Flashcards in diuretics Deck (88)
A substance or drug that tends to increase the discharge of urine.
Carbonic Anhydrase Inhibitors MOA
methazolamide, and dichlorphenamide inhibit CA in luminal membrane of proximal tubule, reducing proximal HCO3- reabsorption.
Osmotic Diuretics MOA
Freely filterable, non-reabsorbable osmotic agents like mannitol, glycerol, and urea act primarily on the proximal tubule to reduce the reabsorption of H2O and solutes including NaCl.
loop diuretics MOA
Furosemide, bumetanide, torsemide, and ethacrynic acid inhibit the Na+/ K+/2Cl- cotransport system in the thick
ascending limb of Henle's loop (ALH).
Chlorothiazide, hydrochlorothiazide, chlorthalidone, metolazone, indapamide inhibit NaCl cotransport in
early distal convoluted tubule (DCT).
K+ sparing diuretics MOA
Spironolactone & eplerenone competitively block the actions of aldosterone on the collecting tubules.
Amiloride and triamterene reduce Na+ entry across the luminal membrane of the principal cells of the collecting
ADH antagonist MOA
Doxycycline, lithium, tolvaptan, conivaptan, mozavaptan, etc. prevent ADH induced water reabsorption in the
principal cells of the collecting tubule
what are the 6 classes of diuretics?
Carbonic Anhydrase Inhibitors
K+ sparing Diuretics
acetazolamide is what type of diuretic and where does it primarily work
acts primarily in the PCT as a prototypical CA inhibitor. At its maximal effect, it can inhibit 85% of NaHCO3 reabsorption.
mannitol is what type of diuretic and where does it work
Mannitol is a prototypical osmotic diuretic, which limits water reabsorption in the water-permeable segments of the nephron (PCT, thin descending limb, and CT (with ADH)).
Furosemide is what type of diuretic and where does it work
Furosemide is a prototypical loop diuretic, which inhibits Na+/K+/2Cl- cotransport in the thick ascending limb of Henle’s loop.
where do thiazide diuretics work
inhibit NaCl co-transport in the DCT.
where do K+ sparing diuretics work
K+-sparing diuretics act on the CT by inhibition of aldosterone actions or directly blocking Na+ channels.
where do ADH antagonist work
ADH antagonists prevent the ADH-stimulated reabsorption of H2O in the CT.
what is the primary therapeutic goal of diuretic use
reduce edema (must have NaCl output greater than intake)
Most diuretics exert their effects from which side of the lumen? what are the exceptions?
Mostly from the luminal side of the nephron.
Exceptions are spironolactone and some ADH antagonist
how do diuretics enter the nephron and what is the consequence of this
Most are secreted across the proximal tubule via the organic acid/base secretory pathway
exception is Mannitol which is filtered
therefore decreased renal blood flow or renal failure reduces diuretic effectiveness as well as drugs that compete for the secretory pump
Na+ reabsorption is primarily driven by
the Na+/K+ ATPase on the basolateral (blood side) of the epithelial cells
where is bicarbonate reabsorbed
proximal convoluted tubule
ACETAZOLAMIDE belongs to which class and what is the mechanism of action?
CA inhibitor, reversible inhibition of CA (inhibiting reabsorption of HCO3- in the proximal tubule
Acetazolamide adverse effects
Calcium phosphate stones
Drowsiness, paresthesias & hypersensitivity rxns (sulfa drug)
Cirrhosis (increased urine pH reduces NH3 secretion and thereby increases serum NH3)
Dichlorphenamide is what kind of drug
CA inhibitor - 30x more potent than acetazolamide
Methazolamide is what kind of drug
CA inhibitor - 5x more potent than acetazolamide
Dorzolamide is what kind of drug
CA inhibitor - topical preparation for ocular use (avoids systemic effects)
ACETAZOLAMIDE clinic uses
Diuretic agent: weak, but ok as backup
Glaucoma: reduction of intraocular pressure
Urinary alkalinization: drug overdose/some stones
Acute mountain sickness: buy’s some time only
Major osmotic effects in proximal tubule and descending limb of the loop of Henle; collecting ducts too, if ADH is present
Can mannitol be given orally
No - not absorbed must be given via IV to reach the kidneys
how does Mannitol enter the nephron
via filtration in the glomerulous- adverse effects predominiate if filtration is impaired