Loop Diuretics

Question 1

Loop diuretic example

Answer 1

Furosemide (Lasix)

Question 2

Loop Diuretics (site of action)

Answer 2

must enter tubular fluid… (ThickALH)

Question 3

Loop diuretics (MOA)

Answer 3

–block luminal Na/K/2Cl symporter
–inhibit ability of macula densa to sense NaCl
–Stimulate biosynthesis of prostaglandins (currency of kidneys)
–Increase total RBF
–Maintain GFR
–Potently increase renin (in the kidney…not plasma) release b/c…
…….inhibit macula densa, reflexely activate sympathetic NS, stimulate iintrarenal baroreceptor mechanisms

Produces diuresis while maintaining GFR b/c of prostaglandins??

Question 4

Loop diuretics (results)

Answer 4

EXTREMELY potent (b/c ThALH responsible for 20% of NaCl reabsorption

Increased Na, K, Cl, and H20 excretion

Question 5

Furosemide

Answer 5

Lasix

Question 6

Torsemide

Answer 6

Demadex

Question 7

Bumetanide

Answer 7

Bumex

Question 8

Loop diuretics (net effects)

Answer 8

“high-ceiling diuretics”

MOST POTENT class of diuretics in mobilizing NaCl

• -copious diuresis and significant NaCl loss
• -Increase urinary excretion of K/H
• -Increase excretion of Ca and Mg
• -Impair kidney’s ability to concentrate urine

Question 9

Loop diuretics (Therapeutic uses)

Answer 9

• -Edema of cardiac, hepatic, or renal origin
• -Pulmonary edema
• -Hypercalcemia to mobilize Ca++
• -Protect against renal failure (related to prostaglandin and GFR)
• -Washout toxins by increasing urine flow
• -antihypertensive diuretics used w/ other drugs

Question 10

How loop diuretics can help Pulmonary edema

Answer 10

• -decrease pulmonary wedge pressure
• -increase compliance of pulmonary vessels
• -Increase peripheral venous capacitance
• -Reduce left ventricular filling pressure
• -Cause brisk diuresis

Question 11

Furosemide (Lasix)…general

Answer 11

• -Sulfonamide type drug
• -administered orally and IV/IM
• **Secreted by organic acid transporter to inhibit luminal symporter (this secretion capacity is impaired when renal failure, so must give pts much higher doses!

**Wide margin of saftey

–Dose-response curve influenced by renal disease (impaired secretion)

Question 12

Furosemide (Lasix)…Effects

Answer 12

–copious diuresis w/ significant NaCl losses
–Increases in…
urinary excretion of K/H, Ca, Mg and increase in renal prostaglandins and venous capacitance (dec. blood going to heart…good!)

Question 13

Furosemide (Lasix)…Dosage and pharmacokinetics

Answer 13

***Must be secreted into tubule in PCT
Diuretic response in 30 min., lasting ~8hr.
Short half-life (1.5 hr)
***extensively protein bound
Excreted in urine 65%

Question 14

Furosemide (Lasix)…Side-effects

Answer 14

abnormalities of fluid and electrolytes

• -hypokalemia and disorders of pH (mostly alkalosis)
• -requires initial monitoring… must hydrate pts.

Elevated BUN, (hyperglycemia, hyperuricemia…in almost all diuretics)

Ototoxicity (change hemodynamics here, too)
sialadentitis (inflammation of salivary glands)

Question 15

Furosemide drug interactions

Answer 15

Li
indomethacin (prostaglandin inhibitor…all NSAIDS not good, but this one really bad)
probenecid
warfarin

Question 16

Bumetanide (Bumex)

Answer 16

• -Forty times more potent than furosemide

- -Substituted for furosemide in pts receiving warfarin!

Question 17

Torsemide (Demadex)

Answer 17

• -Loop diuretic that also lowers blood pressure

- -Has longer half-life than other loop diuretics