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Flashcards in diuretics Deck (88)
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define diuretic

A substance or drug that tends to increase the discharge of urine.


Carbonic Anhydrase Inhibitors MOA

Acetazolamide, dorzolamide,
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).


Thiazide MOA

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
Osmostic Diuretics
Loop Diuretics
K+ sparing Diuretics
ADH antagonists


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

Metabolic acidosis
Calcium phosphate stones
Drowsiness, paresthesias & hypersensitivity rxns (sulfa drug)


Acetazolamide contraindicaitons

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)



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


Mannitol MOA

Osmotic diuretic
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


Mannitol adverse effects

Adverse effects
• Major toxicity due to increased plasma osmolality. With reduced glomerular filtration rate (CHF or renal failure) mannitol is retained in ECF. This moves water out of cells into ECF potentially worsening heart failure. In addition, Na+ follows water movement out of cells leading to hyponatremia.
• Acute pulmonary edema
• Dehydration
• Headache, nausea & vomiting