Diuretics

Question 1

Loop diuretics example

Answer 1

ethacrynic acid, bumetanide, furosemide

Question 2

Loop diuretics mechanism

Answer 2

inhibit NKCC

• reduce reabsoprtion of Na and Cl
• reduce reabsroption of Mg and Ca
• increase loss of K+ and H+

Question 3

Adverse effect of loop diuretics

Answer 3

• Hyponatremia
• Hypokalemia, arrhythmia
• Metabolic alkalosis
• Hypocalcemia (rare)
• Hypomagnesemia, arrhythmia
• Hyperuricemia, due to hypovolemia, increasing reabsoption of uric acid, gout
• Hyperlipidemia and glycemia (unknown mechanism)
• Ototoxicity (inhibition of electrolyte transport in the inner ear, reversible)
• sufonamide-related allergy (except ethacrynic acid)

Question 4

Use of loop diuretics

Answer 4

• reduce oedema in heart failure and kidney disease (salt retention)
• reduce pulmonary congestion and oedema due to increase systemic venous capacitance
• hypertension (short half life, may lead to postdiuretic Na reabsorption)

Question 5

Resistance to loop diuretics

Answer 5

• Reduced renal blood flow (kidney disease reduces delivery, accumulation of endogenous organic anion reduces drug active transport at proximal)
• Drug interactions (NASID reduces prostaglandin thus renal blood flow, competition for organic anion transport system)
• Increased proximal tubule sodium reabsorption (heart failure and nephrotic) -> reduced delivery to loop

Question 6

Thiazide diuretic examples

Answer 6

Hydrochlorothiazide

Question 7

Mechanism of thiazide diuretics

Answer 7

inhibit Na/Cl cotransporter in distal

lead to increased Ca reabsorption (driven by Na/K ATPase and Na/Ca exchanger and luminal Ca channels)

Question 8

Adverse effect of thiazide

Answer 8

mostly similar to loop

• hypercalcemia (rare)
• Hyperlipidemia (milder)
• Hyperglycemia (activation of ATP sensitive K channels, hyperpolarisation of pancreatic beta cells, reduce secretion of insulin)

Question 9

Use of thiazide diuretics

Answer 9

• odema (less effective than loop)

- hypertension (preferred, synergistic with other anti-HT, safe once daily dosage and few contraindications)

Question 10

Potassium sparing diuretics example and mechanism

Answer 10

Amiloride: inhibit ENaC
Eplerenone/ Spironolactone: MR/aldosterone antagonist
inhibit Na+ reabsorption and K+ dumping

Question 11

Adverse effect of K sparing

Answer 11

• Hyperkalemia (reversed if use with thiazide)
• Metabolic acidosis
• Impotence and menstrual irregularities (only with spironolactone: androgen and progesterone antagonist)

Question 12

Use of K sparing

Answer 12

• combined with other diuretics (to treat hypokalemia and enhance diuretic functions)
• Hyperaldosteronism (refractory oedema due to secondary hypera in heart failure and nephrotic)