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Expert Opinion on Drug Metabolism &... Jun 2024Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). (Review)
Review
INTRODUCTION
Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).
AREAS COVERED
Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.
EXPERT OPINION
Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed. The classical D-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT-RA, dexamethasone and a NK-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.
Topics: Humans; Nausea; Vomiting; Antiemetics; Antineoplastic Agents; Dopamine Antagonists; Animals; Dopamine D2 Receptor Antagonists; Receptors, Dopamine D3
PubMed: 38878283
DOI: 10.1080/17425255.2024.2367593 -
Federal Practitioner : For the Health... Apr 2024Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and...
BACKGROUND
Acute agitation frequently occurs in the emergency department. Appropriate management is critical for the safety of all parties involved. Benzodiazepines and antipsychotics are commonly used for agitation, but safety concerns exist with these medications in older adults, even with acute use. The purpose of this study was to compare prescribing practices of anti-agitation medications between adults aged 18 to 64 years and those aged ≥ 65 years.
METHODS
This study was a retrospective chart review of patients who presented to the Veteran Affairs Southern Nevada Healthcare System emergency department and received haloperidol, droperidol, lorazepam, olanzapine, or ziprasidone from August 1, 2019, to July 31, 2022. Veterans were excluded if they had alcohol intoxication, alcohol withdrawal, benzodiazepine withdrawal, or medication administration unrelated to agitation. Safety outcomes included oxygen saturation < 95%, supplemental oxygen use, intubation, QTc prolongation, and new hypotension within 1 hour of medication administration.
RESULTS
For the 232 patients who met inclusion criteria, baseline characteristics differed significantly. When comparing patients aged 18 to 64 years and those aged ≥ 65 years, the younger cohort had higher rates of substance use disorder diagnosis (55.3% vs 27.5%, < .001), positive urine drug screen (69.7% vs 22.5%, < .001), and 72-hour legal hold (59.9% vs 32.5%, < .001), and lower rates of cognitive impairment or dementia (0.7% vs 48.8%, < .001), and altered mental status-related diagnosis (2.0% vs 18.8%, < .001). Anti-agitation medication selection significantly differed based on age ( = .02). Other than lorazepam ( = .007), no significant differences were noted in the dose ordered. No significant differences were observed for safety outcomes or additional anti-agitation doses.
CONCLUSIONS
Anti-agitation prescribing practices may differ between adults aged 18 to 64 years and those aged ≥ 65 years. The findings of this study also suggest that the most common agitation etiologies may differ based on patient age. Additional higher-quality studies are needed to further explore acute agitation in older adults.
PubMed: 38813266
DOI: 10.12788/fp.0456 -
Academic Emergency Medicine : Official... May 2024The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the...
Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department.
The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE-4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE-4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence].
Topics: Humans; Emergency Service, Hospital; Alcoholism; Vomiting; Adult; Substance Withdrawal Syndrome; Cannabinoids; Benzodiazepines; Syndrome; Marijuana Abuse; Male; Female; Cannabinoid Hyperemesis Syndrome
PubMed: 38747203
DOI: 10.1111/acem.14911 -
RSC Advances May 2024Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer...
Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.
PubMed: 38716106
DOI: 10.1039/d4ra01469c -
Drug Design, Development and Therapy 2024To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery.
PATIENTS AND METHODS
141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded.
RESULTS
The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05).
CONCLUSION
Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.
Topics: Female; Humans; Alfentanil; Ambulatory Surgical Procedures; Antiemetics; Benzodiazepines; Flumazenil; Gynecologic Surgical Procedures; Postoperative Nausea and Vomiting
PubMed: 38465267
DOI: 10.2147/DDDT.S444313 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
Cureus Dec 2023Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an...
Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an unintended result of surgical invasion. This study assessed the benefits of a postoperative SNB at the subgluteal space for patients who underwent TKA. Methodology This was a single-center, retrospective cohort study. Patients who underwent TKA under general anesthesia between May 2018 and June 2019 at the Teikyo University School of Medicine were screened for inclusion. They received either a preoperative femoral nerve block alone (control group; n = 87) or a preoperative femoral nerve block and postoperative SNB at the subgluteal space (post-SNB group; n = 40). The primary outcome was the pain-related Numerical Rating Scale (NRS) scores. The secondary outcomes were postoperative nausea and vomiting (PONV), intravenous patient-controlled analgesia (iv-PCA) suspension, and postoperative complications. Results No significant differences were observed in the characteristics, NRS scores, time to first drug use for pain, and iv-PCA suspension between groups. However, the incidence of PONV was significantly lower in the post-SNB group (p = 0.03). Logistic regression analysis revealed that droperidol doses of iv-PCA and the presence of postoperative SNB were independently associated with PONV occurrence [A1] {(p = 0.008, 95% confidence intervals (CI) [0.46, 0.89] and (p = 0.02, 95% CI [0.25, 0.88])}. Conclusions A postoperative SNB at the subgluteal space following TKA does not improve postoperative pain control; however, it may have contributed to reduced PONV.
PubMed: 38249241
DOI: 10.7759/cureus.50882 -
BMC Chemistry Jan 2024A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone,...
A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The 14 mixtures were chromatographed via HPLC-DAD method which employed 0.05 mol/L potassium dihydrogen phosphate solution-acetonitrile as the mobile phase, the analytes were gradient elution on a SinoChrom ODS-BP C column with a total separation time of 35 min, and 14 mixtures showed a good linear relationship in the linear range. The Limit of Quantitation (LOQ) ranged from 0.10 to 20.0 µg/mL, the inter-day and intra-day precision of each analyte is within 1.1-2.0% and 0.4-1.3%, and the average absolute recovery of all compounds was above 98%. The LC-MS/MS method was used to successfully separate the 14 mixtures within 10 min which employed 0.1% formic acid-acetonitrile as the mobile phase, the analytes were gradient elution on a ACQUITY UPLC-BEH C column with a total separation time of 13 min, and 14 mixtures showed a good linear relationship in the linear range. The LOQ ranged from 0.005 to 0.2 ng/mL, the inter-day and intra-day precision of each analyte is within 1.2-4.1% and 0.6-3.3%, and the average absolute recovery of all compounds was above 93%. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines.
PubMed: 38200560
DOI: 10.1186/s13065-024-01113-6 -
The Primary Care Companion For CNS... Dec 2023To assess the efficacy and safety of loxapine in acute agitation. PubMed, Cochrane database, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify...
To assess the efficacy and safety of loxapine in acute agitation. PubMed, Cochrane database, EMBASE, PsycINFO, and ClinicalTrials.gov were searched to identify relevant articles published in English or French from inception to March 15, 2022. The term "Loxap*" was searched in titles and abstracts. Interventional studies that compared the effectiveness of loxapine to any other intervention (including another administration route or dosage of loxapine, other drugs, and placebo) in acute agitation were included. From the 1,435 articles initially identified, and after the assessment of 73 full texts, 7 articles were selected, encompassing 1,276 participants. Two reviewers independently extracted data of interest using a predefined form. Among included studies, 5 were double-blind, 2 were open-label, and all were randomized. The risk of bias was low for 2 studies, involving 658 participants. Four articles compared loxapine to placebo, and 3 compared it with haloperidol, aripiprazole, and droperidol. Loxapine was found to be more effective and faster regarding acute agitation control. Also, across included studies, loxapine was well-tolerated, with mildly or moderately severe adverse effects. Notwithstanding methodological limitations of the included studies, this systematic review provides reassuring results regarding the use of loxapine in acute agitation. However, further studies with methodological optimizations might be of interest. .
Topics: Humans; Loxapine; Antipsychotic Agents; Administration, Inhalation; Psychomotor Agitation; Aripiprazole; Randomized Controlled Trials as Topic
PubMed: 38134395
DOI: 10.4088/PCC.23r03552 -
Anaesthesiology Intensive Therapy 2023
Topics: Humans; Droperidol; Metoclopramide; Neuroleptic Malignant Syndrome; Antiemetics; Postoperative Complications; Rhabdomyolysis; Double-Blind Method
PubMed: 38084576
DOI: 10.5114/ait.2023.132910