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Nursing Pharmacology Chapter 26: Renal Pharmacology
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The enzyme, carbonic anhydrase exhibits the following characteristics.
Its major location is the luminal proximal tubule membrane.
Carbonic anhydrase catalyzes
dehydration of carbonic acid, H2CO3, required for bicarbonate reabsorption
Blockade of carbonic anhydrase activity induces a sodium bicarbonate diuresis, which reduces body bicarbonate levels
Carbonic anhydrase inhibitors are
unsubstituted sulfonamides which are bacteriostatic.
These agents promote alkaline diuresis and a hyperchloremic metabolic acidosis.
Prototype drug: acetazolamide (Diamox)
Acetazolamide: (Diamox) is well absorbed orally and is excreted by tubular secretion, at the proximal tubule.
In renal insufficiency a dose reduction is appropriate.
At maximal carbonic anhydrase inhibition, a 45% inhibition of bicarbonate reabsorption is observed.
This level of inhibition results in significant bicarbonate loss and a hyperchloremic metabolic acidosis.
Acetazolamide (Diamox) administration causes a reduction in aqueous humor and cerebrospinal fluid production
Glaucoma
Because acetazolamide decreases the rate of aqueous humor production, a decline in intraocular pressure occurs.
Management of glaucoma is the most common
indication for use of carbonic anhydrase inhibitors.
Dorzolamide (Trusopf), another carbonic anhydrase inhibitor exhibits no diuretic or systemic metabolic effect; however, administration of this agent causes a reduction in intraocular pressure.
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 are 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
Hypokalemia periodic paralysis
Increase urinary phosphate excretion during severe hyperphosphatemia.
Hyperchloremic metabolic acidosis
Due to reduction of body bicarbonate stores
Renal stones
Bicarbonate loss is associated with phosphaturia and hypercalciuria (calcium salts are relatively insoluble it alkaline pH).
Renal potassium loss
Increased sodium bicarbonate in the collecting tubule increases the lumen-negative electrical potential -- enhances potassium excretion
Counteracted by potassium chloride administration
Others
Drowsiness, parathesias
Accumulation in renal failure (CNS toxicity)
Hypersensitivity reactions
Contraindications
Hepatic cirrhosis
Urinary alkalinization will decrease ammonium ion trapping, increasing the likelihood of hepatic encephalopathy.
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Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp. 685- 713
Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732
