Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of the effect of analgesics in the newborn is difficult in the clinical situation and resort must be made to animals. Pethidine given within 1 hour of delivery is believed to cause less depression than when the time interval is longer. This study investigates whether it is pethidine or its metabolites which cause respiratory depression by comparing the respiratory effects of pethidine and its metabolites in the newborn rabbit. Fentanyl and buphrenorphine were also investigated as alternative analgesics. The response in the newborn rabbit to anoxia, is periods of dyspnoea, primary apnoea, and gasping. The metabolites of pethidine increased the primary apnoea signifying depression almost as much as pethidine. Depression was also produced when anoxia was induced 5 minutes after pethidine. Fentanyl caused less depression than pethidine or its metabolites excepting normeperidinic acid. Buphrenorphine administration resulted in the least depression with little difference between the low and high doses. Thus both pethidine and its metabolites are factors in the persisting depression, while buphrenorphine compared well with pethidine and fentanyl.
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PMID:The role of analgesics in respiratory depression: a rabbit model. 1 6

The effect of meperidine (3 X 10(4) M) on the action potential of frog sciatic nerve was examined by means of the double sucrose gap technique. Meperidine decreased the amplitude, maximum rate of depolarization, and maximum rate of repolarization of the action potential but had no effect on the resting potential. This depression in amplitude and maximum rate of rise was partially blocked by naloxone (1 X 10(-8) M) while the maximum rate of depolarization was further depressed. The data suggest that the effect of meperidine is due to two mechanisms, a nonspecific local anaesthetic like effect and an opiate receptor mediated effect.
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PMID:An opiate receptor on frog sciatic nerve axons. 22 29

The addition of d-amphetamine to morphine has been reported to result in an increase of analgesic potency in experimental animals and man, but no data on the toxicity of such combinations are available. This study is intended to provide systematic information on the toxicity, analgesic potency and degree of physical impairment (swimming endurance) of a combination of 12 mg morphine sulfate with 10 mg d-amphetamine HCl per ml which is now under clinical investigation. Mice were used as experimental subjects. Meperidine, methadone and pentazocine were substituted for morphine using clinically equally analgesic doses and keeping the d-amphetamine amount constant. The toxicity of all analgesics especially that of morphine was enhanced in the combination, least so in the case of meperidine. The degree of increase of analgesic power by the addition of d-amphetamine was greatest with morphine and quantitatively in satisfactory agreement with present clinical experiences. However, the relationship between the increases of toxicity and of analgesia is not necessarily most favorable for this drug. For the other three analgesics increases in toxicity and analgesia were more in line, meperidine showing the best ratio. Swimming endurance was decreased with full analgesic doses of all four compounds. The presence of d-amphetamine tended to reverse this depression. The data were analyzed in relation to their possible predictive value for the use of such combinations in man for the therapeutic dose range and in the event of overdosage.
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PMID:A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice. 24 3

The Early Neonatal Neurobehavioural Scale (E.N.N.S.) tests, first described by Scanlon, et al.1 were administered to 920 neonates on the first and second days of life. Meperidine was not given to 389 mothers, 50 mg was given to 358 mothers and 75 to 150 mg to 173 mothers within four hours of delivery. The delivery was conducted under chloroprocaine epidural anaesthesia in 280, ketamine-nitrous oxide general anaesthesia in 180, thiopentone-nitrous oxide general anaesthesia in 180 and lidocaine pudendal block in 280. All babies were over 2500 grams in weight with an Apgar score of at least 8 at one minute and 10 at five minutes. All were delivered from healthy women 18 to 35 years of age following a normal labour. The evaluator was unaware of the anaesthetic management, the method of delivery or the perinatal risk factors. There was no significant difference between the mothers and babies in the three meperidine dosage groups for maternal parity, maternal age, birth weight, number of forceps deliveries or duration of labour. Administration of meperidine was associated with a broad spectrum depression of most items on the E.N.N.S. on both the first and second days of life. The depression was greatest with the highest dose of meperidine. The depression produced by anaesthetic agents and meperidine were additive and the highest scores on this scale were obtained in those babies delivered under chloroprocaine epidural anaesthesia without meperidine.
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PMID:Double-blind comparison of the neurobehaviour of neonates following the administration of different doses of meperidine to the mother. 35 10

Pethidine is commonly used in single doses as a preoperative medication or in multiple doses as an analgesic. The clinical consequences of altered disposition are more likely to result from its analgesic use. Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects. The current practice of intermittent pethidine administration (intravenous, intramuscular and oral) for analgesia results in fluctuations in pethidine plasma concentrations which are associated with incomplete pain relief and side effects. Continuous intravenous infusion of pethidine may avoid these difficulties. Changes in pethidine disposition have been observed in patients with liver disease and in the elderly. Measurement of plasma pethidine concentrations may be helpful as an aid to the management of such patients. In renal disease, metabolites may accumulate and cause side effects.
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PMID:Clinical pharmacokinetics of pethidine. 35 12

Pethidine or an epidural injection of bupivacaine are common forms of obstetric analgesia in Britain. Bupivacaine has been thought to have little effect on the fetus, but neurobehavioural studies have cast doubt on this. We therefore investigated the elimination of these drugs by babies in similar population groups. Bupivacaine was largely eliminated in just over one day, while pethidine required between 2 and 6 days. This could account for the persisting depression in babies whose mothers had received pethidine.
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PMID:Elimination of pethidine and bupivacaine in the newborn. 92 10

In 5 normal subjects we measured ventilation and P0.1, the pressure generated by the first 0.1 sec of inspiratory effort against a closed airway, in response to hypercapnia and hypoxia with and without added inspiratory resistance before and after oral meperidine (1.1 to 1.3 mg per kg). CO2 responses were studied in the steady state, whereas progressive hypoxia was used to elicit hypoxic responses. In general, resistance decreased ventilatory responses to hypercapnia but increased P0.1 responses to both hypoxia and hypercapnia. Meperidine depressed both ventilatory and P0.1 responses, more so in hypoxia than in hypercapnia. The combination of resistance and merperidine was additive in depressing responses to hypercapnia but in hypoxia produced little more depression than did meperidine alone. In both hypercapnia and hypoxia, meperidine decreased the augmentation of P0.1 that was associated with increased resistance. Normal subjects responded to acute increases of inspiratory resistance by increasing inspiratory motor output; this increase was distinctly blunted by meperidine.
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PMID:Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance. 97 24

The newborn rabbit responds to acute anoxia, as a result of breathing nitrogen, with successive periods of dyspnoea, primary apnoea, gasping and terminal apnoea. Pethidine caused an increase in the period of primary apnoea and a decrease in the duration and rate of gasping. When nalorphine was combined with pethidine the period of primary apnoea was still increased although the duration and number of gasps were restored to control values. Naloxone, in contrast, acted as a mild respiratory stimulant, shown as a longer phase of dyspnoea. Also it completely abolished the respiratory depression produced by pethidine. Naloxone may be preferable to nalorphine as a drug to reverse the effects of pethidine immediately after birth.
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PMID:The effect of narcotic and narcotic-antagonist drugs in the newborn rabbit. 103 13

The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro-electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0-35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60-90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(-5) to 3 X 10(-4) mM) at 70-90 min blocked the second phase of the meperidine-induced depression. 4. With lower concentrations of meperidine (0-18 and 0-07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1-5 X 10(-2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non-specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.
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PMID:Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non-specific and opiate drug receptor mediated blockade. 108 25

Because hydroxyzine hydrochloride is frequently used to tranquilize patients, who are receiving narcotic analgesics for pain relief, its effect alone and in combination with meperidine on arterial blood gases and ventilation in patients at rest was evaluated in 65 healthy volunteers, who gave informed consent. Hydroxyzine hydrochloride, 1.5 mg/kg IV given over 30 seconds, caused no decrease but rather a significant (P less than .001) increase in PaO2 and no increase in PaCO2 and/or pH at 5, 10, 20, 30, and 60 minutes (N = 29; mean age = 47.0 years). Meperidine, 1.5 mg/kg IV given over 30 seconds, caused a significant (P less than .01) reduction in PaO2 at 5 minutes indicating ventilatory depression but no increase in PaCO2 and/or pH (N = 19; mean age = 32.4 years). The combination of the same doses of hydroxyzine with meperidine IV caused a significantly greater decrease in PaO2 only at 10 minutes but a greater increase in PaCO2 and pH at all times for 60 minutes than did meperidine alone (N = 17; mean age = 39.5 years), which indicates greater ventilatory depression with the combination than with hydroxyzine alone. However, PaO2, PaCO2 and pH remained within the awake normal ranges for PaO2, PaCO2, and pH for the age group of volunteers even at 10 minutes after IV injection of the drug combination when most of the volunteers were asleep. In conclusion, hydroxyzine even when given IV in excess of the maximum IM therapeutic doses caused no changes in PaO2, PaCO2 or pH, which would indicate clinically important ventilatory depression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hydroxyzine and meperidine on arterial blood gases in healthy human volunteers. 249 48


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