Loop Diuretics

Question 1

Site of axn?

Answer 1

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

Question 2

MOA of furosemide and other loop diuretics?

Answer 2

• 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)

Question 3

Effx of furosemide?

Answer 3

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

Question 4

Clinical applications of furosemide?

Answer 4

• 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

Question 5

PKs of furosemide?

Answer 5

• 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

Question 6

Toxicities of furosemide?

Answer 6

• Hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia
• hypochloremic metabolic alkalosis
• Hyperglycemia
• Hyperuricemia
• ↑ cholesterol and Tgs
• Ototoxicity: vertigo, hearing impairment, tinnitus (+/- reversible)
• Sulfonamide –> HS rxn

Question 7

Torsemide?

Answer 7

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

Question 8

Bumetanide?

Answer 8

Sulfonamide similar to furosemide, but more predictable PO absorption

Question 9

Ethancrynic acid?

Answer 9

Non-sulfonamide loop diuretic reserved for those with sulfa allergy

Question 10

Drug interactions of loop diuretics?

Answer 10

• 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

Question 11

General statement regarding loop diuretics

Answer 11

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