Polypharmacy and Drug Interactions in the COVID-19 Pandemic.

The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included.

Clinical and biochemical short-term effects of hyperbaric oxygen therapy on SARS-Cov-2+ hospitalized patients with hypoxemic respiratory failure.

Background: Hyperbaric oxygen therapy (HBOT) has been proposed to address COVID-19- associated respiratory failure. However, its biochemical effects are poorly known.

Method: 50 patients with hypoxemic COVID-19 pneumonia were divided into C group (standard care) and H group (standard care plus HBOT).

Development and Implementation of the Hdc.DrApp.la and SIMDA Programs to Reduce Polypharmacy and Drug-drug Interactions in Patients Hospitalized in Internal Medicine.

Objectives: We evaluated polypharmacy and possible drug-drug interactions (p-DDIs) in hospitalized patients before and after using the SIMDA Computerized Medical Decision Support System (CMDSS).

Materials And Methods: We included the prescriptions of ≥ 18 years hospitalized patients in the internal medicine department. We developed and implemented the Hdc.

Pharmacokinetic and pharmacodynamic study of three products of epoetin alfa as single subcutaneous dose in healthy volunteers.

Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980s and has been present in that market since 1991.

Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial.

Background: Hyperbaric oxygen (HBO) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction.

Methods: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020.

Precision Medicine in the Renin-Angiotensin System: Therapeutic Targets and Biological Variability.

Pathologies linked to the renin-angiotensin system are frequent, and the drugs used in them are numerous and show great variability in therapeutic effects and adverse reactions. Genetic variants have been detected in the angiotensinogen gene (6), angiotensin-converting enzyme (9), angiotensinconverting enzyme 2 (1), and angiotensin receptor Type 1 (4) among others. However, the large number of studies that have analyzed each of them makes it complex and almost impossible to consider all the existing information.

Dextrophropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levels.

Objective: To evaluate frequency and risk factors for dextropropoxypheneinduced QT-interval prolongation in the clinical setting.

Design: Prospective, noninterventional, observational, longitudinal cohort approach. Electrocardiograms were blindly evaluated by independent professionals.

Drug-induced QT Interval Prolongation in the Intensive Care Unit.

Background: The most common acquired cause of Long QT syndrome (LQTS) is drug induced QT interval prolongation. It is an electrophysiological entity, which is characterized by an extended duration of the ventricular repolarization. Reflected as a prolonged QT interval in a surface ECG, this syndrome increases the risk for polymorphic ventricular tachycardia (Torsade de Pointes) and sudden death.

Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid-phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses.

Rationale: Several opioid analgesics have been related to the prolongation of cardiac repolarization, a condition which can be fatal. In order to establish a correct estimation of the risk/benefit balance of therapeutic doses of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene, it was necessary to develop an analytical method to determinate plasma concentrations of these opioids.

Methods: Here we describe a method which incorporates strong alkaline treatment to obtain norpropoxyphene amide followed by a one-elution step solid-phase extraction, and without further derivatization.

In vivo Phenotyping Methods: Cytochrome P450 Probes with Emphasis on the Cocktail Approach.

Background: Differences in drug response among patients are common. Most major drugs are effective in only 25 to 60 percent of the patients, in part due to the CYP enzymes, whose activity vary up to 50-fold between individuals for some index metabolic reactions. Several factors affect CYP activity, among which genetic polymorphisms have been studied as the major cause for long time.

Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations .

Unlabelled: A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine).

Objective: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine.

Research Design And Methods: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation.

A Systematic Approach to Assess the Burden of Drug Interactions in Adult Kidney Transplant Patients.

Aim: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population.

Methods: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs.

Comparative bioavailability of two tablet formulations of emtricitabine/tenofovir in healthy, fasting volunteers: a single-dose, randomized-sequence, open-label crossover study.

Objective: To evaluate the relative bioavailability of a new formulation of emtricitabine (EMT) 200 mg and tenofovir disoproxil fumarate (TNF) 300 mg and to compare with reference formulation to meet regulatory criteria in Argentina.

Methods: A randomized-sequence, open-label, twoperiod crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of T or R formulations was followed by a 7-day washout period.

Relative bioavailability between two teriparatide formulations in healthy volunteers.

Objective: To compare the pharmacokinetics, relative bioavailability (RB), immunogenicity, and safety after a single dose of test or reference formulation of teriparatide in healthy human volunteers in order to demonstrate whether both products are similar.

Research Design And Methods: We compared pharmacokinetic parameters, immunogenicity, and safety after a single dose of two formulations (Osteofortil® and Forteo®) of teriparatide in a randomizedsequence, open-label, two-period crossover study in 24 healthy volunteers. The washout period between formulations was 7 days.

Tramadol Induced QTc-Interval Prolongation: Prevalence, Clinical Factors and Correlation to Plasma Concentrations.

Unlabelled: In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol.

Objective: To evaluate the effect of tramadol on QT-interval in the clinical setting.

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

Objective: The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed.

Age-distribution and genotype-phenotype correlation for N-acetyltransferase in Argentine children under isoniazid treatment.

Introduction: Metabolic clearance of isoniazid (INH) may be up to 10 times faster in individuals who are rapid acetylators compared with slow acetylators. In addition, the acetylation phenotype has been suggested to change with age. A better knowledge of the age distribution of the acetylation genotype and phenotype in children requiring INH for tuberculosis treatment or prevention could be important to optimize safety and efficacy of INH use.

Severe neutropenia in a renal transplant patient suggesting an interaction between mycophenolate and fenofibrate.

Objective: To describe a patient in whom initiation of micronized fenofibrate precipitated mycophenolate induced neutropenia.

Case Summary: A 57-year-old man was admitted to the hospital because of febrile neutropenia. He had undergone kidney transplantation seventeen years ago.

Pharmacovigilance and the cardiovascular system: two sides to every story.

Purpose: The objective of the present study was to quantify the reported cardiovascular adverse reactions and adverse reactions to cardiovascular drugs to help to design and implement monitoring and prevention strategies.

Methods: The pharmacovigilance unit (PU) is a peripheral effector of National Pharmacovigilance Center and receives adverse drug reactions notifications from 10 teaching hospitals. Data on adverse reactions beginning in 2004 and notified to the PU were extracted from the database.

Comparative bioavailability of 2 tablet formulations of levodopa/benserazide in healthy, fasting volunteers: a single-dose, randomized-sequence, open-label crossover study.

Background: Currently, levodopa administered with decarboxylase inhibitors is the gold standard for the management of the motor symptoms of Parkinson's disease, a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. In Argentina, only 1 commercial product is available with such composition; this study was contracted by the manufacturer to comply with new generic product regulations.

Objective: The aim of this study was to evaluate the fasting bioavailability of a new generic formulation of levodopa 200 mg/benserazide 50 mg tablets (test) and compare this generic formulation with the branded formulation (reference) to meet regulatory criteria for marketing the test product in Argentina.

Other drugs acting on nervous system associated with QT-interval prolongation.

Several drugs acting on the nervous system have been implicated in the prolongation of the QT interval. Leaving aside the antidepressant and antipsychotic drugs, some have shown to prolong the QT interval in vivo. These include opioids, particularly methadone, inhalational anesthetics, and some preparations used for treatment of cough.

Prokinetic agents and QT prolongation: a familiar scene with new actors.

Prokinetic agents are a very large family of drugs with different mechanisms of action. Only QT prolongation by cisapride has made notable impact and deserved its partial restriction and/or withdrawal from the market. Postmarketing surveillance initially showed that cisapride was generally safe and well tolerated, but in the past decade, more recent data have shown some risk in the patient populations.

Antihistamines: past answers and present questions.

Antihistamines are drugs frequently used. Several drugs in this family had to be withdrawn from the market or limited in their marketing due to potentially fatal adverse events. These events were related to the ability of some antihistamines to affect cardiac potassium channels and prolong the QT interval with an excessive risk of serious arrhythmias such as Torsades de Pointes (TdP).