L-cysteine whether a nutritional booster or a radical scavenger for Plasmodium.

INTRODUCTION: Plasmodium falciparum is the most noxious species among other Plasmodium species that cause malaria. Attention is required to understand more about the pathophysiology and parasite biology to obscure this disease. The fact is, very little is known about the nutritional requirement in sense of carbohydrate, lipid, nucleic acid, and amino acid metabolism that regulate the growth of parasite and out of this, studies related to the metabolism of amino acid are exceptionally limited. Out of several amino acids, L-cysteine is essential for the continuous erythrocytic growth of Plasmodium. However, the exact role of L-cysteine in regulating the growth of Plasmodium is unknown. Here, we tried to investigate how does L-cysteine affects the growth of Plasmodium in in vitro culture, and also the study was aimed to find whether there is a synergism with chloroquine on the Plasmodium growth in vitro. MATERIALS AND METHODS: Parasite inhibition assay based on schizont maturation inhibition following WHO protocol on P. falciparum chloroquine-sensitive strain (MRC-2) was employed to determine IC50 value and drug interaction pattern was shown through fractional inhibitory concentration index. RESULTS: Inhibitory effect of L-cysteine hydrochloride on Plasmodium growth was depicted with IC50 1.152 ± 0.287 µg/mL and the most synergistic pattern of interaction was shown with chloroquine. CONCLUSIONS: The present study anticipates two important findings, firstly inconsistent results from previous findings and secondly, synergistic effect with chloroquine suggests its potency that may be used as an add-on therapy along with chloroquine. However, further study is needed to validate the above findings in vivo models.

Concomitant use of dexamethasone and tetracyclines: a potential therapeutic option for the management of severe COVID-19 infection?

Introduction: The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes.Areas covered: Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19.Expert opinion: The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.

Tafenoquine for Plasmodium vivax malaria: Concerns regarding efficacy & safety.

Plasmodium vivax (P. vivax) malaria is a major problem in various countries such as America, Southeast Asia, Africa and the Eastern Mediterranean. The major barrier in controlling P. vivax malaria is its ability to remain in the liver as a hypnozoite form which is responsible for relapse of P. vivax malaria; hence it is necessary to target both the blood (schizont) as well as the liver (hypnozoite) stages of P. vivax to prevent its relapse. A number of factors limit the use of primaquine (PQ), the currently available therapy for P. vivax (hypnozoite stage), such as haemolysis in glucose-6-phosphate dehydrogenase-deficient patients and being contraindicated in pregnant women. Another problem associated with PQ is the poor adherence rate to the 14-day treatment regimen. Single-dose tafenoquine (TQ), an 8-aminoquinoline, has recently been approved by the U.S. FDA for the treatment of P. vivax malaria along with a blood schizonticidal. TQ is active against all stages of P. vivax lifecycle. In published studies, TQ is considered a better alternative to PQ in terms of adherence, but there are some concerns regarding its safety, efficacy and study designs of trials conducted on TQ. In this context, this review, discusses the potential safety concerns, efficacy data, summary and an appraisal of findings of the important published trials of TQ.

Potential Role of Dexamphetamine in the Treatment of Non-alcoholic Fatty Liver Disease: Hopes and Pitfalls.

Non-alcoholic fatty liver disease (NAFLD) is one of most frequent causes of chronic liver disease. Global prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) with advanced fibrosis is increasing day by day. Patients with NAFLD are more susceptible to encounter cardiovascular morbidity and mortality. Apart from lifestyle changes and dietary modifications, no effective pharmacotherapy is available to prevent the progression of NAFLD to NASH and advanced stages of hepatic fibrosis and cirrhosis. Dexamphetamine is the d-isomer of amphetamine, which acts by inhibiting monoamine reuptake and direct stimulation of dopamine and noradrenaline release. Presently, dexamphetamine is indicated for the treatment of attention deficit hyperactivity disorder and narcolepsy, but since its use was found to be associated with weight loss, it is also now used as an off-label drug for the treatment of obesity. Direct or indirect evidence is present in the form case reports, case series and from effects of related drugs to support the potential role of dexamphetamine in NAFLD. There is an urgent need to initiate preclinical and clinical studies involving robust methodology and adequate sample sizes to explore the potential of dexamphetamine in patients with NAFLD. In this review, we will discuss the therapeutic potential of dexamphetamine for the treatment of NAFLD.

Minocycline for the management of multiple sclerosis: repositioning potential, opportunities, and challenges.

INTRODUCTION: Multiple sclerosis (MS) is a chronic demyelinating inflammatory disorder with variable clinical and pathologic characteristics reflecting multiple underlying pathophysiologic mechanisms. Repositioning of existing drugs for the new indications offers several advantages including significant reduction in the cost and time of drug development and exemption from early phase clinical trials. Minocycline has been reported to exhibit immunomodulation in several pre-clinical and clinical studies through suppression of migratory inflammatory cells, modulation of peripheral immune response, and inhibition of microglial activation within the CNS. AREAS COVERED: Here, the authors review the repositioning potential of minocycline for the treatment of MS along with appraisal of the evidence obtained from preclinical and clinical research. The authors also discuss the advantages and potential safety concerns related to the use of minocycline for the management of MS. EXPERT OPINION: Minocycline offers several distinct advantages in terms of well-known safety profile, lower cost of therapy, widespread availability, and being available as an oral formulation. The authors call upon the public and private funders to facilitate well designed and adequately powered randomized clinical trials that can provide conclusive evidence regarding the safety and efficacy of minocycline in patients with MS.

Combining hydroxychloroquine and minocycline: potential role in moderate to severe COVID-19 infection.

INTRODUCTION: Patients with moderate to severe COVID-19 infection require specific drugs to prevent the morbidity and mortality. Hydroxychloroquine (HCQ) has shown some promise in the management of COVID 19. Minocycline, because of its anticytokine and other useful properties can be an ideal candidate for combining with HCQ. AREAS COVERED: Here we review the need and mechanisms and reasons for combining HCQ and minocycline moderate to severe COVID-19 infection. We also reviewed the advantages, potential safety concerns and precautions to be taken, while combining HCQ and minocycline. EXPERT OPINION: Combining HCQ and minocycline offers many advantages in the management of moderate to severe COVID-19 infection. Both drugs are cheaper, widely available and long-term safety data and contraindications are well known. We do not recommend this combination for prophylaxis or use in asymptomatic or mild disease patients as this can lead to unnecessary safety concerns. Additive antimicrobial and anticytokine effects of both drugs may reduce the morbidity and mortality among patients with COVID-19 and may act as a cheaper alternative to the costlier drugs, however, thorough clinical research is warranted. We call upon public and private healthcare bodies to come up with large well-designed clinical studies for generating evidence-based recommendations.

Repurposing Potential of Ketamine: Opportunities and Challenges.

Ketamine is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor which also interacts with various other receptors that account for its myriad actions. Originally approved as a general anesthetic, it is being explored to be repurposed for numerous other indications such as depressive disorders, suicidal ideation, substance-use disorders, anxiety disorders, chronic pain, refractory status epilepticus, and bronchial asthma exacerbations. Numerous trials are ongoing for the same. The nasal spray of esketamine, a more potent S (+) enantiomer of ketamine, has been approved by the United States Food and Drug Administration (USFDA) for treatment-resistant depression along with the oral antidepressants. However, there are concerns about its safety on long term use, given its psychedelic effects and potential abuse. In this review, we discuss repurposing ketamine for potential therapeutic use and about the safety concerns related to ketamine and esketamine.

Lack of Awareness of Pharmacovigilance among Young Health-care Professionals in India: An Issue Requiring Urgent Intervention.

BACKGROUND: Young healthcare professionals (HCPs) are the pillar of healthcare system. The objective of the present study was to assess the knowledge, attitude, and practices of young HCPs regarding adverse drug reactions (ADRs) reporting. METHODS: This cross-sectional questionnaire-based study was conducted on young HCPs in a tertiary care teaching hospital of North India. The study instrument was semi-structured, prevalidated questionnaire. The responses obtained were compared among doctors and nursing professionals. RESULTS: We obtained response from 84 HCPs (61 doctors and 23 nurses). The mean age of the doctors and nurses was 25.0 ± 2.4 versus 26.3 ± 3.4 years, respectively. No significant difference was observed in questions related to definition of ADR, components of pharmacovigilance (PV), who can report ADRs and medications for which ADRs are to be reported. Only 9.8% doctors and 26.1% nurses were aware of ADR reporting system in India, of which 6 (26%) nurses and none of the doctors were aware of its name. About 16.4% doctors as compared to 61% nurses admitted to have reported an ADR (P < 0.001). The main discouraging factor in ADR reporting was time constraint while lack of knowledge was also highlighted by the HCPs. More nurses as compared to doctors (78.3% vs. 49.2%, P = 0.01) were of the opinion that holding continuing medical education/workshop could encourage reporting. CONCLUSION: There is an urgent need to increase awareness about PV among young HCPs, and adequate interventions should be instituted to encourage PV practices.

Spurious and counterfeit drugs: a growing industry in the developing world.

Spread of spurious/counterfeit/substandard drugs is a modern day menace which has been recognised internationally, especially so in developing countries. The problem assumes added significance in view of rapid globalisation. The market of spurious and counterfeit drugs is a well-organised, white collar crime. Poverty, high cost of medicines, lack of an official supply chain, legislative lacunae, easy accessibility to computerised printing technology, ineffective law enforcement machinery, and light penalties provide the counterfeiters with an enormous economic incentive without much risk. The consequences of the use of such medicines may vary from therapeutic failure to the occurrence of serious adverse events and even death. Proper drug quality monitoring, enforcement of laws and legislation, an effective and efficient regulatory environment, and awareness and vigilance on part of all stakeholders can help tackle this problem.

Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.

BACKGROUND: Antihypertensive agents are selected primarily for their ability to prevent morbidity and mortality related to hypertension. METHODS AND RESULTS: Prescribing trends and the cost of antihypertensive drugs were studied in 300 patients attending an internal medicine clinic. Beta-blockers were the most frequently used group of drugs (46.7%), followed by calcium-channel antagonists (34.3%) and angiotensin-converting enzyme inhibitors (30%). Diuretics were used in only 13.2% of the prescriptions. Atenolol (36%), amlodipine (29.3%) and enalapril (19%) were the most frequently used individual drugs. Propranolol, furosemide, amlodipine and atenolol were the least expensive drugs used, with annual drug acquisition costs of Rs 80, 102, 182 and 318, respectively. Benazepril (Rs 1778), diltiazem SR (Rs 1777), lisinopril (Rs 1660), prazosin (Rs 1416) and losartan (Rs 1365) were the most expensive drugs in terms of annual drug acquisition costs. CONCLUSIONS: The results of our study emphasize the need to encourage frequent use of diuretics. Since the costs of different antihypertensives vary considerably, newer and relatively expensive antihypertensives should be prescribed only when clearly indicated.

Differential effect of selected antiarrhythmic drugs on coronary artery ligation-induced ventricular arrhythmias on the right or left sides.

The differential effect of the antiarrhythmic agents quinidine, propranolol, verapamil and sotalol was studied on right and left sided ventricular arrhythmias induced by ligation of the right coronary artery or anterior descending branch of the left coronary artery, respectively. Quinidine (0.30 mg/kg/min), propranolol (0.30 mg/kg/min), sotalol (0.25 mg/kg/min) and verapamil (0.018 mg/kg/min) were injected in unanesthetized dogs 18-24 h after coronary artery ligation. The doses of test drugs required for suppression of the ventricular arrhythmias were higher in the case of quinidine, sotalol and verapamil, but not in case of propranolol. The potency of the selected drugs in abolishing ventricular ectopics was, in descending order: verapamil, sotalol, propranolol and quinidine. The differential antiarrhythmic effect of these drugs in ventricular arrhythmias is discussed.

Differential effect of some antiarrhythmic drugs in right- or left-sided aconitine-induced experimental atrial arrhythmias.

The differential effect of different antiarrhythmic agents, quinidine, propranolol, verapamil and sotalol was studied on right- and left-sided aconitine-induced atrial arrhythmias in dogs. In control experiments the time required for the reversion of right aconitine-induced atrial arrhythmias to normal sinus rhythm was higher as compared to left-sided aconitine-induced atrial arrhythmias. All the drugs studied were effective in reverting atrial arrhythmias to normal sinus rhythm, and doses required for suppression of the right atrial arrhythmias as compared to the left atrial arrhythmias were significantly higher in the case of quinidine, sotalol and verapamil, but not in the case of propranolol. The differential antiarrhythmic effect of these drugs in atrial arrhythmias is discussed.