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PubMedDate not supplied

Central action of narcotic analgesics. V. Participation of serotonin in the mechanism of action of narcotic analgesics.

The influence of serotonergic system on the changes in locomotor activity of mice and rats brought about by morphine, fentanyl, codeine and pentazocine and on morphine induced catalepsy in rats was studied. p-Chlorophenylalanine (pCPA) did not affect the behavioral changes produced in mice by morphine, fentanyl, codeine and pentazocine but reduced the behavioral depression produced by these drugs in rats. 5-Hydroxytryptophan (5-HTP) but not tryptophan (TP) reversed the action of pCPA on the effect of morphine and fentanyl. After reserpine the depression produced in rats by morphine and fentanyl was more pronounced. TP did not change the depression produced by combination of reserpine and morphine but counteracted the depression observed after combination of reserpine and fentanyl. In mice reserpine protected against hypermotility produced by morphine or fentanyl and TP potentiated the depression produced by the combination of reserpine and morphine or reserpine and fentanyl. Serotonin precursors, 5-HTP and TP evidently potentiated the morphine induced catalepsy. pCPA counteracted only the enhancement of the catalepsy observed after TP administration. Naloxone abolished the catalepsy after combined treatment with morphine and TP. Similarly but weaker acted cyproheptadine. The results suggest that the serotonin system plays a role in the effects of morphine and fentanyl on rat locomotor activity. An increase in the cerebral serotonin level increases the morphine catalepsy in rats.

Analgesics, Opioid↗
PubMed1994

Appropriate and inappropriate prescribing of narcotics for ambulatory HIV-positive patients.

OBJECTIVE: To assess the appropriateness of narcotic-prescribing practices in an ambulatory clinic for patients infected with HIV. DESIGN, SETTING, AND PATIENTS: The medical records of 220 (190 HIV-positive) patients, seen in a clinic primarily designed for the long-term follow-up of ambulatory HIV-infected patients and located in an inner-city, public teaching hospital, were retrospectively reviewed to determine the prevalence and appropriateness of prescribing Drug Enforcement Administration schedule 2 narcotics. Appropriateness was based on published guidelines for the use of narcotics in the treatment of cancer patients. MEASUREMENTS AND MAIN RESULTS: The prevalence of narcotic use among the HIV-positive patients was 15%. Narcotics were prescribed for 38% of the patients who died, 33% of those with AIDS [Centers for Disease Control and Prevention (CDC) clinical class C], 4% of those with AIDS-related complex (ARC) (CDC clinical class B), and 5% of asymptomatic HIV-positive patients (CDC clinical class A). None of the HIV-negative patients seen in the clinic received narcotics. Narcotics were more likely to be prescribed for patients with AIDS than for patients with ARC (p < 0.001) or for HIV-positive patients (p < 0.001). For the three CDC clinical classes, there was no significant difference among the proportions of patients receiving narcotics inappropriately (p = 0.108). Among the risk groups, intravenous drug abusers were more likely to be prescribed narcotics inappropriately than were men who were homosexual (p < 0.001) or individuals who were heterosexual (p = 0.013); transfusion recipients were also more likely to be prescribed narcotics inappropriately than were homosexual men (p = 0.026) or heterosexual men or women (p = 0.032). Narcotics were more likely to be prescribed for patients with disseminated histoplasmosis (p = 0.022), Pneumocystis carinii pneumonia (p = 0.001), candidal esophagitis (p = 0.020), Kaposi's sarcoma (p < 0.001), or wasted appearance (p = 0.043). Inappropriate prescriptions were more likely to be given to patients with dementia (p = 0.005) or wasted appearance (p = 0.019). CONCLUSIONS: Physicians tend to prescribe narcotics inappropriately to patients known to have previously abused drugs and to those who appear wasted or have dementia. Physicians have a duty to prescribe narcotics appropriately as guided by recognized medical indications and the patients' views concerning their current medical needs.

AIDS-Related Complex↗
PubMed1998

[Legal determinations concerning narcotics which are important for the veterinarian].

In January 1998 the German legislation of narcotic drugs was subject of important changes also concerning the use of narcotic drugs in veterinary practice. The annexes I-III of the law of narcotic drugs (BtMG) containing all substances classified as narcotics were reorganized. Furthermore, the directive on the prescription of narcotic drugs (BtMVV) was changed with the aim to facilitate the prescription as well as the supply of narcotic drugs by veterinarians in their home dispensary. The directive on inland trade of narcotics (BtMBinHV) regulating the distribution of narcotic drugs from wholesalers to veterinarians remained unchanged. The following regulations of prescription or distribution of narcotic drugs by veterinarians for treated animals are described in detail: notification of participation on supply of narcotic drugs, general principles of the use of narcotic drugs, safety measurements, inactivation of narcotics, prescription for patients or for use in veterinary practice/clinics, details of prescription, supply to animal owners by the veterinarian home-dispensary, book-keeping, purchase of narcotic drugs.

Animals↗
PubMedDate not supplied

Trends in reported illegal narcotic use in Canada: 1956-1973.

Information on reported narcotic users aids in the development of drug control policy as well as programmes of prevention, treatment, and rehabilitation. In Canada, such information may be obtained from a narcotic users index which classifies known narcotic drug users into three categories: "illicit", "licit", and "professional". This paper presents trend data on known narcotic users in Canada from 1956 to 1973 by category, location, initially reported drug, sex and age. Between 1956 and 1973, the number of known "licit" and "professional" narcotic drug users steadily decreased, while the number of "illicit" narcotic drug users increased by 283 per cent, with the greatest increase taking place after 1969. Heroin was the most frequent initially reported drug (representing between 80 per cent and 89 per cent of known "illicit" narcotic drug users). Cocaine, as an initially reported "narcotic", had the largest proportional increase from 1956 to 1973. There were generally more reported male users than female in all age groups, a trend that increased over the time span considered. There were recent dramatic increases in the numbers and rates of reported users in the 20-24 year-old group, which has become the dominant pattern among new cases in recent years. Although the index on which this paper is based does not provide figures on total narcotic use in Canada, it is a valuable resource for epidemiologic research. This narcotic user index may be used to make minimum estimates of the extent and geographic and social distribution of narcotic-related problems in Canada.

Adolescent↗
PubMed1971

Effects of narcotic analgesics and antagonists on the in vivo release of acetylcholine from the cerebral cortex of the cat.

1. In cats under light allobarbitone anaesthesia, the effects of intravenous injections of narcotic and non-narcotic analgesics, of a general depressant, and of narcotic antagonists were investigated on the spontaneous release of acetylcholine (ACh) from the surface of the sensorimotor cortex.2. The narcotic analgesics morphine (0.1, 1.0 and 5 mg/kg), meperidine (1.0 and 2.0 mg/kg), methadone (1.0 mg/kg) and codeine (5.0 and 10.0 mg/kg) greatly reduced ACh release.3. The non-narcotic analgesics pentazocine (1.0 and 2.0 mg/kg) and propoxyphene (5.0 and 10.0 mg/kg) as well as the depressant chlorpromazine (0.25, 0.5 and 1.0 mg/kg) also greatly reduced ACh release.4. Two of the three narcotic antagonists examined, levallorphan (0.1, 1.0 and 5 mg/kg) and nalorphine (1.0 mg/kg) had the property of reducing ACh release. They were thus partial agonists. With levallorphan the greatest reduction occurred with the smallest dose injected and the effect was regularly obtained, whereas with nalorphine a reduction was obtained in some experiments only. The third, naloxone, was a specific narcotic antagonist and did not reduce the ACh release in any dose (0.01, 0.1, 0.5 and 1.0 mg/kg) examined. In a dose of 1.0 mg/kg it actually produced a small increase in Ach release.5. Naloxone (0.1-1.0 mg/kg) restored the reduction in ACh release produced by the narcotic analgesics and by the partial agonist levallorphan. It partially restored the reduction produced by the non-narcotic analgesics and by nalorphine, but had no effect on the reduction produced by chlorpromazine.6. The relevance of these results with regard to analgesia and to the narcotic abstinence syndrome is discussed.

Acetylcholine↗
PubMed1994

Difficulties in diagnosing narcotic overdoses in hospitalized patients.

OBJECTIVE: To describe the clinical presentation of narcotic overdose in hospitalized patients and to differentiate this circumstance from other conditions often misdiagnosed as overdose. DESIGN: Case series. SETTING: Two acute-care teaching hospitals. PATIENTS: Forty-three hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Two investigators independently evaluated each incident to determine whether the patient had a narcotic overdose. The patients were judged to have had an overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MEASUREMENTS: The clinical presentation of a narcotic overdose in hospitalized patients was defined. Conditions misdiagnosed as an overdose were determined. MAIN RESULTS: Symptoms improved rapidly with the administration of naloxone in 28 incidents (65 percent) and were designated overdose. In 15 other instances there was no improvement in symptoms; these patients were designated nonoverdose. Only half of the overdose patients had a respiratory rate < 8 breaths/min immediately prior to naloxone administration. Only two of the overdose patients had the classic triad of symptoms (respiratory depression, coma, and pinpoint pupils). Other overdose patients had only one or two of the classic signs. The clinical presentation of narcotic overdoses in hospitalized patients did not include respiratory depression, hypotension, or coma in the majority of patients. All overdose patients showed a decrease in mental status. The majority of nonoverdose patients had pulmonary conditions that were misdiagnosed as a narcotic overdose. CONCLUSIONS: Narcotic overdoses in hospitalized patients seldom fit the classic description. The lack of respiratory depression does not mean the absence of a narcotic overdose. Patients who receive narcotics and develop a significant decrease in mental status should be evaluated for a possible overdose. Pulmonary, neurologic, cardiovascular, and electrolyte abnormalities often are misdiagnosed as a narcotic overdose in hospitalized patients.

Adolescent↗
PubMed1987

Narcotic pharmacokinetics and dynamics: the basis of infusion applications.

Morphine, pethidine and fentanyl have similar pharmacokinetic profiles with moderately long elimination half-lives (3 to 4 hours), large steady-state volumes of distribution (2 to 4 l/kg), and high hepatic clearances (10 to 20 ml/kg/min). Alfentanil has a shorter terminal elimination half-life (1 1/2 hours) because of a decreased steady-state volume of distribution (0.5 to 1 l/kg). Physicochemical properties and blood:brain tissue solubility can explain the clinical differences in the rate of onset and dissipation of narcotic effect for these four narcotics. Morphine's low lipid solubility and limited rate of blood:brain barrier penetration results in the slow onset and dissipation of narcotic effect relative to pethidine or fentanyl. Alfentanil's lower blood:brain solubility results in the very rapid onset of narcotic effect when compared to fentanyl. All of the narcotics have a very steep blood concentration:narcotic effect curves. Thus, small changes of narcotic blood concentrations can have profound changes of narcotic effect. Finally, different degrees of perioperative stimuli result in different narcotic blood concentration requirements. Thus, narcotic infusion rates need be varied during surgical procedures to adjust for the varying opiate requirement.

Analgesics, Opioid↗
PubMed1999

Postoperative pain after lumbar disc surgery: a comparison between parenteral ketorolac and narcotics.

OBJECTIVE: Lumbar discectomy is a common elective surgical procedure but many patients still experience postoperative back pain which may delay hospital discharge. We therefore evaluated the efficacy of a parenteral non-steroidal antiinflammatory agent, ketorolac, for the management of post-surgical pain. METHODS: Fifty three patients undergoing lumbar discectomy at a Medical School affiliated Veterans Administration hospital were randomly assigned to receive either: 1) 30 mg intramuscular ketorolac upon surgical closure and every 6 hours for 36 hours and narcotic analgesics as needed (PRN); or 2) only narcotic analgesics as needed. A blinded observer recorded the average, minimum and maximum postoperative pain intensity using a Numeric Pain Intensity Scale; total postoperative narcotic consumption, complications, length of hospitalization (from surgery to discharge) and outcome at 6 weeks. RESULTS: The patients who received ketorolac reported significantly lower average (p < 0.001), minimum (p < 0.001), and maximum (p < 0.001) pain scores than patients receiving only narcotic analgesics. Cumulative narcotic doses (standardized to parenteral morphine) were significantly lower in the ketorolac group (p < 0.001). There was no significant difference between groups in the frequency of side effects, and no complication specifically associated with ketorolac use was observed. Mean length of hospitalization was significantly shorter (p = 0.05) in patients receiving ketorolac than in patients receiving only narcotics. Six weeks after surgery 5 (19.2%) patients who received only narcotics were troubled by persistent back pain. By contrast, all patients who received ketorolac were free of back pain at follow-up (p = 0.03). CONCLUSIONS: These results suggest that ketorolac, when used with PRN narcotics, is more effective than PRN narcotics alone for postoperative pain following lumbar disc surgery. In addition, this strategy also may contribute to early discharge from hospital after lumbar disc surgery.

Adult↗
PubMed1989

The cognitive effects of the administration of narcotic analgesics in patients with cancer pain.

Forty patients with cancer pain receiving intermittent narcotics were admitted to a prospective study designed to assess the cognitive effects of narcotics. Twenty patients had undergone no change in narcotic dose or type greater than or equal to 7 days (stable dose, SD, group), and 20 patients had undergone an increase of greater than or equal to 30% in dose less than or equal to 3 days before (increased dose, ID, group). Age, primary tumor, type, dose and route of narcotic were not different between the SD and ID group. Cognitive tests (finger tapping, FT, 10 and 30 sec, arithmetic, A, reverse memory of digits, RM, and visual memory, VM) were performed in all patients before and 45 min after their morning dose of narcotics for 2 consecutive days. Mean percentual change in FT 10 sec, FT 30 sec, A, RM, and VM after the narcotic dose were 97 +/- 9%, 100 +/- 14%, 100 +/- 13%, 100 +/- 15%, 98 +/- 19%, in the SD group, vs. 77 +/- 14% (P less than 0.001), 83 +/- 13% (P less than 0.001), 124 +/- 21% (P less than 0.001), 60 +/- 21% (P less than 0.001) and 68 +/- 21% (P less than 0.001) in the ID group, respectively. Our results suggest that patients who undergo a significant increase in the dose of intermittent narcotics experience significant cognitive impairment, that disappears after 1 week of the increase. More research is needed to better characterize the cognitive toxicity of intermittent narcotics, and to determine the cognitive effects of long acting narcotics, continuous infusions, or of the addition of amphetamines.

Analgesics↗