Genitourinary Pharmacology
Table of Contents

Diuretics

• Osmotic diuretics: small non-membrane permeable molecules that stays in the lumen and increase osmotic pressure. Reabsorption of water is hence limited in the water soluble segment of the nephron (proximal tubule and descending limb of loop of henle)
- Manitol: highly charged so not reabsorbed
- Glucose: diabete mellitus patients produce a lot of urine and tastes sweet. Insipidus patients have normal water urine.
- Administration of osmotic diuretics: IV causes osmotic diuresis and oal causes osmotic diarrhoea, e.g. manitol
• Applications of osmotic diuresis:
- Relieve raised intracranial pressure from head injuries and surgery on brain
- Flush out potential nephrotoxins, e.g. in acute haemolysis, the patent have black water fever and severe malaria. The urine is dark with haemoglobin that s not reabsorbed. The haemoglobin can crystallize and damage the tubules.
• Carbonic anhydrase inhibitors: the HCO3- is not reabsorbed and hence increased excretion.
- Carbonic anhydrase is used to recover urine bicarbonate
- Inhibition can cause alkaline urine and systemic acidosis
- Example Acetazolamide (blocks H2CO3 to H2O and CO2)
- Administration: oral
• Application of carbonic anhydrase:
- Glaucoma (CA aids formation of aqueous humour in the eye so inhibitor can reduce formation and relieve intraocular pressure)
- Acute mountain sickness
- Metabolic alkalosis
• Loop diuretics: frusemide
- Inhibition of the Na+/K+/2Cl- co-transporters at the luminal surface of ascending thick portion of loop of Henle. This leads to major decrease in Na+ reabsorption causing osmotic water loss.
- Secondary decrease in Ca2+ due to decreased membrane potential
- Secondary decrease in K+ reabsorption due to increased delivery to collecting duct. Hypokaelmia leads to weak muscles and cardiac arrhythmia
- Adverse effect of loop diuretics: hypovolaemia and hypotension, hypokaelemia (required K+ supplements), ototoxicity (damage to inner ear and hearing defect), hyperuricaemia (competition for organic anion secretary transport in proximal tubule)

• Frusemide properties:
- Very high efficiency with small changes in dose leads to a big chance in Na+ excretion.
- Twice the efficacy of thiazides
- Administration: IV for pulmonary oedema (rapid effect), oral, larger doses in renal failure (frusemide is filtered hence in renal failure, GFR is low and higher dose is needed)
• Application of loop diuretics:
- Heart failure and hypercalcaemia
• Thiazide diuretics: inhibition of Na+/Cl- co-transporter at luminal surface of distal tubule and so osmotic water loss, e.g. bendrofluazie
- Secondary increase of Ca2+ reabsorption due to lower intracellular Na+
- Secondary loss of K+ due to increased load (aldosterone sensitive Na+/K+ exchanger)
- Administration: oral, low dose is effective
• Application of thiazide diuretics
- Hypertension
- Heart failure
- Osteoporosis
• Adverse effects of thiazide diuretics
- Hypokalaemia
- Hyponatraemia (due to water retention more than sodium loss)
- Hyperuricaemia (competition for organic anion secretory transport in proximal tubule)
- Hyperlipidaemia
• Potassium sparing drugs:
- inhibition of Na+ transport in collecting duct, e.g. amiloride, triamterene.
- Competitive antagonism of aldosterone, e.g. spironolactone
- Desmopressin block ADH receptors and reabsorption of water (leads to diabetes insipidus)
• Diuretic combination:
- Diuretic resistance: in severe heart failure, renal failure, liver failure
- Loop and thiazide: loop diuretic delivers increased Na+ load while thiazide inhibit reabsorption of the load in tubule
• Nephrotoxicity:
- Perfusion of kidney: cyclosporine leads to direct kidney damage
- Proximal tubule: gentamicin does not get absorbed but amine groups transporters can absorb a minor amount and cause direct tubular damage
- Loop of henle
- Distal tubule
- Col
- lecting duct: lithium can cause brain damage
- Papillae: NSAIDS such as paracetamol, aspirin by acting on papilla and cause damages

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