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At least 325 records · Page 18Linked to original sources
PubMed1980

Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM).

Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol), at concentrations from 10(-8) to 10(-4) M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10(-8) to 10(-6) M except for small but significant (P < .05) increases in all three parameters at 10(-6) M fentanyl, and small but significant increases in dT/dt at 10(-8) to 10(-6) M meperidine. At 10(-5) M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-alpha-acetylmethadol (-11%). For all six narcotics, the 10(-4) M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10(-4) M) did not prevent this reduction of contractile performance except at the highest concentration (10(-4) M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-alpha-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 X 10(-7) M) elicited a positive inotropic response whether administered in the presence of 10(-4) M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert nonspecific, local anesthetic effect on the myocardium.

Analgesics, Opioid↗
PubMed1983

Modification of behavioral effects of morphine, meperidine and normeperidine by naloxone and by morphine tolerance.

Lever-press responding of morphine-tolerant and nontolerant squirrel monkeys was maintained under a multiple fixed-interval 5-min, fixed-interval 5-min schedule of food or electric shock presentation. Under the multiple schedule, the first response after a 5-min interval produced either food or shock depending on the prevailing stimulus. Responding maintained by either food or shock was characterized by patterns of positively accelerated responding during the 5-min interval. Morphine (0.1-1.0 mg/kg), meperidine (0.3-10.0 mg/kg) and normeperidine (1.0-17.0 mg/kg) produced dose-related decreases in rates of responding and produced small changes in the temporal pattern of responding in monkeys not tolerant to morphine. Food- and shock-maintained responding generally were affected similarly. Naloxone (0.1-3.0 mg/kg) had no effect when given alone to nontolerant monkeys. Both morphine tolerance and naloxone administration reversed the rate-decreasing effects of morphine and shifted the morphine dose-effect function to the right. Naloxone administration and morphine tolerance also reversed the rate-decreasing effects of meperidine and normeperidine, but unlike with morphine, combinations of naloxone and meperidine or normeperidine disrupted temporal patterns of responding and, at the higher doses, increased rates of responding well above control values. Drug effects in morphine-tolerant or naloxone-treated monkeys were not dependent on the event maintaining responding as comparable local rates of responding maintained by food or shock presentation were affected similarly. It was concluded that meperidine and normeperidine possess behavioral effects in common with those of morphine as well as pronounced non-morphine-like effects which are revealed by interference with the receptors upon which morphine acts.

Animals↗
PubMed1982

Effects of ethinyl estradiol on pharmacokinetics of meperidine and pentobarbital in the rat.

Effects of estrogen administration on in vivo hepatic microsomal drug metabolism have been frequently assessed, but there has been little study of the effects of estrogen treatment on in vivo drug pharmacokinetics. After administration of ethinyl estradiol (5 mg/kg daily for 5 days), meperidine and pentobarbital pharmacokinetics were determined both in vivo and in the isolated perfused rat liver. Estrogen pretreatment caused a 45% reduction in systemic meperidine clearance in vivo and perfusate disappearance of both meperidine and its major metabolite, normeperidine, was slower in isolated liver experiments from ethinyl estradiol-treated animals as compared with propylene glycol-treated controls. In contrast to meperidine, clearance of pentobarbital was not decreased by estrogen treatment. These studies demonstrate that estrogen treatment singularly can alter drug pharmacokinetics in the rat and raise the question as to whether clinically important alterations in drug pharmacokinetics occur in humans receiving estrogen therapy.

Animals↗
PubMed1981

Competition by meperidine for the organic cation renal excretory system.

Renal tubular excretory transport of meperidine was studied using the Sperber preparation in chickens. When urine samples from infused and uninfused kidneys were analyzed for meperidine by gas chromatography, meperidine was always present in greater amounts in the urine from the infused kidney, demonstrating active tubular excretion. Meperidine at an infusion rate of 1 mumole/min, also inhibited the excretion of the organic cations choline and acetylcholine, indicating occupation of the renal organic cation excretory system in the chicken.

Acetylcholine↗
PubMedDate not supplied

Pharmacokinetics and local responses to submucosal meperidine compared with other routes of administration.

The objective of this study was to determine the time course of the plasma levels of meperidine administered by various routes. Ten healthy adults received 0.8 mg/kg of meperidine given intravenous, submucosal, intramuscular, and 1.4 mg/kg orally in a randomized sequence at a minimum of one-week intervals. Blood samples were collected at 0, 10, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 720 min. The plasma was separated by centrifugation at room temperature. Plasma samples were analyzed for unchanged meperidine by a high-pressure liquid chromatographic assay. Pharmacokinetic parameters were calculated according to standard techniques. Data analysis was accomplished using a 4 x 11 analysis of variance and the Scheffe test for multiple comparisons. Pain response and tissue changes also were assessed using 4-point scales. Significant interaction effects (P < 0.00001) were found between the administration route and the time intervals. The maximum observed concentration of meperidine for the IV and SM routes occurred at the first sample point at 10 min, for the IM route at 20 min, and for the PO route at 45 min. There were no significant differences between the IV and the SM routes at any time interval measured. Post hoc comparisons of the peak values demonstrated significant differences between the IM and PO values (1.4 mg/kg) when compared with the IV and SM routes (P < 0.01). SM route caused greater tissue response and pain reaction, however, the differences were not statistically significant.

Administration, Oral↗
PubMed1997

[Analysis and assessment of meperidine and normeperidine concentrations in urine].

In this study, urine concentrations of meperidine and normeperidine after a single therapeutic dose of meperidine in 5 healthy volunteers have been measured and compared the results to those in meperidine addicts. The results showed that there was a significant difference between two groups in the ratio of metabolite to parent drug. If can be concluded that the ratio should be aid in making a cause of meperidine injection.

Adult↗
PubMed1975

Meperidine kinetics in man. Intravenous injection in surgical patients and volunteers.

The plasma concentration-time profiles of meperidine following intravenous injection in surgical patients and volunteers were investigated by reference to a classical two-compartment open model. Physiologic characteristics of the subject and variables associated with the surgery and anesthesia were screened as determinants of the kinetic patterns observed. When meperidine administration preceded induction of anesthesia, induction was consistently followed by an increase in venous plasma concentrations that prevented classical kinetic analysis. To facilitate calculations in subsequent studies in patients, meperidine injections were made following induction of anesthesia. Type of anesthesia or premedication, patients' sex, or cigarette smoking did not appear to be important factors in this evaluation. Increasing alcohol consumption was associated with increasing volumes of distribution. Increasing age was associated with increasing fraction of drug unbound in plasma. These factors may relate directly to clinical observations that heavy alcohol consumers tend to be more refractory to central nervous system (CNS) depressants and that elderly patients are more susceptible to respiratory depression from narcotics.

Adolescent↗
PubMed1995

Response to maternal separation in infant guinea pigs exposed to intrapartum meperidine.

We investigated whether opiate analgesics as commonly administered to women during labor would affect later response to maternal separation in infant guinea pigs. Meperidine hydrochloride (10-15 mg/kg i.m.) was administered to late-pregnant guinea pigs 5 min prior to labor induction with oxytocin. On Day 11 or 12 postnatal, pup distress vocalizations, locomotor activity, and plasma cortisol were measured under one of two conditions: alone (alone in a novel environment for 30 min) or mother (with the dam in the novel environment). Female pups exposed to intrapartum meperidine emitted fewer vocalizations than controls in the alone condition. Plasma cortisol was higher in meperidine females in the alone condition than in controls at the end of the separation period, but the difference was not significant. There was no drug effect on vocalizations or cortisol in males. Neither test condition nor drug affected activity level. The data suggest that intrapartum opiates may alter separation-induced distress in female guinea pig infants.

Animals↗
PubMedDate not supplied

The clinical pharmacology of meperidine--comparison of routes of administration.

The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered.

Administration, Oral↗
PubMed1980

Double-blind comparison of intravenously injected butorphanol and meperidine in parturients.

One hundred women with moderate-to-very-severe prepartum pain participated in a double-blind study of intravenously injected butorphanol and meperidine that compared the analgesic properties, effect on the process of labor, condition of the newborn and the incidence of side effects associated with the two drugs. Cervical dilation, infant birth weight and Apgar scores were not significantly different between the test groups. The mean fetal heart rate for the butorphanol group was significantly faster than that of the meperidine group. Butorphanol provided significantly more analgesia than meperidine at 30 minutes and one hour after administration, based on pain intensity and pain relief scores. Some side effects, including sedation, dizziness, lightheadedness, nausea, vomiting and pain at the injection site, were reported for both drugs.

Adolescent↗
PubMed1983

Quantitation of meperidine hydrochloride in pharmaceutical dosage forms by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the quantitative determination of meperidine hydrochloride in pharmaceutical dosage forms was developed. The method is reproducible and precise with relative standard deviations (based on six readings) of 1.2% with hydroxyzine and 0.93% with hydroxyprogesterone caproate as the internal standards. A variety of other active and inactive ingredients which were mixed with meperidine hydrochloride did not interfere with the assay procedure. Among the ingredients tested were acetaminophen, atropine sulfate, disodium edetate, metacresol, phenol, promethazine, and sodium metabisulfite. This method appears to be stability-indicating since a hydrolyzed sample of meperidine showed zero potency and a new peak with a different retention time.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1989

Prolactin and cortisol levels during spontaneous and oxytocin induced labour and the effect of meperidine.

The effect of stress during labour on the plasma concentration of prolactin and cortisol was studied in 30 healthy multiparous women. The plasma concentrations of prolactin and cortisol were measured by radioimmunoassay during oxytocin induced labour, spontaneous labour, delivery and postpartum 24 h. The parturients were divided into three groups. The first group was given oxytocin for the induction of labour, the second group was also given oxytocin for the induction of labour and 100 mg of meperidine was administered intramuscularly for relief of pain and anxiety, and the third group was the control group with normal parturients who did not receive any medication. The prolactin levels showed a fall during labour in all the groups, but this fall was more marked in the first group where stress was evident. The concentrations of cortisol tended to increase during labour and reached a maximum at delivery in all three groups but in the meperidine group this level was significantly lower than the first and control groups. These results give further support to the hypothesis that maternal stress leads to a reduced concentration of prolactin and increased concentration of cortisol whereas relief of pain and maternal anxiety with meperidine lessens both effects.

Delivery, Obstetric↗
PubMed1977

Meperidine-halothane interaction in dogs.

We studied the interaction of meperidine and halothane in 24 unmedicated, spontaneously breathing dogs. Intramuscular (i.m.) injections of meperidine, 2.75 mg/kg, 5.5 mg/kg and 11.0 mg/kg reduced the minimal alveolar concentration (MAC) of halothane required for anaesthesia. The magnitude and duration of MAC depression were dose related. Plasma meperidine concentrations following an i.m. injection of 2.75 mg/kg were lower in the awake, unsedated dogs than in the dogs anaesthetized with halothane.

Anesthesia↗
PubMed1977

Meperidine and morphine as intravenous surgical premedicants.

Morphine 5 mg and 10 mg and meperidine 50 mg and 100 mg were studied as intravenous surgical premedicants in 160 patients. Relief of anxiety, sedation, lack of recall and side effects were the variables evaluated. Neither morphine nor meperidine proved to be particularly good surgical premedicants. There appeared to be no significant differences between the two drugs, but what differences there were tended to favor meperidine.

Adolescent↗
PubMed1980

Mechanism for gastric accumulation of meperidine and effect of antacid.

The effect of hydrogen ion activity (pH) on the degree of meperidine sequestration in gastric contents was studied in 15 patients. Those patients with higher gastric juice cH+ (lower pH) showed greater accumulation with time. At a cH+ more than 10,000 nmol/l, (pH < 5) concentration usually reached 100 micrograms/ml within the 60-minute period after administration of 200 mg of meperidine. When cH+ was less than 100 nmol/l (pH > 7) gastric concentrations remained low, being only slightly greater than those of plasma. Oral administration of antacid may be a practical method for preventing sequestration of meperidine in gastric juice.

Adult↗
PubMed1982

Meperidine-promethazine combination and learning function of mice and of their progeny.

Twenty mice aged three to four months and trained to find food in a six compartment maze after a 24 hour fast, were divided into two equal groups. For just over one month the group which had received intraperitoneal meperidine 3 microgram.g-1 and promethazine 1.66 microgram.g-1 performed significantly slower than the group which had received intraperitoneal physiological saline. Because of this marked effect, it was decided to investigate the action of the drug combination on brain development and to assess whether it produced permanent retardation in learning function. The dams of a second group of 12 mice were, therefore, given either the same dose of drug combination or saline. At the age of seven weeks, the six pups born to dams which had received intramuscular saline and the six born to dams which were given intramuscular promethazine with meperidine performed equally well in a series of tests conducted in a T maze and in the six compartment maze after a 24 hour fast. In the T maze they had to distinguish between the presence of food provided in diminishing amounts or no food. In the six compartment maze they were tested with multiple maze pattern sequences. Meperidine and promethazine given during early labor does not permanently affect the learning function of the progeny of mice.

Aging↗
PubMed1992

Comparison of meperidine and pancuronium for the treatment of shivering after cardiac surgery.

Shivering after cardiac surgery can produce adverse haemodynamic and metabolic sequelae. In this study, the metabolic effects of shivering and the efficacy of treatment with meperidine or pancuronium were studied, using a metabolic cart, in 61 patients who had undergone cardiac surgery. The patients received premedication with morphine, perphenazine and diazepam or lorazepam, and were anaesthetised with fentanyl or sufentanil and diazepam. Muscle relaxation was achieved with pancuronium. Patients were monitored with a radial arterial line, pulmonary artery catheter and oesophageal and urinary bladder temperature probes. Rewarming to an oesophageal temperature of 38 degrees C was achieved before the termination of CPB and was maintained for a minimum of 15 min reperfusion time. Every 15 min after surgery, the patients' temperature at three sites (pulmonary artery, oesophagus, bladder) and shivering scores were monitored. Hourly measurements were made of haemodynamic variables (MAP, PAOP, CVP, SVR, PVR, CI), carbon dioxide production, oxygen consumption and respiratory quotient. If the patient shivered, the measurements were recorded prior to drug treatment and repeated 30 min later following randomization to either: meperidine 0.25 mg.kg-1 (Group 1), meperidine 0.5 mg.kg-1 (Group 2) or pancuronium 0.06 mg.kg-1 intravenously (Group 3). Thirty-two patients shivered and mean VO2 and VCO2 values were greater in the shivering group than in the nonshivering patients (VO2 334.8 +/- 17.6 vs. 240.5 +/- 8.8 ml.min-1; VCO2 238.8 +/- 17.2 vs 199.2 +/- 8.4 ml.min-1, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Self-administered intranasal meperidine for postoperative pain management.

Recent studies have demonstrated that intranasal is comparable to intravenous opioid titration in its pain-relieving effect. In these studies, however, the intranasal opioid titration was performed by the investigator, and the treatment period was two hours or less. The purpose of this randomized, prospective study was to investigate whether intranasal opioid administration by the patients themselves for a prolonged postoperative period may be regarded as a therapeutic alternative for postoperative pain management. Forty-four orthopaedic patients were studied over a 12-hr period on the first day after surgery. Twenty-two had free access to intranasal meperidine (nasal group) and were allowed to administer six intranasal puffs (27 mg per dose). The next self-administration was only permitted after a delay of at least ten minutes. Another 22 patients received intermittent subcutaneous meperidine injections (25 or 50 mg) on request (sc group). Pain intensity was recorded at 30-min intervals with the aid of the 101-point numerical rating scale. The pain score was lower in the nasal than in the sc group at the 30, 150 to 330, 420 to 480 and 540 to 600 min measuring points (P = < 0.05). The meperidine requirement was 112.9 +/- 81.3 mg in the nasal and 103.4 +/- 41.5 mg in the sc group (NS). Two patients in each group complained of nausea and vomiting. Thirteen of the 21 nasal and nine of the 15 sc patients who completed the final questionnaire rated the pain management as excellent or good (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗