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Current Opinion in Pharmacology Oct 2023Gastroparesis is a neuromuscular disorder of the upper gastrointestinal tract. Patients typically complain about early satiety, postprandial fullness, nausea and... (Review)
Review
Gastroparesis is a neuromuscular disorder of the upper gastrointestinal tract. Patients typically complain about early satiety, postprandial fullness, nausea and vomiting. Etiology is multifactorial. Treatment strategies include nutritional support, pharmacologic agents or surgery for refractory cases. Metoclopramide is the first and only FDA approved pharmacologic agent for (diabetic) Gastroparesis. A couple of compounds are currently in clinical testing. Some beacons of hope have failed recently, however. Here we present an update on possible future treatment options.
Topics: Humans; Gastroparesis; Metoclopramide
PubMed: 37639905
DOI: 10.1016/j.coph.2023.102395 -
British Journal of Clinical Pharmacology Dec 2023Bruxism is a movement disorder of uncertain aetiology. Beside local peripheral and central psychological factors, drugs were suspected. Using the World Health...
Bruxism is a movement disorder of uncertain aetiology. Beside local peripheral and central psychological factors, drugs were suspected. Using the World Health Organization (WHO) global pharmacovigilance database, Vigibase®, we investigated through disproportionality analyses potential associations between exposure to drugs and bruxism reports. All reports of bruxism in adults between 01/01/2000 and 31/12/2022 were included. Results are expressed as reporting odds ratio (ROR). Among the 564 reports of bruxism, an association was found with eight antidepressants (first sertraline followed by escitalopram, venlafaxine, vortioxetine, citalopram, paroxetine, fluoxetine, duloxetine) and four antipsychotics (first ziprasidone followed by aripiprazole, olanzapine, risperidone). A signal was also described for oxybate sodium and metoclopramide. For antidepressants, a negative association was found between ROR values and NET (norepinephrine transporter) but not SERT (serotonin transporter) pKi values, suggesting this ADR is more closely linked to norepinephrine than serotonin reuptake inhibition.
Topics: Adult; Humans; Selective Serotonin Reuptake Inhibitors; Pharmacovigilance; Bruxism; Antidepressive Agents; World Health Organization
PubMed: 37574820
DOI: 10.1111/bcp.15884 -
Journal of Controlled Release :... Sep 2023The P-glycoprotein (P-gp/ABCB1) is a major efflux transporter which impedes the brain delivery of many drugs across the blood-brain barrier (BBB). Focused ultrasound...
The P-glycoprotein (P-gp/ABCB1) is a major efflux transporter which impedes the brain delivery of many drugs across the blood-brain barrier (BBB). Focused ultrasound with microbubbles (FUS) enables BBB disruption, which immediate and delayed impact on P-gp function remains unclear. Positron emission tomography (PET) imaging using the radiolabeled substrate [C]metoclopramide provides a sensitive and translational method to study P-gp function at the living BBB. A FUS protocol was devised in rats to induce a substantial and targeted disruption of the BBB in the left hemisphere. BBB disruption was confirmed by the Evan's Blue extravasation test or the minimally-invasive contrast-enhanced MRI. The expression of P-gp was measured 24 h or 48 h after FUS using immunostaining and fluorescence microscopy. The brain kinetics of [C]metoclopramide was studied by PET at baseline, and both immediately or 24 h after FUS, with or without half-maximum P-gp inhibition (tariquidar 1 mg/kg). In each condition (n = 4-5 rats per group), brain exposure of [C]metoclopramide was estimated as the area-under-the-curve (AUC) in regions corresponding to the sonicated volume in the left hemisphere, and the contralateral volume. Kinetic modeling was performed to estimate the uptake clearance ratio (R) of [C]metoclopramide in the sonicated volume relative to the contralateral volume. In the absence of FUS, half-maximum P-gp inhibition increased brain exposure (+135.0 ± 12.9%, p < 0.05) but did not impact R (p > 0.05). Immediately after FUS, BBB integrity was selectively disrupted in the left hemisphere without any detectable impact on the brain kinetics of [C]metoclopramide compared with the baseline group (p > 0.05) or the contralateral volume (p > 0.05). 24 h after FUS, BBB integrity was fully restored while P-gp expression was maximally down-regulated (-45.0 ± 4.5%, p < 0.001) in the sonicated volume. This neither impacted AUC nor R in the FUS + 24 h group (p > 0.05). Only when P-gp was inhibited with tariquidar were the brain exposure (+130 ± 70%) and R(+29.1 ± 15.4%) significantly increased in the FUS + 24 h/tariquidar group, relative to the baseline group (p < 0.001). We conclude that the brain kinetics of [C]metoclopramide specifically depends on P-gp function rather than BBB integrity. Delayed FUS-induced down-regulation of P-gp function can be detected. Our results suggest that almost complete down-regulation is required to substantially enhance the brain delivery of P-gp substrates.
Topics: Animals; Rats; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood-Brain Barrier; Metoclopramide
PubMed: 37562557
DOI: 10.1016/j.jconrel.2023.08.012 -
The Journal of Obstetrics and... Mar 2024The enhanced recovery after surgery (ERAS) method is designed for the patient to recover quickly, have less pain and have a more comfortable period after the surgery;...
BACKGROUND
The enhanced recovery after surgery (ERAS) method is designed for the patient to recover quickly, have less pain and have a more comfortable period after the surgery; that includes preoperative, intra and postoperative processes. ERAS has been started to be applied in cesarean section surgeries as the patients need to recover quickly. In the literature, there is no study about the results of ERAS in cesarean section about pain scores and complications.
OBJECTIVES
It is aimed to compare the results of cesarean section patients using the ERAS method completely in patients who have had cesarean section without meeting some of the postoperative conditions of the ERAS criteria.
STUDY DESIGN
It is a prospective study designed as postoperative metoclopramide, enema and routine opioids in group 1, enema and metoclopramide in group 2, metoclopramide only in group 3 and nothing in group 4. Postoperative pain scoring was done by using visual analog scale (VAS). Analysis of variance tests and t tests were used for results.
RESULTS
There was no difference between groups according to age, parity, and birth weight. As a result, although there was no difference between the groups in terms of discharge time and complications, the VAS score used in pain scoring was found to be significantly lower in group 3 compared to the other groups (p: 0.000). Only metoclopramide group (group 3) had lowest VAS score.
CONCLUSION
It has been revealed that the ERAS procedure does not need to be so detailed in the postoperative period, and the addition of metoclopramide may be sufficient. Since pain can be a subjective factor, other randomized studies are needed in terms of other criteria.
Topics: Pregnancy; Humans; Female; Cesarean Section; Enhanced Recovery After Surgery; Metoclopramide; Prospective Studies; Pain, Postoperative
PubMed: 38115186
DOI: 10.1111/jog.15860 -
Obesity Surgery Oct 2023Postoperative nausea and vomiting (PONV) is a frequent unappealing laparoscopic sleeve gastrectomy (LSG) sequel. The study's purpose was to determine the prevalence,...
PURPOSE
Postoperative nausea and vomiting (PONV) is a frequent unappealing laparoscopic sleeve gastrectomy (LSG) sequel. The study's purpose was to determine the prevalence, risk factors of PONV, and management of PONV after LSG.
PATIENTS AND METHODS
This multicenter retrospective study included patients with morbid obesity who had LSG between January 2022 and April 2023. The age range for LSG was 16 to 65 years, and the eligibility requirements included morbid obesity according to international guidelines.
RESULTS
PONV was experienced by 74.6% of patients who underwent LSG at 6 h postoperative. Multivariate analysis revealed that female gender, smokers, preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were found to be independent protective variables against the development of PONV. Combined intravenous ondansetron and metoclopramide improved 92.6% of patients who developed PONV. Dexamethasone and antihistamines drugs are given for 42 cases with persistent PONV after using intravenous ondansetron and metoclopramide. Pain management postoperatively by opioid-free analgesia managed PONV. Helicobacter pylori status has no role in the development of PONV after LSG.
CONCLUSION
Female gender, smoking, presence of preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were observed to be independent protective factors against the occurrence of PONV. Combined intravenous ondansetron and metoclopramide improved PONV. Dexamethasone and antihistamines drugs are given for persistent PONV.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Postoperative Nausea and Vomiting; Retrospective Studies; Metoclopramide; Ondansetron; Prevalence; Obesity, Morbid; Risk Factors; Pain; Analgesics, Opioid; Gastrectomy; Dexamethasone; Laparoscopy; Gastroesophageal Reflux
PubMed: 37624489
DOI: 10.1007/s11695-023-06803-z -
Medizinische Klinik, Intensivmedizin... May 2024The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients. (Review)
Review
BACKGROUND
The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients.
AIMS, MATERIALS AND METHODS
The following review aims to show the importance of gastrointestinal dysfunction. Multimodal therapy for gastroparesis and paralytic ileus is discussed.
CONCLUSION
Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus.
Topics: Humans; Gastroparesis; Metoclopramide; Combined Modality Therapy; Intestinal Pseudo-Obstruction; Neostigmine; Erythromycin; Enteral Nutrition; Critical Care; Gastrointestinal Agents
PubMed: 37985511
DOI: 10.1007/s00063-023-01082-z -
Molecular Psychiatry Sep 2023Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of... (Meta-Analysis)
Meta-Analysis
Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.
Topics: Adult; Humans; Antipsychotic Agents; Clozapine; Sulpiride; Amisulpride; Sialorrhea; Doxepin; Amitriptyline; Network Meta-Analysis; Propantheline; Trihexyphenidyl; Metoclopramide; Chlorpheniramine; Astemizole; Randomized Controlled Trials as Topic; Cyproheptadine; Diphenhydramine; Ipratropium; Atropine Derivatives
PubMed: 37821573
DOI: 10.1038/s41380-023-02266-x -
Drugs & Aging Dec 2023To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent. (Review)
Review
BACKGROUND
To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent.
OBJECTIVE
This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades.
RESULTS
A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide.
CONCLUSIONS
In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce.
Topics: Humans; Health Personnel; Drug-Related Side Effects and Adverse Reactions
PubMed: 37863868
DOI: 10.1007/s40266-023-01072-y