Questions and Answers
What is the primary effect of diuretics?
Increase in solute excretion, mainly Na+ salts
Which of the following are classes of diuretics?
Diuretic therapy provides relief only from hypertension.
False
What is the mechanism of action for Carbonic Anhydrase Inhibitors?
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Which adverse effect is associated with Carbonic Anhydrase Inhibitors?
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What unique renal response is observed with thiazide diuretics?
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Thiazide diuretics can be used to treat nephrogenic diabetes insipidus.
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The primary therapeutic use of Carbonic Anhydrase Inhibitors is NOT to produce diuresis but in the treatment of ______.
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What is a cause of potassium loss when using Carbonic Anhydrase Inhibitors?
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Study Notes
Renal Pharmacology (Diuretics)
- Diuretics are agents that increase the rate of urine flow via inhibition of electrolyte reabsorption in the kidney.
- The primary effect of diuretics is an increase in solute excretion, mainly Na+ salts.
- Diuretic therapy provides relief from pulmonary congestion, ascites, edema, and hypertension.
Carbonic Anhydrase Inhibitors (CAIs)
- CAIs include acetazolamide, dichlorphenamide, methazolamide, brinzolamide, and dorzolamide.
- MOA: inhibition of proximal tubule brush border carbonic anhydrase decreases bicarbonate reabsorption, accounting for their diuretic effect.
- CAIs affect distal tubule and collecting duct H secretion by inhibiting intracellular carbonic anhydrase.
- Na+/H+ antiporter is regulated by factors including angiotensin II, which increases its activity.
- CAIs increase renal excretion of Na, K, and HCO3, leading to bicarbonate diuresis.
- Diuresis is self-limiting within 2-3 days due to HCO3 depletion.
- Potassium loss is marked (~70%) following CAI inhibition, due to poorly reabsorbable HCO3, inhibition of the Na–H exchange mechanism, and increased delivery of Na+ to the distal nephron.
- Elevated urinary HCO3 excretion leads to alkaline urine and metabolic acidosis.
CAIs - Uses
- Main therapeutic use: treatment of glaucoma, especially with topically applied dorzolamide.
- Also used in epilepsy, particularly absence epilepsy.
- Useful in preventing or treating acute mountain sickness, alkalization of urine in cysteinuria, and restoring acid-base balance in heart failure patients with metabolic alkalosis.
CAIs - Adverse Effects
- Hyperchloremic metabolic acidosis.
- Potassium wasting, leading to hypokalemia.
- Alkalization of urine, causing precipitation of calcium salts and renal stones.
- May lead to development of hepatic encephalopathy in patients with hepatic impairment.
- Sulfonamide sensitivity (contraindicated if history of sulfonamide hypersensitivity).
- Other adverse effects: loss of appetite, drowsiness, confusion, tingling in the extremities (paresthesia).
Thiazide Diuretics
- 2 distinct groups: thiazide diuretics (contain a benzothiadiazine ring) and thiazide-like diuretics (lack the heterocyclic structure but contain an unsubstituted sulfonamide group).
- Mechanism of Action: act in the distal convoluted tubule, blocking Na-Cl co-transport.
- At usual clinical doses, thiazide diuretics increase excretion of Na and Cl, with accompanying loss of K and not NaHCO3.
- Unique renal responses: decrease Ca2+ excretion (hypocalciuria/hypercalcemia) and are used in treating nephrogenic diabetes insipidus.
- Thiazides have antihypertensive properties, initially mediated by reduction in plasma volume and cardiac output, and chronically by lowering peripheral resistance.
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