isepamicin and arbekacin

Aminoglycoside antibiotics are known to produce a depression of neuromuscular function which may cause prolonged paralysis of respiratory muscles. However, differences in the effects of aminoglycoside antibiotics on diaphragm and limb muscles have not been investigated. We determined the neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate, isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular block was assessed by mechanical response with single twitch stimulation. Cumulative drug dose-response curves were obtained for three different muscles in 24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis anterior and soleus muscles were calculated. The neuromuscular blocking effects of all the aminoglycosides on ED(50) and ED(95) values were in the order of soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Diaphragm; Dibekacin; Dose-Response Relationship, Drug; Gentamicins; In Vitro Techniques; Male; Muscle Contraction; Muscle, Skeletal; Netilmicin; Neuromuscular Junction; Rabbits

The neuromuscular blocking properties of aminoglycoside group of antibiotics arbekacin sulfate (ABK), astromicin sulfate (ASTM), isepamicin sulfate (ISP), netilmicin sulfate (NTL) and d-tubocurarine were studied in 30 rabbits anesthetized with pentobarbital. The left gastrocnemius tendon was cut and secured to a force-displacement transducer. The left tibial nerve was directly stimulated by electrodes with supramaximal square waves of 0.1 msec duration at a frequency of 0.1 Hz. The resultant force of twitch tension was recorded. The intravenous administration of ABK 60-100 mg/kg, ASTM 160-320 mg/kg, ISP 320-480 mg/kg or NTL 20-40 mg/kg resulted in dose-dependent decreases in twitch tensions. The ED50 values of 4 antibiotics were NTL = 30.2 mg/kg (4.2 x 10(-2) mmol/kg) < ABK = 78.3 mg/kg (1.4 x 10(-1) mmol/kg) < ASTM = 215.2 mg/kg (3.6 x 10(-1) mmol/kg) < ISP = 359.7 mg/kg (6.3 x 10(-1) mmol/kg), respectively. These antibiotics-induced blockades were antagonized by calcium or by neostigmine. Although the relative neuromuscular blocking potencies of 4 antibiotics equipotent to d-tubocurarine on the basis of therapeutic doses in man were below 0.6 mg, it may be concluded that the potential clinical hazard lies in the sequence of administration of the aminoglycoside group of antibiotics.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Dibekacin; Dose-Response Relationship, Drug; Gentamicins; Netilmicin; Neuromuscular Blocking Agents; Rabbits; Tubocurarine