W9.4_Pharmacology of Diuretics

Question 1

Define diuretics. Explain their uses (2).

Answer 1

• Definition: drugs that increase amount of fluid and salts excreted by kidneys
• Uses: reduce oedema and hypertension
• Increase urine production -> draws more fluid from swollen areas -> reduce swelling
• Increase urine volume -> reduce blood volume -> reduce pressure on blood vessels

Question 2

Explain the salt-moving mechanism in kidney tubules.

Answer 2

• Active transport via pumps/transporters: Na+/K+-ATPase, Na+/Cl–ATPase, Na+/K+/2Cl–-ATPase)
• Passive transporter via channels in openings in membrane (ion selective, no energy required)
• Water follows the direction of salts due to osmosis

Question 3

Regarding loop diuretics, explain their use, site of action, examples, mechanism, efficacy, and directions.

Answer 3

• For oedema (severe heart failure, acute ventricular failure/pulmonary oedema) (X hypertension)
• Site of action: thick ascending limb of Loop of Henle -> metabolised in liver, excreted in urine
• Ex. furosemide, bumetanide, torasemide
• Mechanism: blocks Na+/K+/2Cl–ATPase -> increase excretion of Na+, K+, Cl-
• Efficacy: very powerful as it acts on main site of sodium reabsorption (20% of filtered sodium excreted, urine flow rate x8, high ceiling concentration)
• Directions: act within an hour and up to 6 hours (distal compensation), given twice daily (morning and no later than 4pm)

Question 4

Regarding loop diuretics, explain their side effects and cautions.

Answer 4

• Side effects: hypokalaemia (confusion, dizziness, arrhythmias), hypo-nataraemia/-calcaemia/ -magnesemia (tiredness, lethargy, muscle fatigue), deafness at very high IM/IV doses (8th cranial nerve damage effects production of inner ear fluid)
• Caution: pregnancy and breastfeeding, weight and fluid balance monitoring required (prevent hypovolaemia, hypotension, AKI)

Question 5

Regarding thiazides and related diuretics, explain their use, site of action, examples, mechanism, efficacy, and directions.

Answer 5

• For oedema (mild heart failure, liver and kidney diseases, steroid/hormone treatment), long-term hypertension (relax blood vessels by opening K+ channels for short amount of time)
• Site of action: distal convoluted tubule -> metabolised in liver, excreted in urine
• Ex. bendroflumethiazide, metolazone, chlorthalidone, indapamide, xipamide
• Mechanism: blocks Na+/Cl–ATPase -> increase excretion of Na+/Cl- and K+ (follows Na+)
• Efficacy: potent but less potent than loop diuretics (8% of filtered sodium excreted, urine flow rate x3, low ceiling concentration)
• Directions: act within 1-2 hours and up to 24 hours, given in the morning

Question 6

Regarding thiazides and related diuretics, explain their side effects and cautions.

Answer 6

• Side effects: hypokalemia, hypo-calcaemia/magnesemia, hyperuricemia (gout), hyperglycaemia (diabetes due to reduced insulin sensitivity)
• Caution: weight and fluid balance monitoring required
• Relatively ineffective in stage 4/5 CKD (unless co-prescribed with loop diuretic) -> metolazone is prescribed instead (also works on PCT)

Question 7

Regarding potassium-sparing diuretics, explain their use, site of action, examples, mechanism, efficacy, and directions.

Answer 7

• For oedema (heart failure, liver diseases), hypertension, hypokalemia with loop diuretics/thiazides, primary hyperaldosteronism/Conn’s syndrome (spironolactone only)
• Site of action: late DCT and collecting duct -> metabolised in liver, excreted in urine and bile
• Ex. sodium channel blockers (triamterene, amiloride), aldosterone antagonists (spironolactone, eplerenone) (antagonists to aldosterone receptors)
• Mechanism: increase Na+ and water excretion (Cl-, Ca2+ too), reduce K+ and H+ excretion
• Efficacy: fairly weak diuretics (2-3% of filtered sodium excreted) (∴ X first-line treatment)
• Directions: act within 1-2 hours and up to 24 hours, given in the morning

Question 8

Regarding potassium-sparing diuretics, explain their side effects and cautions.

Answer 8

• Side effects: hyperkalaemia, metabolic acidosis
• Caution: monitor electrolyte levels if patients have renal disease, are on ACE inhibitors, ARBs, ß-adrenoceptor antagonists

Question 9

Regarding antidiuretics, explain their use, site of action, examples, mechanism, and the differences between the two medications.

Answer 9

• For central diabetes insipidus (due to lack of ADH)
• Site of action: collecting duct
• Ex. vasopressin, desmopressin
• Mechanism: increase number of aquaporins which increase passive reabsorption of water
• Vasopressin: short action duration, injection/infusion only, can increase blood pressure (bind to AVPR1 in smooth muscle)
• Desmopressin: long action duration, nasal spray/tablets, no effects on blood pressure (only bind to AVPR2)