Diuretics

Question 1

Acetazolamide

Answer 1

• Carbonic anhydrase inhibitor
• MOA
• prevents dehydration of H₂CO₃ and hydration of CO₂ in proximal convoluted tubule
• Effects
• reduce reabsorption of HCO₃^- causing self-limited diuresis
• hyperchloremic metabolic acidosis
• reduce body pH
• reduce intraocular pressure
• Clinical
• glaucoma, mountain sickness, edema with alkalosis
• Kinetics, tox, int.
• oral, topical, duration 8-12h
• tox: metabolic acidosis, renal stones, hyperammonemia in cirrhotics

Question 2

Canagliflozin

Answer 2

• SGLT2 inhibitor
• MOA
• SGLT2 (sodium/glucose cotransporter) inhibition resulting in decreased Na⁺ and glucose reabsorption
• Effects
• inhibition of glucose reabsorption reduces serum glucose, reduced Na⁺ reabsorption causes mild diuresis
• Clinical
• DM (not approved as a diuretic)
• Kinetics, tox, int.
• oral, t_1/2 10-12h
• contraindicated in severe renal or liver disease

Question 3

Furosemide

Answer 3

• Loop diuretic
• MOA
• inhibition of Na/K/2Cl transporter in ascending loop of Henle
• Effects
• marked increase in NaCl excretion, some K wasting, hypokalemic metabolic alkalosis, increased urine Ca & Mg
• Clinical
• pulmonary edema, peripheral edema, heart failure, hypertension, acute hypercalcemia, anion overdose
• Kinetics, tox, int.
• oral, parenteral, duration 2-4h
• tox: ototoxicity, hypovolemia, K wasting, hyperuricemia, hypomagnesemia

Question 4

Hydrochlorothiazide

Answer 4

• Thiazide diuretic
• MOA
• inhibition of Na/Cl transporter in distal convoluted tubule
• Effects
• modest increase in NaCl excretion, some K wasting, hypokalemic metabolic alkalosis, decreased urine Ca
• Clinical
• hypertension, mild heart failure, nephrolithiasis, nephrogenic diabetes insipidus
• Kinetics, tox, int.
• oral, duration 8-12h
• tox: hypokalemic metabolic alkalosis, hyperuricemia, hyperglycemia, hyponatremia

Question 5

Spironolactone

Answer 5

• Potassium-sparing diuretic
• MOA
• pharmacologic antagonist of aldosterone in collecting tubules
• weak antagonism of androgen receptors
• Effects
• reduces Na retention and K wasting in kidney, poorly understood antagonism of aldosterone in heart and vessels
• Clinical
• aldosteronism, hypokalemia, post-MI
• Kinetics, tox, int.
• slow onset & offset, duration 24-78h
• tox: hyperkalemia, gynecomastia, additive interaction with other K-retaining drugs

Question 6

Amiloride

Answer 6

• Potassium-sparing diuretic
• MOA
• blocks epithelial Na channels in collecting tubules
• Effects
• reduces Na retention and K wasting
• increases lithium clearance
• Clinical
• hypokalemia, reduces lithium-induced polyuria
• Liddle’s syndrome
• Kinetics, tox, int.
• oral, duration 24h
• tox: hyperkalemic metabolic acidosis

Question 7

Mannitol

Answer 7

• Osmotic diuretic
• MOA
• physical osmotic effect on tissue water distribution because it is retained in the vascular compartment
• Effects
• marked increase in urine flow, reduced brain volume, decreased intraocular pressure, initial hyponatremia then hypernatremia
• Clinical
• renal failure due to increased solute load (rhabdomyolysis, chemotherapy), increased intracranial pressure, glaucoma
• Kinetics, tox, int.
• IV
• tox: nausea, vomiting, headache

Question 8

Conivaptan

Answer 8

• ADH antagonist
• MOA
• antagonist at V_1a and V₂ ADH receptors
• Effects
• reduces water reabsorption, increases plasma Na concentration, vasodilation
• Clinical
• hyponatremia, congestive heart failure
• Kinetics, tox, int.
• IV
• tox: infusion site reactions, thirst, polyuria, hypernatremia

Question 9

Tolvaptan

Answer 9

• ADH antagonist
• MOA
• selective antagonist at V₂ ADH receptors
• Effects
• reduces water reabsorption, increases plasma Na concentration
• Clinical
• hyponatremia, SIADH
• Kinetics, tox, int.
• oral, duration 12-24h
• tox: polyuria, thirst, hypernatremia