Combination of both loop diuretics (furosemide) and aminoglycosides (gentamicin) increases the risk of ototoxicity. Both of these agents are individually associated with a risk of ototoxicity; their co-administration results in an additive effect, which manifests as tinnitus (ringing in the ears), vertigo, hearing impairment, or deafness.
Loop diuretics inhibit the Na-K-2Cl symporter in the thick ascending limb of the renal tubules and are commonly used for treating renal failure or edematous symptoms secondary to congestive heart failure. Toxic effects of furosemide can include: ototoxicity, hypokalemia, hypomagnesemia, hypocalcemia, hypotension, dehydration, acute interstitial nephritis, and gout. Gentamicin is an aminoglycoside that is used to treat severe Gram-negative rod infections, and it is often administered with beta-lactam antibiotics for synergistic effects. Adverse effects of gentamicin can include: ototoxicity, nephrotoxicity, and teratogenicity.
Bates et al. describe the potential mechanism for the additive risk of ototoxicity seen with concurrent use of furosemide and gentamicin. The interaction of the aminoglycoside with cell membranes in the inner ear theoretically permits higher concentrations of loop diuretics into the cells, causing more extensive damage.
Deamer and Dial describe how to best minimize the risk of adverse effects associated with aminoglycoside therapy. Because of the nephrotoxicity and ototoxicity seen with aminoglycoside therapy, dosing regimens are often altered from standard dosing every eight to 12 hours to once daily dosing, which not only reduces the toxic effects but may also provide better outcomes and decrease costs.
Illustration A summarizes the sites of diuretic action on the renal tubules.
Answer 2: Loop diuretics, such as furosemide, are potassium wasting and would NOT be expected to cause hyperkalemia.
Answer 3: Anemia is not a common adverse effect of furosemide or gentamicin use.
Answer 4: This “red-man syndrome” is classically associated with vancomycin use.
Answer 5: These side effects are classically seen with clindamycin use; pseudomembranous colitis is the result of C difficile overgrowth often secondary to clindamycin action in the digestive tract.
Deamer RL, Dial LK. The evolution of aminoglycoside therapy: a single daily dose. Am Fam Physician. 1996 Apr;53(5):1782-6.
PMID:8623702 (Link to Abstract)
Bates DE, Beaumont SJ, Baylis BW. Ototoxicity induced by gentamicin and furosemide. Ann Pharmacother. 2002 Mar;36(3):446-51.
PMID:11895059 (Link to Abstract)
USMLE World Step 1 QBank Question #685. Copyright © USMLEWorld, LLC 2012