Effect of chronic ethanol and withdrawal on the mu-opioid receptor- and 5-Hydroxytryptamine(1A) receptor-stimulated binding of [(35)S]Guanosine-5'-O-(3-thio)triphosphate in the fawn-hooded rat brain: A quantitative autoradiography study. (65/2131)

Previous studies have shown that chronic ethanol influences the density of central mu-opioid receptors and serotonin(1A) (5-hydroxytryptamine(1A)) receptors. To determine whether the functional coupling of these two receptors to G proteins in the rat brain, particularly in mesocorticolimbic regions, is affected by ethanol, receptor-mediated [(35)S]guanosine-5'-O-(3-thio)-triphosphate ([(35)S]GTPgammaS) binding stimulated by [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO) or L694,247 was used. By quantitative autoradiography, receptor-mediated [(35)S]GTPgammaS binding activated by the two agonists was mapped throughout brain sections at the level of the nucleus accumbens and hippocampus from groups of alcohol-preferring Fawn-Hooded (FH) rats after different ethanol consumption paradigms. Significant DAMGO (mu-opioid receptor agonist)-stimulated binding of [(35)S]GTPgammaS was obtained in the striatum, nucleus accumbens, and lateral septum, whereas L694,247 (5-hydroxytryptamine(1A/1B/1D) receptor agonist)-stimulated binding of [(35)S]GTPgammaS was observed in the lateral septum, amygdala, and cingulate cortex. Chronic ethanol self-administration significantly reduced DAMGO-stimulated [(35)S]GTPgammaS binding in the nucleus accumbens (-19%), lateral septum (-15%), and striatum (-23%), which recovered toward control levels after ethanol withdrawal. However, chronic ethanol, as well as ethanol withdrawal, failed to produce any significant alteration in L694,247-stimulated [(35)S]GTPgammaS binding in all tested brain regions. The region-specific and receptor-specific alteration of agonist-stimulated [(35)S]GTPgammaS binding suggests that the change of functional coupling of mu-opioid receptors to G proteins induced by chronic ethanol drinking may have a pathophysiological role in the consequences of ethanol consumption.  (+info)

EEG controlled rapid opioid withdrawal under general anaesthesia. (66/2131)

We performed rapid opioid detoxification under propofol anaesthesia in 30 opioid addicts, using the opioid receptor antagonist naltrexone. Two strategies to obtain a sufficient depth of anaesthesia and to avoid anaesthetic overdose were evaluated. Patients were allocated randomly to one of two groups. In group 1, the effects of propofol were monitored by observing clinical signs, and in group 2, depth of anaesthesia was controlled using an EEG threshold method. Withdrawal symptoms and post-anaesthetic recovery time were assessed. All patients remained stable and no anaesthetic complications were noted. There were significant differences in the total dose of propofol given (group 1, mean 72 (SD 9) mg kg-1; group 2, 63 (8) mg kg-1; P < 0.01), duration of anaesthesia (318 (53) min vs 309 (42) min; P < 0.05), duration of recovery time (49 (13) min vs 40 (12) min; P < 0.01) and frequency of withdrawal symptoms between groups. In addition, the incidence of side effects was different between groups (62 vs 29 points on a withdrawal symptom scale; P < 0.01). To obtain a sufficient depth of anaesthesia but to avoid inappropriately large doses of anaesthetic, we consider that EEG monitoring is valuable during rapid opioid detoxification.  (+info)

Can we use anxiolytics during pregnancy without anxiety? (67/2131)

QUESTIONOne of my patients suffers from anxiety and was using lorazepam to treat it. When she became pregnant, she stopped the medication immediately, but now she is worried about the potential effect on the baby because she was using the drug just after conception. Is this class of drugs safe during pregnancy? What should she do if she needs antianxiety treatment during the rest of her pregnancy?ANSWEREvidence to date from cohort studies did not identify a notable association between use of benzodiazepines and increased risk of major malformations, including oral cleft. In contrast, data from case-control studies show a slightly increased risk of oral cleft. Hence, level 2 ultrasonography is recommended to rule out visible forms of cleft lip. Using benzodiazepines late in pregnancy could cause withdrawal syndrome in newborns.  (+info)

Polypharmacy in a general surgical unit and consequences of drug withdrawal. (68/2131)

AIMS: To identify drug usage/withdrawal in surgical patients and the relative risk this imposes on postoperative surgical complications. METHODS: A prospective survey of patients' medicines, oral intake (food/fluids/ medicines) and postoperative complications was carried out in the General Surgical Unit, Dunedin Hospital, Dunedin, New Zealand. RESULTS: One thousand and twenty-five general surgical patients aged >/= 16 years, were entered into the study. Half of the patients were taking medicines unrelated to surgery. On average these patients received 9 different drugs (range 1-47) from a selection of 251, of which 21% were released in the last 10 years. The mean number of these drugs taken increased with age, vascular surgery and other major procedures. The majority of patients (53%) were taking drugs for cardiovascular problems. Only 8% of admissions were on the drugs more traditionally recognized to be of importance to the surgery, i.e. steroids and diabetic therapy. With respect to risk, taking a drug unrelated to surgery was associated with an increased relative risk of a postoperative complication by 2.7 (95% C.I. 1.76-4.04) compared with those who were not taking any drug. Cardiovascular drugs contributed significantly to this risk; when they were excluded from analysis, the risk dropped to 1.8 (95% C.I. 1.14-2.93). Death may be more common in those taking ACE inhibitors. Drug withdrawal and complications were analysed and as the time without medicines increased (range 1-42 days) so did the complication rate (chi2 = 14.7, DF = 2, P = 0.007). Of those patients who were taking a cardiovascular medicine and were without their normal medicines for a period of time postoperatively, 12% suffered a cardiac complication. CONCLUSIONS: Many patients admitted to a general surgical ward, are taking medicines unrelated to surgery. Drug therapy unrelated to surgery is a useful predictor for increased postoperative complications and one for which preventive action can be taken. This study provides evidence that withdrawal of regular medicines may add significant risk to the surgery and further complicate outcome. The longer patients were without their regular medicines the more nonsurgical complications they suffered. Reintroduction of patients' regular medicines early in their postoperative course may decrease morbidity and mortality in-patients.  (+info)

Alcohol withdrawal and hypokalaemia: a case report. (69/2131)

A case is presented where a 25-year-old man developed a serious hypokalaemia (K(+) 2.2 mmol/l) during alcohol withdrawal, despite intravenous saline treatment and normal feeding. As hypokalaemia can be symptom-free, we want to draw attention to the combination of vomiting, malnutrition and alcohol withdrawal, as these can cause lethal complications. We therefore recommend that potassium serum level should be routinely monitored during alcohol withdrawal, even when this is being managed in the community.  (+info)

Factors that determine a propensity for cocaine-seeking behavior during abstinence in rats. (70/2131)

Individual differences in locomotor responses to novelty and psychostimulants, and sensitization following repeated drug exposure, predict increased sensitivity to the reinforcing effects of psychostimulants and are thought to underlie vulnerability to drug addiction. This study tested whether these factors determine another core feature of drug addiction, the propensity for drug-seeking behavior during abstinence in rats with prior cocaine-self-administration experience. Low and high response groups for each of these factors were determined in outbred rats by the median locomotor response to novelty and amphetamine prior to cocaine self-administration (pre-test), and to amphetamine during abstinence (post-test). Cocaine-seeking behavior during abstinence was measured by the level of drug-paired lever responding during extinction, and also during reinstatement induced by cocaine-associated cues, an amphetamine priming injection, and footshock stress. Animals with low and high locomotor responses to novelty and the amphetamine pre-test showed similar levels of cocaine-seeking behavior during extinction and reinstatement testing. Locomotor responses to amphetamine following cocaine self-administration (post-test) also failed to determine amphetamine's ability to reinstate cocaine-seeking behavior. Conversely, high levels of amphetamine-induced reinstatement were associated specifically with escalating cocaine intake during prior self-administration. These animals also developed locomotor sensitization to amphetamine following cocaine self-administration (post-test vs. pre-test), but the capacity to develop locomotor sensitization was not sufficient to determine a propensity for cocaine-seeking behavior. The findings suggest that the relationship between locomotor responses to novelty, amphetamine and behavioral sensitization a,nd the propensity for cocaine-seeking behavior during abstinence is complex, while the level of drug intake during prior self-administration is a primary determinant of this behavior.  (+info)

Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) (71/2131)

OBJECTIVES: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic effects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users. METHODS: A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. RESULTS: Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not differ significantly in their performance from the non-users. CONCLUSIONS: The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are sufficient to cause neurotoxicity in humans.  (+info)

An approach to drug abuse, intoxication and withdrawal. (72/2131)

The symptomatic effects of drug abuse are a result of alterations in the functioning of the following neurotransmitters or their receptors: acetylcholine, dopamine, gamma-aminobutyric acid, norepinephrine, opioids and serotonin. Anticholinergic drugs antagonize acetylcholine receptors. Dissociative drugs affect all transmitter sites. Opiates act on both opioid and adrenergic receptor sites. Psychedelic drugs stimulate serotonin release, and sedative-hypnotic drugs potentiate the gamma-aminobutyric acid receptor. Specific signs and symptoms are associated with the neurotransmitters and receptors affected by each drug class. By recognizing symptomatic changes related to particular neurotransmitters and their receptors, family physicians can accurately determine the drug class and intervene appropriately to counteract drug-induced effects.  (+info)