3 in the tubular fluid so that less C02 diffuses back into the cells.o The net effect is inhibition of HCO3- (and accompanying Na+) reabsorption in PT - alkaline diuresis.o Secretion of H+ in DT and CD is also inhibited. Though H+ is secreted at this site by H+-ATPase, it is generated in the cell by CAse mediated reaction. As such, this is a subsidiary site of action of CAse inhibitors,o For the same degree of natriuresis CAse inhibitors cause most marked kaliuresis compared to other diuretics.Read belowCollecting tubule is the most important site of K+ secretion by the kidney.K+ secretion occurs in exchange with Na+If Na+ load is higher in collecting tubels it will be absorbed in exchange with K+ and more K+ will be secreted, i.e. higher the Na+ load in CD, higher will be K+ excretion in urine.Carbonic anhydrase inhibitors act on proximal tubules, where maximum Na+ (70%) is absorbed -they block this absorption and will cause maximum kaliuresis (K+ excretion in urine).o Extrarenal actions of acetazolamideLowering of IOT due to decreased formation of aqueous humour.Decreased gastric HCL and pancreatic NaHCO3 secretion.Raised level of CO2 in brain and lowering of pH - sedation and elevation of seizure threshold.Alteration of CO2 trasport in lungs and tissues,o Uses of CAse inhibitors* Glaucoma# Acute mountain sickness# Periodic paralysis* Epilepsy# To alkalinise urine for UTI or to promote excretion of acidic drugso Dorazolamide and brinzolamide are used topically for glaucoma.o Adverse effectsHypersensitivity reactions in patients sensitive to sulfonamides (CAse inhibitors are sulfonamide derivatives).Bone marrow depression, metabolic acidosis, hypokalemia, drowsiness, paresthesias, fatigue and abdominal discomfort.In hepatic diseases may precipitate hepatic coma by interfering with urinary elimination of NH3.o Contraindications for carbonic anhydrase inhibitors.COPD # Hepatic cirrhosis # Hyperchloremic acidosiso Carbonic anhydrase inhibitor (acetazolamide) can cause allergic reactions in patients hypersensitive to sulfonamides.
Allopurinol
Acetazolamide
Bimatoprost
Dipivefrine
Pharmacokinetics