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)

The activity of clonidine and its interaction with morphine was assessed in the mouse tail flick assay. In this assay, clonidine was found to be 10 times more potent than morphine. Clonidine potentiated morphine antinociceptive activity approximately five-fold and morphine potentiated clonidine activity four-fold. Clonidine's agonstic activity was not reversed by naloxone hydrochloride (10 mg/kg) while the potentiating effect of clonidine by morphine was. Tolerance to the antinociceptive effect of morphine was observed in morphine pellet-implanted mice but no cross tolerance was observed for clonidine. These data indicate that clonidine-induced analgesia is not a result of an interaction at morphine receptors; but rather, common pathway(s) are present which appear to complement the agonistic interaction of each.
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PMID:Antinociceptive activity of clonidine and its potentiation of morphine analgesia. 49 34

Opiate-adrenergic interactions were investigated by studying the effect of the selective alpha 2-adrenergic agonist, clonidine, on the analgesia produced by intravenous placebo and by the predominantly kappa-opiate agonist, pentazocine, in patients with dental postoperative pain. Clonidine did not affect the pain level when administered with intravenous placebo. When administered with pentazocine, clonidine caused a statistically significant increase in pentazocine analgesia. Comparison is made to other opiate-adrenergic interactions and possible mechanisms are discussed.
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PMID:Enhancement of pentazocine analgesia by clonidine. 135 Mar 40

Intraspinally administered alpha 2-adrenergic agonists are being examined for postoperative analgesia, yet their effects on the hemodynamic response to acute hemorrhage have not been examined. In this study chronically prepared conscious sheep received thoracic intrathecal saline or clonidine 300 micrograms followed in 15 min by rapid removal of 1,000 ml blood. In saline-treated ewes blood pressure was maintained and heart rate steadily increased during hemorrhage of up to 700 ml blood, with further blood removal resulting in rapid decreases in both variables. In contrast, heart rate never increased and blood pressure was maintained only up to 400 ml blood loss in animals receiving intrathecal clonidine. Compared to saline controls, clonidine did not alter blood pressure or heart rate at the end of hemorrhage or during blood pressure restitution during the next hour. Clonidine inhibited the increase in plasma epinephrine at the end of hemorrhage without altering plasma norepinephrine, vasopressin, renin, or atrial natriuretic factor. Intrathecal idazoxan, a specific alpha 2-adrenergic antagonist, reversed clonidine's effect on blood pressure during hemorrhage. Intravenous DG-5128, a poorly lipid-soluble alpha 2-adrenergic antagonist, also reversed clonidine's effect and additionally completely blocked any reduction in blood pressure and heart rate during hemorrhage. These data suggest that intrathecal clonidine interferes with maintenance of blood pressure during hemorrhage, likely because of a spinal sympatholytic effect, but does not affect the ultimate decrease in blood pressure after rapid removal of 1,000 ml blood. This difference in effect during the two phases of hemorrhage can be explained by the relative importance of the sympathetic nervous system in each.
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PMID:Intrathecal clonidine and the response to hemorrhage. 135 38

The role of central nor-epinephrine (NE) in electroacupuncture (EA) analgesia is a controversial question., it is probably due to the complication of adrenergic receptors. The present results show: (1) Clonidine 30 micrograms/2ml/kg ip had no significant effect on the pain threshold, but decreased the analgesic effect of EA. Clonidine 1.5 and 3 micrograms were injected into the lateral cerebral ventricles. After 45 minutes, the analgesic effect of EA was lowered as compared with the saline controls respectively. (2) Yohimbine had no significant effect on the basal pain threshold, but (icv Yoh 50 micrograms) elevated the analgesic effect of EA. (3) 2-adrenoceptor agonist methoxamine decreased the analgesic effect of EA. (4) Another 2-adrenoceptor antagonist prazosin (icv 16 micrograms) enhanced the analgesic effect of EA. These results suggest that an activation of alpha 1- or alpha 2-adrenoceptors would decrease the analgesic effect of EA.
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PMID:[Effects of four adrenergic drugs on electroacupuncture analgesia]. 136 74

Clonidine (Cl) added to local anaesthetics (LA) prolongs the duration of both anaesthesia and analgesia after peripheral nerve blocks. In this study, we investigated the dose-dependent effect of Cl added to mepivacaine (M) on clinical efficacy, onset, and regression time of brachial plexus block. METHODS. Ninety patients were randomly assigned to one of three groups. Every patient received 46 ml of a mixture containing 400 mg M (pH adjusted with NaHCO3 to 7.25) and either 0.9% NaCl (group A), 0.12 mg Cl (group B), or 0.24 mg Cl (group C). The axillary block was performed using the catheter technique. In a double-blind fashion, the onset of sensory and motor blockade was tested every 5 min for 30 min. Duration of anaesthesia, analgesia, and motor blockade (time between injection and return of sensation, onset of pain, or ability to move, respectively) was assessed using a questionnaire. M plasma levels were measured by HPLC in 10 patients from each group for up to 120 min. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured for up to 120 min. Sedation was assessed using a verbal rating scale. RESULTS. There was no difference in the onset of blockade. There was dose-dependent prolongation of the duration of anaesthesia, analgesia, and motor blockade with significant differences between groups C and A regarding all three parameters, between groups C and B regarding duration of anaesthesia, and between groups B and A regarding duration of analgesia. There was no significant difference in M plasma levels. Although there was only a slight but significant decrease in mean BP values in groups B+C and no difference in HR and RR, 2 patients (1 group B, 1 group C) had marked decreases in BP and HR (less than 70 mmHg systolic resp. less than 50/min) after 120 and 210 min. Sedation occurred in most patients receiving Cl. CONCLUSIONS. Addition of Cl to LA produces a dose-dependent prolongation of anaesthesia, analgesia, and motor blockade. Neither the onset time nor the number of patients with adequate surgical anaesthesia was influenced by Cl. Considering the M plasma levels, it is unlikely that the prolongation of the block is caused by local vasoconstriction, which is proposed to be the mechanism of action of epinephrine. The mean differences in haemodynamic parameters were not of clinical relevance, but the two dramatic drops in BP and HR, probably caused by Cl, were significant.
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PMID:[The effect of adding clonidine to mepivacaine. Axillary brachial plexus blockade]. 141 11

Central and systemic morphine analgesia as well as both opioid and nonopioid forms of swim analgesia display gender differences with male rats showing greater magnitudes of analgesia than female rats. Since nonopioid swim analgesia is dependent upon muscarinic cholinergic and alpha 2-noradrenergic mechanisms, the present study evaluated in rats whether gender, adult gonadectomy or estrous phase altered analgesia induced by either the muscarinic cholinergic receptor agonist, pilocarpine or the alpha 2-noradrenergic receptor agonist, clonidine. Pilocarpine (1-10 mg/kg) analgesia was significantly greater in male rats. Female rats displayed 7-fold and 3-fold rightward shifts in peak analgesia on the tail-flick and jump tests respectively. Clonidine (100-500 micrograms/kg) analgesia was significantly greater on both nociceptive tests in males, but only produced a 2-fold rightward shift in peak analgesia in females on the jump test. Whereas castration failed to shift either dose-response curve, ovariectomy mitigated the gender differences in pilocarpine and clonidine analgesia. Both pilocarpine and clonidine analgesia were not altered by estrous phase changes. These data indicate that gender differences in analgesia are not specific to opioid systems.
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PMID:Roles of gender and gonadectomy in pilocarpine and clonidine analgesia in rats. 153 65

Clonidine, an alpha 2-adrenergic agonist, can potentiate opioid-induced analgesia. In a double-blind placebo-controlled study in human volunteers, we sought to determine whether clonidine also potentiates opioid-induced respiratory depression. Hypercapnic ventilatory responses (minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure) were measured in five healthy male volunteers on two separate occasions (with or without clonidine, approximately 3.5 micrograms.kg-1 orally) under the following conditions: baseline, 2 h after clonidine/placebo (alfentanil concentration of 0), and during computer-controlled alfentanil infusions to approximate plasma concentrations of 5, 10, 20, 40, and 80 ng.ml-1. Plasma alfentanil concentrations were measured before and after each rebreathing test, and clonidine concentrations were measured after each rebreathing test. The end-tidal CO2 (PET(CO2)) was measured continuously. Data were analyzed by repeated-measures analysis of variance. The PET(CO2) and measured concentrations of alfentanil were included as covariates, and a compound symmetry error analysis was assumed. Statistical significance was achieved when P less than 0.05. For minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure there was a statistically significant relationship to the covariates of PET(CO2) and plasma alfentanil concentration. Clonidine, when compared to placebo, caused a small but significant depression of mean inspiratory flow rate. There was similarly a small, but statistically insignificant, depression of minute ventilation by clonidine. The mouth occlusion pressure was not affected by clonidine treatment. Clonidine treatment did not potentiate alfentanil-induced respiratory depression. Although the combination of an opioid and an alpha 2-adrenergic agonist may act synergistically for the analgesic response, there is no synergistic effect by this drug combination on respiratory depression.
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PMID:Ventilatory effects of clonidine alone and in the presence of alfentanil, in human volunteers. 159 10

Although clonidine analgesia appears to be mediated by the same central alpha 2-adrenoceptors that mediate its hypotensive effect, it is short-lasting when compared to the fall in blood pressure. This has been investigated by combined pharmacokinetic-pharmacodynamic analysis in 10 healthy volunteers who received (double-blind and crossover) clonidine 200 micrograms orally + placebo i.v. and clonidine orally + naloxone i.v. (2.8 mg/5 h). Analgesia was assessed by measuring the subjective (VAS) and objective (RIII) pain thresholds after transcutaneous electrical stimulations of the sural nerve; the mean arterial blood pressure (MAP), salivary flow (SF), and plasma clonidine concentrations were also monitored. A combined pharmacokinetic (first order absorption - 1 compartment) - pharmacodynamic (linear) model, including a hypothetical effect compartment with and without tolerance, were fitted to the data. Clonidine and clonidine + naloxone increased subjective and objective pain thresholds for 4 h. The concentration-effect plot for MAP showed distinct hysteresis. The t1/2s for effect compartment equilibration were 29 and 42 min for clonidine + naloxone and clonidine. The concentration-effect curves for RIII had the same shape as MAP but the starting hysteresis suddenly collapsed, suggesting acute tolerance. The best fit was obtained with a model where the linear relationship between concentration in the effect compartment and analgesia changed acutely after the third hour. The short-lived analgesia was probably related to an acute change in pain sensitivity induced by food, suggesting that it is not mediated solely by the alpha 2-adrenoceptors responsible for hypotension.
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PMID:Pharmacokinetic-pharmacodynamic modeling of the effects of clonidine on pain threshold, blood pressure, and salivary flow. 162 8

In this prospective study, the postoperative analgesic effects of intraoperative iv clonidine were evaluated. Two hundred consecutive patients undergoing major abdominal surgery were randomly assigned to either balanced anaesthesia with iv clonidine (Group 1) or balanced anaesthesia alone (Group 2). A PCA infuser was connected immediately after tracheal extubation. It was programmed to deliver morphine "on demand" iv boluses at doses of 1 mg for patients greater than 65 yr and 1.5 mg for women or 2 mg for men less than 65 yr old. A blinded observer assessed postoperative analgesia by recording the analgesic demands (both met and unmet), patient pain scores, sedation scores, and any side effects during the first 36 hr after surgery. Intraoperative clonidine reduced the number of analgesic demands during the observation period (45 +/- 27 demands in Group 1 vs 81 +/- 60 in Group 2, P = 0.0001). This resulted in a reduction in morphine delivered (55.4 +/- 30.6 mg vs 67.1 +/- 45.1 mg, P less than 0.05), mainly during the first 12 hr (19.7 +/- 11.1 mg vs 27.6 +/- 18.1, mg P less than 0.001) and the unmet demand rate was also reduced at all time intervals (P less than 0.01). Clonidine did not exacerbate sedation or side effects. However, clonidine provided better analgesia in men and in patients less than 65 yr of age. Intraoperative iv clonidine enhances morphine analgesia after abdominal surgery.
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PMID:Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia. 164 72

Epidurally administered clonidine represents a new approach to postcesarean section pain therapy, yet the appropriate bolus dose and infusion to provide effective pain relief have not been defined. In addition, whether 2-chloroprocaine, a commonly used local anesthetic for intraoperative anesthesia, interferes with clonidine's analgesia, as it does with that of opioids, has not been examined. In this study, using a randomized, blinded design, 63 women received either bupivacaine or 2-chloroprocaine for epidural anesthesia for cesarean section and then received, upon request for analgesia in the recovery room, epidural clonidine 400 micrograms or 800 micrograms bolus, each followed by a 24-h infusion of 40 micrograms/h, or an equivalent volume bolus and infusion of saline. In the bupivacaine group, both clonidine doses produced equivalent analgesia, as determined by pain scores and time to first supplemental intravenous morphine request, and sustained analgesia was produced by clonidine infusion, as measured by need for supplemental morphine. In contrast, 2-chloroprocaine diminished analgesia from 800 micrograms by 21% and abolished analgesia from 400 micrograms clonidine. After 2-chloroprocaine, sustained analgesia from continuous clonidine infusion was present only in the group who had received 800 micrograms clonidine. Clonidine did not alter resolution of residual local anesthetic sensory blockade, as measured by 2- or 4-segment regression following either local anesthetic, but did prolong duration of motor blockade in women receiving bupivacaine. Clonidine produced small decreases in heart rate and blood pressure. One patient received iv fluids for hypotension; one had asymptomatic bradycardia resolving without therapy; and one had mild hypoxemia with snoring during clonidine-induced sedation, responding to supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidural clonidine after cesarean section. Appropriate dose and effect of prior local anesthetic. 173 94


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