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PubMed1980

Recovery of thebaine and cryptopine from Indian opium.

The thebaine content of the opium collected in the Madhya Pradesh region of India has been estimated and reported to range from 1.5 to 2.0 per cent. A technological process for the recovery of thebaine from the mother liquor remaining after the separation of natural codeine in the Government Opium and Alkaloid Works, Neemuch, has been developed in the laboratory and stepped up to an industrial scale. A method for the recovery to thebaine from the waste slaked-lime residues obtained from crude alkaloid cake mother liquor in the Government Opium and Alkaloid Works at Ghazipur has been worked out and the technical details of the process described. The recovery of thebaine would help to increase the production of codeine, and thebaine can also be used as a raw material for the manufacture of other drugs. Cryptopine has also been recovered from the mother liquor after the separation of thebaine.

Alkaloids↗
PubMed1982

Effect of a low-fat diet and antidiarrhoeal agents on bowel habits after excisional surgery for classical Crohn's disease.

The effect of dietary restriction and/or antidiarrhoeal agents on the bowel habits in relation to amount of ileal resection was studied in 63 patients after excisional surgery for classical Crohn's disease. Satisfactory function, i.e. one to three bowel movements per day was achieved in all patients with a moderate distal ileal resection (less than 100 cm) after such treatment. One quarter of these patients preferred codein phosphate or diphenoxylate and about one half a low fat diet, either alone or in combination with the above mentioned drugs. About one quarter did not need any form of anti-diarrhoeal therapy. In patients with a more extensive distal small bowel resection (greater than 100 cm), codein phosphate or diphenoxylate was mostly ineffective to control diarrhoea. However, by means of a low fat diet satisfactory bowel habits were achieved in the majority of these patients, although many of them had to combine this treatment with additional amounts of anti-diarrhoeal drugs. Thus, the result was considered unsatisfactory only in three of the 17 patients receiving such a treatment. Two of these patients were previously cholecystectomized however, and the third patient had been subjected to an almost 80% small bowel resection. Low fat diet appears to be an effective therapy for regulation of the disturbances in bowel function occurring after ileal resection and has a particularly important place in patients with extensive resections.

Antidiarrheals↗
PubMed1982

[Effects of methanobenzazonine (2,3,4,5,6,7-hexahydro-1,6-methano-1H-4-benzazonine) derivatives on the cough reflex and respiration].

Antitussive and respiratory effects of three newly synthesized methanobenzazonine derivatives and their d- and l-isomers were investigated to understand the relationship between the cough and respiratory centers. Antitussive effects were evaluated with the PEC (puncture electrode-induced cough) method in conscious d-, dl-, and l-ST-2123; d-, dl-, and l-ST-2121 into the right carotid artery at a dose range of 0.2-0.8 mg caused no effect on respiration. dl-ST-2121 at 0.4 to 0.8 mg and l-ST-2121 at 0.2 to 0.8 mg depressed respiration dose-dependently. Codeine (0.2-0.8 mg) depressed respiration slightly. Morphine (0.2-0.8 mg) depressed respiration more strongly. All the methanobenzazonine derivatives used, when given intraperitoneally, showed antitussive potencies that were 1/3-1/2 the potency of codeine. The antitussive potencies of the d-, dl-, and l-isomers of the three derivatives used were discussed on the bases of chemical structures and drug receptors. These results provide evidence of a discrepancy between the cough and respiratory centers in the brain stem.

Animals↗
PubMedDate not supplied

Zomepirac sodium. A new nonaddicting analgesic.

Zomepirac sodium (Zomax) is a new orally effective nonopioid analgesic that can relieve mild to severe pain. It is more effective than aspirin or codeine alone and is as effective as analgesic combinations containing codeine or other narcotics. Given orally, zomepirac has provided analgesia comparable with usual intramuscular doses of morphine in postoperative pain. With long-term use, neither tolerance to its analgesic effect nor psychic or physical dependence has been demonstrated. Like aspirin, zomepirac has anti-inflammatory and antipyretic actions and inhibits the synthesis of prostaglandins. Zomepirac is generally well tolerated with both short-term and long-term use; gastrointestinal reactions are the most frequently occurring side effects.

Analgesics↗
PubMed1994

Analgesic potency of mu and kappa opioids after systemic administration in amphibians.

The relative analgesic potency of 11 opioid agents was assessed by using the acetic acid test in amphibians. Systemic administration of the mu agonists, fentanyl, levorphanol, methadone, morphine, meperidine and codeine; the partial mu agonist, buprenorphine; and the kappa agonists nalorphine, bremazocine, U50488 and CI-977 was made by s.c. injection into the dorsal lymph sac of the Northern grass frog, Rana pipiens. All agents produced a dose-dependent and long-lasting analgesia which persisted for at least 4 hr. The analgesic effects of single doses of each agent were significantly blocked or reduced by pretreatment with naltrexone. Systemic opioids produced log dose-response curves which yielded ED50 values ranging from 1.4 nmol/g for fentanyl to 320.9 nmol/g for nalorphine. Comparison of ED50 values gave a rank order of analgesic potency = fentanyl > CI-977 > levorphanol > U50488 > methadone > bremazocine > morphine > buprenorphine > meperidine > codeine > nalorphine. The relative analgesic potency of mu opioids in amphibians was significantly correlated with relative analgesic potency of these same agents obtained on the mouse writhing and hot plate tests. These data suggest that the amphibian model may serve as an adjunct or alternative model for the testing of opioid agents. Furthermore, given the inactivity of kappa opioids on rodent hot plate and tail-flick tests, the acetic acid test in amphibians may be especially well-suited for the assessment of opioid analgesia after administration of kappa-selective opioids.

Analgesics↗
PubMed1993

Hepatic oxygen consumption and cytochrome P450 activity in experimental faecal peritonitis.

OBJECTIVE: To study hepatic oxygen consumption and cytochrome P450 activity in pigs with septic shock induced by faecal peritonitis. DESIGN: Controlled experimental study. ANIMALS: 12 pigs weighing 19-27 kg. INTERVENTION: The animals were divided into a control group (n = 6) and a peritonitis group (n = 6). Peritonitis was induced by intraperitoneal instillation of a standard amount of autologous faeces. The animals were then observed for 300 minutes. Liver biopsy specimens were taken at 0 and 300 minutes. MAIN OUTCOME MEASURES: Hepatic oxygen delivery (DO2) and consumption (VO2). Cytochrome P450 activity was studied by measuring O- and N-demethylation of codeine at 0 and 300 minutes. RESULTS: Hepatic DO2 was reduced, whereas VO2 was increased during sepsis. There were no significant changes in the N- and O-demethylation of codeine. CONCLUSIONS: Hepatic VO2 did increase during sepsis, possibly because of the increased metabolic demand. Cytochrome P450 activity was unaffected by the septic challenge.

Animals↗
PubMed1994

A comparison of meconium, maternal urine and neonatal urine for detection of maternal drug use during pregnancy.

A large scale drug screening study was done to determine the prevalence of drug use in a large metropolitan, obstetric population. Meconium and first voided urine, as well as maternal urine were collected from 423 consecutive deliveries. Urine samples and methanolic extracts of meconium were initially screened by Enzyme Multiplied Immunoassay Technique (EMIT) and then confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Analysis of cocaine metabolite as benzoylecogonine, cannabinoid as carboxy-THC, codeine, morphine and methadone were included in the study. The positive rate for benzoylecgonine was virtually identical for meconium, maternal urine and neonatal urine (12%). Analysis of meconium was found to be more reliable than analysis of maternal or neonatal urine for the detection of benzoylecgonine. Meconium did not appear to offer an advantage over maternal or neonatal urine for detection of cannabinoid, codeine, morphine, or methadone.

Adult↗
PubMed1994

Analgesic nephropathy in Belgium is related to the sales of particular analgesic mixtures.

Analgesic nephropathy, a chronic progressive renal disease induced by the abuse of drugs containing analgesics and potentially addictive substances (e.g. caffeine, codeine), continues to be a serious problem in Belgium. A recent investigation (1990) of Belgian dialysis patients, including 54 of the 55 dialysis centres, established that 15.6% of the patients had analgesic nephropathy, showing a small decrease in prevalence compared to the 1979 and 1984 estimates. Considerable changes were observed in the sales figures of analgesic during the period 1983-1991. Phenacetin completely disappeared from the market and single analgesics, particularly paracetamol, gained large market shares. The total sales of single analgesics slowly increased, whereas the sales of analgesic mixtures decreased from 12.5 million to 8 million packages per year. In recent years the composition of most analgesic mixtures has been reduced to a single analgesic component in combination with caffeine and/or codeine. In comparing the geographical distribution of the sales of different analgesic products (1983) with the prevalence of analgesic nephropathy (1990), a strong correlation could be observed with particular analgesic mixtures, whereas this was not the case with single analgesics. This observation suggests that a careful analysis of sales data showing a high volume of analgesic mixtures sold, containing two analgesic substances combined with potentially addictive components, is a pharmacoepidemiological indicator for the presence of analgesic nephropathy in a given population.

Adult↗
PubMedDate not supplied

[Abuse of psychotropic drugs during driving].

The responsibility of psychotropic drugs as a cause of road traffic accidents remains difficult to evaluate with precision. Different studies performed in many countries provide a certain precision in relation to percentage of injured drivers whose blood contained psychotropic substances (8 to 10% according to studies). On the other hand, it is practically impossible to really know either these products were or were not the cause of the accidents because underlying or associated pathologies can equally create problems such as lack of attention and other vigilance deficits. There is also a possibility of suicidal or aggressive tendencies. A certain number of circadian and other chronobiological parameters also complicate the problem since the schedule (hour) as well as the day of the week or even the season can considerably modify vigilance and reaction time. Available medications able to create such problems are numerous and their mechanisms of action varied. They can influence vision, impulsiveness and vigilance. They can act either by direct mechanisms of sedation or, on the contrary, by raising inhibition through secondary mechanisms: delay in drug elimination or provoked insomnia. For the most part, incriminated medications belong to the different classes of sedative medicines: benzodiazepines, antiepileptics, some antihistaminic agents, some antidepressants, some thymo-regulators and some anti-hypertensives. Also included are desinhibitors or stimulant classes: amphetamines and related drugs, caffeine and codeine. Some of them can be used for their psychodysleptic properties: codeine and anticholinergic drugs. Finally, drug and medicinal associations can have unforeseen effects: for example, anticholinergics + alcohol + valpromide, etc. If it appears methodologically impossible that research could ever precisely quantify the share of responsibility of psychotropic drugs in causing road traffic accidents, this relation remains highly probable. It is therefore necessary that in the course of university and post-academic training, potential prescribers might regularly be advised of these risks. Lastly, public needs to be constantly informed.

Accidents, Traffic↗
PubMed1997

Human UGT2B7 catalyzes morphine glucuronidation.

A human UDP-glucuronosyltransferase (UGT) catalyzing the glucuronidation of morphine has been identified. A full length cDNA was isolated from a human liver cDNA library and found to be identical to the UGT2B7 form having a tyrosine at position 288. This cDNA was transfected into HK 293 cells, and stable expression was achieved. Cell homogenates and membrane preparations from HK 293 cells expressing UGT2B7 catalyzed the glucuronidation of morphine and other clinically significant opioid agonists, antagonists, and partial agonists. UGT2B7 catalyzed morphine glucuronidation at the 3- and 6-hydroxy positions and also mediated the formation of codeine-6-glucuronide from codeine. This represents the first demonstration of a UGT capable of catalyzing the glucuronidation of both the 3- and 6-positions of opioids. Since humans excrete morphine-3-glucuronide and morphine-6-glucuronide after morphine administration, it is likely that UGT2B7 is a major isoform in humans responsible for the metabolism of this important drug and its surrogates.

Cell Line↗
PubMed1997

[Dependence producing substances in the practice of the Insitute of Forensic Experts in Krakow].

Different pieces of evidence connected with drug addiction have been used as material for studies carried out at the institute of Forensic Research in Kraków since the end of the sixties. The number of expert's opinions concerning these questions is constantly on the increase. Work done by the institute in this field has led to the creation of a list of dependence producing substances and their substitutes used by addicts, the methods of illicit production, and the ways and usable forms in which they are introduced into the system. The author describes the most popular drugs and their substitutes used in Poland. The number of these substitutes is big. Among them are: different medicines (e.g. Parkopan, Aviomarin) and solvents (toluene), various vegetable raw materials (e.g. Folium Stramonli, Pallocybe semilanceata). At the same time the use of genuine narcotics like morphine derivatives originating from Papaver somniferum and Cannabis sativa products, obtained by unusual methods of domestic production, was observed. The number of cases involving amphetamine and its analogues increased last year. The presence of opium alkaloids (morphine, codeine, papaverine, thebaine and narcotine as well as acetyl derivatives of morphine (heroine, 3-monoacetylmorphine, 6-monoacetylmorphine) and codeine (acetylcodeine) was detected in "kompot" by means of TLC, HPLC and GC/MS methods. The author also presents, from the analyst's point of view, analytical and interpretational problems of drugs of abuse, and regulations connected with drug addiction and with road traffic offences.

Forensic Medicine↗
PubMed1996

Drug abuse in Nepal: a rapid assessment study.

A rapid assessment of drug abuse in Nepal was conducted at different sites, including eight municipalities in the five development regions of the country. To interview various groups of key informants, such methods as semi-structured interviews, in-depth interviews and focus group discussions were used. A snowball sampling strategy for respondents who were drug abusers and a judgemental sampling strategy for the non-drug-using key informants were applied. About one fifth of the sample was recruited from the treatment centres and the rest from the community. Drug abusers in prison were interviewed, and secondary data from treatment centres and prisons analysed. The study revealed that the sample of drug abusers had a mean age of 23.8 years and was overwhelmingly male. Most respondents lived with their families and were either unemployed or students. About 30 per cent of the sample was married. A large majority of the sample had a family member or a close relative outside the immediate family who smoked or drank alcohol and a friend who smoked, drank or used illicit drugs. Apart from tobacco and alcohol, the major drugs of abuse were cannabis, codeine-containing cough syrup, nitrazepam tablets, buprenor-phine injections and heroin (usually smoked, rarely injected). The commonest sources of drugs were other drug-using friends, cross-border supplies from India or medicine shops. The commonest source of drug money was the family. There has been a clear trend towards the injection of buprenorphine by abusers who smoke heroin or drink codeine cough syrup. The reasons cited for switching to injections were the unavailability and rising cost of non-injectable drugs and the easy availability and relative cheapness of injectables. About a half of the injecting drug users (IDUs) commonly reported sharing injecting equipment inadequately cleaned with water. Over a half of IDUs reported visiting needle-exchange programmes at two of the study sites where such programmes were available. Infection by the human immunodeficiency virus (HIV) appears to be low among IDUs, although systematic surveillance is absent. Two thirds of the sample had experienced sexual intercourse. The last sex partners reported by respondents were commercial sex workers, wives or girl friends. Condom use was low with primary partners and relatively high with sex workers. Treatment facilities, mostly located in the central urban areas of the country, are meagre. An overwhelming majority of drug abusers felt the need to stop abusing drugs. Cost-effective drug treatment and HIV prevention programmes for IDUs are urgently needed in all areas of the country.

Adult↗
PubMed1965

PHOTOCHEMICAL ACTION SPECTRUM OF THE TERMINAL OXIDASE OF MIXED FUNCTION OXIDASE SYSTEMS.

The reversal of the carbon monoxide inhibition by bands of monochromatic light was determined for the oxidative demethylation of codeine and monomethyl-4-aminopyrine and the hydroxylation of acetanilide by rat liver microsomes and for the hydroxylation of 17-hydroxyprogesterone at carbon-21 by bovine adrenocortical microsomes. Maximum reversal occurred at 450 millimicrons, the light absorption maximum of the CO compound of the CO-binding pigment of microsomes. The agreement between photochemical action spectrum and spectrophotometric difference spectrum supports the conclusion that the CO-binding pigment is the terminal oxidase of mixed function oxidase systems of mammals.

Acetanilides↗
PubMed1981

Aspirin and acetaminophen as constituents of analgesic combinations.

Aspirin and acetaminophen are the mainstays of oral analgesic combinations. One group of combinations is composed of antipyretic-analgesics combined with each other. The superior efficacy of such combinations as compared with an optimal dose of one of the constituents remains to be proved, and there is little evidence that such combinations have less adverse-effect liability than a single agent. On the other hand, there is substantial evidence that combinations of an optimal dose of aspirin or acetaminophen with a narcotic (eg, codeine, hydrocodone, or oxycodone) produce an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equianalgesic dose of a single constituent.

Acetaminophen↗
PubMed1984

Continuous naloxone infusion in pediatric narcotic overdose.

A 31-month-old girl required constant intravenous (IV) infusion of naloxone hydrochloride to treat codeine-induced respiratory and CNS depression. The infusion rate was 0.4 mg/hr (27 micrograms/kg/hr) over nine hours, without apparent side effects or evidence of toxic effects, for a total naloxone hydrochloride dose of 4.1 mg (280 micrograms/kg). Constant naloxone hydrochloride infusion at an initial rate of 0.4 mg/hr in pediatric narcotic poisoning should be considered if the patient responds inadequately to an initial 0.01-mg/kg bolus, requires repeated administration to reverse narcotic-induced effects, or has ingested long-acting agents. Continuous IV naloxone infusion is a convenient, safe, and effective method to treat narcotic overdose.

Acetaminophen↗
PubMed2000

Single dose dihydrocodeine for acute postoperative pain.

BACKGROUND: Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from a variety of electronic databases including Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double blind design, adult patients, pain of moderate to severe intensity at baseline, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs. DATA COLLECTION AND ANALYSIS: Data collection and analysis: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-harm. MAIN RESULTS: Fifty-two reports were identified as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 patients) compared dihydrocodeine with placebo and one (120 patients) compared dihydrocodeine (30 mg or 60 mg) with ibuprofen 400 mg. For a single dose of dihydrocodeine 30 mg in moderate to severe postoperative pain the NNT for at least 50% pain relief was 8.1 (95% confidence interval 4.1 to 540) when compared with placebo over a period of 4-6 hours. Pooled data showed significantly more patients to have reported adverse effects with dihydrocodeine 30 mg than with placebo. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior. REVIEWER'S CONCLUSIONS: A single 30 mg dose of dihydrocodeine is not sufficient to provide adequate pain relief in postoperative pain. Statistical superiority of ibuprofen 400 mg over dihydrocodeine (30 mg or 60 mg) was shown.

Acute Disease↗
PubMed1975

Cause and management of high volume output salt-depleting ileostomy.

Ileostomy function was studied in 12 patients with an established ileostomy following proctocolectomy, in 6 of whom minimal amounts (less than 9 cm) and in 6 significant amounts (30-120 cm, mean 60 cm) of terminal ileum had been removed. Patients who had undergone significant ileal resection had daily faecal volumes considerably greater than those with minimal ileal resection (1202 +/- 284 ml versus 401 +/- 92 ml, P less than 0.001), and also greater daily outputs of sodium (146 +/- 53 mEq versus 43 +/- 12 mEq) and potassium (12.7 +/- 9.0 mEq versus 4.0 +/- 0.99 mEq). The percentage water content of the ileostomy fluid was greater in patients who had had the ileum resected (93.1 +/- 1.8% versus 89.8 +/- 2.5%). In addition, the sodium/potassium ratio in the urine in patients with a properly acting ileostomy after ileal resection was low. It is concluded that when recurrent inflammatory bowel disease, partial small bowel obstruction and intraperitoneal sepsis have been excluded there remains a number of patients whose high ileostomy output is due entirely to the amount of ileum resected. The management of patients with a high output ileostomy with codeine phosphate, Lomotil and oral administration of sodium chloride tablets is discussed.

Adult↗
PubMed1978

Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain.

Two consecutive, randomized, double-blind trials were performed to test the analgesic properties of a synthetic nitrogen analog of tetrahydrocannabinol (NIB). In the first trial, the test preparation was superior to placebo and approximately equivalent to 50 mg of codeine phosphate. In the second study, the tetrahydrocannabinol analog was superior to placebo and to 50 mg secobarbital. NIB is not useful clinically because of the frequency of side effects.

Analgesics↗