Neuromuscular blocking drug pharmacodynamics after chronic exposure to H2- antagonists.
This study tested the hypothesis that chronic exposure to H2-antagonists may affect neuromuscular function. Cimetidine or ranitidine was administered to rats for twenty one days as subcutaneously implanted biodegradable pellets. Control rats received placebo pellets. Serum cimetidine and ranitidine concentrations ranged from 0.1 to 0.5 micrograms/mL over this period. On the study day, surgically prepared anaesthetized rats received either succinylcholine (SCh) or atracurium (ATr) to achieve complete paralysis of the tibialis anterior muscle. After recovery an infusion dose of each neuromuscular blocker was titrated to produce 50% muscle paralysis with each blocker. Exposure to cimetidine or ranitidine did not alter SCh or ATr dose to maximum paralysis or the time course of recovery from the initial paralysis. SCh or ATr infusion rates required to elicit 50% paralysis were also unaffected by cimetidine or ranitidine pretreatment. These results indicate that chronic exposure to cimetidine or ranitidine at human therapeutic concentrations does not affect the neuromuscular pharmacodynamics of SCh or ATr in rats.
Rana
J
J
Department of Pharmacy, University of Sydney, NSW, Australia.
Ramzan
I
I
D000818:Animals; D001279:Atracurium / Q000097:blood / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000097:blood / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013390:Succinylcholine / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D006635:Histamine H2 Antagonists; D009467:Neuromuscular Depolarizing Agents; D001279:Atracurium; D002927:Cimetidine; D011899:Ranitidine; D013390:Succinylcholine