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The separation and quantitation of the narcotic components of illicit heroin using reversed-phase high performance liquid chromatography.

The separation of heroin from other narcotic components of illicit preparations is achieved by high performance liquid chromatography. Using an aminopropyl bonded silica packing and a mixture of 85% acetonitrile and 15% 0.005 M tetrabutylammonium phosphate as the mobile phase, caffeine, heroin, acetylcodeine, 6-acetylmorphine, codeine, and morphine are separated from each other and are accurately quantified. Papaverine, noscapine, thebaine, and strychnine are also separated from these principal components.

Caffeine↗

Comprehensive screening procedure for detection of stimulants, narcotics, adrenergic drugs, and their metabolites in human urine.

An analytical procedure for the detection of stimulants, narcotics, beta-blockers, beta-agonists, and many of their metabolites in urine using a solid-phase extraction procedure and gas chromatography-mass spectrometry (GC-MS) is described. These substances have been specifically banned by the Medical Commission of the International Olympic Committee (IOC) in order to prevent their abuse in sports. Urine samples are submitted to an enzymatic hydrolysis (beta-glucuronidase arylsulfatase) and extracted by means of Bond-Elut Certify columns. The residues are then selectively derivatized with N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA), which enables the formation of trimethylsilyl derivatives of hydroxyl, acidic, and phenolic groups, and N-methyl-bis-trifluoroacetamide (MBTFA), which enables the formation of trifluoroacetamide derivatives of primary and secondary amines. A GC-MS system working in scan mode is sensitive and specific enough to detect and identify approximately 100 compounds and metabolites in urine for at least 24 h after the administration of doses typically encountered in therapeutics. Detection in selected ion monitoring mode is needed for the determination of beta-agonist agents. The method was successfully used in doping control of urine samples during the 25th Olympic Games, July 1992, in Barcelona, Spain.

Adrenergic Agents↗

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia.

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dose-response relationship and infusion requirement of cisatracurium besylate in infants and children during nitrous oxide-narcotic anesthesia.

BACKGROUND: To determine the effect of age on the dose-response relation and infusion requirement of cisatracurium besylate in pediatric patients, 32 infants (mean age, 0.7 yr; range, 0.3-1.0 yr) and 32 children (mean age, 4.9 yr; range, 3.1-9.6 yr) were studied during thiopentone-nitrous oxideoxygen-narcotic anesthesia. METHODS: Potency was determined using a single-dose (20, 26, 33, or 40 microg/kg) technique. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor pollicis to supramaximal train-of-four stimulation of the ulnar nerve at 2 Hz. RESULTS: Least-squares linear regression analysis of the log-probit transformation of dose and maximal response yielded median effective dose (ED50) and 95% effective dose (ED95) values for infants (29+/-3 microg/kg and 43+/-9 microg/kg, respectively) that were similar to those for children (29+/-2 microg/kg and 47+/-7 microg/kg, respectively). The mean infusion rate necessary to maintain 90-99% neuromuscular block during the first hour in infants (1.9+/-0.4 microg x kg(-1) x min(-1); range: 1.3-2.5 microg x kg(-1) x min(-1)) was similar to that in children (2.0+/-0.5 microg x kg(-1) x min(-1); range: 1.3-2.9 microg x kg(-1) x min(-1)). CONCLUSION: The authors conclude that cisatracurium is equipotent in infants and children when dose is referenced to body weight during balanced anesthesia.

Age Factors↗

Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established.

Administration, Oral↗

Simple screening technic to estimate postoperative narcotic use.

The General Health Questionnaire, a 30-item, self-response inventory, identified individuals who required significantly more pain medication after elective cholecystectomy. The questionnaire is well tolerated by surgical patients and is easy to score. It can identify those individuals prone to request excessive narcotic medication postoperatively.

Adult↗

Intraspinal narcotic analgesia in the treatment of chronic pain.

The results of intraspinal narcotic analgesia (INA) in 43 patients with chronic nonmalignant pain syndromes are reviewed. A protocol has been established to improve proper patient selection and includes three phases of study. Most of the patients have had INA for 2 years now. In those patients qualifying for continuous delivery systems (CDS), 65% had good to excellent relief of pain while 34% were considered failures for a variety of reasons. Apparent tolerance development in many of the patients was, in fact, due to technical problems with the epidural catheter instead.

Analgesia↗

The effect of non-steroidal anti-inflammatory drugs and other commonly used non-narcotic analgesics on blood pressure level in adults.

This review explores the blood pressure effects of three non-narcotic analgesics: non-selective non-steroidal anti-inflammatory drugs (NSAID), paracetamol and aspirin. The current evidence suggests that in normotensive, otherwise healthy adults, short-term use (1-2 weeks) of NSAIDs is not associated with a significant increase in blood pressure. Those with existing hypertension are more likely to see a blood pressure elevation, although the magnitude of the effect is less predictable and may vary with age, baseline blood pressure, type of NSAID and concurrent antihypertensive therapy. The magnitude of the blood pressure increase appears to be similar for both NSAIDs and paracetamol, while low-dose aspirin may have more modest effects. In hypertensive adults who experience deterioration of blood pressure control on NSAIDs, there is some, albeit suboptimal, evidence that the blood pressure-raising effects of NSAIDs are less when used in conjunction with dihydropyridine calcium-channel blockers than angiotensin-converting enzyme inhibitors.

Acetaminophen↗

The effect of four narcotics on cholecystokinin octapeptide stimulated gallbladder contraction.

In an attempt to find the ideal analgesic to treat biliary tract pain we compared the effects of saline and equianalgesic doses of morphine, pentazocine, pethidine, and butorphanol on CCK-OP stimulated gallbladder emptying in healthy volunteers. Morphine produced a profound delay in gallbladder emptying while the other narcotics produced a significant delay in comparison to saline, but less than morphine. None of the drugs affected common bile duct diameter, bilirubin, liver enzymes or amylase. We recommend avoiding the use of morphine in the treatment of biliary and pancreatic pain, but although pethidine, pentazocine and butorphanol may be potentially detrimental we could find no definite superiority of one versus the others.

Adolescent↗

The propriety of narcotic usage in hospitalized patients.

The propriety of narcotic usage at the Hadassah Hospital has been studied in 35 cancer patients and 70 post-operative patients. Eighty-three per cent of the cancer patients and 66% of the surgical patients remained in moderate to severe distress in spite of the analgesic therapy. Insomnia and anxiety, plus depression in the cancer patients, were the major results of uncontrolled pain. The inadequacy of the treatment was attributed to the incorrect selection of medication, usage "as needed' policy and smaller daily doses than advocated. This resulted mainly because of exaggeration of the risk of tolerance and addiction by both patients and personnel.

Drug Utilization↗

The effect of narcotic analgesics on the uptake of 5-hydroxytryptamine and (-)-metaraminol by blood platelets.

1. The effects of narcotic analgesic and related drugs were studied on the uptake of 5-hydroxytryptamine (5-HT) and (-)-metaraminol by blood platelets.2. The most potent drug in inhibiting the uptake of 5-HT (10 muM) by human platelets was methadone, followed by pentazocine>piminodine approximately pethidine approximately anileridine approximately cyclazocine approximately thebaine > dextropropoxyphene. Alphaprodine, papaverine, apomorphine, nalorphine, codeine, and morphine were almost without effect. Methadone was slightly less active than desipramine, and had 10% of the activity of imipramine under similar conditions. Naloxone did not antagonize the effect of methadone on 5-HT uptake.3. The most potent inhibitor of metaraminol (3 muM) uptake by human platelets was piminodine, followed by pentazocine>/=anileridine>cyclazocine=methadone > dextropropoxyphene approximately thebaine >/= papaverine approximately alphaprodine >pethidine>morphine. The activity of morphine was 1% of that of piminodine. Piminodine was more potent than desipramine and protriptyline under similar conditions. The order of potency of drugs studied in inhibiting the uptake of metaraminol by rabbit platelets was similar to that obtained with human platelets.4. The effects of the analgesics studied on inhibiting uptake of monoamines did not correlate with their pain-relieving properties.

Alphaprodine↗

Analgesic and other pharmacological activities of a new narcotic antagonist analgesic (-)-1-(3-methyl-2-butenyl)-4-[2-(3-hydroxyphenyl)-1-phenylethyl]-piperazine and its enantiomorph in experimental animals.

Of 1-chclohexyl-4-[2-(3-hydroxyphenyl)-1-phenylethyl]piperazine (I) and its 1-(3-methyl-2-butenyl) derivative (II), the S(+)-isomers were analgesically more active than either their +(-)-isomers or their racemates, having 15 to 44 times the potency of morphine in mice and rats. R(-)-I had comparable analgesic activity to morphine R(-)-II to pentazocine in mice, rats and dogs and they were nearly equipotent with pentazocine in reversing some actions of morphine. The S(+)-isomers and racemates lacked this action. R(-)-II required about 10 times more naloxone to reverse its analgesic activity than was needed to antagonise the S(+)-isomers, morphine and pentazocine. The S(+)-isomers and racemates produce a typical Straub tail reaction and increased spontaneous locomotor activity in mice, but the R(-)-isomers did not. R(-)-II had no significant physical dependence liability in mice, rats and monkeys. From these results, it is suggested that the compounds show an uncommon steroselectivity in comparison with morphine and its surrogates, and that R(-)-II is worth investigating further as a narcotic antagonist analgesic.

Analgesics↗

In vitro models in the study of structure-activity relationships of narcotic analgesics.

Evidence has been adduced for the view that the morphiness receptor or receptors in the myenteric plexus of guinea pig ileum are very similar to the brain receptors that mediate the analgesic action of the narcotic alagesics. Such an in vitro model is very suitable for the study of structure-activity relationships because the angonist and antagonist activities of compounds can readily be assessed. One example is the investigation of the effects of changes at the N atom. Another point of interest is the role of substitutions at the C14 atom in morphine and morphinans. Such alterations in structure may have a profound effect on the relative agonist and antagonist activities and may convert a drug with dual agonist and antagonist actions into an antagonist devoid of agonist action.

Analgesics, Opioid↗

Effects of three narcotic antagonists (naltrexone, diprenorphine, and S-20682) on blood pressure, heart rate and electrical cortical activity.

Three narcotic antagonist drugs (EN-1639 or naltrexone, M-5050 or diprenorphine and the 6-oxo analogue of oxilorphan, S-20682) were evaluated in increasing doses (1-80 micrograms/kg) in the unanaesthetised dog for possible effects on blood pressure, heart rate, respiratory rate, arterial blood gases, and convulsive EEG changes. Compared to the control-awake situation, diprenorphine and S-20682 induced hypotension (maximum fall 15%), bradycardia (maximum 12%) and bradypnoea (maximum 25%). These effects were not increased at doses higher than 20 micrograms/kg. Despite the induced bradypnoea, there were no significant changes in arterial pO2 and pCO2. Simultaneously, with the cardio-respiratory changes, EEG activity shifted from high frequency, low amplitudes of the awake state, to low frequency, high amplitudes of a sleep-like state. Convulsive EEG changes were never recorded with any of the tested compounds. It is suggested that the observed cardiovascular changes are due to a reduced state of vigilance, since auditory stimuli induced an arousal reaction with a reversal of the depressed variables. In contrast, naltrexone induced only bradycardia in the observed dose range (maximum 25%). There were no effects on blood pressure, respiratory rate, arterial blood gases and EEG.

Animals↗

A comparison of cognitive impairment due to benzodiazepines and to narcotics.

In an attempt to determine the source of cognitive impairment in 106 consecutively admitted patients at the Johns Hopkins Chronic Pain Treatment Center, EEG, the Wechsler Adult Intelligence Scale, Memory Quotient, and Bender Gestalt tests were administered. Patients receiving benzodiazepines alone demonstrated alterations in cognitive functioning and EEG evidence of a sedative effect. Patients receiving narcotics alone and a group of patients not receiving medication did not show signs of cognitive impairment. The effects of benzodiazepines on sleep and perception of chronic pain, in combination with the cortical changes that they produce, imply that these drugs should not be used in most patients with chronic pain.

Adult↗

Narcotic smuggling and radiography of the gastrointestinal tract.

The gastrointestinal tract is being used to an increasing extent as a route for smuggling narcotics. Small, swallowed packages overwrapped with condoms or other materials are usually not detected by the customs authorities. Conventional abdominal radiography may indicate foreign bodies surrounded by a characteristic thin layer of gas and located in the gastrointestinal tract. Some short case histories, and the radiologic findings in four heroin 'body packers' are presented.

Adult↗

Zolpidem intoxication mimicking narcotic overdose: response to flumazenil.

Zolpidem is a recently introduced sleep-inducer which is thought to act on the central-type benzodiazepine receptors. This observation is the first report of drug poisoning with this compound. The toxic response was characterized by the development of a profound but short-lasting coma, associated with pin-point pupils and respiratory depression, as observed in a narcotic overdose. These clinical signs were not influenced by the administration of naloxone, but responded dramatically to flumazenil. Some analytical data on zolpidem toxicokinetics are presented.

Adult↗

Pharmacokinetic/pharmacodynamic relationship of eptazocine, a narcotic-antagonist analgesic, in rats.

The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.

Analgesics↗