Carbonic anhydrase inhibitors
CARBONIC ANHYDRASE INHIBITORS
|
-
Bicarbonates penetrate the luminal membrane only very slowly, and its absorption in the proximal tubule is heavily dependent on the presence of an enzyme ‘carbonic anhydrase’.
- This is a zinc containing enzyme whose function is to speed up the attainment of equilibrium of the reaction:
CO2 + H2O –> H2CO3
-
This enzyme is found within the proximal tubule cells and in association with their luminal brush border.
-
The activating step in the process of bicarbonate absorption is the secretion of H+ into the tubule lumen, which is largely responsible for the favourable electrical gradient down which Na+ diffuses into the cell.
-
This H+ is derived from the dissociation of carbonic acid, whose supply is facilitated by the presence of carbonic anhydrase.
-
The carbonic anhydrase inhibitors interfere with the absorption of bicarbonate from the proximal tubule, by reducing the supply of H+ to the membrane pump and by reducing the rate of absorption of carbonic acid from the lumen.
-
Filtered bicarbonate is thus trapped in the urine together with an electrically equal amount of Na+ and an osmotically equivalent amount of water.
-
These drugs cause an increased excretion of bicarbonate with accompanying sodium, potassium and water excretion resulting in an increased flow of alkaline urine and mild metabolic acidosis.
-
They are poor diuretics because there is compensatory reabsorption of Na+ is the segments further down the nephron.
-
These drugs are used in glaucoma and in some types of epilepsy.
-
Their action results in a depletion of extracellular bicarbonate and their effect is self limiting as the blood bicarbonate level falls.
-
Side effects are drowsiness, numbness and tingling of the face and extremities (due to metabolic acidosis) and disturbances of vision.
-
This group of drug is rarely used as diuretics.
-
Acetazolamide used as a carbonic anhydrase inhibitor is a derivative of a sulphonamide but does not possess any antibacterial action.
-
Acetazolamide is a non-competitive, irreversible inhibitor of carbonic anhydrase.
|
Last modified: Wednesday, 25 April 2012, 12:12 PM