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Neurotoxicity Research Dec 2021Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD)...
Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), recreational MDMA use occasionally elicits hyperthermia and hyponatremia, sometimes with a fatal outcome. Specific risk factors for both adverse effects are profuse sweating while vigorously dancing under unfavorable conditions such as high ambient temperatures and insufficient fluid suppletion which result in dehydration. Concomitant use of MDMA and alcohol is highly prevalent, but adds to the existing risk, because alcohol facilitates the emergence of MDMA-induced adverse events, like hyperthermia, dehydration, and hyponatremia. Because of potential health-related consequences of concomitant use of MDMA and alcohol, it is important to identify the mechanisms of the interactions between alcohol and MDMA. This review summarizes the main drivers of MDMA-induced hyperthermia, dehydration, and hyponatremia and the role of concomitant alcohol use. It is shown that alcohol use has a profound negative impact by its interaction with most of these drivers, including poikilothermia, exposure to high ambient temperatures, heavy exercise (vigorous dancing), vasoconstriction, dehydration, and delayed initiation of sweating and diuresis. It is concluded that recreational and clinical MDMA-users should refrain from concomitant drinking of alcoholic beverages to reduce the risk for adverse health incidents when using MDMA.
Topics: Alcohol Drinking; Animals; Drug Interactions; Humans; Hyperthermia; N-Methyl-3,4-methylenedioxyamphetamine; Risk Factors
PubMed: 34554408
DOI: 10.1007/s12640-021-00416-z -
The Oncologist Feb 2024Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is...
INTRODUCTION
Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is still unknown. The aim of this study was to provide objective evidence on the optimal design of hydration schemes to prevent CIN based on an update of the literature.
METHODS
A Pubmed and Embase search were conducted in December 2021 and repeated in April 2022 and March 2023. Two independent reviewers screened the articles. The included articles were categorized and reviewed per category.
RESULTS
Twenty-seven articles met the inclusion criteria. The included studies varied widely. Four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme. All six studies investigating duration and amount of volume of hydration found that a short-hydration scheme resulted in less CIN than a longer hydration scheme. Seven out of nine articles evaluating the role of electrolytes found that magnesium supplementation reduced the risk of nephrotoxicity. Three studies investigated the safety of oral hydration and concluded that nephrotoxicity did not occur more frequently after oral hydration.
CONCLUSION
The hydration scheme of cisplatin should be short and consist of a relatively small amount of volume. The scheme should include mannitol and magnesium supplementation. Head-to-head studies are needed to investigate the safety of furosemide compared with mannitol and the dose of mannitol and magnesium.
Topics: Humans; Cisplatin; Antineoplastic Agents; Magnesium; Mannitol; Renal Insufficiency
PubMed: 37995306
DOI: 10.1093/oncolo/oyad297 -
Frontiers in Pharmacology 2019Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials...
Appraisal of Non-Cardiovascular Safety for Sodium-Glucose Co-Transporter 2 Inhibitors: A Systematic Review and Meta-Analysis of Placebo-Controlled Randomized Clinical Trials.
Whereas the cardiovascular safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors has been well reported, there is limited data from controlled clinical trials regarding the non-cardiovascular safety. This was the focus of our study. We systematically searched MEDLINE, EMBASE, and Cochrane Library (5 Sep 2018) for randomized controlled trials (RCTs) that reported safety data for SGLT2 inhibitors and placebo. Relative risks (RRs) and their 95% confidence intervals (CIs) were pooled using random-effects models. Seventy RCTs (83 studies enrolling 36,958 patients in 78 publications) were identified. SGLT2 inhibitors were associated with a lower risk of serious adverse events (RR 0.90, 95% CI 0.86 to 0.94, < 0.001), death (RR 0.78, 95% CI 0.64 to 0.94, < 0.05), gastroenteritis (RR 0.38, 95% CI 0.20 to 0.72, < 0.05), arthralgia (RR 0.72, 95% CI 0.54 to 0.96, < 0.05), hypertension (RR 0.61, 95% CI 0.50 to 0.75, < 0.001), and edema/peripheral edema (RR 0.49, 95% CI 0.33 to 0.72, < 0.001) compared to placebo. SGLT2 inhibitors were associated with higher risk of infections compared to placebo (RR 1.27, 95% CI 1.17 to 1.37, < 0.001), especially for genital mycotic infection (GMI) (RR 3.71, 95% CI 3.19 to 4.32, < 0.001). Other significant effects were observed for osmotic diuresis-related AEs (RR 2.73, 95% CI 2.20 to 3.40, < 0.001), volume-related AEs (RR 1.26, 95% CI 1.08 to 1.46, < 0.05), renal-related AEs (RR 1.36, 95% CI 1.02 to 1.80, < 0.05), hypoglycemia (RR 1.18, 95% CI 1.10 to 1.26, < 0.001), and increased blood ketone bodies (RR 2.00, 95% CI 1.01 to 3.97, < 0.05). Subgroup and sensitivity analyses strengthened the robustness of primary results. Results from RCTs confirmed lower risk of death, serious adverse events, hypertension, and edema associated with type 2 diabetes mellitus (T2DM) patients treated with SGLT2 inhibitors when compared with placebo. The use of SGLT2 inhibitors were associated with higher risk of infection, osmotic diuresis, volume depletion effects, renal related AEs, and higher blood ketone bodies when compared with placebo.
PubMed: 31616297
DOI: 10.3389/fphar.2019.01066 -
British Journal of Clinical Pharmacology Apr 2018Osmotherapy constitutes a first-line intervention for intracranial hypertension management. However, hyperosmolar solutes exert various systematic effects, among which... (Comparative Study)
Comparative Study
AIM
Osmotherapy constitutes a first-line intervention for intracranial hypertension management. However, hyperosmolar solutes exert various systematic effects, among which their impact on systemic haemodynamics is poorly clarified. This review aims to appraise the clinical evidence of the effect of mannitol and hypertonic saline (HTS) on cardiac performance in neurosurgical and neurocritical care patients.
METHOD
A database search was conducted to identify randomized clinical trials and observational studies reporting HTS or mannitol use in acute brain injury setting. The primary end-points were alterations of cardiac output (CO) and other haemodynamic variables, while the impact of osmotic agents on intracranial pressure, brain relaxation, plasma osmolality, electrolyte levels and urinary output constituted secondary outcomes.
RESULTS
Eight studies, enrolling 182 patients in total, were included. HTS exerted a more profound cardiac output augmentation than mannitol, but no distinct difference between groups occurred. Central venous pressure, stroke volume and stroke volume variation were favourably affected by both osmotic agents, whilst the reported changes in blood pressure were inconclusive. HTS infusion yielded a larger intracranial pressure reduction than mannitol but had an equivalent effect on brain relaxation. Mannitol presented a more potent diuretic effect than HTS. Effect on serum osmolality was alike in both osmotic agents, but contrary to HTS-promoted hypernatraemia, mannitol use induced transient hyponatraemia.
CONCLUSIONS
Mannitol or HTS administration seems to induce an enhancement of cardiac performance; being more prominent after HTS infusion. This effect combined with mannitol-induced enhancement of diuresis and HTS-promoted increase of plasma sodium concentration could partially explain the effects of osmotherapy on cerebral haemodynamics.
Topics: Cardiac Output; Critical Care; Diuretics, Osmotic; Hemodynamics; Humans; Intracranial Hypertension; Intracranial Pressure; Mannitol; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 29247499
DOI: 10.1111/bcp.13492