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Current Drug Safety 2023The risk of sudden cardiac death (SCD) can be increased with the use of drugs. However, it has been described heterogeneously in the literature. (Review)
Review
BACKGROUND
The risk of sudden cardiac death (SCD) can be increased with the use of drugs. However, it has been described heterogeneously in the literature.
OBJECTIVE
This study aims to systematically review epidemiological studies dealing with druginduced sudden death, describe their methodologies, and summarize the results found.
METHODS
A scoping review has been carried out using Medline electronic database. The search was limited up to 2020. Epidemiological studies were included, and case reports or case series were excluded.
RESULTS
Out of 3,114 potential articles, 74 were included. Most studies originated from North America (40.5%) or Europe (39.2%). Case-control (47.3%) or cohort (40.5%) studies were the most common designs. The data for outcomes and exposure were retrieved mainly from administrative databases (37.8%) or medical charts/hospital discharge reports (32.4%), but most studies used several sources of information. A composite variable of sudden death or SCD, mainly with ventricular arrhythmia, was the most frequently used endpoint. Only 18.9% of the studies included autopsy results to confirm the death. Psychotropic drugs were the most frequently studied. An increased risk of different outcomes for typical antipsychotics, tricyclic antidepressants, domperidone, and antiepileptics is suggested.
CONCLUSION
The methodologies used were highly heterogeneous, and the results were, in general, not conclusive. An improvement of the methodologies is needed to achieve a conclusion regarding the risk of SCD associated with drug use.
Topics: Humans; Arrhythmias, Cardiac; Domperidone; Death, Sudden, Cardiac; Antipsychotic Agents; Risk Factors
PubMed: 35619276
DOI: 10.2174/1574886317666220525115232 -
International Journal of Molecular... Apr 2022The link between substance abuse and the development of schizophrenia remains elusive. In this study, we assessed the molecular and behavioural alterations associated...
The link between substance abuse and the development of schizophrenia remains elusive. In this study, we assessed the molecular and behavioural alterations associated with schizophrenia, opioid addiction, and opioid withdrawal using zebrafish as a biological model. Larvae of 2 days post fertilization (dpf) were exposed to domperidone (DMP), a dopamine-D2 dopamine D2 receptor antagonist, and morphine for 3 days and 10 days, respectively. MK801, an N-methyl-D-aspartate (NMDA) receptor antagonist, served as a positive control to mimic schizophrenia-like behaviour. The withdrawal syndrome was assessed 5 days after the termination of morphine treatment. The expressions of schizophrenia susceptibility genes, i.e., , , , and , in brains were quantified, and the levels of whole-body cyclic adenosine monophosphate (cAMP), serotonin and cortisol were measured. The aggressiveness of larvae was observed using the mirror biting test. After the short-term treatment with DMP and morphine, all studied genes were not differentially expressed. As for the long-term exposure, was downregulated by DMP and morphine. Downregulation of and was observed in the morphine-treated larvae, whereas and were upregulated by DMP. The levels of cAMP and cortisol were elevated after 3 days, whereas significant increases were observed in all of the biochemical tests after 10 days. Compared to controls, increased aggression was observed in the DMP-, but not morphine-, treated group. These two groups showed reduction in aggressiveness when drug exposure was prolonged. Both the short- and long-term morphine withdrawal groups showed downregulation in all genes examined except , suggesting dysregulated reward circuitry function. These results suggest that biochemical and behavioural alterations in schizophrenia-like symptoms and opioid dependence could be controlled by common mechanisms.
Topics: Animals; Hydrocortisone; Larva; Morphine; Opioid-Related Disorders; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Substance Withdrawal Syndrome; Zebrafish
PubMed: 35563106
DOI: 10.3390/ijms23094715 -
Ethosomal gel for rectal transmucosal delivery of domperidone: design of experiment, and evaluation.Drug Delivery Dec 2022Despite high efficiency of domperidone (DOM) in prophylaxis of emesis accompanied with radiotherapy and chemotherapy, it still can bother cancer patients by its powerful...
Despite high efficiency of domperidone (DOM) in prophylaxis of emesis accompanied with radiotherapy and chemotherapy, it still can bother cancer patients by its powerful side effects and difficulty of its oral administration. The study was designed to develop and optimize DOM loaded ethosomal gel for rectal transmucosal delivery. Ethosomal formulations were prepared using a 2, 5 full-factorial design where the impact of lecithin concentration and additives were investigated. The optimum ethosomal vesicles were subsequently incorporated in Carbopol gel base where rheological behavior, spreadability, mucoadhesion, and pharmacokinetic parameters were studied. Based on Design Expert software (Stat Ease, Inc., Minneapolis, MN), the optimum formulation illustrated entrapment efficiency of 70.02%±5.52%, and vesicular size of 112 ± 3.3 nm, polydispersity index of 0.32 ± 0.01, zeta potential of -59 ± 0.28 mV, and % drug released after 6 h of 76.30%±2.45%. Moreover, permeation through rabbit intestinal mucosa increased four times compared to free DOM suspension. The gel loaded with ethosomes showed excellent mucoadhesion to rectal mucosa. DOM ethosomal gel showed a raise in and AUC of DOM by twofolds compared to free DOM gel. The study suggested that ethosomes incorporated in gels could be an efficient candidate for rectal transmucosal delivery of DOM.
Topics: Administration, Cutaneous; Animals; Domperidone; Gels; Humans; Liposomes; Rabbits; Skin; Skin Absorption
PubMed: 35543451
DOI: 10.1080/10717544.2022.2072542 -
Journal of Movement Disorders May 2022
PubMed: 35531621
DOI: 10.14802/jmd.21151 -
Cureus Apr 2022Globally, a substantial number of people are tormented by dystonia. Domperidone, a D-2 receptor antagonist acts outside the blood-brain barrier in the brain stem as well...
A Rare Case of Domperidone-Induced Acute Dystonia in a Young Adult Due to Consumption of Combination Drug (Proton Pump Inhibitors With Domperidone) and Its Possible Pathomechanism.
Globally, a substantial number of people are tormented by dystonia. Domperidone, a D-2 receptor antagonist acts outside the blood-brain barrier in the brain stem as well as on the gastrointestinal tract. In India, domperidone is conveniently obtainable over the counter as a combination drug with proton pump inhibitors (PPIs) for dyspepsia and gastro-esophageal reflux disease. We present a rare case of domperidone-induced acute dystonia in a young adult presented within 72 hours after consuming two oral doses of this combination drug (PPIs with domperidone) for dyspepsia. Drug-induced extra pyramidal symptoms (EPS) are often misdiagnosed as some psychiatric condition and undoubtedly its expeditious diagnosis staves off unnecessary investigations and ameliorates prognosis. Our case ignites alertness amongst practitioners in India over the judicious use of PPIs with domperidone as the latter may trigger EPS. Such combination drugs can be prescribed if absolutely mandatory by the treating physician. The possible pathomechanism of this hyperkinetic motor phenomenon, perturbing the equilibrium of the cortical-subcortical circuit and resulting in an overflow of muscular activity, is attempted to be explained here, although the explicit mechanism is still blurry.
PubMed: 35509739
DOI: 10.7759/cureus.23723 -
Clinical Case Reports Apr 2022Pityriasis rosea is a common, acute, self limiting inflammatory skin disease. Pityriasis rosea-like eruptions (PR-LE) have been reported after drugs. The clinical...
Pityriasis rosea is a common, acute, self limiting inflammatory skin disease. Pityriasis rosea-like eruptions (PR-LE) have been reported after drugs. The clinical presentation of PR-LE can be distinguished from pityriasis rosea. We reporte a 41-year-old woman who developed PR-LE 5 days after administration domperidone.
PubMed: 35414911
DOI: 10.1002/ccr3.5674 -
Scientific Reports Mar 2022The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires treatments with rapid clinical translatability. Here we develop a...
The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires treatments with rapid clinical translatability. Here we develop a multi-target and multi-ligand virtual screening method to identify FDA-approved drugs with potential activity against SARS-CoV-2 at traditional and understudied viral targets. 1,268 FDA-approved small molecule drugs were docked to 47 putative binding sites across 23 SARS-CoV-2 proteins. We compared drugs between binding sites and filtered out compounds that had no reported activity in an in vitro screen against SARS-CoV-2 infection of human liver (Huh-7) cells. This identified 17 "high-confidence", and 97 "medium-confidence" drug-site pairs. The "high-confidence" group was subjected to molecular dynamics simulations to yield six compounds with stable binding poses at their optimal target proteins. Three drugs-amprenavir, levomefolic acid, and calcipotriol-were predicted to bind to 3 different sites on the spike protein, domperidone to the Mac1 domain of the non-structural protein (Nsp) 3, avanafil to Nsp15, and nintedanib to the nucleocapsid protein involved in packaging the viral RNA. Our "two-way" virtual docking screen also provides a framework to prioritize drugs for testing in future emergencies requiring rapidly available clinical drugs and/or treating diseases where a moderate number of targets are known.
Topics: Binding Sites; Coronavirus Papain-Like Proteases; Humans; Nucleocapsid Proteins; RNA, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Drug Treatment
PubMed: 35351926
DOI: 10.1038/s41598-022-08320-y -
Archivos Argentinos de Pediatria Apr 2022Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy...
Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/ kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.
Topics: Adult; Benzofurans; Child; Domperidone; Gastric Emptying; Gastroparesis; Humans; Male
PubMed: 35338825
DOI: 10.5546/aap.2022.eng.e98 -
Animals : An Open Access Journal From... Mar 2022Canine Leishmaniosis (CanL) is a chronic and potentially fatal disease. In economically disadvantaged regions, costs associated with long-term patient monitoring may...
Canine Leishmaniosis (CanL) is a chronic and potentially fatal disease. In economically disadvantaged regions, costs associated with long-term patient monitoring may determine that some owners decline veterinary follow-up of their dogs. This online, questionnaire-based survey aimed to assess how Portuguese veterinary practitioners perform long-term patient monitoring and recognize relapses. More than 50% of respondents reported that 50-100% of dog owners declared financial restraints. Hence, in these circumstances, most veterinary practitioners only performed clinical examination and serology. However, when owners did not declare financial restriction, other tests were additionally performed, such as renal and hepatic profiles, hemogram, serum protein electrophoresis and urine protein creatinine ratio. The mean number of exams performed when owners presented financial restraints was significantly lower than the number of exams performed without economic limitations. Most veterinary practitioners prescribed allopurinol or until disease remission and domperidone. CanL relapses were recognized by more than half of respondents "Always", through the reappearance or worsening of clinical signs, whereas about a quarter detected an increase in anti- antibody levels and identified abnormalities in the serum protein electrophoresis profile. The relapse rate was higher in the Lisbon Metropolitan Area and north, the most economically favored regions of Portugal. This study confirms that owner financial restraints negatively influence veterinary follow-up and relapse recognition, ultimately compromising clinical decision making and favoring the maintenance of infection endemicity.
PubMed: 35327128
DOI: 10.3390/ani12060731 -
BMJ (Clinical Research Ed.) Mar 2022To estimate the risk of ischaemic stroke associated with antidopaminergic antiemetic (ADA) use.
OBJECTIVE
To estimate the risk of ischaemic stroke associated with antidopaminergic antiemetic (ADA) use.
DESIGN
Case-time-control study.
SETTING
Data from the nationwide French reimbursement healthcare system database Système National des Données de Santé (SNDS).
PARTICIPANTS
Eligible participants were ≥18 years with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for any ADA in the 70 days before stroke. Frequencies of ADA reimbursements were compared for a risk period (days -14 to -1 before stroke) and three matched reference periods (days -70 to -57, -56 to -43, and -42 to -29) for each patient. Time trend of ADA use was controlled by using a control group of 21 859 randomly selected people free of the event who were individually matched to patients with stroke according to age, sex, and risk factors of ischaemic stroke.
MAIN OUTCOME MEASURES
Association between ADA use and risk of ischaemic stroke was assessed by estimating the ratio of the odds ratios of exposure evaluated in patients with stroke and in controls. Analyses were adjusted for time varying confounders (anticoagulants, antiplatelets, and prothrombotic or vasoconstrictive drugs).
RESULTS
Among the 2612 patients identified with incident stroke, 1250 received an ADA in the risk period and 1060 in the reference periods. The comparison with the 5128 and 13 165 controls who received an ADA in the same periods yielded a ratio of adjusted odds ratios of 3.12 (95% confidence interval 2.85 to 3.42). Analyses stratified by age, sex, and history of dementia showed similar results. Ratio of adjusted odds ratios for analyses stratified by ADA was 2.51 (2.18 to 2.88) for domperidone, 3.62 (3.11 to 4.23) for metopimazine, and 3.53 (2.62 to 4.76) for metoclopramide. Sensitivity analyses suggested the risk would be higher in the first days of use.
CONCLUSIONS
Using French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide.
Topics: Antiemetics; Brain Ischemia; Case-Control Studies; Humans; Ischemic Stroke; Stroke
PubMed: 35321876
DOI: 10.1136/bmj-2021-066192