Thursday, April 8, 2010

Clinical Application of Acetazolamide: (Diamox)


-It is well-absorbed orally, excreted by tubular secretion -- proximal tubule
-At maximal carbonic anhydrase inhibition: 45% inhibition of bicarbonate reabsorption

*causes significant bicarbonate loss
* hyperchloremic metabolic acidosis
*limited effectiveness because:
o bicarbonate depletion increases sodium chloride reabsorption
*reduction in aqueous humor and cerebrospinal fluid production

Clinical Application:

Glaucoma:
*decreases rate of aqueous humor production -- leads to a decline in intraocular pressure.
*most common indication for use of carbonic anhydrase inhibitors
*Dorzolamide (Trusopf): carbonic anhydrase inhibitor:
no diuretic or systemic metabolic effects
reduction in intraocular pressure comparable to oral agents


Urinary Alkalinization:
*increased uric acid and cystine solubility by alkalinizing the urine (by increasing bicarbonate excretion)

*for prophylaxis of uric acid renal stones, bicarbonate administration (baking
soda) may be required


Metabolic Alkalosis:
*Results from:
-decreased total potassium with reduced vascular volume
-high mineralocorticoid levels
-These conditions are usually managed by treating the underlying causes;
however, in certain clinical settings acetazolamide may assist in
correcting alkalosis {e.g. alkalosis due to excessive diuresis in CHF
patients}


Acute Mountain Sickness:
*Symptoms: weakness, insomnia, headache, nausea, dizziness {rapid ascension of
all of 3000 meters}; symptoms -- usually mild
*In serious cases: life-threatening cerebral or pulmonary edema
*Acetazolamide reduces the rate of CSF formation and decreases cerebral spinal
fluid pH.
*Prophylaxis against acute mountain sickness may be appropriate


Other Uses:
*some role in management of epilepsy
*As weak diuretic for adjunctive treatment of: edema due to cogestive heart failure
*hypokalemia periodic paralysis
*increase urinary phosphate excretion during severe hyperphosphatemia.

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