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Flashcards in Loop Diuretics Deck (11):

Site of axn?

- Thick ascending limb of the loop of Henle (20-25%)


MOA of furosemide and other loop diuretics?

- Directly inhibits reabsorption of sodium and chloride by blocking NaK2Cl co-transporter

- Indirectly inhibits paracellular reabsorption of Ca2+ and Mg2+ by the TAL d/t loss of K+ back-leak responsible for lumen + transepithelial potential

- Max doses --> dissipation of the medillary interstitial gradient --> irrespective of whether urine was dilute or concentrated, get large volume of ~ isotonic urine (max dose leads to profound diuresis)


Effx of furosemide?

- ↑ excretion of water, sodium, potassium, chloride, magnesium, and calcium


Clinical applications of furosemide?

- Management of edema assoc w/ HF, hepatic dz, and renal dz

- Acute pulm edema by ↓ preload --> ↓ EC vol (< 30 min) --> rapid dyspnea relief (< 5 min) in part to PG-mediated venodilation --> ↓ preload

- Trx of HTN (alone or in combo)

- Works in pts w/ low GFR or with ↓ RBF


PKs of furosemide?

- Onset of axn: IV ~ 5min, PO ~ 30-60 min, IM 30 min

- Duration of 6-8 hours if PO and 2 hrs if IV

- Half life ~ 0.5-2 hours, longer in ↓ GFR

- Eliminated primarily as unchanged drug in urine, minor hepatic metabolism


Toxicities of furosemide?

- Hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia

- hypochloremic metabolic alkalosis

- Hyperglycemia

- Hyperuricemia

- ↑ cholesterol and Tgs

- Ototoxicity: vertigo, hearing impairment, tinnitus (+/- reversible)

- Sulfonamide --> HS rxn



- Sulfonamide similar to furosemide with longer half-life, better PO absorption and some evidence that is works better in HF



Sulfonamide similar to furosemide, but more predictable PO absorption


Ethancrynic acid?

Non-sulfonamide loop diuretic reserved for those with sulfa allergy


Drug interactions of loop diuretics?

- Digoxin: frequent since both drugs are often used to trx HF and the risk of digoxin toxicity is ↑ by ↓ potassium d/t diuretic

- Ototoxic drugs: ↑ chance of hearing loss if combined with drugs having similar toxicity (gentamicin)

- Potassium-sparing diuretics can counterbalance potassium-wasting effx

- Can also ↑ lithium toxicity, potentiate effx of other anti-HTN agents and have diuretic effx antagonized by NSAIDs


General statement regarding loop diuretics

Cause the largest sodium loss, are K+ losing, and cause smaller bicarb loss than either thiazide of K+-sparing diuretics