Outline the sites and mechanisms of action of diuretics. Give one example of drug acting at each site and list two side effects for each drug.
Good answers to this question were those that had a tabular format to the structure of the answer — for example columns headed mechanism, sites, drug and side effects. Most common omissions were not to further describe how the different mechanisms of action of diuretics increased urine output, e.g. "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". There was often little mention of increased urine solutes and the effect the electro chemical effect had in promoting a diuresis. Examples of drugs were well done.
Site | Mechanism of diuretic effect | Representative drug & its side effects |
Glomerulus | Increased glomerular filtration rate due to afferent arteriolar vasodilation |
Fenoldopam
|
Increased glomerular filtration rate due to increased cardiac output |
Caffeine
|
|
Proximal tubule | Carbonic anhydrase inhibition: decreased reabsorption of bicarbonate and sodium; therefore increased tubular fluid osmolality |
Acetazolamide
|
Unresorbable fully filtered solute, therefore markedly increased tubular fluid osmolality |
Mannitol
|
|
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". |
Furosemide
|
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 |
Hydrochlorothiazide
|
Collecting duct | Aldosterone receptor inhibition, leading to decreased ENaC channel expression and therefore decreased sodium reabsorption |
Spironolactone
|
ENaC channel blockade, therefore decreased sodium reabsorption and decreased tubulo-medullary osmotic gradient |
Amiloride
|
|
Blockade of vasopressin receptors (V2), decreasing the expression of aquaporins and thereby decreasing the reabsorption of water |
Tolvaptan
|
|
Blockade of water reabsorption by inducing a conformational change in aquaporin proteins |
Mercurial diuretics
|
Wile, David. "Diuretics: a review." Annals of clinical biochemistry 49.5 (2012): 419-431.
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.