-
International Journal of Molecular... Oct 2022Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare...
Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from a physical mixture of both components by grinding them with a small volume of solvent and by crystallizing them with complete evaporation of the solvent. The resulting salt was examined by methods such as Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), and Raman spectroscopy. The results of the studies proved that saccharin salt of chlordiazepoxide crystallizes in the orthorhombic bca space group with one chlordiazepoxide cation and one saccharin anion in the asymmetric unit. In the crystal of the title compound, the chlordiazepoxide cation and the saccharin anion interact through strong N-H···O hydrogen bonds and weak C-H···O hydrogen bonds. The disappearance of the N-H band in the FT-IR spectrum of saccharin may indicate a shift of this proton towards chlordiazepoxide, while the disappearance of the aromatic bond band in the chlordiazepoxide ring in the Raman spectrum may suggest the formation of intermolecular hydrogen bonds between chlordiazepoxide molecules. The melting point of the salts differs from that of the starting compounds. Thermal decomposition of the salt begins above 200 °C and shows at least two overlapping stages of mass loss. In summary, the results of the research showed that the crystalline salt of the saccharin and chlordiazepoxide can be obtained by various methods: grinding with the addition of acetonitrile and crystallization from acetonitrile or a mixture of methanol with methylene chloride.
Topics: Acetonitriles; Calorimetry, Differential Scanning; Chlordiazepoxide; Methanol; Methylene Chloride; Powders; Protons; Saccharin; Salts; Solubility; Solvents; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 36233346
DOI: 10.3390/ijms231912050 -
British Medical Journal Mar 1973
Topics: Adolescent; Adult; Anorexia Nervosa; Female; Humans; Menstruation Disturbances; Neurotic Disorders; Pregnancy; Premenstrual Syndrome; Progesterone; Pseudopregnancy; Scopolamine; Stress, Psychological; Water-Electrolyte Balance
PubMed: 4735136
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2019Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol withdrawal syndrome (AWS) is a distressing and life-threatening condition that usually affects people who are alcohol dependent when they discontinue or decrease their alcohol consumption. Baclofen shows potential for rapidly reducing symptoms of severe AWS in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review first published in 2011 and last updated in 2017.
OBJECTIVES
To assess the efficacy and safety of baclofen for people with AWS.
SEARCH METHODS
We updated our searches of the following databases to June 2019: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language.
SELECTION CRITERIA
We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included four RCTs with 189 randomised participants (one RCT new for this update). None of the included studies reported the primary outcomes of alcohol withdrawal seizures, alcohol withdrawal delirium, or craving. For the comparison of baclofen and placebo (1 study, 31 participants), there was no evidence of a difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores in eight-hour periods from days one to five (very low-quality evidence). For the comparison of baclofen and diazepam (2 studies, 85 participants), there was no evidence of a difference in change from baseline to days 10 to 15 on CIWA-Ar scores (very low-quality evidence, meta-analysis was not performed due to insufficient data). In one study (37 participants), there was no evidence of a difference in participants with at least one adverse event (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low-quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low-quality evidence). For the comparison of baclofen and chlordiazepoxide (1 study, 60 participants), there was no evidence of a difference in difference from baseline to nine-day decremental fixed-dose intervention: CIWA-Ar scores (mean difference (MD) 1.00, 95% CI 0.70 to 1.30; very low-quality evidence), global improvement (MD 0.10, 95% CI -0.03 to 0.23; very low-quality evidence), 14/60 participants with adverse events (RD 2.50, 95% CI 0.88 to 7.10; very low-quality of evidence), dropouts (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.06 to 0.06; very low-quality evidence). None of the RCTs provided information on random sequence generation or allocation concealment, therefore, we assessed them at unclear risk of bias. Two RCTs were not of double-blind design and had a high risk of bias in blinding (Addolorato 2006; Girish 2016). One RCT had more than 5% dropouts with high risk of attrition bias (Lyon 2011). We could not assess reporting bias as none of the prepublished protocols were available.
AUTHORS' CONCLUSIONS
No conclusions can be drawn about the efficacy and safety of baclofen for the management of alcohol withdrawal because we found insufficient and very low-quality evidence.
Topics: Alcoholism; Baclofen; Craving; GABA Agonists; Humans; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 31689723
DOI: 10.1002/14651858.CD008502.pub6 -
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 -
The Journal of Pharmacy Technology :... Apr 2018To report a case of chlordiazepoxide-associated Stevens-Johnson syndrome (SJS). This case provides insight into a serious adverse drug reaction secondary to a drug not...
To report a case of chlordiazepoxide-associated Stevens-Johnson syndrome (SJS). This case provides insight into a serious adverse drug reaction secondary to a drug not commonly associated with SJS. A 29-year-old female presented with a 4-day history of rash and pruritus. The rash started on her arms and spread all over her body. The patient was started on chlordiazepoxide 3½ weeks ago. On examination, there were multiple, raised, round erythematous lesions in various stages of healing. Skin erosions were noted on her lips and buccal mucosa. However, the rash did not involve the conjunctiva, inner ears, or genitalia. The patient was discharged home with a follow-up appointment with dermatology and instructions to discontinue chlordiazepoxide. Two days after her initial presentation, the patient's rash spread to her eyes and genitalia. A painful, white film developed on her tongue, and she was unable to tolerate oral intake. She was emergently sent back to hospital and transferred to a Burn Unit. The biopsy report revealed full-thickness necrotizing keratinocytes in the epidermis consistent with SJS. To our knowledge, there is only one other case report of chlordiazepoxide-associated SJS. Chlordiazepoxide is thought to be the cause of this patient's biopsy-confirmed SJS and overall presentation. SJS is a rare but serious condition that is usually a result of drug exposure. The close temporal relationship between chlordiazepoxide initiation and onset of SJS provides a convincing theory as to the etiology of SJS in our patient.
PubMed: 34860942
DOI: 10.1177/8755122517753595 -
Frontiers in Psychiatry 2018The Alcohol Withdrawal Syndrome (AWS), which may occur with or without delirium, is a frequent consequence of sudden alcohol cessation in patients with moderate to... (Review)
Review
The Alcohol Withdrawal Syndrome (AWS), which may occur with or without delirium, is a frequent consequence of sudden alcohol cessation in patients with moderate to severe Alcohol Dependence Syndrome (ADS). Withdrawal as a result of habituation to alcohol is part of the definition of the Alcohol Dependence Syndrome (ICD10). Since the recognition of Delirium Tremens, in the early nineteenth century, the management of the syndrome, an acute medical emergency, has proven controversial. The barbiturates, chlormethiazole, and recently the safer benzodiazepines transformed the management of these conditions. The benzodiazepines, particularly diazepam and chlordiazepoxide, are now the most used first line agents in the treatment of AWS. In addition, a number of other agents, including baclofen, a GABA-B receptor agonist, have the potential to suppress the alcohol withdrawal syndrome. In this review we review the potential use of baclofen in its role to treat AWS. We summarize initial case reports as well as more recent randomized trials of AWS treatment with baclofen. We conclude that currently there is not enough evidence to support the use of baclofen as a first line treatment for AWS. More research will be needed to determine where baclofen might have a role in second-line management of the Alcohol Withdrawal Syndrome on its own or in combination with benzodiazepines or other agents.
PubMed: 30723432
DOI: 10.3389/fpsyt.2018.00773 -
British Medical Journal Apr 1968
Topics: Central Nervous System; Chlordiazepoxide; Chlorpromazine; Diazepam; Haloperidol; Humans; Meprobamate; Phenothiazines; Promethazine; Tranquilizing Agents
PubMed: 5653035
DOI: No ID Found -
Journal of Neurogastroenterology and... Apr 2020The treatment of refractory functional dyspepsia (FD) is a challenge. Clidinium/chlordiazepoxide is a combination of antispasmodic and anxiolytic drugs that has been...
BACKGROUND/AIMS
The treatment of refractory functional dyspepsia (FD) is a challenge. Clidinium/chlordiazepoxide is a combination of antispasmodic and anxiolytic drugs that has been used as an adjunct treatment for FD in clinical practice with limited supporting evidence of efficacy. The aim of the study is to assess the efficacy and safety of clidinium/chlordiazepoxide as an adjunct treatment to a proton pump inhibitor (PPI) in refractory dyspepsia.
METHODS
We performed a study of patients who met the Rome IV criteria for FD who failed to respond to PPIs. Patients were randomly assigned to groups that received clidinium/chlordiazepoxide or placebo as an add-on treatment to PPI for 4 weeks. The primary outcome was the rate of responders, which was defined as a > 50% reduction in dyspepsia symptom score after 4 weeks of treatment. The secondary outcomes were an improvement in the quality of life and the safety profile.
RESULTS
Between March 2017 and February 2018, 78 patients were enrolled. The rates of responders in the clidinium/chlordiazepoxide group and placebo groups were 41.03 % and 5.13% at week 4 ( < 0.001). The clidinium/chlordiazepoxide group also showed significant improvement in overall quality of life over placebo. However, the clidinium/chlordiazepoxide group had more frequent drowsiness than the placebo group (30.27% vs 6.52%, = 0.034). There were no major adverse events in either group.
CONCLUSIONS
Clidinium/chlordiazepoxide significantly improved dyspeptic symptoms and quality of life. This combination may be used as an add-on therapy in FD patients without major adverse events.
PubMed: 32235033
DOI: 10.5056/jnm19186 -
Indian Journal of Pharmacology 2014Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS.
MATERIALS AND METHODS
This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective.
RESULTS
The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03).
CONCLUSION
Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.
Topics: Adolescent; Adult; Aged; Baclofen; Chlordiazepoxide; Cost-Benefit Analysis; Drug Administration Schedule; Drug Costs; Ethanol; Female; Humans; Male; Middle Aged; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult
PubMed: 25097273
DOI: 10.4103/0253-7613.135947 -
The Journal of Clinical Psychiatry Aug 2022The half-life of a drug is the time taken for the blood level of the drug to fall by half, provided that no more doses of the drug are administered in the intervening...
The half-life of a drug is the time taken for the blood level of the drug to fall by half, provided that no more doses of the drug are administered in the intervening period. Many psychotropic drugs and their active metabolites, if any, have very long half-lives that extend for 2 days or longer. Examples are chlordiazepoxide, diazepam, fluoxetine, vortioxetine, aripiprazole, brexpiprazole, cariprazine, penfluridol, donepezil, and memantine. Other drugs with long half-lives that psychiatrists may prescribe include levothyroxine and zonisamide. Psychotropic drugs with long half-lives take long to reach steady state; this is seldom a problem. They also take long to wash out; this is an advantage because the risk of drug withdrawal or discontinuation syndromes is small, and a disadvantage if rapid washout is desired for any reason, including the experience of drug adverse effects or toxicity, or the discovery of an unplanned pregnancy. Other clinical issues related to drugs with long half-lives include the relevance of occasional missed doses, the possibility of once-weekly dosing, and the need for pregnancy planning.
Topics: Female; Fluoxetine; Half-Life; Humans; Pregnancy; Psychotropic Drugs; Substance Withdrawal Syndrome; Vortioxetine
PubMed: 35921503
DOI: 10.4088/JCP.22f14593