Current drug safety最新文献

Background: The kidneys, intricate organs responsible for maintaining fluid and electrolyte balance, are susceptible to damage from diverse nephrotoxic insults, including drugs, toxins, and metabolic disorders. In recent years, flavonoids, bioactive compounds abundant in fruits, vegetables, and herbal extracts, have emerged as promising candidates for renal protection due to their potent antioxidant and anti-inflammatory properties.

Methods: We have collected the data that supported this idea to conduct a comprehensive review by using scientific databases, such as Pub Med ®, ScienceDirect ®, Google Scholar ®, and MEDLINE ®. An attempt was made to refer to all English-language articles published between 2000 to 2020 using keywords like flavonoids potential in nephrotoxicity and nephrotoxicity treatment approaches with herbal remedies.

Conclusion: This comprehensive review delves into the molecular mechanisms underlying the reno-protective effects of flavonoids. By scavenging reactive oxygen species, inhibiting inflammatory mediators, and modulating intracellular signalling pathways, flavonoids can mitigate oxidative stress and inflammation, thereby preserving renal function and integrity. Preclinical studies have demonstrated the potential of specific flavonoids in ameliorating drug-induced nephrotoxicity, renal ischemia-reperfusion injury, diabetic nephropathy, and other kidney diseases. Furthermore, epidemiological evidence highlights the inverse relationship between flavonoid intake and the risk of developing kidney diseases. Nevertheless, understanding the molecular mechanisms of flavonoids in nephroprotection offers exciting prospects for developing novel therapeutic strategies to combat kidney diseases and promote kidney health.

Depression, a pervasive mental health disorder, affects millions worldwide, necessitating the widespread use of synthetic anti-depressant medications. While these pharmaceutical interventions have demonstrated efficacy in alleviating depressive symptoms, they are not without their associated side effects. This review provides a comprehensive overview of the side effects of synthetic anti-depressants, aiming to enhance the understanding of their clinical implications. Common side effects explored include gastrointestinal disturbances, sexual dysfunction, insomnia, weight gain, and cognitive impairments. Additionally, this review delves into less frequent but potentially severe adverse events, such as serotonin syndrome, hyponatremia, and cardiac complications associated with specific classes of synthetic anti-depressants. Moreover, the review examines the interplay between side effects and treatment adherence, emphasizing the importance of monitoring and managing these effects in clinical practice. It also discusses strategies to mitigate side effects, including dose adjustments, combination therapy, and alternative treatment approaches. In conclusion, this comprehensive review sheds light on the multifaceted landscape of side effects associated with synthetic anti-depressants. By providing clinicians with a nuanced understanding of these effects, it aims to facilitate informed decision-making, personalized treatment plans, and improved patient outcomes in managing depression.

Background: Acute Pancreatitis (AP) is an uncommon complication that rarely occurs during Rheumatoid Arthritis (RA). Among the varied etiologies of AP, Drug-induced Pancreatitis (DIP) remains a rare entity and a rather challenging condition. A large panel of drugs have been reported to cause pancreatitis; however, there are no cases of tofacitinib-induced pancreatitis reported in the literature.

Case presentation: We have, herein, reported the case of a Tunisian 58-year-old woman with a four-year history of RA who experienced two episodes of AP; the first one occurred on the second day of a 3-day series of methylprednisolone intravenous injections, and the second episode occurred on the sixth-day of tofacitinib administration. Each time, she presented acute abdominal pain with characteristic radiation to the back. Symptoms resolved spontaneously once the suspected drug was discontinued. In the event of a negative investigation, including abdominal ultrasonography and magnetic resonance imaging, and assessment of albumin, calcemia, triglyceridemia, serum ferritin, and IgG4 levels, DIP was the most likely diagnosis.

Conclusion: Although DIP is still a rare condition, it remains serious with an increased risk of mortality. We intended to alert clinicians that in addition to the known side effects of tofacitinib, pancreatitis may be induced by this drug, especially in predisposed patients.

Introduction: Serotonin syndrome is a potentially life-threatening condition that can occur as a result of the therapeutic use of serotonergic medications or drug interaction. In this study, we describe two cases of serotonin syndrome-associated hypertensive crisis following linezolid use.

Case presentation: The first patient was a 52-year-old female who was admitted due to a diabetic foot infection and pneumonia associated with a decreased consciousness level. Serotonin syndrome occurred 24 hours after starting the linezolid use. Resistant hypertension was the main hemodynamic finding. It could not be controlled with amlodipine, valsartan, prazosin, and nitroglycerin infusion. Resistant hypertension and other symptoms of serotonin syndrome were resolved about 48 hours after discontinuation of linezolid use. The second case was a man with a history of kidney transplant, diabetes, and hypertension. He was admitted to the ICU due to severe COVID-19. Broad-spectrum antibiotics [linezolid, cefepime], and remdesivir was initiated. Following intubation, continuous infusion of fentanyl was used for sedation. Within 24 hours after fentanyl and linezolid initiation, severe agitation, eye clonus, hyperreflexia, hypertension [160-186 /90-110 mmHg], and tachycardia [>100/min] were noted. With the possible diagnosis of serotonin syndrome, fentanyl was discontinued, and morphine was initiated. The patient's symptoms improved 48 hours after discontinuation of fentanyl.

Conclusion: Both patients had a history of well- controlled hypertension. Hypertensive crisis has occurred after recent or concurrent use of serotonergic agents with linezolid. A thorough evaluation of the patient's medical history and current condition can help clinicians prevent this syndrome in critically ill patients.

Background: The COVID-19 pandemic has called for the rapid development and use of antiviral drugs to effectively control the disease. Nirmatrelvir/Ritonavir (Paxlovid), Molnupiravir, and Remdesivir have been pivotal in therapeutic approaches, although they raise concerns regarding adverse drug reactions (ADRs).

Objective: This study aimed to thoroughly assess the ADRs associated with these drugs by utilizing the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration (FDA).

Methods: ADR reports for Paxlovid, Molnupiravir, and Remdesivir throughout the period of January 2022 to May 2023 were extracted and classified according to the severity, type of reaction, and demographic variables. Reporting Odds Ratios (RORs) with 95% confidence intervals were calculated to evaluate the relationship between antiviral medications and various ADRs.

Results: The study established notable correlations between Paxlovid and the recurrence of the disease (40.08%) and dysgeusia (16.29%). Molnupiravir was linked to gastrointestinal (16.73%) and skin reactions (9.47%), while Remdesivir had impairments in the liver (25.21%) and kidneys (13.34%). ADRs were more commonly observed in female patients treated with Paxlovid (57.95%) and Molnupiravir (49.40%), whereas Remdesivir ADRs were mostly reported in males (58.56%). Paxlovid and Remdesivir ADRs were frequently reported in adults between the ages of 18 and 64 (46.01% and 45.01%), while Molnupiravir ADRs were more common in older individuals aged 65 to 85 (40.38%).

Conclusion: This thorough assessment emphasizes the importance of careful surveillance and control of ADRs linked to COVID-19 antiviral therapies. It is essential to customize treatments by considering specific patient histories, particularly for pre-existing diseases.

Background: Emerging studies have reported the potential anticancer activity of FDA-approved benzimidazole-based anthelmintics against lung cancer. Therefore, the current systematic review aimed to explore the anticancer activity of benzimidazole-based anthelmintics in lung cancer animal models.

Method: The databases including Pubmed, ScienceDirect, and Google Scholar were searched till April 2024 for the animal studies evaluating the anticancer activity of benzimidazole-based anthelmintics against lung cancer. The relevant data was extracted in the prepared format in Microsoft Excel. Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias (RoB) was used to assess the quality of included studies. The protocol for this study has been registered in PROSPERO (Registration number: CRD42022352141).

Results: Initially, we obtained 4150 articles, and finally eight articles were included in the current study. The information in the included studies was a bit diversified including different benzimidazole- based anthelmintics, dosage, route of administration, and duration of experiments. However, all studies reported that exposure to benzimidazole-based anthelmintics decreased tumor size and tumor volume in animal models of lung cancer.

Conclusion: In conclusion, benzimidazole-based anthelmintics have the potential to treat lung cancer. However, more controlled and thorough preclinical studies are required to evaluate its efficacy, safety, and mechanism of anticancer activities.

Introduction/aim: The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems.

Method: Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2-deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase.

Results: Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8- HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level (p < 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests.

Conclusion: Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

The blood-brain barrier (BBB) is based on the unique pattern of the microvasculature of the central nervous system (CNS), which controls the transport of molecules between the CNS and the blood. The blood-brain barrier is mainly composed of endothelial cells, pericytes, and basement membrane, as well as the astrocytes and immune cells as perivascular macrophages and microglial cells. The dysfunction of this barrier can cause serious neuronal disorders due to the transport of hazardous molecules and immune cells to the CNS. Mitochondria plays a major role in cellular homeostasis in terms of health and disease. This review evaluated the published data about the effect of the drugs on the cells of BBB. Only seven articles were found that considered the effect of drugs on the barrier endothelial cells and mitochondria via different assays. Further studies are recommended to evaluate the impact of used medications on BBB cell bioenergetics. Also, the effect of the newly studied pharmaceutical agents on the BBB bioenergetics should be included within their safety profile studies.

Background: Paxlovid (nirmatrelvir/ritonavir) is the first oral therapy approved by the US FDA to treat patients with mild-to-moderate COVID-19.

Objective: Our current review focuses on clinical data related to tacrolimus toxicity induced by Paxlovid currently available.

Methods: A number of online databases, including LitCovid, Scopus, Web of Science, Embase, EBSCO host, Google Scholar, Science Direct, and the reference lists were searched to identify articles related to Paxlovid-induced tacrolimus toxicity, using keywords, like drug interactions, Paxlovid, ritonavir, nirmatrelvir, tacrolimus, pharmacokinetic interactions, and CYP3A.

Results: Tacrolimus is a substrate of CYP3A enzymes and ritonavir of Paxlovid has been identified as a potent inhibitor of CYP3A enzymes. Hence, Paxlovid can inhibit the CYP3A-mediated metabolism of tacrolimus, resulting in elevated plasma concentrations of tacrolimus and toxicity.

Conclusion: A number of case reports and case series have been published to highlight the association of Paxlovid and tacrolimus toxicity in transplant recipients with COVID-19 infection. Various recommendations have been proposed to prevent and mitigate the adverse events related to the DDI of Paxlovid and tacrolimus. Transplant physicians should be aware of this DDI and collaborate with clinical pharmacists on this issue.