Abstract
The neuromuscular blocking effects of polymyxin and colistin were investigated in the unanesthetized rabbit, in the cat sciatic nerve–tibialis anterior muscle preparation in vivo, and in the frog rectus abdominis preparation in vitro. These antibiotics, along with certain others used for comparison, produced paralyses of different intensities in rabbits, depending on the dose, with no preceding fasciculation. In this regard, polymyxin was the most potent antibiotic studied. Polymyxin B sulfate (3–5mg/kg) and colistimethate sodium (60–90mg/kg) caused a blockade of neuromuscular transmission, partial paralysis of respiration, and hypotension in cats. The intraarterial injection of these antibiotics did not elicit muscle contraction; the response to the intraarterial injection of acetylcholine was reduced or abolished during the block; calcium and epinephrine antagonized the block; posttetanic potentiation occurred; edrophonium and decamethonium produced brief antagonism of the block; neostigmine, tetraethylammonium, and choline were without effect; and tubocurarine accentuated the block. During the block, muscle action potentials were reduced or abolished, and nerve action potentials were unaffected. (Response of the muscle to direct stimulation was reduced compared to the predrug response.) Both agents depressed muscle twitches elicited at the faster rate of stimulation (60/min) while the slow rate twitches (6/min) were hardly depressed. The serum ionic calcium level was not altered significantly by these antibiotics. Thus, the neuromuscular block displayed characteristics of a postsynaptic, nondepolarizing type that was noncompetitive in nature, with possible presynaptic elements and a depressant action on muscle fibers. Both polymyxin and oolistin possess transient ganglionic blocking action.
Published Version
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