Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many drugs potentiate the action of non depolarizing relaxants. These interactions are of clinical importance if such drugs are administered during the perioperative period. H2 Antagonists are increasingly often used for premedication. Cimetidine inhibits the elimination of a number of drugs used in the perioperative period. We therefore investigated whether H2 antagonists enhanced neuromuscular blockade by vecuronium, a medium short acting non depolarizing muscle relaxant. METHODS. The study was carried out in 24 female patients (ASA class I or II) scheduled for microsurgical procedures. Neuromuscular transmission was recorded electromyographically using four stimulations every 20 s to the ulnar nerve. After induction with thiopentone, anesthesia was maintained with fixed concentrations of volatile anesthetics. Fentanyl was administered for additional analgesia. Vecuronium was used as the sole muscle relaxant. Fixed repetitive doses of vecuronium (0.8-1.2 mg) were injected whenever the T1 returned to 25%. This time interval was defined as the T1-25 period. The study proper started when the T1-25 period had stabilized. After two control periods, six patients in each group received either 200 or 400 mg cimetidine or 100 mg ranitidine. The fourth group was the control group. The T1-25 periods and the maximal EMG depression were recorded automatically for at least two further periods. The first measured period was recorded as 100% and the length of each other periods was calculated as a percentage of the control period. This method enables an intraindividual comparison of the length of the T1-25 period and the maximal EMG depression before and after administration of the H2 antagonists. A two-tailed Student's t-test was used to test statistical significance, P less than 0.05 being accepted as significant. RESULTS. In the control group and in the group with 200 mg cimetidine or 100 mg ranitidine no statistical significant prolongation of the T1-25 period or of the maximal EMG depression could be observed, while after 400 mg cimetidine there was significant prolongation (mean 161 +/- 14.8%) of the T1-25 period and significantly greater EMG depression compared with the pre-cimetidine values. In the groups with 200 mg cimetidine or 100 mg ranitidine few patients showed prolongation of the T1-25 period up to 130%. DISCUSSION. Our results confirm experimental studies that have shown cimetidine to enhance aminoglycoside--relaxant interactions. Because we found an immediate response to the administration of the H2 antagonists, the interaction cannot be on the elimination side; it must be at the neuromuscular junction. Experimental investigation has shown that calcium reverses the cimetidine effects. It is therefore probable that the cimetidine--relaxant interaction occurs at the presynaptic level. Careful observation seems to be necessary if H2 antagonists, especially cimetidine, are administered intraoperatively at the same time as drugs that also enhance
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PMID:[Interactions of H2 antagonists and non-depolarizing muscle relaxants]. 256 80

Antagonism of the H-2 receptor with cimetidine and other histaminergic receptor antagonists has been used to differentiate nonopioid and opioid forms of footshock analgesia which are mediated by neural mechanisms. Cimetidine reduces nonopioid footshock analgesia while potentiating an opioid form of this analgesia. The present study examined whether cimetidine altered the nonopioid, neurohormonal analgesia induced by either continuous cold-water swims (CCWS: 2 degrees C for 3.5 min) or the opioid analgesia induced by intermittent cold-water swims (ICWS: 2 degrees C, 18 10-sec swims, 18 10-sec recovery periods). Vehicle or cimetidine (10, 50, 100 mg/kg) injections were administered alone or paired with either CCWS or ICWS; tail-flick latencies, jump thresholds and core body temperatures were then measured. Cimetidine (100 mg/kg) significantly potentiated CCWS and ICWS analgesia and hypothermia, while having minimal effects upon basal thresholds. Lower cimetidine doses produced transitory effects on these measures. These data demonstrate dissociations between neural and neurohormonal forms of nonopioid analgesia following cimetidine treatment. The latter effect may be attributed to changes in stress responsiveness or thermoregulation rather than pain inhibition.
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PMID:Potentiation of opioid and nonopioid forms of swim analgesia by cimetidine. 285 66

The inhibition of hindpaw (non-opiate) footshock-induced analgesia (HP-FSIA) by cimetidine, the histamine H2-receptor antagonist, was characterized in rats, and the drug's presence in brain was demonstrated. Cimetidine (100 mg/kg, IP) inhibited HP-FSIA when administered 30 min before testing, but was inactive when testing began sooner (15 min) or later (1-4 hr) than this time. Lower doses (20 mg/kg) were also ineffective when given 30 min before testing, whereas higher doses (200 mg/kg) effectively inhibited the response. Increasing the footshock current from 4 mA (which elicited cimetidine-sensitive analgesia) to higher currents (5 and 6 mA) yielded cimetidine-insensitive analgesia. Administration of isotopically labeled cimetidine (100 mg/kg, IP, 30 min) yielded whole brain cimetidine levels of 1.95 nmols/g, respectively, with a brain/blood ratio of 0.017. These findings confirm a limited penetration of brain by cimetidine, and show that large peripheral doses of cimetidine are required to block brain H2-receptors. The specific dose and time requirements for cimetidine to inhibit the HP-FSIA are probably attributable to the brain drug levels that can be achieved after peripheral administration.
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PMID:Cimetidine penetrates brain and inhibits non-opiate footshock-induced analgesia. 348 1

The effects of the opiate antagonist naloxone (10 mg/kg) and the histamine H2-antagonist cimetidine (100 mg/kg; both administered i.p.) were studied on the analgesia elicited by 3 currents of continuous-scrambled AC footshock (FSIA). Repeated analgesic measurements were made in each animal by use of the radiant heat tail-flick test. As shown by others, naloxone effectively inhibited the FSIA produced by 3 min of 2.0 mA, but had no effect on the responses elicited by higher currents (2.5 and 3.5 mA) of the same duration. Cimetidine significantly reduced the naloxone-insensitive FSIA after 3.5 mA, had no effect on that produced by 2.5 mA and potentiated the naloxone-sensitive analgesia elicited by 2.0 mA. These findings add to existing data supporting a role for brain histamine as a mediator of naloxone-insensitive analgesia, and also suggest the possibility that histamine may mediate hyperalgesic responses.
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PMID:Opposing actions of cimetidine on naloxone-sensitive and naloxone-insensitive forms of footshock-induced analgesia. 370 33