Describe the site of action, mechanism of action and the biochemical effects of five different classes of diuretics; include an example in each class.
This question was best structured using the headings supplied in the stem (site, mechanism of action, biochemical effects and an example). Some answers utilised a table format which often meant that the content was squashed. Given the amount of information required a better format was simply to use separate sections for each class. Non-biochemical effects did not attract any marks. Similarly, an introductory statement about diuretics was not required and attracted no marks. Biochemical effects were not answered clearly or completely. Effect on acid-base was answered correctly by very few candidates. Vague statements such as "increased sodium" did not score as well as more precise terminology like "hypernatraemia" or "raised serum sodium". A few answers incorrectly stated that the mechanism of action of thiazides was ENaC inhibition.
| Site | Mechanism of diuretic effect | Biochemical side effects | |
| Carbonic anhydrase inhibitors (acetazolamide) | |||
| Proximal tubule |
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| Loop diuretics (furosemide) | |||
| Thick ascending limb |
NKCC2 sodium-chloride-potassium transport inhibition; therefore "disruption of the counter current multiplier system by decreasing absorption of ions from the loop of Henle into the medullary interstitium, thereby decreasing the osmolarity of the medullary interstitial fluid". |
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| Thiazides (hydrochlorothizide) | |||
| Distal convoluted tubule | NCC sodium and chloride transporter inhibition; therefore increased delivery of sodium to the distal nephron, preventing the reabsorption of urinary water by decreasing the tubulo-medullary osmotic gradient |
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| Aldosterone receptor antagonists (spironolactone) | |||
| Aldosterone receptor inhibition, leading to decreased ENaC channel expression and therefore decreased sodium reabsorption |
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| Vasopressin receptor antagonists (Tolvaptan) | |||
| Collecting duct | Blockade of vasopressin receptors (V2), decreasing the expression of aquaporins and thereby decreasing the reabsorption of water |
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Lang, H-J., and M. Hropot. "Discovery and development of diuretic agents." Diuretics. Springer, Berlin, Heidelberg, 1995. 141-172.
Puschett, Jules B. "Pharmacological classification and renal actions of diuretics." Cardiology 84.Suppl. 2 (1994): 4-13.
Clarke, Paul, and Karen H. Simpson. "Diuretics and renal tubular function." Bja Cepd Reviews 1.4 (2001): 99-103.
Brater, D. Craig. "Diuretic pharmacokinetics and pharmacodynamics." Diuretic Agents. Academic Press, 1997. 189-208.