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PubMed2002

Dietary and developmental influences on induced detoxification in an oligophage.

Many plant secondary compounds induce detoxification activity in herbivorous insects. Although inducibility may be advantageous as a means of reducing costs associated with maintenance of metabolism, another benefit of inducibility is that it may allow insects to tailor their detoxification profiles to multiple substrate toxins in their diets. The parsnip webworm, Depressaria pastinacella, must contend with many types of furanocoumarins, toxins present in abundance in all of its host plants. Previous studies have documented that cytochrome P-450s are responsible for metabolism of furanocoumarins in this species and that this overall activity is inducible. In this study, we examined the effects of ingestion of single furanocoumarins on metabolism of multiple furanocoumarins and the ability of webworms to adjust their metabolism profiles to match artificial diets with furanocoumarin content differing qualitatively and quantitatively from the average content found in their principal host. That detoxification rates of newly molted sixth instars prior to feeding did not differ from those of actively feeding fifth or sixth instars suggests that constitutive activities of furanocoumarin-metabolizing enzymes are maintained in the absence of substrates. All of the induction assays in this study were performed with ultimate instars. Each of the furanocoumarins assayed was found to induce metabolism of five different furanocoumarin substrates; however, the induction profile was independent of the inducing agent. Consistent with this finding, webworms were incapable of matching their detoxification profiles to diets with different furanocoumarin compositions. Thus, the profile of detoxification within individuals of this species appears to be genetically fixed, although there is considerable variation in profiles among individuals.

Adaptation, Physiological↗

PubMed2004

Abstinence incentive effects in a short-term outpatient detoxification program.

Despite being widely available, outpatient detoxification has limited efficacy as a stand-alone treatment. This study examined whether abstinence-contingent incentives would improve outcomes for patients entering outpatient opiate detoxification. Participants (N = 211) received a 100 US dollars voucher on the last day of detoxification either contingent on opiate and cocaine abstinence or noncontingently. Urine samples were collected at intake, on Wednesday, Friday (the last day of detoxification), and the following Monday. Among contingent-voucher participants, 31% were drug-free on Friday compared with 18% of noncontingent controls (Z = 2.4, p < .05). Few (12-13%) participants tested negative on Monday. Results support the ability of vouchers to produce modest improvements in abstinence initiation rates during brief detoxification but suggest that additional interventions are needed to sustain improvements.

Adult↗

PubMed1999

[Forced opioid detoxification under general anesthesia--a new challenge for anesthetists and intensive care physicians].

Treatment of opioid addicts by means of competitive opioid receptor antagonists was developed at the University of Vienna in 1987 by Loimer and co-workers. They compared two withdrawal regimens: The short Opiate withdrawal using a staggered naloxone regimen and the rapid opiate detoxification during general anesthesia by means of high doses of naloxone. Based on the latter concept, various modifications have been developed world-wide using either naloxone or as an alternative, naltrexone, an antagonist available for oral administration only. However, there are considerable objections to opioid detoxification during general anasthesia. The main criticism is based an the supposedly unacceptable high risk:benefit-ratio, the higher costs, the lack of psycho-social support, and the lack of prospective studies. However, first results suggest that rapid detoxification procedures are more successful in decreasing relapse than methods which are based on psychiatric treatment alone. As sympathetic hyperfunction is common in rapid detoxification procedures using high doses of opioid receptor antagonists, it is essential to avoid severe autonomic imbalance with possible subsequent impairment of organ functions. To prevent those disturbances, general anesthesia plays an important role. So far, there is almost no information about such methods in the anesthesiological literature. In this article the clinical relevance of such methods is discussed summarizing both the available literature and our own experience and we conclude that rapid opioid detoxification under general anesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms and who have failed repeatedly to complete conventional withdrawal.

Anesthesia, General↗

PubMed2004

[Buprenorphine or methadone for detoxification of young opioid addicts?].

OBJECTIVE: Comparison of buprenorphine vs. methadone to determine which medication is better for the detoxification of young opioid addicts. METHOD: 93 consecutive opioid-dependent patients (ICD-10) from an in-patient detoxification unit for adolescents were investigated, of which 42 chose buprenorphine and 51 chose methadone for detoxification. Both groups did not differ with regard to different sociodemographic and addiction-specific variables such as age, gender, initiation of drug consumption and duration of opioid intake. RESULTS: 23.5 % of the methadone patients and 38.1 % of the buprenorphine patients finished detoxification successfully, in addition the buprenorphine patients finished detoxification 1.62 days earlier. There was no significant difference concerning these items. CONCLUSION: Buprenorphine seems to be at least as effective as methadone for opioid withdrawal in young addicts.

Adolescent↗

PubMedDate not supplied

Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol.

This study compared the effects of alcohol and cocaine dependence severity on the outcome of outpatient detoxification from alcohol and cocaine. Subjects included 84 subjects with both alcohol and cocaine dependence admitted for outpatient detoxification. Fifty-three of the 84 subjects (63%) completed detoxification. Baseline cocaine use, cocaine craving, and cocaine withdrawal symptoms predicted detoxification outcome, whereas alcohol use, alcohol craving, and alcohol withdrawal symptoms did not. Among cocaine- and alcohol-dependent subjects, cocaine dependence severity appears to be a more important predictor of detoxification success than alcohol dependence severity.

Adult↗

PubMedDate not supplied

Sex hormones during alcohol withdrawal: a longitudinal study of 29 male alcoholics during detoxification.

It is a well-known fact that alcohol affects sex hormone levels in males. Even in the absence of liver dysfunction, there is still a direct toxic effect of ethanol on testosterone synthesis resulting in acutely decreased values. This study is based on 29 male alcoholics without severe signs of liver disease treated on the alcohol detoxification ward at Huddinge hospital in Stockholm, Sweden during 1995. The aim was to study levels of sex hormones in male alcoholics during detoxification with benzodiazepines and after 3 weeks of sobriety. Blood samples were taken three times: one day after admission (day 2) when the patient was sober, at discharge (day 5) and after 3 weeks of sobriety (day 21). Levels of testosterone and sex hormone-binding globulin (SHBG) showed the same pattern during detoxification and follow-up. They were both low, but generally within normal limits, on days 2 and 5, but raised after 3 weeks of sobriety. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were initially high, but were substantially depressed during detoxification. Levels of FSH recovered after 3 weeks, whereas LH remained at the same level. Most patients exhibited generally low levels of both FSH and LH, however. Levels of oestrone decreased steadily. There were no correlations between levels of sex hormones and the number of milligrams of oxazepam administered to the patients during detoxification either at admission, at discharge or at follow-up. In summary, the endocrinological response to alcohol intake is complex. This study suggests that the duration of endocrinological recovery after drinking is a quite long-lasting process, that different hormones need different times to recover and that the normal glandular-pituitary feed-back processes may be partly put out of order.

Alcoholism↗

PubMedDate not supplied

The detoxification experience of alcoholic in-patients and predictors of outcome.

This paper reports the detoxification experience and outcome at 6 months and 1 year following detoxification from alcohol in 160 patients admitted to a south-east London in-patient detoxification unit. Patients' socio-demographic characteristics are also described. The sample was predominantly middle-aged, mainly male, and highly dependent on alcohol. Subjects had been drinking heavily for many years and suffered physical and social complications in consequence. The rate of convulsions was 3.1% and of delirium tremens 1.25%. The details of the level of drug usage during detoxification and the assessment of severity of the withdrawal syndrome are also reported. The severity of the withdrawal syndrome and the incidence of significant complications of withdrawal were higher in those with a previous history of four or more episodes of detoxification, a previous history of withdrawal fits or evidence of high levels of tolerance and dependence assessed either by the Severity of Alcohol Dependence Questionnaire (SADQ) or by drinking on a typical heavy drinking day in excess of 24 U of alcohol. It is suggested that subjects with one or more of these attributes should be treated on an in-patient, rather than an out-patient, basis unless adequate support and monitoring systems are in place. Overall, patients made improvements on a wide range of social and psychological variables, but the 'abstinent' and 'controlled drinking' groups made significantly higher improvements on all variables in both follow-up periods. When patients improved their drinking status and reduced the levels of drink-related physical and social complications, in both time periods, their use of social and health resources decreased significantly. Living circumstances at intake were predictive of drinking status at both follow-up stages. The amount drunk on a heavy drinking day, at both follow-up stages, was predicted by severity of withdrawal, SADQ and living circumstances at intake in that order of importance.

Adult↗

PubMed2000

Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns.

OBJECTIVE: Mu-Opioid receptor blockade during general anesthesia is a new treatment for detoxification of opioid addicted patients. We assessed catecholamine plasma concentrations, oxygen consumption, cardiovascular variables, and withdrawal symptoms after naloxone and tested the hypothesis that variables are influenced by the anesthetic administered during detoxification. DESIGN: Prospective randomized clinical study. SETTING: Intensive care unit of a university hospital and psychiatric ward. PATIENTS: Twenty-five mono-opioid addicted patients with mild to moderate systemic disease (ASA II classification) in a methadone substitution program. INTERVENTION: General anesthesia with either propofol (129+/-7 microg x kg(-1) x min(-1), mean +/- SEM) or methohexital (74+/-14 microg x kg(-1). min(-1)), mu-opioid receptor blockade by naloxone in a stepwise fashion (increasing doses of 0.4 mg, 0.8 mg, 1.6 mg, 3.2 mg, and 6.4 mg at 15 min intervals followed by 0.8 mg x hr(-1) for 24 hrs) and naltrexone 50 mg x day(-1) orally for > or =4 wks. Clonidine was started 180 mins after the first naloxone dose and its infusion rate was individually adjusted to mitigate withdrawal symptoms during weaning and after extubation. MEASUREMENTS AND MAIN RESULTS: During propofol and methohexital anesthesia, naloxone induced a 30-fold increase in epinephrine and a significant three-fold increase in norepinephrine plasma concentrations without a significant difference between groups. This increase in catecholamine plasma concentrations was associated with increased oxygen consumption and marked cardiovascular stimulation with both anesthetics, as shown by increased cardiac index, heart rate, and systolic atrial pressure whereas diastolic pressure remained unchanged. Patients receiving propofol could be extubated significantly earlier after discontinuation of the anesthetics. Although the maximum degree of withdrawal symptoms (Short Opioid Withdrawal Scale) on the day after detoxification was similar with both anesthetics, subsequent withdrawal symptoms decreased significantly more rapidly after propofol anesthesia. CONCLUSIONS: Naloxone treatment, in opioid-addicted patients, induced a marked increase in catecholamine plasma concentrations, metabolism, and cardiovascular stimulation during anesthesia with both propofol and methohexital. Although both anesthetics appear suitable for detoxification treatment, the use of propofol is associated with earlier extubation and, surprisingly, a shortened period of long-term withdrawal symptoms during detoxification.

Adult↗

PubMed2001

Combining median electroencephalography frequency and sympathetic activity in an index to evaluate opioid detoxification in patients.

During rapid opioid detoxification, increased sympathetic activity and a greater median frequency (MF) of activity on electroencephalography (EEG) have been reported. The purpose of this study was to evaluate a new index for detoxification that combines sympathetic activity and MF data. After informed consent was obtained, eight patients were sedated with propofol. The MF of EEG activity derived from frontal electrodes was determined. Heart rate variability was evaluated in 256-second segments by power spectral analysis, and sympathetic activity was determined by the low frequency component. The Hoffman Index for narcotic detoxification was weighted 70% to sympathetic activity and 30% to MF to normalize the difference in scales and to provide adequate weight to the sympathetic component. Opioid detoxification was produced by infusion of 25 mg naloxone for 30 minutes, followed by a 24-hour infusion of 1 mg per hour. The MF showed a rapid increase during high-dose infusion of naloxone, but the peak response occurred 1 to 2 hours later. Sympathetic activation and the Hoffman Index increased more slowly after the start of naloxone infusion, but peak increases in all components occurred at approximately the same time. The peak increases in Hoffman Index (110% of baseline), MF (260%), and sympathetic activity (304%) during administration of naloxone were significant and correlated with respect to time (r = 0.89-0.94). The Hoffman Index showed an early increase related to MF and a well-defined peak response indicative of sympathetic and MF activity. The behavior of the Hoffman Index in relation to the MF and sympathetic activity more clearly indicated the onset of opioid detoxification and the maximum response to opioid reversal than did MF or sympathetic activity alone.

Electrocardiography↗

PubMed2006

Deficient UDP-glucuronosyltransferase detoxification enzyme activity in the small intestinal mucosa of patients with coeliac disease.

BACKGROUND: Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP-glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes-P450, glutathione S-transferases and UDP-glucuronosyltransferases. AIM: To compare the UDP-glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls. METHODS: We assessed UDP-glucuronosyltransferase enzyme activities towards 4-methylumbelliferone in small intestinal biopsies of patients with coeliac disease (n = 22) and age- and sex-matched controls (n = 27). RESULTS: Small intestinal UDP-glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 +/- 0.27 vs. 0.35 +/- 0.16 nmol/min mg protein, respectively (mean +/- s.d., P = 0.005). DISCUSSION: The low small intestinal UDP-glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients.

Carcinogens↗

PubMed1979

A model enzymic extracorporeal detoxification system.

Preliminary studies at the University of Oklahoma have incorporated the use of a continuous, seal-less blood centrifuge as an extracorporeal detoxification unit to aid in the removal of foreign chemicals from the blood. Detoxification is performed by immobilized enzymes in conjunction with a cofactor (NADPH) bound to a water-soluble macromolecule. A drug enters the device with the plasma and then passes across a semipermeable membrane which serves to retain the cofactor. At this point, a combination of the drug, the cofactor and the enzyme react to form the drug-oxide. The oxide then passes back through the membrane into the blood and back into the body. Concurrently, the macro-NADP+ is reduced by G-6-P and G-6-PD in the cofactor regeneration portion of the device. To facilitate detoxification, the centrifuge is employed to provide plasma rich in toxins, but void of potentially interfering blood components such as platelets and whole blood cells. These components tend to dilute the toxins or adhere to the interfacing membrane, decreasing the permeability of these toxins into the detoxification unit. It is felt that the centrifuge-detoxification combination will provide a potentially efficient hepatic assist device.

Aniline Compounds↗

PubMed2003

Oxidative stress in Synechococcus sp. strain PCC 7942: various mechanisms for H2O2 detoxification with different physiological roles.

This study focuses on the mechanisms for hydrogen peroxide detoxification in Synechococcus sp. strain PCC 7942. To gain better understanding of the role of different routes of hydrogen peroxide detoxification, we inactivated TplA (thioredoxin-peroxidase-like), which we recently identified. In addition, we inactivated the gene encoding catalase-peroxidase and examined the ability to detoxify H(2)O(2) and to survive oxidative stress in both of the single mutants and in the double mutant. Surprisingly, we observed that the double mutant survived H(2)O(2) concentrations that the single catalase-peroxidase mutant could not tolerate. This phenotype correlated with an increased ability of the double mutant to detoxify externally added H(2)O(2) compared to the catalase-peroxidase mutant. Therefore, our studies suggested the existence of a hydrogen peroxide detoxification activity in addition to catalase-peroxidase and thioredoxin-peroxidase. The rate of detoxification of externally added H(2)O(2) was similar in the wild-type and the TplA mutant cells, suggesting that, under these conditions, catalase-peroxidase activity was essential for this process and TplA was dispensable. However, during excessive radiation, conditions under which the cell might experience oxidative stress, TplA appears to be essential for growth, and cells lacking it cannot compete with the wild-type strain. Overall, these studies suggested different physiological roles for various cellular hydrogen peroxide detoxification mechanisms in Synechococcus sp. strain PCC 7942.

Catalase↗

PubMed2004

Orthoptic status before and immediately after heroin detoxification.

AIM: To determine whether changes in orthoptic status take place during withdrawal from heroin and/or methadone. METHOD: A prospective study of patients, using a repeated measures design, attending a 5 day naltrexone compressed opiate detoxification programme. RESULTS: 83 patients were seen before detoxification (mean age 27.1 (SD 4.6) years) and 69 after detoxification. The horizontal angle of deviation became less exo/more eso at distance (p<0.001) but no significant change was found at near (p = 0.069). Stereoacuity, visual acuity, and convergence were found to be reduced in the immediate post-detoxification period. Prism fusion range, refractive error, subjective accommodation, and objective accommodation at 33 cm did not reduce but a small decrease was found in objective accommodation at 20 cm. CONCLUSIONS: The eso trend found in these patients may be responsible for the development of acute concomitant esotropia in some patients undergoing heroin detoxification. However, the mechanism for this trend does not appear to be caused by divergence insufficiency or sixth nerve palsy.

Accommodation, Ocular↗

PubMed1986

Prevalence and diagnostic reliability of methadone maintenance detoxification fear.

The authors identified a pathological fear of methadone detoxification in 22%, 25%, and 32% of random samples of patients in three disparate methadone maintenance programs. Patients with a pathological fear of detoxification had higher scores on the Detoxification Fear Survey Schedule, had longer histories of addiction, had been addicted for a larger percent of their life spans, and were older than patients without this fear. A greater proportion of the female patients had this fear, and a greater proportion of the patients with this fear had drug-free urinalyses. The authors recommend the use of the Detoxification Fear Survey Schedule as well as intervention to help rehabilitated opioid addicts initiate and complete detoxification.

Adult↗

PubMed1993

Organic mood syndrome associated with detoxification from methadone maintenance.

OBJECTIVE: The authors delineate the clinical characteristics of mood state changes that occur in stable opioid-dependent patients undergoing therapeutic detoxification from methadone maintenance treatment. METHOD: Twenty-four patients participated in a blinded protocol for gradual methadone dose reduction that included weekly assessments of affective state using the Profile of Mood States (POMS) as well as weekly assessments of signs and symptoms of opioid withdrawal. Data obtained before methadone dose reduction and during the 2-week period of maximal dysphoric symptoms were compared. Changes in affective and opioid withdrawal measures were compared in patients who differed in their success in completing the detoxification regimen. RESULTS: Sustained increases in POMS scores of greater than 20 points were observed in 12 of the 24 patients during the course of detoxification. The emergence of symptoms of dysphoria was accompanied by insomnia, loss of appetite, and somatic complaints consistent with symptoms of opioid withdrawal but only minimal levels of objective signs of withdrawal. Greater changes from baseline in mood state and opioid withdrawal measures occurred in patients who were unable to complete the detoxification regimen. CONCLUSIONS: The development of an organic mood syndrome is a common occurrence in patients undergoing slow detoxification from methadone maintenance treatment and is associated with a poor outcome.

Adult↗

PubMed1994

Methadone maintenance outcome as a function of detoxification phobia.

OBJECTIVE: Methadone maintenance outcome as a function of detoxification phobia was examined. METHOD: Opiate addicts (N = 271) in a 1983 random sample of methadone maintenance patients from three diverse populations were studied. Subjects from an individually assessed follow-up sample (N = 102) were compared on detoxification phobia. Logistic regression analysis yielded best predictors of the phobia. RESULTS: Phobic patients were more likely to be white, female, and abstinent; to have had fewer detoxification attempts and longer periods on maintenance; to show persistence of the phobia; to meet diagnostic criteria for depressive or anxiety disorders; and to have Addiction Severity Index scores above the 75th percentile for psychological problems. CONCLUSIONS: Detoxification phobia has a complex relationship to methadone maintenance outcome. It is associated with greater abstinence for patients in methadone maintenance treatment. However, for rehabilitated phobic patients it presents a barrier to successful detoxification and a drug-free adjustment that is often associated with other psychopathology but could be ameliorated by targeted assessment and treatment.

Adult↗

PubMed2000

The effect of copayments on drug and alcohol treatment following inpatient detoxification under managed care.

OBJECTIVE: The study examined the rate and duration of outpatient substance abuse treatment following inpatient detoxification under managed care. METHODS: Seven years of claims data from a large behavioral health care carve-out plan were used to identify patients. Rates and duration of formal substance abuse treatment following detoxification were calculated, and regression models were used to explore factors that may affect participation in treatment. RESULTS: Seventy-nine percent of the detoxification patients received formal substance abuse treatment, the majority within the week following discharge. Formal follow-up care lasted an average of ten weeks, with visits occurring on average about once a week. When other variables likely to influence participation in substance abuse treatment were controlled for, the level of outpatient copayments significantly affected the rate of participation in treatment. CONCLUSIONS: These findings indicate that the rate of participation in outpatient treatment after detoxification is high, but room for improvement remains. The results suggest that reducing copayment levels is one mechanism for increasing the likelihood that individuals with severe drug and alcohol problems will receive subsequent treatment. The need for such treatment is underscored by the severity of illness of those who undergo detoxification and the societal costs of untreated substance use disorders.

Adult↗

PubMed2004

Mirtazapine improves alcohol detoxification.

The objective of the present study was to determine whether a combined psychotherapeutic-psychopharmacological (with mirtazapine) treatment of collateral anxiety and depressive symptomatology during the post-withdrawal phase of alcoholism facilitates the process of alcohol detoxification, which is a decisive stage in the treatment of alcohol-dependent individuals. For that purpose, the rate of remission of anxiety and depressive symptoms over a 4-week detoxification period was evaluated between two groups: the first group followed a standard detoxification protocol (n = 33) and the second group was assigned to mirtazapine in addition to standard treatment (n= 35). A marked reduction of anxiety and depressive symptoms was demonstrated in both groups. However, patients on mirtazapine improved more and at a faster rate compared to controls. Thus, mirtazapine, used adjunctively to short-term psychotherapy, may help the detoxification process by minimizing physical and subjective discomfort. Consequently, it may improve patient compliance in alcohol detoxification programs and facilitate the initial phase treatment of alcohol abuse dependence.

Adolescent↗