Treatment Of Withdrawal Syndrome Research Articles

Neonatal Opioid Withdrawal Syndrome Treatment Guidelines and Birth Hospital Utilization.

In November 2020, the American Academy of Pediatrics published guidelines for management of neonatal opioid withdrawal syndrome (NOWS), recommending nonpharmacologic treatment as the first-line approach, unless pharmacologic treatment is needed for severe NOWS. Using data from tertiary care pediatric hospitals, we examined the impact of the guidelines on use of pharmacotherapy, length of stay, and NICU admission for infants with NOWS. We extracted birth hospitalization data for newborns diagnosed with NOWS discharged from 2019 to 2022 from the Pediatric Health Information System. We compared hospital utilization and pharmacologic treatment pre- and postguidelines and used interrupted time series regression to examine trends over time. We included N = 824 newborns (n = 434 pre, n = 390 post) with NOWS from 11 hospitals. The use of pharmacologic treatment was significantly lower in the postguidelines period (59.0% pre versus 50.3% post; P = .01). Median length of stay was similar pre and post (P = .55). NICU admission was significantly lower in the postguidelines period (78.6% pre versus 46.7% post; P < .001), with an immediate decrease (β = -23.0%; P < .001) and a decrease over time in the postguidelines period (β = -0.7% per month; P = .03). Most hospitals reduced pharmacologic treatment (8 of 11; 73%) and NICU use (10 of 11; 91%) postguidelines. There was a reduction in the use of pharmacologic treatment and NICU utilization for infants with NOWS after the release of American Academy of Pediatrics guidelines for NOWS management.

Further Evidence of Relationship Between Thiamine Blood Level and Cognition in Chronic Alcohol-Dependent Adults: Prospective Pilot Study of an Inpatient Detoxification with Oral Supplementation Protocol.

The relationship between thiamine blood level (TBL) and cognition remains uncertain including amongst alcohol-dependent persons (ADP) AIM: To evaluate this relationship during protocol-driven inpatient alcohol detoxification treatment including thiamine supplementation (AD+Th) METHODS: Prospective 3-week study with 100 consecutively admitted detoxification-seeking ADP (47.7±11 years-old, 21% females) without superseding comorbidities requiring treatment. TBL and Montreal Cognitive Assessment (MoCA) were measured at admission (t1, pre-AD+Th) and discharge (t3, post-AD+Th). Frontal Assessment Battery (FAB) was performed at t1. AD+Th included abstinence, pharmacological alcohol withdrawal syndrome treatment and oral thiamine supplementation (200 mg/day for 14 days). Regression and mediation analyses assessed TBL-cognition relationships. We found no cases of Wernicke Encephalopathy (WE) and only one case of thiamine deficiency. Both MoCA and TBL significantly improved across AD+Th (with medium-to-large effect sizes). At t1, TBL significantly predicted MoCA and FAB sum scores (medium effect sizes; extreme and very strong evidence, respectively). The clear TBL-MoCA association disappeared at t3. In multivariate regression and mediation analyses exploring key influential factors of cognition (identified by LASSO regression), the TBL-MoCA interactions did not relevantly change at t1 and t3. Age, serum transaminases, vitamin D levels, drinking-years and depression score weakly modified the relationship. TBL was a robust predictor of pre-detoxification cognitive impairment, and both TBL and cognition improved significantly during AD+Th (including abstinence) in our ADP population, supporting routine thiamine supplementation for ADP, even those at low WE-risk. TBL-cognition relationship was minimally confounded by age, alcohol-toxicity proxies, mood, and vitamin D levels. https://osf.io/b54eh/.

Delivery timing for the opioid–exposed infant

The prevalence of opioid use disorder and medication-assisted treatment in pregnancy is increasing. Compared with term infants, preterm infants have a lower incidence of neonatal opioid withdrawal syndrome. It is unknown whether early term delivery compared with full or late-term delivery decreases the risk of neonatal opioid withdrawal syndrome. This study aimed to compare the neonatal outcomes among opioid-exposed infants born in the early, full, and late-term periods. This was a retrospective cohort study of opioid-exposed pregnancies delivering at a single center from 2010 to 2017 at ≥37 weeks gestation. Participants with multiple gestations or fetal anomalies were excluded. Maternal opioid exposurewas defined as prescription (including medication-assisted treatment) or nonprescription opioid use or a positive urine drug screen in pregnancy for opiates. The primary outcome was a neonatal composite of respiratory distress syndrome, neonatal sepsis, neonatal seizures, hypoxic ischemic encephalopathy, jaundice requiring treatment, 5-minute Apgar <5, neonatal intensive care unit admission, neonatal opioid withdrawal syndrome, or neonatal death. The secondary outcomes included individual components of the primary outcome, birthweight, need for and length of neonatal opioid withdrawal syndrome treatment, length of hospital admission, and maximum Finnegan scores. Early (37-<39), full (39-<41), and late (41-<42 weeks) term groups were defined by the American College of Obstetricians and Gynecologists. Of 399 infants, 136 (34.1%), 229 (57.4%), and 34 (8.5%) were born in the early, full, and late-term periods, respectively. Two hundred and seventy patients (67.7%) received medication-assisted treatment for opioid use disorder, and the baseline characteristics were similar in all the groups except for history of intranasal heroin use, positive urine toxicology screen for heroin or any opiates, and delivery indication (P<.05). The primary composite outcome occurred in 313 (78.4%) neonates, and 296 (74.2%) neonates had neonatal opioid withdrawal syndrome. More than half (219 [54.9%]) of opioid-exposed neonates were admitted to the neonatal intensive care unit, and 160 (40.1%) required pharmacologic neonatal opioid withdrawal syndrome treatment for a mean duration of almost 3 weeks (19.0±16.1 days). There were no significant differences in the primary composite outcome, incidence of neonatal opioid withdrawal syndrome, or other secondary outcomes (except birthweight) between neonates born in the early, full, or late-term periods. Although neonatal morbidity was frequent among opioid-exposed neonates, the incidence and severity of neonatal opioid withdrawal syndrome or other neonatal outcomes were not different between neonates delivered in the early, full, and late-term periods, suggesting that opioid-exposed infants may not benefit from early term delivery.

Pharmacological Treatment of Alcohol Withdrawal

Excessive chronic alcohol users, and particularly patients with alcohol use disorder, may present an alcohol withdrawal syndrome if they abruptly stop drinking. Alcohol withdrawal syndrome requires pharmacological treatment for the treatment of withdrawal symptoms and to prevent withdrawal complications. Medically assisted withdrawal treatment is used in alcohol treatment units, but it is also frequently required in patients admitted to hospital for other conditions. Review of major guidelines covering treatment of withdrawal syndrome with the aim to describe recent evidence and recommendations about the pharmacological treatment for alcohol withdrawal syndrome. Four major guidelines concerning treatment of withdrawal syndrome were selected (National Institute for Health and Care Excellence, American Society of Addiction Medicine, World Federation of Societies of Biological Psychiatry and American Psychiatric Association) and screened for the recommendations and level of evidence on drug prescribing for alcohol withdrawal syndrome. The Maudsley guidelines were also considered in this review. All the four reviewed guidelines recommended benzodiazepines as the first line treatment for alcohol withdrawal syndrome. The association of anticonvulsivants, adrenergic alpha-2 agonists, betablockers and antipsychotics with benzodiazepines is recommended for symptom reduction in severe alcohol withdrawal syndrome. Thiamine should be administered to all patients to prevent Wernicke-Korsakoff encephalopathy. If there is any electrolytic imbalance it should be corrected. Maintaining a high level of suspicion for alcohol withdrawal syndrome is important across all clinical settings, and it should be promptly treated.

Intervensi Farmakologi Sindrom Putus Obat pada Penyalahguna Opioid

Opioid withdrawal syndrome appears after abrupt discontinuation of opioids characterized by watery eyes, runny nose, muscle pain, anxiety, yawning, gooseflesh, mydriasis, gastrointestinal discomfort, and rapid heartbeat. Globally, opioid abuse remains a significant problem, necessitating adequate treatment of drug syndrome in opioid addicts, particularly pharmaceutical therapy. Therefore, this study aimed to identify, evaluate, and analyze pharmacological management in opioid abusers. The articles used were retrieved based on specific limitations using the main keywords "opioid withdrawal syndrome treatment" and additional keywords "heroin, fentanyl, morphine" that were published in PubMed, ScienceDirect, and SpringerLink. From the 21 articles included, heroin abuse was the most prevalent. The primary treatment for opioid abuse is substitution therapy of opioid or non-opioid such as lofexidine, naltrexone, buprenorphine, dronabinol, methadone, pregabalin, oxytocin, antagonist corticotropin-releasing factor type 1 (CRF1), tramadol, clonidine, and pioglitazone. Additionally, the patient received symptomatic therapy based on the condition. The drugs used for treatment and willingness to obtain therapy are the factors for the withdrawal completion rate. The results were evaluated using opioid withdrawal assessment, either from a subjective, objective, or clinical perspective.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum.Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0–T4 continuum to advance the care of hospitalized patients who experience SAWS.Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0–T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps.Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non–γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice.Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Selegiline alleviates the depressive-like behaviors of methamphetamine withdrawal syndrome through modulating mitochondrial function and energy hemostasis

Background: Methamphetamine (METH) is considered the second most commonly abused drug in the world. There is limited or no evidence concerning the effective treatment of METH withdrawal symptoms, such as depression and anxiety. Mode of action of selegiline (increase of the brain neurotransmitter activity) suggests that it might be useful in METH withdrawal syndrome treatment, being capable of diminishing the preference and depression involved in drug degeneration and addictive activities. Methods: Mice were randomly divided into 10 groups (n= 10): five METH-nondependent groups treated with normal saline intraperitoneal (i.p) for two weeks, to which, from the 15th day, selegiline (10, 20 and 40 mg/kg; i.p) or fluoxetine (5 mg/kg; i.p) was administrated for 10 consecutive days. Other groups injected METH (2 mg/kg, at 12-h intervals) for 14 days. From the 15th day, the 10-day period of METH abstinence started and the above-mentioned doses of selegiline or fluoxetine were injected. Then, the mice were evaluated for depression and biochemical assessments from the 25th day of the study. Results: Our data indicated that post-treatment with selegiline (10-40 mg/kg; i.p) for 10 days reversed METH-induced depressive-like behaviors in the forced swimming test (FST), tail suspension test (TST), and splash test with exerting no effects on the locomotor activity. Furthermore, none of the previously proposed treatments affected the behavioral abnormality in the control animals. Moreover, both selegiline and fluoxetine as standard antidepressant drug, substantially improved the levels of mitochondrial reduced glutathione (GSH), malondialdehyde (MDA), and adenosine triphosphate (ATP). Conclusion: Our findings demonstrated that selegiline produced antidepressant-like effects following METH withdrawal and prevented the mitochondrial dysfunction in the male mice.

The effectiveness and tolerability of anti‐seizure medication in alcohol withdrawal syndrome: a systematic review, meta‐analysis and GRADE of the evidence

AbstractBackground and AimsAnti‐seizure medications (ASMs) have been used historically as treatment options in alcohol withdrawal syndrome (AWS). In the past 10 years, there have been no large‐scale meta‐analyses comparing ASMs with placebo or the current AWS treatment standard, benzodiazepines. We aimed to evaluate the efficacy and tolerability of ASMs in AWS.MethodsSystematic review and meta‐analysis of randomised controlled trials (RCTs) via searching Medline, Embase and PsychINFO from database inception to March 2020 involving adults age &gt;18 years with AWS. We included 24 RCTs reporting on a total of 2223 participants. Efficacy outcomes included the number of participants experiencing AWS related seizures or delirium, Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA‐Ar) score reduction and rescue medication requirements. Tolerability outcomes included adverse event rate and dropout because of adverse events, alongside severe and life‐threatening adverse event rates. Quality was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsThere was no evidence of significant improvements in any efficacy outcomes when comparing ASMs with placebo or benzodiazepines. When compared with benzodiazepines, ASMs demonstrated significantly increased odds of requiring rescue medications (OR = 3.50, 95% CI = 1.32, 9.28; P = 0.012). When comparing ASMs with placebo, there were significantly more dropouts because of adverse events (OR = 1.86, 95% CI = 1.05, 3.28; P = 0.034). Most results were of very low quality with the majority of included studies conducted before 2000.ConclusionsThis systematic review and meta‐analysis found no evidence to support general first line clinical use of anti‐seizure medications in alcohol withdrawal syndrome treatment.

Delirium Tremens in the Older Adult.

Caring for patients experiencing alcohol withdrawal syndrome can be challenging. Patients 65 and older are at increased risk for alcohol withdrawal syndrome related complications. The higher prevalence of co-morbidities, including cognitive impairment, longer drinking history and greater sensitivity to alcohol withdrawal syndrome treatment are the result of decreased ability of the brain to adapt to stressors such as illness, trauma, or surgery. Symptoms may appear earlier from the last drink and present with a wide range of symptoms. The most effective interventions require high-quality nursing care delivery to prevent, decrease the severity and shorten the duration of delirium. Strategies that help minimize these challenges starts with obtaining the patient's selfreport of their alcohol use history. Nurses should be diligent in their monitoring for signs of active alcohol withdrawal. Screening and assessment tools such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised should guide pharmacological management. To support nurses in identifying delirium tremens, this manuscript seek to describe the underlying pathophysiology, key assessment components and nursing management of delirium tremens in the older adult.

Assessment and treatment of the withdrawal syndrome in paediatric intensive care units: Systematic review.

Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients. A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia. Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs. The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.

Delivery dose of methadone, but not buprenorphine, is associated with the risk and severity of neonatal opiate withdrawal syndrome

Data on the relationship between the dose of opioid replacement therapy in pregnancy and the risk and severity of neonatal opioid withdrawal syndrome are conflicting and have methodological limitations. To assess the association of methadone and buprenorphine dose at delivery with neonatal opioid withdrawal syndrome in a large cohort. We performed a retrospective cohort study using data from a comprehensive perinatal opioid dependency program from 2000 through 2016. Women with a history of opioid use disorder enrolled in a medication-assisted treatment program were included. Strict neonatal opioid withdrawal syndrome case definition and neonatal treatment guidelines were utilized throughout the study epoch. Comparisons were made between women on methadone and buprenorphine. The dose of opioid replacement at delivery and the risk and severity of neonatal opioid withdrawal syndrome were assessed with univariable analysis and multivariable logistic regression. In all analyses, methadone and buprenorphine dosing were evaluated as a continuous variable. Four hundred eighty two of 709 women (68.0%) met inclusion criteria including 344 on methadone (71.4%) and 138 on buprenorphine (28.6%). Nonopioid polysubstance abuse, body mass index, medication-assisted treatment compliance, birthweight, and other characteristics were similar between groups. Overall, the frequency of neonatal opioid withdrawal syndrome was not significantly different between the methadone and buprenorphine groups (56.8% vs 52.0%, P= .35). Dose at delivery ranged at 0-165 mg for methadone and 0-30 mg for buprenorphine. In a univariable analysis, methadone dose at delivery was associated with neonatal opioid withdrawal syndrome (83.0 ± 34.2 mg vs 71.9 ± 35.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P < .001), but buprenorphine dose at delivery was not (8.4 ± 4.4 vs 7.6 ± 4.8 mg for neonatal opioid withdrawal syndrome vs nonneonatal opioid withdrawal syndrome neonates, P= .30). Peak neonatal opioid withdrawal syndrome score, duration of neonatal opioid withdrawal syndrome treatment, and cumulative neonatal morphine exposure were significantly associated with delivery methadone dose but not buprenorphine dose. The association between delivery methadone dose and neonatal opioid withdrawal syndrome persisted in multivariable regression. The dose of methadone at the time of delivery is associated with the frequency and severity of neonatal opioid withdrawal syndrome, with higher doses associated with more severe neonatal opioid withdrawal syndrome when analyzed continuously. These data may inform future prospective studies on methadone dosing in pregnancy. While medication-assisted treatment agent and dose may have an impact on pertinent neonatal outcomes related to neonatal opioid withdrawal syndrome, the provision of medication-assisted treatment in pregnancy should reflect the goal of prevention of recidivism and maternal mortality and utilize an approach that balances fetal and maternal risk to optimize outcomes.

Incidence and risk factors for readmission to a paediatric intensive care unit.

Unscheduled readmission to a paediatric intensive care unit can lead to unfavourable patient outcomes. Therefore, determining the incidence and risk factors is important. Previous studies on such readmissions have only focused on the first 48 hours after discharge and described the relative risk factors as unmodifiable. To identify the incidence and risk factors of unscheduled readmission to a paediatric intensive care unit within 7 days of discharge. This was a retrospective observational study. Our study population comprised consecutive patients admitted to the paediatric intensive care unit of our tertiary hospital in Japan in 2012 to 2016. We determined the incidence of unscheduled readmission to the unit within 7 days of discharge and identified potential risk factors using multivariable logistic regression analysis. Among the 2432 admissions (1472 patients), 60 admissions (2.5%, 44 patients) were followed by ≥1 unscheduled readmission. The median time to readmission was 3.5 days. The most common causes for readmission were respiratory issues and cardiovascular symptoms. The significant risk factors for readmission within 7 days of discharge were unscheduled initial admission (odds ratio [OR]: 3.02; 95% confidence interval [CI:] 1.45-6.31), admission from a general ward (OR: 5.13; 95% CI: 1.75-15.0), and withdrawal syndrome during the initial stay (OR: 3.95; 95% CI: 1.53-10.2). The incidence of unscheduled readmission within 7 days was not high (2.5%), and one of the three identified risk factors for readmissions (withdrawal syndrome) is potentially modifiable. Appropriate treatment of withdrawal syndrome may reduce readmissions and improve patient outcomes. Although unscheduled initial admission and admission from general ward are not modifiable risk factors, careful discharge judgement and follow up after discharge from paediatric intensive care units for high-risk patients may be beneficial.

Antioxidant Potential of Phoenix dactylifera Linn Extract and its Effects on Calcium Channel Antagonist in the Treatment of Withdrawal Syndrome in Morphine Dependent Rats

Antioxidant Potential of Phoenix dactylifera Linn Extract and its Effects on Calcium Channel Antagonist in the Treatment of Withdrawal Syndrome in Morphine Dependent Rats

Cannabinoid Type 1 Receptor (CB1) Ligands with Therapeutic Potential for Withdrawal Syndrome in Chemical Dependents of Cannabis sativa.

Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. By using computational tools, the aim of this study was to propose drug candidates for treating withdrawal syndrome based on the natural ligands of the cannabinoid type 1 receptor (CB1). One compound in particular, 2-n-butyl-5-n-pentylbenzene-1,3-diol (ZINC1730183, also known as stemphol), showed positive predictions as a human CB1 ligand and for facile synthetic accessibility. Therefore, ZINC1730183 is a favorable candidate scaffold for further research into pharmacotherapeutic alternatives to treat C. sativa withdrawal syndrome.

Transcutaneous electrical acupoint stimulation for the treatment of withdrawal syndrome in heroin addicts.

To assess the therapeutic effect of transcutaneous electric acupoint stimulation (TEAS) for the treatment of withdrawal syndrome in heroin addicts. A total of 63 male heroin addicts with withdrawal score higher than 20 were recruited in the Detoxification Center of Zhongshan city, Guangdong province, China. They were randomly distributed into two groups: TEAS group (n = 31) received TEAS by using a Han's acupoint nerve stimulator (HANS) model 200A with two output channels, 2-3 sessions per day, 30 minutes per session for 10 consecutive days. Electrical stimulation of alternating frequencies of 2- and 100-Hz with 3 second each, and with intensity of 10-15 mA was applied on Hegu (LI-4) and Laogong (PC-8) points on one hand, and Neiguan (PC-6) and Waiguan (SJ-5) points on the other forearm via electroconductive skin pads of 4 cm × 4 cm in size. The control group (n = 32) was treated with similar procedure except that the leads of the output of the stimulator was disconnected. Assessments of the severity of the withdrawal syndrome were conducted one day before and on each day during the whole treatment period of 10 days. Buprenorphin of 1 mg per day sublingually was provided to all subjects in the first two days, and then to those with withdrawal score over 20 in the following days. The TEAS treatment dramatically alleviated the withdrawal syndrome during heroin detoxification. No significant difference was found in withdrawal scores between the two groups at the beginning of the observation. Withdrawal scores showed a more marked drop in TEAS group than the control starting from the second day, and maintained at a lower level for the whole course of treatment. The area under the curve of withdrawal score in TEAS group was only 40% of that in the control (P < 0.001, two way repeated measures analysis of variance), and the requirement of buprenorphine was only 10% of that in the control. No adverse effects were observed in either group. TEAS of 2/100 Hz for 10 days in abrupt abstinence of the heroin addicts resulted in a marked reduction of the withdrawal syndrome as well as a reduced requirement for rescue opioids.

Reviews on Calcium Mediated Secondary Messengers in Chronic Opioids Exposure/Addiction

Background: Addiction and withdrawal are problems disturbing the health of the individual and also causes difficulties for society, raising the rates of divorce, unemployment and government spending on legal and medical systems. Objective of present review: Opioids show an important pharmacological effect in the treatment of pain, with extremely addictive potential. Chronic opioid exposure is known to produce the complex behaviors of tolerance and dependence, a state exposed by opioid abstinence leading to withdrawal syndrome, as well as oxidative stress. Review of Literature: Studies show that calcium mediated secondary messengers play a crucial role in the mechanism of addictive process and oxidative stress induced by chronic opioid usage. Calcium / calmodulin-dependent protein kinase II (CaMKII), is a major calcium regulated signal transducer that controls many neuronal systems and play important role in neuronal plasticity and can act as a key and direct promoting opioid tolerance and dependence and identifying such a direct mechanism may be useful for designing a pharmacology treatment for these conditions, recent studies, has been shown that calcium channels antagonist can be used in the treatment of withdrawal syndrome. Conclusion: Chronic opioid exposure associated with tolerance, dependence withdrawal syndrome and oxidative stress. Studies has shown that calcium mediated secondary messengers involved in the genesis of these conditions, better understanding of biological mechanisms underlie reduction in neuronal cell excitability could help in the identification of pharmacological targets for treatment.

Is it prime time for alpha2-adrenocepter agonists in the treatment of withdrawal syndromes?

The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.

Withdrawal syndrome in the pediatric intensive care unit. Incidence and risk factors

ObjectiveTo determine the incidence of withdrawal syndrome after prolonged infusion of fentanyl and midazolam in children, and the associated risk factors. DesignHistoric or retrospective cohort study. SettingPediatric Intensive Care Unit in an academic center. PatientsForty-eight pediatric patients who received sedation and analgesia only with fentanyl and midazolam through continuous infusion for at least 48h. InterventionsNone. Main variables of interestCollected data included demographic and clinical parameters, dose and duration of sedation received, and incidence, severity and treatment of withdrawal syndrome. ResultsFifty percent of the patients developed withdrawal syndrome. There were significant differences between the patients who developed withdrawal syndrome and those who did not, in terms of the duration of infusion and the cumulative doses of both drugs. A cumulative fentanyl dose of 0.48mg/kg, a cumulative midazolam dose of 40mg/kg, and a duration of infusion of both drugs of 5.75days were risk factors for the development of withdrawal syndrome. Most children developed mild or moderate disease, beginning about 12–36h after weaning from infusion. Methadone was used in most cases for treating withdrawal. ConclusionsThere is a high incidence of withdrawal syndrome in children following the continuous infusion of midazolam and fentanyl. The duration of infusion of both drugs and higher cumulative doses are associated with the development of withdrawal syndrome.

Pregabalin for Alcohol Dependence: A Critical Review of the Literature

Alcohol dependence represents a severe pathological disorder associated with a significant rate of morbidity and mortality. To date, limited pharmacological agents exist to treat this disorder, and there is a growing interest for new therapies. In this context, pregabalin represents a promising strategy. Pregabalin, like gabapentin, selectively binds to the α(2)δsubunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. The main focus of this review is the clinical use of pregabalin in alcoholic patients, but the authors also reported some data about chemistry, pharmacology, and pharmacokinetics of this drug. The authors conducted a PubMed search of clinical human studies published in English from January 2000 to August 2012 using the following search terms: pregabalin alcohol dependence, pregabalin alcohol withdrawal, pregabalin alcoholism. The search revealed a total of five studies: two trials for the treatment of alcohol relapse and three articles for the management of alcohol withdrawal syndrome with pregabalin. The critical review of the literature suggests that pregabalin could be a novel and effective treatment option for the management of alcohol relapse in detoxified patients, whereas until now there have been mixed results for the treatment of alcohol withdrawal syndrome. In particular, pregabalin showed a greater beneficial effect on patients with comorbid conditions such as alcoholism and generalized anxiety disorders. The exact mechanism of action of pregabalin in the management of alcoholism is not well understood but it is thought to be due mainly to the modulation of neurotransmitters such as glutamate and norepinephrine by inhibiting activity-dependent calcium influx in nerve terminals. Pregabalin, within a dosage of 150-450 mg/day, showed beneficial effects for alcohol relapse prevention and contrasting results for the treatment of the withdrawal syndrome. Its use appears to be safe and well tolerated.

ENDOGENOUS OPIOID SYSTEM AS A MEDIATOR OF ACUTE AND LONG-TERM ADAPTATION TO STRESS. PROSPECTS FOR CLINICAL USE OF OPIOID PEPTIDES

It has been well established that opioid peptides (OPs) affect various hormonal systems. Opioids exhibit stress-limiting and gastro-protective effects in stressed animals, acting via mu- and delta-opioid receptors (OR). Peripheral mu-OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to pathological consequences of stress. Enhancement ofprostacyclin synthesis, decrease of thromboxane production as well as suppression of lipid peroxidation can be directly responsible for cardioprotective effects of OPs in stressed animals. Adaptive responses are accompanied by increased OP levels in blood and tissues. Reduction of ventricular arrhythmias induced by repeated short-term immobilization stress is mediated via mu-OR stimulation by endogenous opioids, while delta-OR account for an antiarrhythmic effect of adaptation to chronic intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of continuous normobaric hypoxia involves both mu- and delta-OR stimulation. Peptide OR agonists can be considered in future clinical practice for treatment of withdrawal syndrome, stress-related cardiac disease or myocardial injury caused by ischemia-reperfusion insult.