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At least 19 recordsLinked to original sources
PubMed1991

Vecuronium infusion requirements in children during halothane-narcotic-nitrous oxide, isoflurane-narcotic-nitrous oxide, and narcotic-nitrous oxide anesthesia.

We were interested in determining the infusion rate of vecuronium required to maintain approximately 95% neuromuscular blockade in children during halothane-narcotic-nitrous oxide (0.8% end-tidal concentration), isoflurane-narcotic-nitrous oxide (1.0% end-tidal concentration), or narcotic-nitrous oxide anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Effective vecuronium infusion requirements averaged 1.5 +/- 0.1 micrograms.kg-1.min-1 (mean +/- SEM) during isoflurane-narcotic-nitrous oxide anesthesia, 1.9 +/- 0.1 micrograms.kg-1.min-1 during halothane-narcotic-nitrous oxide anesthesia, and 2.4 +/- 0.3 micrograms.kg-1.min-1 during narcotic-nitrous oxide anesthesia. Infusion requirements significantly decreased after the first 30 min of infusion in the presence of both potent inhalation anesthetics, but did not change with time during narcotic-nitrous oxide anesthesia. There was no evidence of decreasing infusion requirements during prolonged vecuronium infusion (2.5 h). There was no difference in the rate of spontaneous or pharmacologically induced recovery between anesthetic groups. The mean recovery index (T25-75) after termination of the infusion was 13.7 min.

Anesthesia, General↗
PubMed1975

Narcotic antagonists: a reasonable method of treating narcotic dependency.

Historically, narcotic dependence has been treated primarily by substituting one narcotic drug for another. One alternative chemical treatment for narcotic dependency is through the use of a narcotic antagonist. The present study involves the observed side effects and outcome results of treating 40 male heroin addicts with the narcotic antagonist, cyclazocine, in the context of a comprehensive psychotherapeutic program. It is concluded that the side effects of cyclazocine are minimal, that cyclazocine is not diverted to the streets, and that it is an effective tool in the context of a comprehensive treatment program for narcotic-dependent individuals.

Aftercare↗
PubMed1992

Availability of narcotics and pharmacists' attitudes toward narcotic prescriptions for cancer patients.

OBJECTIVE: To determine narcotic availability and pharmacist apprehension toward dispensing narcotics for cancer patients. DESIGN: Mailing of a one-page survey. SETTING: All pharmacies in the state of New Mexico. PARTICIPANTS: Of the 309 pharmacies, 76.1 percent (235) completed the survey. MEASUREMENTS AND MAIN RESULTS: Apprehension was significantly elevated for methadone, hydromorphone, and for morphine doses greater than 500 mg/d (p less than 0.001). The most common reasons listed for apprehension were forgery (46.4 percent), theft (40.4 percent), high dosages (23.8 percent), narcotic investigations (18.7 percent), and patient addiction (9.4 percent). Hydromorphone was available (in stock) in 80.5 percent of the pharmacies, followed by morphine 30-mg sustained-release tablets (64.5 percent) and methadone (53.4 percent). The vast majority of pharmacists were willing to order strong narcotics for specific patients. Pharmacists working in chain stores expressed a higher level of apprehension toward dispensing methadone and more frequently cited forgery as a reason for apprehension. Distance from a metropolitan area and practice setting best predicted apprehension to forgery (p = 0.01). CONCLUSIONS: Pharmacists do not appear to be a major obstruction to adequate analgesia for cancer patients in New Mexico but may require further education regarding lack of narcotic addiction and dosing in patients with cancer.

Attitude of Health Personnel↗
PubMed1975

Narcotic and narcotic antagonist pKa's and partition coefficients and their significance in clinical practice.

The pKa's, partition coefficients and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and where possible for their congener narcotic antagonist. These studies were carried out by a novel microelectrometric titration technique as a function of temperature and pH. This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities and oil-water distribution of these various drugs. The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values. This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations among which are cited hyperventilation under a general anesthetic while concomitantly under a narcotic analgesic, obstetetrical analgesia, and medical and anti-abuse usage of narcotic antagonists. The partition coefficients and drug distribution coefficients were noticeably different at 20degreesC (where such measurements are customarily made) from those at 37degreesC (body temperature). Furthermore, various drugs exhibit very non-equivalent increases in drug distribution coefficients with increasing temperature, ranging from 21% for naltrexone. This non-regularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures. Even the true partition coefficients increase with temperature from 20degrees to 37degreesC.

Chemical Phenomena↗
PubMedDate not supplied

Theoretic significance of pH dependence of narcotics and narcotic antagonists in clinical anesthesia.

Determination of the effect of pH and temperature on pKa partition, and drug distribution coefficients in a series of common narcotics and their antagonists has shown that within the range of blood pH (7.1 to 7.7) encountered in the practice of anesthesiology, marked differences of distribution of the drugs between a model lipid (octanol) and water can occur. When these data are considered in the light of clinical experience with narcotics used in patients undergoing or recovering from surgical procedures, a correlation between the depth and duration of narcosis or the efficacy of narcotic antidotes and ventilatory status is seen. This correlation can be explained in part if the influence of blood pH on the probable CNS/blood distribution of a given drug is taken into consideration. Support is given to this proposal by representative studies in the literature. The very different drug distribution coefficients of two closely related narcotic antagonists, naloxone and naltrexone, correctly predicted the faster onset and shorter duration of the former, which was confirmed by reported clinical observations.

Anesthesia↗
PubMed1976

A test for antinociceptive activity of narcotic and narcotic antagonist analgesics in the guinea pig.

Ethylenediamine tetraacetic acid (EDTA) was used as a nociceptive stimulus intradermally in the guinea pig. The responses evoked by EDTA included vocalization, biting and scratching at the site of injection and escape behavior. Nociception by EDTA was shown to be the result of its cation chelating activity. The suppression of EDTA-induced responses proved to be a rapid and effective antinociceptive test. The narcotic analgesics morphine, codeine, meperidine and methadone and the narcotic antagonist analgesics cyclazocine, cyclorphan, nalorphine and pentazocine were active. The slopes of the dose-response curves of the narcotic antagonist analgesics were significantly shallower than those of the narcotic analgesics. The test was highly specific for these analgesics. Antipyretic analgesics and various nonanalgesic drugs were inactive.

Analgesics↗
PubMed1978

Narcotic cuing and analgesic activity of narcotic analgesics: associative and dissociative characteristics.

By using a discrete-trial, two-lever, food-reinforced discrimination learning paradigm, rats were trained to discriminate the narcotic analgesic fentanyl (0.05 mg/kg) from saline. Stimulus generalization experiments with lower fentanyl doses (0.0025 to 0.02 mg/kg) were carried out to generate individual threshold doses. The latter were compared with the sensitivity of the same rats to the analgesic effect of fentanyl, and it was found that there is no correlation between these two sets of data. In a time-effect experiment, the duration of fentanyl's cuing effect was compared with that of its analgesic effect, and it was found that the time-effect characteristics of the narcotic cue are similar to those of analgesia. Again, however, there was no correlation between the duration of both effects within the same group of animals. The results further deliniate the associative and dissociative characteristics of the narcotic cue and narcotic analgesia.

Analgesics↗
PubMed1976

On the ability of narcotic antagonists to produce the narcotic cue.

The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability.

Analgesics, Opioid↗
PubMed1977

Toxic interactions of stimulants, narcotics and narcotic antagonists.

This study examines the lethality of combinations of central nervous system stimulants, narcotics and narcotic antagonists in rodents housed individually. The lethality of mice and rats from d-amphetamine was potentiated by methadone, cyclazocine and morphine, in that order of potency. Naloxone did not enhance lethality from d-amphetamine in mice, whereas it did antagonize lethality from morphine-d-amphetamine interactions. Naloxone did slightly enhance lethality from d-amphetamine in rats, but at a higher dose than those found to antagonize the lethality from morphine-d-amphetamine combinations. Methadone also enhanced the lethality from cocaine. These results have important implications for drug abusers and for patients being treated for narcotic addiction with either a methadone maintenance program or a cyclazocine administration program.

Animals↗
PubMed1975

The narcotic cue: evidence for the specificity of the stimulus properties of narcotic drugs.

Various non-narcotic drugs with intrinsic stimulus properties were found not to be generalized with fentanyl treatment in rats trained to discriminate fentanyl (0.04 mg/kg, s.c., t-30') from its solvent (s.c., t-30'). In contrast, five typical narcotic analgesics yielded dose-dependent generalization with fentanyl treatment. The results evidence the specific character of the narcotic cue in rats.

Animals↗
PubMedDate not supplied

[The effect of narcotic analgetic fenaridine and narcotic antagonist FI on the level of cyclic nucleotides in the brain of albino rats].

Content of cAMP and cGMP was estimated in rat brain corpus striatum after treatment with narcotic analgetic fenaridin and antagonist of narcotic analgetics F1 which are similar chemically. Various concentrations of fenaridin increased the cAMP content, whereas that of cGMP was not altered. At the same time, administration of the antagonist of narcotic analgetics F1 led to an increase in content of cGMP and to a distinct elevation of cAMP content.

4-Aminopyridine↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The I.V. administration in dogs of high and massive doses of narcotics produced an acute rise in CO2 consumption, a rise of plasma catecholamines and other slight biochemical and metabolic perturbances. A general trend towards metabolic acidosis and hypermetabolism was noticed but important differences appeared according the drugs and doses chosen. The safety margin for metabolic toxicity (ratio between IV doses producing severe metabolic side-effects and doses necessary for deep surgical analgesia) were calculated for each narcotic and found as follows: 1 for pethidine, 3.3 for piritramide, 13 for morphine and phenoperidine, 12.5 for R 39 209, 60 for fentanyl, 800 for sufentanil and 4 000 for R 34 995. Drug associations may decrease or increase the metabolic safety margin of the narcotics. Beneficial associations with morphinomimetics are found with droperidol, etomidate and flunitrazepam.

Acidosis↗
PubMed1979

Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, piritramide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. II. Comparative study on the epileptoid activity of the narcotics used in high and massive doses in curarised and mechanically ventilated dogs.

The experimental design, described in part I, was again used here. The electrocortical activity was registered with an EEG amplifier using a bipolar derivation of needle electrodes fixed in the scalp of a dog in the fronto-occipital position. In this situation the convlusion threshold for the 8 substances is as follows: pethidine 20 mg.kg-1 I.V., piritramide 30, morphine 180, phenoperidine 4, R 39 209 5, fentanyl 4, sufentanil 4 and R 34 995 10 mg.kg-1 I.V. Comparing the I.V. doses producing severe convulsions with the doses necessary for deep surgical analgesia a safety margin of neurological toxicity was calculated. This was for pethidine 2.2, for piritramide 6.6, for phenoperidine 16, for R 39 209 62.5, for morphine 72, for fentanyl 160, for sufentanil 1 000 and for R 34 995 10 000. It is concluded that for pure narcotics there exists an inverse relationship between analgesic potency and neurological toxicity which is always accompanied by a hyperactivity of the automatic nervous system. Factors modifying the convulsive level of the narcotics are still under investigation. In the meanwhile it can be stated that the association of a strong narcotic with flunitrazepam, droperidol or etomidate will increase the convulsion threshold of the morphinomimetics.

Acidosis↗
PubMed1976

Discriminative stimulus properties of analgesic drugs: narcotic versus non-narcotic analgesics.

Using a food-reinforced two-lever operant procedure, rats (n=6) were trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o., t-60'). The administration of another narcotic analgesic (pethidine) produced a dose-related generalization with the standard fentanyl treatment; six non-narcotic analygesics (suprofen, acetylsalicylic acid, indomethacin, phenacetin, phenylbutazone, tolmetin) were found not to do so. It is concluded that the ability of drugs to produce analgesia is not a sufficient condition for the drugs to produce the narcotic cue as well.

Analgesics↗
PubMed1975

Microelectrometric titration measurement of the pKa's and partition and drug distribution coefficients of narcotics and narcotic antagonists and their pH and temperature dependence.

The pKa's, partition coefficients, and drug distribution coefficients (apparent partition coefficients) have been investigated for a number of narcotics and, where possible, for their congener narcotic antagonists. These studies were carried out by a microelectrometric titration technique as a function of temperature and pH. This method enables one to determine not only the dissociation constants to deconvolute overlapping pKa's, but also to determine the solubilities of oil-water distribution of these various drugs. The drug distribution coefficients displayed marked sensitivity to pH at values which span the range of attainable human physiological pH values. This has significant pharmacological implications for proper choice and scaling of drug dosages under various clinical situations. The partition coefficients and drug distribution coefficients were noticeably different at 20 degrees (where such measurements are customarily made) than at 37 degrees (body temperature). Furthermore, various drugs exhibit very nonequivalent increases in drug distribution coefficients with increasing temperature, ranginf from 21% for morephine to 200% for naltrexone. This nonregularity indicates that it will not be valid to extrapolate by any constant factor the measurements made at lower temperatures. Even the true partition coefficients increase with temperature from 20 degrees to 37 degrees. There is more of a difference in the drug distribution coefficients for naloxone and naltrexone than might have been expected from the similarities in their structures with naltrexone being significantly less lipophilic than naloxone. This would imply that this would lead to naloxone having a more rapid onset for antagonist activity and likewise a shorter duration of action than naltrexone.

Electrochemistry↗
PubMed1975

Bacteriological studies with morphine-like narcotics: relevance to narcotic actions in mammals?

A search for active bacterial growth inhibitors among seven highly potent morphine-like narcotics revealed that NIH 7591 and etorphine inhibited the rates of growth of Escherichia coli by 50% at 1.9 x 10(-4) M. Bacterial cultures escaped from growth inhibition by NIH 7591 after times which were proportional to the drug concentrations and inversely proportional to the initial bacterial densities. Populations of E. coli could adapt to resist and cross-resist growth inhibitions by NIH 7591 and phenazocine. Resistance was lost after growth in drug-free medium for a few doubling times. The agonist-antagonist pair, etorphine and diprenorphine, inhibited growth of E. coli additively without any indication of antagonism. Actions of narcotics in bacteria is considered a theme in its own right.

Drug Synergism↗
PubMed1975

On the narcotic cuing action of fentanyl and other narcotic analgesic drugs.

Using a food-reinforced two-levers operant procedure, rats could be trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o.,t60)treatment. The administration of the other narcotic analgesics bezitramide, dextromoramide, methadone and morphine produced a dose-related stimulus generalization with the standard fentanyl treatment. The results further evidence the validity of the narcotic cue.

Analgesics, Opioid↗
PubMedDate not supplied

Central action of narcotic analgesics. I. Catalepsy and stereotypy in rats and narcotic analgesics.

The action of four analgesics, belonging to various pharmacological groups (morphine, codeine, fentanyl, pentazocine), was investigated in rats in tests for catalepsy and stereotypy, the tests depending on dopaminergic brain mechanisms. Interactions of the analgesics with a number of compounds known to affect dopaminergic brain functions in tests of catalepsy and stereotypy were also studied. In some experiments nalorphine, an antagonist of narcotic analgesics, was used. Morphine, codeine and fentanyl produced catalepsy, while pentazocine, at doses up to 60 microgram/kg, did not produce this effect. Reserpine, 2 mg/kg 3 hr before drugs, potentiated catalepsy produced by analgesics, while haloperidol, 0.2 mg/kg, 2 hr earlier, did not influence morphine and codeine catalepsy, but moderately potentiated fentanyl-induced catalepsy. alpha-methyl-p-tyrosine potentiated the cataleptogenic action of fentanyl and codeine, and also, less markedly, the action morphine. D-amphetamine (2.5-10 mg/kg) and apomorphine (5 mg/kg) moderately antagonized the catalepsy induced by analgesics, while atropine did not affect it. Nalorphine, 5 mg/kg, effectively abolished the catalepsy produced by narcotic analgesics, but did not affect that produced by neuroleptics. Morphine, codeine and fentanyl slightly inhibited apomorphine stereotypy, and evidently antagonized stereotypy produced by amphetamine. Pentazocine did not affect or slightly potentiated the both types of stereotypy. It is concluded that morphine, codeine and fentanyl, in contrast to pentazocine, inhibit behavioral activities depending on central dopaminergic functions in the rat. The mechanism of this action is most probably indirect, and seems to be related to the dopaminergic presynaptic functions.

Animals↗