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PubMed1988

Evidence for the delivery of narcotic antagonists to the colon as their glucuronide conjugates.

Morphine-dependent rats were used to evaluate the effects of the narcotic antagonists, naloxone and nalmefene, and their glucuronide conjugates on the gastrointestinal tract and various parameters of brain-mediated withdrawal. When administered s.c. nalmefene HCl caused a dose-dependent tail skin temperature increase, whereas nalmefene glucuronide was ineffective. Nalmefene precipitated brain-mediated morphine withdrawal at doses as low as 10 micrograms/kg, whereas nalmefene glucuronide was ineffective at doses as high as 1 mg/kg. After p.o. administration of the drugs, naloxone HCl and nalmefene HCl caused diarrhea, withdrawal behavior and tail skin temperature responses by 15 min. In contrast, after p.o. administration of the glucuronide conjugate of either narcotic antagonist, diarrhea was delayed for 75 to 203 min. This latency probably reflects the required transit time to the lower gastrointestinal tract inasmuch as direct colonic administration of either nalmefene or nalmefene glucuronide caused diarrhea within 5 to 8 min. Additionally, the magnitude of brain-mediated withdrawal was smaller and its time of occurrence was delayed and compared to the diarrhea response after p.o. administration of the conjugated forms of the narcotic antagonists. Our calculations indicate that about 0.2 to 0.5% of the dose of the narcotic antagonist administered orally as the glucuronide was absorbed systemically. These results indicate that p.o. administration of the glucuronide conjugates of naloxone and nalmefene results in delivery of the narcotic antagonists to the colon. As such these conjugates may be useful in the prevention or relief of constipation caused by opiate use, without interfering with the central analgesic effects of the narcotics.

Animals↗
PubMed1976

The correlation between antinociceptive activity of narcotics and their antagonists as measured in the mouse tail-flick test and increased synthesis of brain catecholamines.

The effects of several narcotics, narcotic antagonists-analgesics and narcotic antagonists on the synthesis of dopamine and norepinephrine in mouse brain were estimated and related to their activity in the tail-flick test. Catecholamine synthesis was estimated by measuring the accumulation of 3H-dopamine and 3H-norepinephrine formed from an injection of 3H-tyrosine. Morphine produced dose-related increases in both tail-flick activity and catecholamine synthesis. Each of the narcotic analgesics produced a significant increase in catecholamine synthesis 30 minutes after the subcutaneous injection of an antinociceptive dose (ED80). Under these same conditions, drugs which are inactive in the tail-flick test, such as pentazocine, produced a decrease in catecholamine synthesis and cyclazocine; naloxone and naltrexone were without significant effect. However, cyclazocine, which was inactive in the tail-flick test and did not alter catecholamine synthesis 30 minutes after administration, demonstrated tail-flick activity and produced increased catecholamine synthesis 2 minutes after its administration. Morphine was devoid of either activity 2 minutes after administration. Similarly, at 2 hours after the administration of a dose of morphine (10 mg/kg) that was active in the tail-flick test and increased catecholamine synthesis at 30 minutes, neither tail-flick activity nor increased catecholamine synthesis was observed. Naloxone blocked both the antinociceptive action and the increased catecholamine synthesis produced by both morphine and methadone. The results of these studies indicate that a correlation exists between tail-flick activity of narcotic-like drugs and their ability to increase catecholamine synthesis. These data support the hypothesis that brain catecholamines may be involved in the central mediation of the tail-flick response and other actions of the narcotic analgesics.

Analgesics, Opioid↗
PubMed1986

Intravenous narcotic therapy for children with severe sickle cell pain crisis.

Few studies have been published about analgesic management practices during sickle cell pain crisis. Therefore, we reviewed the records of all hospitalized children with this complication during a recent five-year period. The 38 patients (98 painful episodes) who received intravenous narcotic therapy were the subjects of this review. In 76 patients, an initial intravenous bolus injection of morphine sulfate or meperidine hydrochloride was followed by a continuous intravenous infusion of one of these two drugs. To achieve adequate pain control, adjustments in infusion rates were made according to a written protocol. In 22 other patients, subsequent narcotic treatment consisted only of intermittent intravenous bolus injections of meperidine. Satisfactory pain relief was achieved in all 98 episodes. Patients given continuous infusions required more narcotic to control their pain and had more side effects than those treated with bolus injections alone, suggesting a dose-response relationship between narcotic dose and several known side effects. Common side effects included nausea and vomiting, lethargy, and abdominal distention. Although clinically evident respiratory depression was quite uncommon, chest syndrome was a frequent complication, and severe respiratory distress occurred in three patients. Narcotic withdrawal or addiction was not observed. With careful monitoring (including special attention directed to avoiding dosing error), continuous intravenous narcotic infusions are safe and provide effective pain relief for severe sickle cell pain crisis.

Adolescent↗
PubMed1976

Components of respiratory depression after narcotic premedication in adolescents.

The effects of narcotics on ventilatory control were assessed in 13 adolescents and young adults. Both a narcotic and narcotic-phenothiazine significantly depressed the CO2 response curve. Using an occlusion pressure technique (Pm100) to evaluate those neuromuscular processes that generate forces acting on the ventilatory pump, it was found that narcotic agents reduced neuromuscular drive. In most subjects, narcotics had an additional action that contributed to the overall ventilatory depression. Using carbon dioxide to vary neuromuscular drive before and after drug administration at constant levels of neuromuscular drive the drugs reduced tidal-volume responsiveness of the pump. We conclude that narcotics impair ventilation through a combination of two effects; first, reduced neuromuscular drive, most probably due to central depression, and second, increased impedance of the ventilatory pump, most probably due to a decrease in chest-wall compliance.

Adolescent↗
PubMed1985

Narcotic utilization for back pain patients housed in private and semi-private rooms.

Hospital records from 40 back pain patients in private rooms and 40 back pain patients in semi-private rooms were reviewed to determine: (a) if patients in private rooms used more narcotics than patients in semi-private rooms; and (b) whether room type was a predictive variable for narcotic utilization. Patients in private rooms were found to be more likely to use intramuscular request-contingent narcotics than similar patients in semi-private rooms. No differences in the amount of narcotics were observed for other categories of narcotic analgesics. Room type, relevant medical, and demographic variables failed to account for this difference in medication utilization, suggesting that other factors such as medical staff and patient personality variables may be playing an important role in contributing to the use of narcotic analgesics by back-pain patients.

Adolescent↗
PubMed2006

Multimodal analgesia without routine parenteral narcotics for total hip arthroplasty.

Methods for managing pain after a total hip replacement have changed substantially in the past 5 years. We documented the outcome of patients treated with a multimodal pain program designed to avoid parenteral narcotics. Avoidance of parenteral narcotics can essentially eliminate the complications of respiratory depression, ileus, and narcotic-induced hypotension. It can minimize nausea and vomiting which cause dissatisfaction with an operation. Twenty-one of 140 patients (15%) needed parenteral narcotics postoperatively with only nine patients (6.4%) using parenteral narcotics after the day of surgery. Mean pain scores were below 3 of 10 on all postoperative days. There were no patients with respiratory depression or ileus, and four (2.9%) with urinary retention. Nausea occurred with 35 patients (25%) in the recovery room and in 28 patients (20%) thereafter. Emesis occurred in five patients (3.6%) with two incidences in the recovery room. One hundred and thirty-eight patients (98.6%) were discharged home at a mean of 2.7 seven days postoperatively with 98 (70%) on a single assistive device. The multimodal pain management program, which avoided parenteral narcotics, was effective in providing pain relief, nearly eliminating emesis, and eliminating the severe complications of respiratory depression, urinary tract infection and ileus, as well as accelerating function.

Adult↗
PubMed1990

The effects of incisional bupivacaine on postoperative narcotic requirements, oxygen saturation and length of stay in the post-anesthesia care unit.

We compared postoperative pain and narcotic requirements, oxygen saturation (SaO2) and length of stay in the post-anesthesia care unit (PACU) in patients who received 30 ml of either 0.25% bupivacaine (B) or saline placebo (S) infiltrated into the operative incision. Twenty ASA I-III patients undergoing abdominal surgery were studied in a double-blinded randomized prospective trial. Study and control groups were not different in patient age, procedure, intra-operative narcotics administered or preoperative SaO2. In the PACU, patients receiving B had significantly lower analog pain scores (6.0 vs 8.3, P = 0.02). They had lower respiratory rates (15.6 b/min vs 19.1, P = to 0.02), required significantly less narcotic (4.5 mg morphine sulphate vs 11.0, P = to 0.03) and were discharged from the PACU almost an hour sooner than patients receiving S (P = 0.02). Patients receiving B had significantly higher minimum SaO2 than those receiving S (93.3% vs 89.9, P = 0.04). Discharge pain scores, SaO2 and respiratory rates were not significantly different between B and S groups. Finally, mean requirements for narcotics for the first 24 h were reduced by approximately 30% (from 406.9 mg meperidine to 255.5 mg, P = 0.006). This study demonstrates that infiltration of a long-acting local anesthetic lowers initial pain scores and requirements for narcotics in the PACU. The effect can be seen for at least the first 24 h. A lower requirement for postoperative narcotics is accompanished by faster wake-up, more alert patients, and, most importantly, higher SaO2 and shorter PACU stay. This may have a significant effect on pulmonary morbidity following abdominal operations.

Adult↗
PubMedDate not supplied

Narcotic use in the hospital: reasonably safe?

OBJECTIVE: To determine the causes and frequency of overdoses associated with the administration of opioid analgesics in hospitalized patients. DESIGN: Case series. SETTING: Two acute care teaching hospitals. PATIENTS: Eighty-one hospitalized patients who received naloxone for a clinically suspected narcotic overdose. INTERVENTIONS: Three investigators reviewed each patient who received naloxone during a 12-month period. The patients were judged to have a narcotic overdose if caregivers documented an immediate improvement in mental status, respiratory rate, or blood pressure after naloxone administration. MAIN OUTCOME MEASURES: The number and causes of narcotic overdoses were determined. The frequency of morphine and meperidine overdoses was calculated. The number of incidents reported using incident or adverse drug reaction reports or the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. RESULTS: In the 22 overdoses that occurred, 14 (64 percent) were caused by medication prescribing, compounding, or administration errors and potentially were preventable. The remaining eight patients experienced an overdose despite receiving appropriate amounts of opioids. The frequency of overdoses was 0.4 and 0.2 percent of total patients receiving morphine or meperidine, respectively, at the two hospitals. Nonreporting of these narcotic overdoses was frequent. In one hospital, 1 incident report and 3 adverse drug reactions were reported for 17 overdoses. At the second hospital, 1 incident report and 1 adverse drug reaction were reported for 6 overdoses. None of the patient charts included an ICD-9-CM code that documented the problem. CONCLUSIONS: The causes of overdoses are not limited to prescribing and administration errors. Some patients, despite proper execution of appropriate orders, develop a narcotic overdose. Caregivers must be aware of this problem and monitor patients for a decrease in mental status and respiratory rate. In addition, we conclude that an important number of hospitalized patients develop an overdose even though the frequency is low related to the number of patients receiving narcotics.

Adverse Drug Reaction Reporting Systems↗
PubMed1978

Quantitative and temporal relationships of alcohol use in narcotic addicts and methadone maintenance patients undergoing alcohol detoxification.

Evidence exists that alcohol abuse frequently coexists with narcotic addiction and methadone maintenance treatment, and it is the major factor in the development of cirrhosis and liver failure. This study of patients hospitalized for alcohol detoxification compares the quantity of alcohol consumed by alcohol abusers, addicted to narcotics or in a methadone maintenance treatment program, to that consumed by patients not involved with narcotic addiction. Mean daily alcohol consumption was not significantly different in either group using narcotics, including methadone, or in the subgroup of methadone maintenance patients, from the amount consumed by nonnarcotic abusers. Determination of temporal sequence in the use of these substances revealed that in 68% regular alcohol abuse preceded narcotic use. Alcohol abuse reportedly began after entering a methadone maintenance treatment program in 29% of our patients. Alcohol abusers who were in a methadone maintenance treatment program were significantly younger than those who did not use narcotics, including methadone. Time interval according to the patients' estimates, from onset of regular alcohol consumption to heavy drinking, was not significantly different in the two groups.

Age Factors↗
PubMed1988

Continuous narcotic infusion with patient-controlled analgesia for chronic cancer pain in outpatients.

STUDY OBJECTIVE: To determine the feasibility and safety of outpatient continuous narcotic infusions with additional bolus capabilities (patient-controlled analgesia) in patients with cancer pain. DESIGN: A single arm (non-randomized) series. SETTING: Outpatient with contact by telephone and through outpatient clinic. PATIENTS: Consecutive series of 18 patients with poorly controlled cancer pain or significant side effects from regular administration of various narcotics. INTERVENTIONS: Patients taught and supervised to use portable pump capable of delivering a continuous narcotic infusion with bolus capabilities. MEASUREMENTS AND MAIN RESULTS: All patients had improvement in pain control as judged by the use of a linear analogue scale. Side effects and safety profile were highly acceptable. Narcotics used and maximum doses were meperidine, 50 mg/h; morphine, 80 mg/hr; and hydromorphone, 60 mg/hr. Infusion duration ranged from 7 to 225 days (mean, 54 days). CONCLUSIONS: Continuous narcotic infusions using a programmable portable pump with bolus capabilities is a safe and reliable method of delivering narcotics to outpatients.

Adult↗
PubMed1995

An alternative method for the identification of potential habitual narcotic users from a managed care claims database.

The purpose of this study was to identify an alternative method of initial narcotic abuse screening to distinguish members who have a greater likelihood of being correctly classified as potential narcotic abusers. Members 10 years of age and older, who had one or more pharmacy claims for narcotics within a quarter were included in the analysis. Members were classified according to the number of narcotic prescriptions, unique pharmacies, and unique physicians in a quarter. Those with excluded medical conditions and abuse-related diagnoses were identified. A narcotic abuse decision tree was developed to identify population(s) with the highest likelihood for a potential abuse history. Using a combination of variables, especially age, strengthened the likelihood of identifying potential narcotic abusers.

Data Interpretation, Statistical↗
PubMed2006

Acute pain and narcotic use does not impair the ability to provide informed consent: evaluation of a competency assessment tool in the acute pain patient.

Patients evaluated in acute pain will often have narcotics withheld until after the patient has been evaluated by a surgeon and has given informed consent. Concern that the patient would have impaired judgment due to narcotic effects often prevents the administration of timely pain relief. The Hopkins Competency Assessment Tool (HCAT) is a validated instrument for both psychiatric and medical patients; it has not been validated to evaluate drug effects on judgment. Thirty consecutive patients agreed to participate in the trial over a 12-month period. The HCAT was administered prior to the planned major elective procedure and repeated on each postoperative day up to and including postoperative day 5. Narcotic use (as morphine equivalents), HCAT scores, demographic data, and surgical procedures were recorded. The average age of our patients was 53 years. Twenty-seven patients passed the initial HCAT, and one patient failed subsequent exams. No correlation was seen between HCAT score and narcotic dose. Narcotic administration sufficient for pain control does not impair the ability to provide informed consent. The only patient who failed the HCAT after an initial passing score was somnolent on the narcotic dose.

Acute Disease↗
PubMed1988

Pain scores and ventilatory and circulatory sequelae of epidural morphine in cancer patients with and without prior narcotic therapy.

Pain scores and respiratory and circulatory sequelae of epidural morphine were studied in 25 patients with cancer, classified into two groups: 15 with and 10 without a history of previous narcotic analgesic therapy. Morphine, 2.5 mg initially and 5.0 mg 12 hours later, was given through an indwelling lumbar epidural catheter. Pain scores, heart rate, blood pressure, respiratory rate and minute volume, arterial PO2 and PCO2, and arterial pH were measured for 24 hours. Both groups had the same degree of analgesia after each epidural dose, suggesting that local morphine concentrations seen with epidural administration may be sufficient to overcome any degree of tolerance that may have developed at the spinal level during previous systemic narcotic administration. Statistically significant dose-dependent hypoventilation and concomitant respiratory acidosis were seen in both groups, the changes being significantly greater in opiate-naive patients. These results demonstrate that the ventilatory depressant actions of opioids are attenuated but not eliminated in narcotic-familiar cancer patients and that epidural narcotics are as effective in relieving pain in narcotic-naive patients as in patients previously exposed to narcotics for relief of cancer pain.

Adult↗
PubMed1977

The epidemiology of drug abuse: current issues. Ecological studies of narcotic addiction.

Narcotic addiction is concentrated in certain places and among particular social groups. Heretofore it has not been possible to assess which environmental factors are critical for the initiation of narcotic use, its transition to narcotic addiction; and subsequently, entry into treatment or whether there are environments which select those particularly prone to social deviancy while others migrate out. There are few systematic descriptions of the social and environmental distribution of narcotic addicts. This paper describes the initial results of assessing the characteristics of the social environment (1970 Federal Census) of 3,000 individual narcotic addicts from the Lower East Side of Manhattan who were treated at the Beth Israel Medical Center. Pearson correlations between treated addiction ratios and 1970 Census characteristics were calculated for 13 health areas. Out of 103 socio-economic characteristics from the NIMH Mental Health Demographic Profile System, 29 were statistically significant at p less that 0.01 and 28 at 0.01 less than p less than 0.05. Highly significant correlations were found for households with children, female headed (r = .94, F= 90.3) and population in poverty (r = .89, F = 41.7). Correlations with density (over 1.01 persons per room) or population mobility (residing in different house five years ago) were not statistically significant. This paper has outlined some of the methodological and theoretical problems of ecological studies of narcotic addiction, and emphasized the need for concentration on the socio-dynamics of diffusion. Methodological problems include consideration of the time and place of onset; demographic standardization; ascertainment differentials; clinical characterization; and assessment within individuals of ecological correlations.

Adolescent↗
PubMed1994

Intrathecal narcotics for obstetric analgesia in a community hospital.

OBJECTIVE: Our objective was to establish whether intrathecal narcotics for obstetric analgesia offer an adequate and cost-effective alternative to epidural analgesia with minimal side effects in our small, semirural community hospital with limited anesthesia coverage. STUDY DESIGN: Low-risk patients at > or = 35 gestational weeks in active labor were offered intrathecal narcotics. A retroactive chart review of every patient receiving an intrathecal injection was compared with a chart review of the next consecutive low-risk patient who did not receive an intrathecal narcotic. Age, parity, and status of labor at the time of application were noted, as was the subsequent rate of labor and the type of delivery. Side effects such as changes in vital signs, headache, vomiting, pruritus, urinary retention, and/or respiratory depression were noted. All study patients received fentanyl, 25 to 35 micrograms, plus 0.25 to 0.3 mg of preservative-free morphine combined with 6 to 8 mg of lidocaine. Within 15 minutes of delivery intravenous nalbuphine (Nubain), 5 mg, and oral naltrexone, 12.5 mg, were administered. Pain relief was recorded as excellent, satisfactory, or unsatisfactory (requiring additional medication). RESULTS: During the 30-month review period, 90 patients (3% of total deliveries) received intrathecal narcotics. There were three sets of twins, for a total of 93 live births. Ten patients (11%) required primary cesarean section, and of the 83 vaginal births 35 (38%) were spontaneous, two (2%) required forceps deliveries, and 46 (49%) were delivered by vacuum extraction, which was significantly higher than the 28 (31%) for controls. The rate of labor was not affected, with both groups requiring a similar rate of oxytocin (Pitocin) augmentation. Significantly more patients receiving intrathecal narcotics experienced pruritus and urinary retention compared with controls. There was no incidence of respiratory depression. Eighty-four (93%) of the 90 patients reported excellent pain relief, five patients had satisfactory relief lasting 2.5 to 6 hours, and one was unsatisfactory. CONCLUSIONS: In our hospital with limited anesthesia services intrathecal narcotics offer excellent labor pain relief with manageable side effects and without adverse obstetric outcome.

Adolescent↗
PubMed2005

Authority for practitioners to dispense or prescribe approved narcotic controlled substances for maintenance or detoxification treatment. Final rule.

DEA is amending its regulations to allow qualified practitioners not otherwise registered as a narcotic treatment program to dispense and prescribe to narcotic dependent persons Schedule III, IV, and V narcotic controlled drugs approved by the Food and Drug Administration specifically for use in maintenance or detoxification treatment. This Final Rule is in response to amendments to the Controlled Substances Act by the Drug Addiction Treatment Act of 2000 (DATA) that are designed to expand and improve treatment of narcotic addiction. This Final Rule is intended to accomplish the goals of DATA while preventing the diversion of Schedule III, IV, and V narcotic controlled drugs approved by the Food and Drug Administration specifically for maintenance / detoxification treatment.

Certification↗
PubMed1976

Acute reductions in serum testosterone levels by narcotics in the male rat: stereospecificity, blockade by naloxone and tolerance.

The effects of a single injection of morphine (20 mg/kg) on serum testosterone levels were examined in the male rat. Within 2 hours after the morphine injection, testosterone levels were significantly lower than control levels. The decline in testosterone levels reached a maximum 4 hours after the administration of morphine, at which time testosterone levels were reduced by more than 85% with respect to controls. The ability of a large number of narcotics to depress serum testosterone levels, 4 hours after their administration, was also examined. All narcotics depressed testosterone levels significantly and their potency relative to morphine was comparable to that observed in several other preparations, such as the guinea-pig ileum and mouse vas deferens. The testosterone-depleting effects of the narcotics appear to represent specific narcotic effects since the (-)-isomers of the narcotics were considerably more potent than the (+)-isomers, naloxone competitively inhibited the effects of morphine on testosterone levels and tolerance developed to the testosterone-depleting effects of these drugs. Acute treatment with morphine also lowered serum luteinizing hormone levels, and this reduction preceded the fall in testosterone levels by 1 to 2 hours.

Animals↗
PubMed1976

A behavioral paradigm for the evaluation of narcotic antagonists.

We have developed an experimental paradigm for the behavioral evaluation of narcotic antagonists. The study specifically examined the heroin-seeking behavior of hard-core narcotic addicts on a research ward under blocked and unblocked conditions. Each patient served as his own control. A long-term follow-up program in the community, with aftercare services, was utilized to determine the relationship between behavior observed on the research ward and behavior that occurred in the community. While preliminary one-month follow-up data offered some cause for an optimistic view of narcotic antagonist treatment, behavioral data observed on the research ward raised serious doubts about the possibility of extinguishing heroin self-administration with antagonists. The behavioral data were not consistent with laboratory descriptions of extinction. Rather, the data suggested that narcotic antagonist programs should emphasize the development of contingencies for the reinforcement of narcotic antagonist self-administration to ensure an opiate-free state, instead of focusing on an extinction approach.

Adult↗