Diuretics Flashcards
Diuretics all work by causing the kidneys to waste __, causing them to also waste water.
Diuretics all work by causing the kidneys to waste sodium, causing them to also waste water.
4 classes of diuretics
carbonic anhydrase inhibitors
loop diuretics
potassium sparing diuretics
thiazide diuretics
site of carbonic anhydrase inhibitor MOA
PCT;
site of nephron where most re-absorption happens
PCT: 60-65%
site where thiazides MOA
DCT
cite of loop diuretics MOA
loop diuretics
site of postassium sparing diuetics MOA
CCD/collecting duct
example of carbonic anhydrase inhibitor. outline the site and MAO
site; PCT– site of most sodium reabsorption
example: aetazolamide
MOA; NORMALLY, carbonic anhydrase on the lumen of the PCT cell converts bicarbonate to H2O and water. this H2O and water enters the cell, where it is buffered to H+ and HCO3-. the H+ gets transported back OUT of the cell into the urine, with Na+ being pumped into the cell through the Na/H+ transporter. Bicarb from the carbonic anhydrase buffering and Na+ get co transported back into blood, causing Na+ reabsorption and water follows. However, when CA is BLOCKED by acetazolamide, there is no bicarb to cotransport with Na+, leaving Na+ in the diltrate. there is sodium wasting and thus promotes diuresis
3 indicatiosn for carbonic anhydrase inhibitors
- altitude sickness; bicarb wasting causes a state of metabolic acisosis– shifts Hb-O2 curve and increases the o2 delivery to tissues
- galucaoma
- seizures
side effects of CAHs and why
- metabolic acidosis; less bicarb is being transported back into the blood (because it goes through the HCo3-/Na+ transporter in the PCT)
- hyponatremia; sodium wasting– sodium also not transported because CA inhibited
- hypokalemia– due to sodium delivery to distal nephron, in combo with RAS activation.
Carbonic anhydrase inhibitors lead to __ and ___ wasting
The most common indication is __ sickness
The most common electrolyte side effect is __
example of a loop diuretic, site, and MOA
ex/ lasix/furosemide.
site; THICK ascending loop of henle
MOA; normally in the ascending loop, Na+ is reabsorbed but it is impermeable to water. the 2NKCC transporter transports Cl, K, and Na from the filtrate back to the cell/. K+ is pumped back out, but Cl- is shuttled into the blood. the Na+ is reabsorbed through the 3Na+in/2K+out exchanger. FUROSEMIDE INHIBITS the 2NKCC channel, preventing any reabsorption of K+, Cl or Na+. Thus, Na+ accumulates in the ascending loop, causing interstitial washout.
indications for furosemide
edema and pulmonary edema. it is a strong diuretic.
electrolyte side effects of loop diuretics/furosemide
hypokalameia; deactivation of NKCC prevents K+ reabsorption, causing distal wasting of K+
hypernatremia: due to interstitial wash out and large H2O diuresis
Hypomagnesemia
Metabolic ALKALOSIS; loops impair Mg2+ reabsorption.
Loop diuretics block the __
Potent salt and water diruresis Used for volume reduction
Most common electrolyte side effect it __ and __
__ is a common side effect
Loop diuretics block the NKCC
Potent salt and water diruresis Used for volume reduction
Most common electrolyte side effect it hypokalemia and hypernatremia Hypovolemia is a common side effect
thiazide diuretics act on the ___. Example, and MOA
act on the DCT. ex/ hydrochlorothiazise, indapamide, chlorthalidone.
MOA: Normally, DCT reabsorbs Na+ and Cl- through Na+/Cl co transporter, and also reabsorbs Mg2+ and Ca2+ through channels. thiazide blocks the Na+/Cl- channel at the DCT, preventing Na+ reabsorption.
indications and electrolyte side effects of thiazide diuretics that work at the DCT
indications; hypertension
electrolyte side effects; hyponatremia, hypokalemmia, hypomagnesemia, hypercalcemia
why is gout a major side effect of thiazide diuretics
Thiazide diuretics are associated with elevated serum uric acid (SUA) levels. They increase direct urate reabsorption in the proximal renal tubules [3]
type of cancer associated with hydrochlorothiazide
squamous cell skin cancer– causes photosensitivity.
Loop diuretics block the __ at the ___
Thiazide diuretics block the __ at the ___
Loop diuretics block the NKCC (Na+K+2Cl- channel)
thiazide diuretics Block the NCCT (Na/Cl- co transport channel)
two broad categories of potassium sparing diuretics and give an example
- mineralcorticoid antagonists– spironolactone and eplerenone
- ENaC blockers– amiloride, triamterine. (epithelial sodium chennal blockers)
Outline the MOA of Mineralcorticoid antagonists and ENACblockers (potassium sparing diuretics)
normally, the principle cell of the collecting tubule reabsorbs Na+ through ENAC, creating a negative luminal charge, which is neutralized by the secretion of K+ removed by the renal outer medullary K+ channel. Aldosterone turns on this function, resulting in increased Na+ absorption and K+ excretion
When MNAs inhibit aldosterone/block its binding, it shuts down the principle cell and prevents na+ reabsorption, causing salt wasting.
- ENACblockers directly inhibit ENaC, so Na+ can’t be reabsorbed even if aldosterone is there.
indications to use diuretics, and electrolyte and non electrolyte side effects
- hypertension
- Conn Syndrome: aldosterone excess syndrome: PSDs can offset aldosterone effects
- left ventricular dysfunction
- ascites from cirrhosis
**KEY NON-ELECTROLYTE side effect is that they are anti-androgens
most common side effect of potassium sparing diuretics
hyperkalemia– recall that Na+ is absorbed from the cell to the blood using Na+/K+ channel, and K+ is pumped out to maintain normal charge. if no Na+ is coming in, K+ doesn’t need to leave. results in K+ hoarding and thus hyperkalemia
