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
- ↑ 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
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