Biomaterial Database

Topical gentamicin and ethacrynic acid: effects on cochlear function. 1998

B J Conlon, and S D McSwain, and D W Smith

Hearing Research Laboratories, Division of Otolaryngology--Head and Neck Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

OBJECTIVE To determine whether concurrent intravenous administration of the loop diuretic ethacrynic acid potentiates the toxicity of the aminoglycoside antibiotic gentamicin applied topically on the round window. METHODS The authors studied the effects on cochlear sensitivity of co-administered intracardiac ethacrynic acid (40 mg/kg) and high-dose topical gentamicin solution (100%) applied to the round window. Comparisons were made with animals receiving ethacrynic acid plus systemic gentamicin (100 mg/kg); topical gentamicin alone; systemic gentamicin alone; and intravenous ethacrynic acid alone. METHODS Experiments were carried out on pigmented guinea pigs weighing 400 to 500 g. Changes in cochlear function were characterized by monitoring shifts in compound action potential (CAP) thresholds by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. RESULTS After 20 days animals receiving ethacrynic acid in combination with topical gentamicin to the round window failed to demonstrate a significant deterioration in cochlear sensitivity, whereas all animals receiving systemic gentamicin plus ethacrynic acid experienced profound increases in CAP thresholds. CONCLUSIONS This study supports the contention that ethacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph. In addition, this study answers important clinical concerns regarding the safety of the use of topical aminoglycoside agents in combination with loop diuretics.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D011897	Random Allocation	A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.	Randomization,Allocation, Random
D003051	Cochlea	The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH.	Cochleas
D004232	Diuretics	Agents that promote the excretion of urine through their effects on kidney function.	Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D004567	Electrodes, Implanted	Surgically placed electric conductors through which ELECTRIC STIMULATION is delivered to or electrical activity is recorded from a specific point inside the body.	Implantable Electrodes,Implantable Stimulation Electrodes,Implanted Electrodes,Implanted Stimulation Electrodes,Electrode, Implantable,Electrode, Implantable Stimulation,Electrode, Implanted,Electrode, Implanted Stimulation,Electrodes, Implantable,Electrodes, Implantable Stimulation,Electrodes, Implanted Stimulation,Implantable Electrode,Implantable Stimulation Electrode,Implanted Electrode,Implanted Stimulation Electrode,Stimulation Electrode, Implantable,Stimulation Electrode, Implanted,Stimulation Electrodes, Implantable,Stimulation Electrodes, Implanted
D004976	Ethacrynic Acid	A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.	Edecrin,Etacrynic Acid,Ethacrinic Acid,Ethacrynate Sodium,Ethacrynic Acid, Sodium Salt,Hydromedin,Acid, Etacrynic,Acid, Ethacrinic,Acid, Ethacrynic,Sodium, Ethacrynate
D005839	Gentamicins	A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.	Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin