Education thérapeutique en psychiatrie (Représentations des soignants, des patients et des familles)

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Drug-induced cardiac toxicity and adverse drug reactions, a narrative review

International audienceDrug-induced cardiotoxicity is a primary concern in both drug development and clinical practice. Although the heart is not a common target for adverse drug reactions, some drugs still cause various adverse cardiac events, with sometimes severe consequences. Direct cardiac toxicity encompasses functional and structural changes of the cardiovascular system due to possible exposure to medicines. This phenomenon extends beyond cardiovascular drugs to include non-cardiovascular drugs including anticancer drugs such as tyrosine kinase inhibitors, anthracyclines and immune checkpoint inhibitors (ICIs), as well as various antipsychotics, venlafaxine, and even some antibiotics (such as macrolides). Cardiac ADRs comprise an array of effects, ranging from heart failure and myocardial ischemia to valvular disease, thrombosis, myocarditis, pericarditis, arrhythmias, and conduction abnormalities. The underlying mechanisms may include disturbances of ionic processes, induction of cellular damage via impaired mitochondrial function, and even hypercoagulability. To mitigate the impact of drug-induced cardiotoxicity, multi-stage evaluation guidelines have been established, following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for in vitro and in vivo testing. Despite preclinical safeguards, post-marketing surveillance remains critical, as certain cardiotoxic drugs may escape initial scrutiny. Indeed, historical data show that cardiovascular ADRs contribute to almost 10% of market withdrawals. The impact of drug-induced cardiotoxicity on cardiac issues, particularly heart failure, is often underestimated, with incidence rates ranging from 11.0% to over 20.0%. We here comprehensively examine different patterns of drug-induced cardiotoxicity, highlighting current concerns and emerging pharmacovigilance signals. Understanding the underlying mechanisms and the associated risk factors is critical in order to promptly identify, effectively manage, and proactively prevent drug-induced cardiac adverse events. Collaborative efforts between physicians and cardiologists, coupled with thorough assessment and close monitoring, are essential to ensuring patient safety in the face of potential drug-induced cardiotoxicity

Insights on the Evidence of Cardiotoxicity of Hydroxychloroquine Prior and During COVID‐19 Epidemic

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Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem

International audienceThe antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly

Drug-Associated Parosmia: New Perspectives from the WHO Safety Database

Parosmia is a qualitative distortion of smell perception. Resulting from central causes, sinonasal diseases, and infections, parosmia has also been associated with medications. Therefore, we aimed to investigate potential signals for drugs associated with parosmia. VigiBase® (the WHO pharmacovigilance database) was queried for all reports of “Parosmia” (MedDRA Preferred Term), registered up to 23 January 2022. Disproportionality analysis relied on the reporting odds ratio and the information component. A signal is detected when the lower end of the 95% confidence interval of the information component is positive. We found 14,032 reports of parosmia, with a median patient age of 53 years. Most reported drugs were antiinfectives, among which COVID-19 vaccines accounted for 27.1% of reports. Antibiotics and corticosteroids were involved in 6.8% and 4.6% of reports. Significant disproportionate reporting was detected for corticosteroids, antibiotics, drugs used in nicotine dependence, COVID-19 and HPV vaccines, serotonin–norepinephrine reuptake inhibitors (SNRI), and incretin mimetics. We suggest potential safety signals involving nicotine replacement therapies and vaccines. We also highlight the potential role of less suspected classes, such as SNRIs and incretin mimetics. An iatrogenic etiology should be evoked when parosmia occurs, especially in the elderly

Spontaneous reporting of adverse-drug reactions as an outlet for patient dismay? The case of Levothyrox(R) change of excipients

Following minor changes of excipients of Levothyrox®, the French Pharmacovigilance Database was overwhelmed by patients' spontaneous reports of adverse drug reactions associated with the new formula. After noticing that most of these reports differed from those related to other drugs, we aimed to characterize their features and compared them with spontaneous reports associated with other chronic treatments as comparators. We randomly sampled patient reports associated with either Levothyrox® new formula (n=200) or with comparator drugs (n=200) from March 2017 till March 2018 from the national pharmacovigilance database. We evaluated the number of incriminated drugs and adverse drug reactions per report, and verified whether they were "expected" or not according to the Summary of Product Characteristics. Levothyrox® associated reports included, on average, more adverse drug reactions (8±4) than comparators (2±2, p0.05), but female predominated in Levothyrox® group (94.5%) as compared with comparators (60.8%, p<0.001). A mere third of the Levothyrox® associated adverse drug reactions were deemed "expected", versus two-third for comparators (p<0.001). The pattern of spontaneous reports associated with Levothyrox®, whether fueled by media or influenced by social networks, appears atypical, as compared with that of comparators. Such reports, by their abundance may impair the automatic detection of relevant concomitant signals

HIV-mediated immune aging in young adults infected perinatally or during childhood

International audienceBACKGROUND: HIV-infected patients progressing towards disease present a premature immune aging profile, characterized by the exhaustion of lymphopoiesis. The development of these anomalies may be prevented in young HIV-infected patients owing to their robust immune resources and lymphocyte regeneration capacities.METHODS: An immunomonitoring substudy was designed for young adults aged between 18 and 25 years, living with HIV since childhood included in the national ANRS Co19 COVERTE Cohort. We compared markers associated with immune aging, including the frequency of circulating hematopoietic progenitors and the phenotype of lymphocyte populations, with those of patients infected with HIV in adulthood.RESULTS: HIV-infected young adults displayed decreasing numbers of CD34 hematopoietic progenitors and mature lymphocytes, indicative of general lymphopenia and reminiscent of the alterations found in patients infected in adulthood or uninfected elderly people. This highlights the strong impact of HIV on the immune system despite patient's young age at infection. Immune aging-related alterations were particularly obvious in young patients who presented high viral loads.CONCLUSION: HIV-infected young adults can present increased markers of immune activation and senescence, related to uncontrolled viral replication. This highlights the issue of noncompliance to antiretroviral therapy in patients at a young age, resulting in loss of viral control, premature immunosenescence, and potentially irreversible damage of their lymphopoietic system

Medications as a Trigger of Sleep-Related Eating Disorder: A Disproportionality Analysis

Sleep-related eating disorder (SRED) is a parasomnia with recurrent, involuntary, amnestic eating episodes during sleep. There is growing evidence of the association between SRED and medications. Therefore, we aimed to rank drugs showing the strongest association. VigiBase&reg; (WHO pharmacovigilance database) was queried for all reports of &ldquo;Sleep-related eating disorder&rdquo;. Disproportionality analysis relied on the Reporting Odds Ratio, with its 95% Confidence Interval (CI), and the Information Component. Our VigiBase&reg; query yielded 676 cases of drug-associated SRED. Reports mostly involved zolpidem (243, 35.9%), sodium oxybate (185, 27.4%), and quetiapine (97, 14.3%). Significant disproportionality was found for 35 medications, including zolpidem (387.6; 95%CI 331.2&ndash;453.7), sodium oxybate (204.2; 95%CI 172.4&ndash;241.8), suvorexant (67.3; 95%CI 38.0&ndash;119.2), quetiapine (53.3; 95%CI 43.0&ndash;66.1), and several psychostimulants and serotonin-norepinephrine reuptake inhibitors (SNRIs). Patients treated with nonbenzodiazepines or SNRIs were significantly older (mean age: 49.0 vs. 37.5; p &lt; 0.001) and their SRED were more likely to be serious (62.6% vs. 51.4%; p = 0.014) than patients treated with sodium oxybate or psychostimulants. Psychotropic drugs are involved in almost all reports. In patients with SRED, an iatrogenic trigger should be searched for