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Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
Proceedings of the Royal Society of... Jan 1965
Topics: Anxiety; Anxiety Disorders; Atropine; Barbiturates; Chlordiazepoxide; Chlorpromazine; Drug Therapy; Humans; Hypotension; Hypotension, Orthostatic; Meprobamate; Preanesthetic Medication; Promazine; Scopolamine; Thiazines; Toxicology; Tranquilizing Agents
PubMed: 14267495
DOI: No ID Found -
Analytical Sciences : the International... Jun 2019Molecularly imprinted polymers (MIPs) for promazine (PZ) and chlorpromazine (CPZ), MIP and MIP, were prepared by multi-step swelling and polymerization using methacrylic...
Preparation and Evaluation of Molecularly Imprinted Polymers for Promazine and Chlorpromazine by Multi-step Swelling and Polymerization: the Application for the Determination of Promazine in Rat Serum by Column-switching LC.
Molecularly imprinted polymers (MIPs) for promazine (PZ) and chlorpromazine (CPZ), MIP and MIP, were prepared by multi-step swelling and polymerization using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a crosslinker. The retention and molecular-recognition properties of MIP and MIP were evaluated using a mixture of potassium phosphate buffer and acetonitrile, or a mixture of ammonium formate and acetonitrile as the mobile phase in LC. PZ and CPZ gave the maximal retentions on MIP and MIP at an apparent pH 8.2 using a mixture of potassium phosphate buffer and acetonitrile as the mobile phase. The retentions of PZ and CPZ decreased with an increase of acetonitrile contents from 70 to 90 vol% using a mixture of ammonium formate and acetonitrile as the mobile phase. The template molecules (PZ and CPZ, respectively) were recognized the most on the respective MIPs, and the imprinting factor of PZ was higher on MIP than on MIP. These results indicate that in addition to shape recognition, ionic and hydrophobic interactions seem to work for the retention and molecular-recognition of PZ and CPZ on the MIPs. MIP was successfully utilized for the selective extraction of PZ in rat-serum samples in column-switching LC with fluorescence detection.
PubMed: 30773513
DOI: 10.2116/analsci.19P011 -
Journal of Clinical and Translational... Jul 2015A reduction in body temperature can be achieved by a downward adjustment of the termoneutral zone, a process also described as anapyrexia. Pharmacological induction of... (Review)
Review
A reduction in body temperature can be achieved by a downward adjustment of the termoneutral zone, a process also described as anapyrexia. Pharmacological induction of anapyrexia could enable numerous applications in medicine. However, little is known about the potential of pharmacological agents to induce anapyrexic signaling. Therefore, a review of literature was performed and over a thousand pharmacologically active compounds were analyzed for their ability to induce anapyrexia in animals. Based on this analysis, eight agents (helium, dimethyl sulfoxide, reserpine, (oxo)tremorine, pentobarbital, (chlor) promazine, insulin, and acetaminophen) were identified as potential anapyrexia-inducing compounds and discussed in detail. The translational pitfalls were also addressed for each candidate compound. Of the agents that were discussed, reserpine, (oxo)tremorine, and (chlor) promazine may possess true anapyrexic properties based on their ability to either affect the thermoneutral zone or its effectors and facilitate hypothermic signaling. However, these properties are currently not unequivocal and warrant further examination in the context of artificially-induced hypometabolism.
PubMed: 30873441
DOI: No ID Found -
British Medical Journal Feb 1965
Topics: Alcohol-Induced Disorders; Alcoholism; Alcohols; Chlorpromazine; Drug Therapy; Humans; Promazine; Psychoses, Substance-Induced; Substance Withdrawal Syndrome
PubMed: 14237940
DOI: 10.1136/bmj.1.5432.450-a -
Environmental Science and Pollution... Jul 2023This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar...
Competitive adsorptive removal of promazine and promethazine from wastewater using olive tree pruning biochar: operational parameters, kinetics, and equilibrium investigations.
This research aims to remove two phenothiazines, promazine (PRO) and promethazine (PMT), from their individual and binary mixtures using olive tree pruning biochar (BC-OTPR). The impact of individual and combinatory effects of operational variables was evaluated for the first time using central composite design (CCD). Simultaneous removal of both drugs was maximized utilizing the composite desirability function. At low concentrations, the uptake of PRO and PMT from their individual solutions was achieved with high efficiency of 98.64%, 47.20 mg/g and 95.87%, 38.16 mg/g, respectively. No major differences in the removal capacity were observed for the binary mixtures. Characterization of BC-OTPR confirmed successful adsorption and showed that the OTPR surface was predominantly mesoporous. Equilibrium investigations revealed that the Langmuir isotherm model best describes the sorption of PRO/PMT from their individual solutions with maximum adsorption capacities of 640.7 and 346.95 mg/g, respectively. The sorption of PRO/PMT conforms to the pseudo-second-order kinetic model. Regeneration of the adsorbent surface was successfully done with desorption efficiencies of 94.06% and 98.54% for PRO and PMT, respectively, for six cycles.
Topics: Wastewater; Promethazine; Olea; Promazine; Kinetics; Adsorption; Charcoal; Water Pollutants, Chemical; Hydrogen-Ion Concentration
PubMed: 37326738
DOI: 10.1007/s11356-023-27688-6 -
International Journal of Molecular... Apr 2022The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide...
The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer's disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of Aβ aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit Aβ aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential.
Topics: Alzheimer Disease; Antipsychotic Agents; Cholinesterase Inhibitors; Endothelial Cells; Hemolysis; Humans; Quetiapine Fumarate; Rivastigmine
PubMed: 35563011
DOI: 10.3390/ijms23094621 -
Acta Poloniae Pharmaceutica 2003The run and analytical application of oxidation reaction of promazine (PM) and thioridazine (TR) hydrochlorides with iron(III) and ferrocyanide(III) are described. The...
The run and analytical application of oxidation reaction of promazine (PM) and thioridazine (TR) hydrochlorides with iron(III) and ferrocyanide(III) are described. The coloured products of oxidation absorb at 512 nm for promazine and 634 nm for thioridazine. This property is a basis of a rapid, accurate and sensitive spectrophotometric method for determination of these phenothiazines. The elaborated methods allow to determine 3-28 microgPM/ml in Fe(III)-PM and 2-11 microgPM/ml in [Fe(CN)6](3-)-PM systems, 2.5-22 microgTR/ml in the Fe(III)-TR and 4-16 microgTR/ml in [Fe(CN)6](3-)-TR systems.
Topics: Oxidants; Oxidation-Reduction; Promazine; Spectrophotometry, Ultraviolet; Thioridazine
PubMed: 15080587
DOI: No ID Found -
Polish Journal of Pharmacology 2003Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, CYP3A seems to be essential for its metabolism... (Comparative Study)
Comparative Study
Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, CYP3A seems to be essential for its metabolism (8-hydroxylation). In the case of 1-N- and, in particular, 7-N-demethylation of caffeine, apart from CYP1A2, other CYP isoenzymes play a considerable role, probably CYP2B and/or CYP2E1. The aim of the present study was to investigate the influence of two classic neuroleptics (promazine and haloperidol) and two atypical ones (risperidone and sertindole) on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that promazine, a phenothiazine neuroleptic with the simplest chemical structure, significantly inhibited 1-N- and 3-N-demethylation and 8-hydroxylation of caffeine via competitive or mixed mechanism (Ki = 21.8, 25.4 and 58.2 microM, respectively). This indicates inhibition by promazine of CYP1A2 (inhibition of 3-N- and 1-N-demethylation), and possibly CYP3A2 (inhibition of 8-hydroxylation), but not of other CYP isoenzymes involved in 7-N-demethylation of caffeine (e.g. CYP2B2 and/or CYP2E1). In contrast to promazine, haloperidol had no effect on the oxidation reactions of caffeine in the applied in vitro metabolic model. The potency of inhibition of caffeine oxidation by risperidone and sertindole resembled rather haloperidol than promazine. Risperidone appeared to be a very weak inhibitor of 3-N-demethylation and 8-hydroxylation (Ki = 202.5 microM) and had no effect on 1-N- and 7-N-demethylation of caffeine. Sertindole was a very poor inhibitor of 1-N- and 7-N-demethylations and 8-hydroxylation pathways of the marker substance (Ki = 132.1, 434.1 and 173.3 microM, respectively); even the observed in vitro inhibition of 3-N-demethylation of caffeine by sertindole (Ki = 68.9 microM) cannot be of practical significance in vivo, considering extremely low pharmacological and therapeutic doses of the neuroleptic. In summary, among the investigated neuroleptics, only promazine showed significant inhibitory activity towards caffeine metabolism in vitro (inhibition of CYP1A2 and possibly CYP3A), which may be of pharmacological and clinical importance in vivo. In contrast to promazine, haloperidol and the investigated atypical neuroleptics had no or very weak effect on caffeine oxidation in vitro,of no in vivo significance. Considering the results of the present and previous studies, it seems highly likely that promazine may cause pharmacokinetic interactions, while atypical neuroleptics seem to be safe in this respect. Moreover, the observed reaction-dependent effects of promazine and sertindole provide indirect evidence that CYP1A2 is not the only isoenzyme important for the metabolism of caffeine, which requires further pharmacological and clinical consideration.
Topics: Animals; Antipsychotic Agents; Caffeine; Cytochrome P-450 Enzyme System; Drug Interactions; Haloperidol; Hydroxylation; Imidazoles; In Vitro Techniques; Indoles; Male; Microsomes, Liver; Oxidation-Reduction; Promazine; Rats; Rats, Wistar; Risperidone
PubMed: 14730101
DOI: No ID Found -
Psychiatria Danubina 2022To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and...
Quetiapine Add-On Therapy May Improve Persistent Sleep Disturbances in Patients with PTSD on Stabile Combined SSRI and Benzodiazepine Combination: A One-Group Pretest-Posttest Study.
BACKGROUND
To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and benzodiazepine therapy, who previously failed to respond to various benzodiazepine and non-benzodiazepine hypnotic adjuvant treatment as well as to first-generation antipsychotic add-on treatment.
SUBJECTS AND METHODS
Fifty-two male PTSD outpatients on stable combination treatment with SSRI and benzodiazepines, with persistent sleep disturbances not responding to prescription of zolpidem, flurazepam, nitrazepam, promazine, and levopromazine, were assessed for sleep disturbances improvements after prescription of quetiapine in the evening. Each patient met both ICD-10 and DSM-IV criteria for PTSD. Psychiatric comorbidity and premorbidity were excluded using the Mini-International Neuropsychiatric Interview (MINI). Improvement on the CAPS recurrent distressing dream item, reduction in the amount of time needed to fall asleep, prolongation of sleep duration, and reduction in average number of arousals per night in the last 7 days before the assessment period were used as efficacy measures.
RESULTS
All sleep-related parameters improved significantly at the end of a five-week follow-up: sleep duration increased by one hour (p<0.001), sleep latency decreased by 52.5 minutes (p<0.001), median number of arousals per night decreased from two to one (p<0.001), CAPS recurrent distressing dream item median decreased from five to four (p<0.001), and the number of patients dissatisfied with their sleep quality and quantity decreased from 45 to two (p<0.001).
CONCLUSION
Quetiapine prescribed in the evening may be successful therapy for persistent sleep disturbances in patients with PTSD and generally good response to an SSRI and benzodiazepine combination, who previously failed to respond to some of the usual hypnotic medication or addition of first-generation antipsychotics: zolpidem, flurazepam, nitrazepam, promazine, and levopromazine.
Topics: Antipsychotic Agents; Benzodiazepines; Flurazepam; Humans; Hypnotics and Sedatives; Male; Methotrimeprazine; Nitrazepam; Promazine; Quetiapine Fumarate; Sleep; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Zolpidem
PubMed: 35772134
DOI: 10.24869/psyd.2022.245