carbonic_anhydrase

Carbonic anhydrase 1st discovered in RBC's (1930's), & sulfanilimide-induced metab.acidosis shown to be inhib. of this enzyme.
Little used as diuretic but still for glaucoma & prevention of ac. mountain sickness;

More than 99% enzyme must be inhib. before physiol.effects apparent but acetazolamide potent reversible inhib. → 50% inhib. in renal cortex @ 10nm [];
inhib. of prox. tub. cytoplasmic carb.anhydrase:
- → decr. availability of protons for Na-H exchange → decr. H excretion;
inhib. of prox. tub. brush border carb.anhydrase:
- → decr. destruction of lumen bicarb. → decr. CO2 diffusion into cell
  - → decr. bicarb. prox. tub. reabs. by 80% → incr. bicarb. excretion;
THUS in urine:
- decr. titratable acidity; decr. ammonia; decr. Cl; incr.pH; incr. bicarb.; incr.Na; incr. K; incr. volume;
- may cause urinary calculi as decr. decr. urinary citrate but N or incr. urinary Ca;

decr. ECF bicarb. (as excreted incr.) → metab. acidosis → decr. renal acetazolamide effect!
decr. ECF K (as excreted incr. via incr. distal tub. secretion) → EC alk. & IC acidosis incr.

decr. rate aq. humor formation as normally ciliary processes → high [bicarb] in aq.humor;

decr. CSF rate of formation; decr. epileptic seizures - ? via acidosis or incr. local CO2;
may transiently incr. CSF pressure via incr. cerebral blood flow;
may cause drowsiness, paraesthesiae; disorientation if hep.cirrhosis ( incr. ammonia?)

inhib. CO2 transport system → incr. CO2 in tissues & decr. CO2 in expired air;
P/K:
readily absorbed from GIT → peak 2hrs with complete excretion within 24hrs;
tightly bound to carbonic anhydrase → incr. [ ] in tissues with incr. [carb.anhyd.] (RBC's/renal);
not metabolised, solely excreted by kidneys with active secretion & passive reabs.;
dose: 250-500mg once every 1-2days if as diuretic or tds to induce metab.acidosis;