2.06 - Modulation Of Renal Excretion By Diuretics Flashcards
What are the seven classes of diuretics?
Osmotic diuretics Carbonic Anhydrase Inhibitors Loop diuretics Thiazide derivatives and analogues Inihibotrs of ENaC Antagonists of Mineralocorticoid Receptors Methylxanthines
Provide an example of an osmotic diuretic
Mannitol Sorbitol Urea
Describe the mechanism of action of osmotic diuretics
PT and TAL (TAL most important target) Substances ‘bind’ water in tubule and will not let it be reabsorbed. Recruit H20 from ICF –> increase in ECF –> increased RBF
What are some indications for the use of osmotic diuretics?
Brain oedema Impending anuria (crush syndrome) Forced diuresis (intoxications)
What are some contraindications for the use of osmotic diuretics?
Heart failure and its complications: because it is drawing water in to the ECF, the heart will have to work harder Persisting oliguria and anuria: have to have excretory side of the kidney open as this is the only way to excrete the osmotic agent
Provide an example of a Carbonic Anhydrase (CAH) Inhibitor
Acetazolamide
Describe the mechanism of action of CAH inhibitors
CAH inhibitors block CAH on the luminal side of tubular cells. This prevents the breakdown of H2CO3 to CO2 and H2O. This then means there is no proton to be exchanged with Na on the luminal side. This result in prevention of Na reabsorption and therefore water loss
List some clinical uses of CAH inhibitors
Open angle glaucoma Oedema (cardiac or toxic)
Provide an example of a Loop Diuretic
Furosemide
Describe the mechanism of action of loop diuretics
TAL Block of Na/2Cl/K (NACK; furosemide has a nack) Reabsorption of 25% of Na+ is blocked Paracellular diffusion is blocked as voltage difference decreases
What are some indications for the use of loop diuretics?
Oedemas Forced diuresis Impending anuria
What are some adverse effects of loop diuretics?
Loss of electrolytes (as they block paracellular diffusion)
Provide an example of a thiazide diuretic
Hydrochlorothiazide
Describe the mechanism of action of Thiazide diuretics
DT Antagonist at Na/Cl symporter Prevent reabsorption of Na and therefore water
What are some indications for the use of thiazide diuretics?
Oedemas with good GFR Hypertension
What are some side effects, and contraindications for the use of thiazide diuretics?
Side effects: Loss of K+ (key), retention of uric acid Contraindications: anuria, hypokalemia
Provide some examples of the Inhibitors of ENaC
Amiloride
Describe the mechanism of action of the inhibitors of ENaC
DT/CD Filtered and secreted in PT Block action of endothelial sodium channel, preventing its reabsorption –> water loss Potassium sparing
List some indications for the use of ENaC inhibitors
Hypertension (in combination with other diuretics)
List some contraindications for the use of ENaC inhibitors
Hyperkalemia Anuria
Provide an example of a mineralocorticoid receptor antagonist
Spironolactone
Describe the effect of mineralocorticoid receptor antagonists
DT/CD Bind to MC-receptor and prevent the action of aldosterone. E.g. block the up regulation of basolateral Na/K pumps and epithelial sodium channels (ENaC). This prevents the reuptake of sodium and thus water diuresis. Potassium sparing Only small sodium load
List some indications for the use of mineralocorticoid receptor antagonists
Hypertension (in combination with other agents) Hyperaldosteronism Diuretic of choice in hepatic cirrhosis
What are some contraindications for the use of mineralocorticoid receptor antagonists?
Hyperkalaemia Hyponatraemia Anuria
Provide an example of a methylxanthine
Caffeine
Describe the mechanism of action of methylxanthines
Increase GFR via a pre-renal mechanism (increase in blood pressure) and slightly decreased Na+ resorption. Not clinically important
Selma Radic, a 35yo female, has been involved in an accident with serious head injuries. To reduce and limit brain oedema, Mannitol is used as a diuretic.
After 12h of therapy, which of the following answers best describes the findings in this patient as compared to “normal” pre-treatment values?
D
