Morphine-induced Respiratory Depression Research Articles

Determination of the relative involvement of μ-opioid receptors in opioid-induced depression of respiratory rate by use of β-funaltrexamine

Using a simple method to measure respiratory rate, it was clearly shown that the depression of respiratory rate caused by morphine, ethylketazocine or [D-Ala 2,D-Leu 5]enkephalin was not altered by the highly selective, irreversible μ-antagonists, β-funaltrexamine (β-FNA) at a dose which produced marked antagonism of morphine antinociception. These results indicated that antinociception and depression of respiratory rate are mediated by different receptor interactions. However using a different method to measure respiratory rate (body plythesmograph), β-FNA caused substantial antagonism of morphine-induced respiratory depression indicating that the degree to which μ-receptor interactions contribute to the depression of respiratory rate depends on the methodology. Possible explanations for this difference are discussed. It is concluded that careful consideration of the methodology must be given when one measures respiratory rate and caution must be exercised if measurement of rate alone is used to assess opioid-induced respiratory depression.

Use of 4-Aminopyridine to Reverse Morphine-Induced Respiratory Depression in Man

Use of 4-Aminopyridine to Reverse Morphine-Induced Respiratory Depression in Man

Endotracheal Administration of Epinephrine During Cardiopulmonary Resuscitation-Reply

In Reply.—The experience of Dr Lindemann is certainly a gratifying validation of our laboratory research and our clinical experiences at The Medical College of Pennsylvania, Philadelphia. Dr Lindemann's observation of endotracheal administration of epinephrine in neonates further demonstrates the usefulness of this route for emergency administration of drugs. As Dr Lindemann noted, this procedure can be invaluable not only in neonates, but in older children and adults as well. It is important to note that several other emergency drugs are efficacious when administered endotracheally. Our most recent experience involved the use of endotracheally administered atropine sulfate.1We could obtain normal BP and pulse rate within two minutes of administering 1.0 mg of atropine sulfate endotracheally in a patient with bradycardiac cardiovascular collapse. Following our report of successful reversal of morphine-induced respiratory depression in rabbits by the use of endotracheally administered naloxone,2colleagues at the University of New

Physostigmine Antagonizes Morphine-Induced Respiratory Depression but Not Analgesia in Dogs and Rabbits

WEINSTOCK, M.; ROLL, D.; EREZ, E.; BAHAR, M.; Brown, Burnell R. Jr. M.D., Ph.D. Author Information

Maternal and Fetal Concentrations of Morphine After Epidural Administration During Labor

In this study of 20 healthy women in labor we attempted to determine the efficacy of epidural morphine as an obstetric analgesic. Four patients experienced some relief of pain while 16 patients reported no effect on pain. One newborn infant demonstrated possible morphine-induced respiratory depression. It was concluded that morphine is ineffective as an obstetric analgesic.

Use of a novel method for investigating muscle relaxant drugs: The effects of clobazam and 1,4-benzodiazepines on morphine-induced rigidity

The aim of the study was to investigate antagonism of the rigidity produced by morphine in rats as a potential method for examining the muscle relaxant properties of benzodiazepines. The force required to displace the hind limbs by 1 cm was measured with an apparatus that was developed for measuring drug-induced changes in the limb muscle tone of conscious, lightly restrained rats. Neither diazepam nor clobazam alone, in doses up to 3 mg/kg Intraperitoneal (IP), had any effects on limb muscle tone. Morphine (7.5 mg/kg) caused a rapid-onset, sustained rigidity, which was partly reversed by diazepam at doses (0.2–0.5 mg/kg) that did not greatly potentiate morphine-induced respiratory depression. In contrast, clobazam (0.2–0.5 mg/kg) had no effect on morphine rigidity. Several other 1,4-benzodiazepines were tested in low doses. Both temazepam and lorazepam partly reversed morphine-induced rigidity, whereas chlordiazepoxide, flurazepam, and clonazepam had no effect. It is concluded that antagonism of morphine rigidity might provide a sensitive method for comparing muscle relaxant properties of benzodiazepines.

USE OF 4-AMINOPYRIDINE TO REVERSE MORPHINE-INDUCED RESPIRATORY DEPRESSION IN MAN

4-Aminopyridine administered to patients antagonized respiratory depression by morphine 033mg kg–1. It is suggested that 4-AP may be useful in the treatment of morphine-induced respiratory depression.

Potentiation of the morphine-induced respiratory rate depression by captopril

The effects of morphine and captopril, an angiotensin-converting enzyme inhibitor, on respiratory frequency have been investigated in non-anesthetized mice. Morphine (10.0 mg/kg) reduced the respiratory frequency which gradually returned to the control level 2 h after the injection. The same dose of morphine when given together with captopril (0.1 and 1.0 mg/kg), caused a similar reduction in respiratory rate. This respiratory depression however, persisted until the end of the observation period. Similar results were obtained with the same dose of morphine in mice pretreated with captopril. The minimal dose of morphine reducing respiratory frequency (3.0 mg/kg), when given to the mice pretreated with captopril (0.1 mg/kg) caused a significant reduction in respiratory frequency and this effect was equal to that obtained with 10.0 mg/kg morphine alone. The results are discussed from the point of the possible inhibitory effect of captopril on the enkephalin degrading enzyme(s).

Antagonists of morphine-induced respiratory depression

Antagonists of morphine-induced respiratory depression

Role of monoaminergic systems in morphine-induced respiratory depression

The respiratory response to morphine sulfate was assessed in rats pretreated with different modifiers of noradrenergic and serotonergic activity and, additionally, the respiratory depression was related to the brain levels of the two amines, serotonin (5-HT) and norepinephrine (NE). At respiratory depressant doses, morphine induced an increase in 5-HT and a decrease in NE levels in the medullapons area. The time sequence of respiratory depression correlated with a decline in NE and a rise in 5-HT levels. Pretreatments which increased 5-HT levels potentiated the respiratory depression and agents which increased NE levels antagonized the depression. A system of antagonistic modulation by the two amines of morphine-induced respiratory depression is proposed, whereby 5-HT functions as a depressant mediator and NE as an excitatory mediator. Naloxone appears to reverse the respiratory depression by altering the serotonergic component of the action of morphine.

Maternal and fetal concentrations of morphine after epidural administration during labor

In this study of 20 healthy women in labor we attempted to determine the efficacy of epidural morphine as an obstetric analgesic. Four patients experienced some relief of pain while 16 patients reported no effect on pain. One newborn infant demonstrated possible morphine-induced respiratory depression. It was concluded that morphine is ineffective as an obstetric analgesic.

Morphine-Induced Respiratory Depression following Bilateral Carotid Endarterectomy

Morphine-Induced Respiratory Depression following Bilateral Carotid Endarterectomy

PHYSOSTIGMINE ANTAGONIZES MORPHINE-INDUCED RESPIRATORY DEPRESSION BUT NOT ANALGESIA IN DOGS AND RABBITS

The ability of physostigmine to antagonize the respiratory depressant effect of morphine was studied in conscious rabbits and ketamine-anaesthetized dogs pretreated with atropine methyl nitrate. Morphine 4 mg kg-1 increased PaCO2 in the rabbit from 3.43 +/- 0.16 to 4.95 +/- 0.28 kPa, decreased arterial pH from 7.45 +/- 0.01 to 7.31 +/- 0.01 and decreased respiratory frequency by 36%. Physostigmine 0.1 mg kg-1 reduced PaCO2 to control values within 10 min and significantly increased arterial pH and respiratory frequency. There was no antagonism of the analgesic effect of morphine. Neostigmine 0.1 mg kg-1 did not reverse the respiratory depressant effect of morphine. In dogs anaesthetized with ketamine, morphine 15 mg kg-1 caused loss of consciousness and marked analgesia, decreased the respiratory frequency by 47%, and increased PaCO2 by 47%. Physostigmine 0.1 mg kg-1 antagonized the effect of morphine on respiration and restored consciousness in the dogs, but did not impair analgesia. It is concluded that physostigmine reverses morphine-induced respiratory depression by prolonging the effect of acetylcholine released from brain-stem neurones. The possibility should be considered of replacing opiate antagonists by physostigmine to reverse postoperative respiratory depression and drowsiness induced by opiates.

Endotracheal naloxone reversal of morphine-induced respiratory depression in rabbits

In an emergency, intravenous access may be difficult to obtain rapidly. Alternate routes of administration for drugs are, therefore, desirable. Our study was performed to determine if naloxone could be efficacious in reversing morphine-induced respiratory depression in rabbits when administered using the endotracheal route. Our results indicate that naloxone administered in this fashion is effective in reversing morphine-induced respiratory depression in the rabbit. Mean minute ventilation was depressed to greater than half of resting baseline levels using morphine sulfate. Endotracheally administered naloxone reversed this respiratory depression and resulted in a greater than five-fold increase in mean minute ventilation above baseline levels. We concluded that endotracheal naloxone is efficacious in reversing morphine-induced respiratory depression in the rabbit. The endotracheal route may be an effective alternative for naloxone administration in man when rapid intravenous access is not obtainable.

The effect of dopaminergic modifiers on morphine-induced analgesia and respiratory depression

The influences of the dopaminergic system on morphine-induced analgesia and respiratory depression were compared using modulators of dopaminergic activity. Blockade of dopaminergic receptors by haloperidol or pimozide produced a potentiation of morphine analgesia, while stimulation of dopaminergic activity by L-dopa methyl ester inhibited morphine analgesia. Morphine-induced depression of respiratory rate was potentiated by haloperidol and inhibited by pimozide or L-dopa methyl ester. These results suggest that the dopaminergic system plays a modulating role in morphine-induced analgesia, but not morphine-induced respiratory depression.

Naloxone for Antagonism of Morphine-Induced Respiratory Depression

LONGNECKER, DAVID E. M.D.; GRAZIS, PETER A. M.D.; EGGERS, G. W. N. JR. M.D. Author Information

Naloxone for Antagonism of Morphine-Induced Respiratory Depression

Naloxone for Antagonism of Morphine-Induced Respiratory Depression

Adrenergic and serotonergic mechanisms in morphine-induced respiratory depression.

The influence of drugs which modify brain amine concentration was studied on morphine-induced respiratory depression in decerebrate cats. Resting and CO2-stimulated respiration were evaluated. The respiratory depression was partially antagonized by pretreatment with reserpine and p-chlorophenylalanine; enhanced by two monoamine oxidase inhibitors, pargyline and tranylcypromine, and, to some extent, by α-methyl-tyrosine. It was not changed by intracerebral 6-hydroxydopamine. The results show that, as with the other central actions of morphine, the presence of 5-HT is necessary for morphine activity to be complete. The change in the level of brain amines also modified the respiratory activity in a way that suggests that the respiratory center is stimulated by adrenergic and damped by serotonergic tone.

Comparative Studies on the Antagonism of Naloxone and Nalorphine to the Morphine-Induced Respiratory Depression in Rabbits

Comparative Studies on the Antagonism of Naloxone and Nalorphine to the Morphine-Induced Respiratory Depression in Rabbits

Nikethamide and doxapram effects on pentazocine- and morphine-induced respiratory depression.

Journal Article Nikethamide and doxapram effects on pentazocine- and morphine-induced respiratory depression Get access Bernard V Franko, Bernard V Franko A. H. Robins Research Laboratories, 1211 Sherwood Avenue, Richmond, Virginia, USA, 23220 Search for other works by this author on: Oxford Academic Google Scholar John W Ward John W Ward A. H. Robins Research Laboratories, 1211 Sherwood Avenue, Richmond, Virginia, USA, 23220 Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 23, Issue 9, September 1971, Pages 709–710, https://doi.org/10.1111/j.2042-7158.1971.tb08750.x Published: 12 April 2011