Hydroxychloroquine for the treatment of COVID-19 and its potential cardiovascular toxicity: Hero or villain?

A variety of treatment modalities have been investigated since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic. The use of antimalarials (hydroxychloroquine and chloroquine) for COVID-19 treatment and prevention has proven to be a cautionary tale for widespread, off-label use of a medication during a crisis. The investigation of antimalarials for COVID-19 has also been a driver for a deluge of scientific output in a short amount of time. In this narrative review, we detail the evidence for and against antimalarial use in COVID-19, starting with the early small observational studies that influenced strategies worldwide. We then contrast these findings to later published larger observational studies and randomized controlled trials. We detail the emerging possible cardiovascular risks associated with antimalarial use in COVID-19 and whether COVID-19-related outcomes and cardiovascular risks may differ for antimalarials used in rheumatic diseases.     

Antipalúdicos en dermatología: mecanismo de acción,indicaciones y efectos secundarios

Antimalarial drugs have been in common use in dermatology since the 1950s. Their mechanism of action is complex, and it is now known that they act through various pathways. We review the indications for antimalarials in dermatology, their adverse effects, and some less well-known effects, such as their antithrombotic and hypolipidemic action. The most recent recommendations concerning ophthalmological screening in patients on antimalarials are also reviewed.     

Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for?

Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory.     

辛酰伯喹在家兔体内的药代动力学研究

本文阐述了辛酰伯喹在家兔体内的药代动力学。应用最优化理论中的单纯形法自编计算机程序处理家兔静注辛酰伯喹丙二醇后的血药浓度-时间数据,拟合曲线以开放性三室模型描述较为适宜,其药代动力学参数为:T_(1/2)(λ_3、λ_2和λ_1相)3.410±1.394,0.5420±0.4373和0.1232±0.1045h;V_c 1.261±1.138 1/kg;Vd(ss)6.383±5.072 1/kg;Vd(λ_3)15.59±9.937 1/kg;AUC 9.108±3.793μg·h·ml~(-1);Cl_s 3.158±1.220 1·kg~(-1)·h~(-1);k_(10) 4.315±2.775h~(-1);k_(12)2.003±1.312h~(-1),k_(21) 2.373±0.7639h~(-1),k_(13) 1.127±0.9859h~(-1),k_(31) 0.3107±0.1158h~(-1)。     

脱羰青蒿素的抗疟活性

青蒿素(1)是从青蒿(Artemisia annua)中分离得到的一个抗疟化合物。青蒿素的发现改变了以往抗疟药物均为含氮杂环化合物的格式,开创了一类以过氧化合物为特征的、对抗氯喹虫株有效的新型抗疟药物。七十年代青蒿素结构发表以来,国内外在化学、药理以及临床方面均进行了大量工作,成为当今抗疟药方面最活跃的一个研究课题。这里简要报道     

Malaria and HIV co-infection in pregnancy in sub-Saharan Africa: impact of treatment using antimalarial and antiretroviral agents

Malaria and HIV infection represent severe public health problems in sub-Saharan Africa, and pregnant women are at increased risk because the two diseases intersect in pregnancy, causing adverse perinatal outcome. As access to antiretroviral drugs is increasing in the sub-region, and new combinations of antimalarial drugs are being implemented while more are being evaluated, there is potential for interactions between these therapies. In this report, the impact of treatment using antimalarial and antiretroviral agents in pregnant women with malaria and HIV co-infection was reviewed, using scientific publications identified through a Medline Entrez-Pubmed search with reference to sub-Saharan Africa. The safety and operational feasibility of use of antimalarial and antiretroviral agents to treat co-infected pregnant women were evaluated. Although use of these therapies was shown to improve the health of pregnant women with co-infection, low adherence, poor-quality drugs, resource scarcity, lack of infrastructure and inadequate treatment in sub-Saharan Africa continue to hamper treatment outcome. The absence of studies on interaction between antimalarials and antiretrovirals, as well as mounting evidence of treatment failure due to drug resistance and adverse drug reactions, in most parts of sub-Saharan Africa, make the establishment of new guidelines for the prevention of malaria and HIV infection during pregnancy imperative.     

Home-based management of fever and malaria treatment practices in Uganda

The Home-Based Management of Fever/Malaria (HBMF) strategy in rural Uganda was evaluated in a quasi-experimental study. The intervention consisted of volunteers educating mothers and providing a 3-day course of pre-packaged chloroquine plus sulfadoxine/pyrimethamine tablets (HOMAPAK), free of charge, for the treatment of under-five fevers. Using a structured questionnaire, information was obtained on care-seeking and treatment practices before (n=498) and 18 months after the introduction of HBMF (n=587). Assessment of the intervention effect indicated 13.5% improvement in the accumulated proportion of patients (1) treated, (2) treated within 24h of illness onset, (3) treated with the recommended antimalarials, (4) treated at an adequate dosage and (5) treated for the correct duration. Combining this with the antimalarial drug efficacy resulted in a 10.4% improvement in the community effectiveness of malaria treatment. HOMAPAK use was reported in 25% of 156 febrile children; 23% in the most poor compared with 50% in the least poor. Using HOMAPAK instead of other allopathic antimalarials increased the likelihood of completing all steps (odds ratio 37, 95% CI 4.8-286). Similar to other large-scale public health interventions, this study demonstrates modest practice changes at the population level. However, practices improved markedly among HOMAPAK users, suggesting that intensifying implementation efforts to increase HOMAPAK use, especially among the poorest, would be beneficial.     

2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物抗鼠疟作用的研究

用伯氏鼠疟模型筛选了17个2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物。初步结果显示,化合物Ⅰ₄,Ⅰ₅,Ⅰ₁₀,Ⅰ₁₁和Ⅰ₁₂口服有较好抗疟作用,对正常敏感株(N)的SD₅₀为0.43～2.4mg/kg×4d,高度抗氯喹株(RC)为0.19～0.42mg/kg×4d,(NK₆₅)株为7.2～100mg/kg×4d,抗磺胺株(ORA)为11～76 mg/kg×4d。上述结果表明,该类化合物对(RC)株的疗效显著优于(N)株,但对(NK₆₅)株的疗效较差,与磺胺类药物有轻度交叉抗性。     

诱发和加重银屑病的药物研究进展

药物摄入可能是诱发或加重银屑病的重要原因,某些药物可能会直接导致易感个体发生银屑病,也可能引起原有银屑病病情复发或加重.药物和银屑病的相关性可分为:明确可诱发和加重银屑病的药物(如锂制剂等);可能与银屑病发生和加重的相关药物(如干扰素等).关于药物诱发和加重银屑病的临床和组织学数据分析有助于银屑病发病机制的研究,这些可能与银屑病诱发或加重的相关药物尚需进一步的研究,对易感个体的预防有重要的意义.