Renal pharmacology Flashcards
What are diuretics?
Drugs that increase the rate of urine flow
and excretion of Na+ and water from the
filtrate.
They decrease the reabsorption of Na+ (and
usually Cl-) from the filtrate
Where do the loop diuretics alter the filtrate?
Thick ascending limb
Where do thiazides alter the filtrate?
DT
Where does amiloride and spironolactone alter the filtrate?
CD
How do carbonic anhydrase inhibitors work as diuretics? (not used anymore)
Stops the bicarb reaction outside the tubule cell so there is no pull for H+ ions and this stops the H+/Na transporter moving the Na into the cell
What limits the use of carbonic anhydrase inhibitors?
As bicarbonate is eliminated, systemic acidosis results.
Diuretic effects in the proximal tubulus can be compensated in more distant part of the tubulus.
How do loop diuretics work?
Na+, K+ and Cl- enter by a cotransport system. Loop diuretics act on the Na+-K+-2Cl- symporter (cotrans-porter) in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption.
How long do loop diuretics work for?
Peak 30min-2hours and action lasts for 6 hours
What is the effect of loop diuretics on GFR?
Loop diuretics interfere with feedback control of glomerular filtration rate! No decrease of GFR!
How do thiazides work as diuretics?
They bind to the Cl- site of the distal tubular Na+/Cl- co-transport system, inhibiting its action.
Inhibit sodium resorption and promote potassium excretion.
How are thiazides excreted?
Excreted in the urine, mainly by tubular secretion
What effect do thiazides have on calcium?
They stimulate Ca2+ reabsorption
How do Triamterene and amiloride work as diuretics?
Amiloride and triamterene work by directly blocking the epithelial sodium channel thereby inhibiting sodium reabsorption in the distal convoluted tubules.
Which acts faster Triamterene or amiloride?
Triamterene is well absorbed in the GI tract, amiloride is less well absorbed and has a slower onset
What is the effect of Triamterene and amiloride on potassium?
They promote the loss of sodium and water from the body, but without depleting potassium.
How do Aldosterone antagonists eg Spironolactone act as diuretics?
The cells are impermeable to Na+ in the absence of aldosterone. Aldosterone acts on a nuclear receptor within the tubule cell and on membrane receptors. Spironolactone competes with aldosterone at its receptor site.
How is spirolactone metabolised?
It is highly protein bound (>90%) and extensively metabolized by the liver to the active metabolite, canrenone. It is primarily eliminated by the kidneys.
How long does spirolactone last?
The onset of action for spironolactone is slow, and effects do not peak for 2-3 days.
What salts does aldosterone move?
Aldosterone is responsible for increasing sodium and chloride reabsorption and potassium and calcium excretion from renal tubules.
How do osmotic diuretics work?
Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.
eg IV mannitol
Where do osmotic diuretics work?
Within the nephron, their main effect is exerted in those parts of the nephron that are freely permeable to water: proximal tubule, descending limb of the loop, and the collecting tubules.
What is the effect of osmotic diuretics on Na?
The result is a decreased concentration of Na+ in lumen (more water!) and a decreased reabsorption of Na+.
