Untitled Quiz

Study Notes

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.

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.

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.

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).

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.