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Recent Developments in Therapies and Strategies Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Misbah Hameed, M. Zia-Ul-Haq, Marius Moga
Hydroxychloroquine (HCQ) and Chloroquine has long been used in malaria. HCQ is a derivative of “Chloroquine” with much less toxicity as compared to chloroquine. HCQ and Chloroquine are effective against rheumatoid arthritis, lupus erythematosus, and influenza A and B virus, HIV-1, and SARS COV-1. Based on previous data it has being trialed against COVID-19 treatment. HCQ and Chloroquine has multiple mechanism of action which supports its usage in the treatment of COVID-19.
Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
The two major antimalarial drugs are chloroquine and quinine. Chloroquine is the primary drug used for the treatment of malaria, as well as for chemoprophylaxis in pregnant women who must travel to endemic areas (Diro and Beydoun, 1982). Although there have been no studies of infants whose mothers were treated for malaria during pregnancy with chloroquine, one study reported no increased frequency of congenital anomalies among 169 infants whose mothers received weekly low doses of the drug for malaria prophylaxis during pregnancy (Wolfe and Cordero, 1985). Quinine is used primarily for chloroquine-resistant falciparum malaria. Although there are no large studies regarding its use during pregnancy, increased malformations have been reported when large doses were used to attempt abortion (Nishimura and Tanimura, 1976). Quinine sulfate tablets have also been utilized for leg cramps, but their efficacy is unproven. Although not recommended for the treatment of leg cramps during pregnancy, the antimalarial quinines should not be withheld in the seriously ill pregnant woman with chloroquine-resistant malaria.
Conventional Pharmacological Strategies, Investigational Drugs, and Immunotherapies for COVID–19
Published in Srijan Goswami, Chiranjeeb Dey, COVID-19 and SARS-CoV-2, 2022
Subhra Bhattacharya, Srijan Goswami, Chiranjeeb Dey
Chloroquine and its analogs belong to the antimalarial group of drugs having multimodal action and are being investigated for their effectiveness in treating malaria and autoimmune disorders. Chloroquine acts by impairing the glycosylation process of ACE-2, restricting its interaction with the spike protein, thus hampering binding. These analogs are known to cause inhibition of protein biosynthesis and enzymatic dysfunction by increasing pH levels. Researchers anticipated that the mechanism of action will be useful in treating COVID-19. Under emergency use authorization, this investigational drug was administered to COVID-19 patients. Clinical trials currently investigating the role of chloroquine in treating COVID-19 patients use doses higher than those recommended for authorized indications. Ongoing scientific evidence shows that chloroquine creates adverse drug reactions such as abnormal electrical activity that affects the heart rhythm (QT-prolongation), liver and kidney damage, nerve cell damage, retinopathy, and hypoglycemia. The clinical data regarding the positive effect of the medicine in the treatment of COVID-19 are limited and inconclusive but there was ample evidence showing serious adverse drug reactions. Because of the serious adverse effects observed in COVID-19 patients receiving the investigational drug, the emergency use authorization on chloroquine was withdrawn by the FDA on June 15, 2020 (EMA, 2020; Office of the Commissioner FDA, 2020; Browning, 2014).
Roles of the ACE/Ang II/AT1R pathway, cytokine release, and alteration of tight junctions in COVID-19 pathogenesis
Published in Tissue Barriers, 2023
Regarding viral endocytosis, recent research has confirmed that clathrin-mediated cellular endocytosis of SARS-CoV-2 is a major aspect of virus infection.24 Then, viral endocytosis is followed by endosome acidification, the step by which SARS-CoV-2 enters the cytoplasm and begins replication.25 It has been found that inhibition of endosome acidification in COVID-19 by various agents – including chloroquine – impaired viral replication and improved the prognosis of viral pneumonia in vivo.25,26 However, chloroquine is not currently used in COVID-19 due to poor therapeutic effects and adverse side effects.27 These results present clathrin as a mediator of cellular endocytosis for SARS-CoV-2, which opens the door to the discovery of more potentially potent drugs that act by interfering with endosome acidification that follows clathrin-mediated endocytosis of SARS-CoV-2, such as Salibinin, which was expected to be a good treatment for the management of COVID-19 from a multi-target perspective.28
Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis
Published in Renal Failure, 2022
Zheng-Ming Liao, Zhong-Min Zhang, Qi Liu
Table 1 presents the main characteristics of the included studies. Among the 21 included studies, 14 considered AKI outcomes, and seven analyzed increased creatinine levels. Of the 14 studies on AKI, six were RCTs, six were cohort studies, and two were nested case-control studies. For the seven studies on increased creatinine levels, six were RCTs, and one was a cohort study. For the 21 studies, 13 clearly specified the age range, with 12 focusing on adults and one focusing on children. The daily total dosage of hydroxychloroquine/chloroquine ranged from 200 mg to 1200 mg (available from 18 studies), with 13 studies providing 400 mg, two studies providing 200 mg, one study providing 600 mg, one study providing 800 mg, and one study providing 1200 mg. The follow-up for the safety outcomes ranged from 3 to 42 days, while three studies did not provide such information. Eight studies were conducted in Europe, seven in Asia, and six in America.
Porphyria: awareness is the key to diagnosis!
Published in Acta Clinica Belgica, 2022
Benjamin Heymans, Wouter Meersseman
Furthermore, there are two specific modalities to treat PCT: regular phlebotomy and hydroxychloroquine. Both have more or less the same efficacy and need the same persistence to induce remission [10]. On the one hand, phlebotomy is the preferred option in case of iron accumulation in the liver. It is often continued till the ferritin level is at the lower border of normal. Adverse events of phlebotomy may be anaemia and syncope. Note that iron chelators are also used sometimes but that they are considered to be less effective than regular phlebotomy [11]. On the other hand, a low dose chloroquine or hydroxychloroquine once a week is an effective alternative. These molecules have shown to mobilize the reservoir of porphyrins in the hepatocytes and will accelerate the urinary elimination of these molecules. This strategy can however lead to more severe photosensitivity in the first months of treatment. Other side effects of chloroquine and hydroxychloroquine are mainly retinopathy and liver injury. The latter makes this option contraindicated in advanced liver failure.