Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients.

The threats involved in the long-term opioid treatment of chronic non-cancer pain (CNCP) have increased notably. Strategies to identify at-risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme.

Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis.

Background & Aims: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA.

Methods: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites.

OPRM1 influence on and effectiveness of an individualized treatment plan for prescription opioid use disorder patients.

Screening for opioid use disorder should be considered in chronic non-cancer pain (CNCP) patients with long-term use of opioids. The aim of our study was to assess the effectiveness of an individualized treatment plan (ITP) for prescription opioid dependence that included screening of pharmacogenetic markers. An observational prospective study was performed using prescription opioid-dependent CNCP outpatients (n = 88).

β2‑adrenergic receptor functionality and genotype in two different models of chronic inflammatory disease: Liver cirrhosis and osteoarthritis.

The present study was designed to investigate the functional status of β2 adrenoceptors (β2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The β2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte β2AR receptor functionality and genotype in LC and OA patients.

Variations of pharmacokinetics of drugs in patients with cirrhosis.

Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies.

Acute effects of dipyrone on renal function in patients with cirrhosis: a randomized controlled trial.

Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis.

Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial.

Introduction: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions.

Objectives: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity.

Ketanserin potentiates morphine-induced antinociception mediated by kappa-receptor activation.

How can we treat patients with reduced morphine doses without loosing the pain killing effect or morphine antinociceptive effects (MAE)? To address this question, we hypothesized that serotonin (5-HT2) receptor antagonism could enhance MAE mediated by kappa-opioid receptors. We pretreated mice with ketanserin, a 5-HT2 receptor antagonist, and measured the morphine dose required to observe analgesia. The morphine dose effective in 50% of animals (ED(50)) was reduced from 4.

The existence of a relationship between increased serum alanine aminotransferase levels detected in premarketing clinical trials and postmarketing published hepatotoxicity case reports.

Background: Drug-induced liver injury (DILI) profile in most drugs' available information is based on both the incidence of alanine aminotansferase (ALT) elevations in clinical trials and published case reports.

Aim: To assess the relationship between ALT elevations in clinical trials and the number of published case reports in the postmarketing setting.

Methods: Hepatotoxic drugs were identified from product labelling and classified in high-medium risk (Black Box Warning or Precautions section) or low risk (a statement in the Adverse Reactions section).

Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis.

Background & Aims: Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels, probably because of a combined effect of norfloxacin on bowel flora and neutrophils.

Methods: Thirty-one patients with cirrhosis receiving norfloxacin (400 mg/day) were included. Blood samples were collected at 0.

Women's health and gender-based clinical trials on etoricoxib: methodological gender bias.

Background: The aim of this study was to determine compliance with published good practice guidelines for gender and clinical trials using etoricoxib. The rationale for choosing etoricoxib was that it is widely used by women and there is evidence of potential interaction with contraceptives and hormone replacement therapy as highlighted in the product characteristics.

Methods: The study reviewed 58 etoricoxib published trials (54 papers) to determine if they met the gender recommendations of the Guidelines of Food and Drug Administration (1993) and the Sex, Gender and Pain Special Interest Group Consensus Working Group Report (2007).

Causality assessment of liver injury after chronic oral amiodarone intake.

Background/aim: The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury.

Methods: Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials.

Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.

We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs.

The diagnosis of drug-induced liver disease.

The diagnosis of drug-induced liver injury is often one of exclusion with initial suspicion based on circumstantial evidence. The natural history, characteristics and limitations of this exclusion process are revised. Also, the numerous published attribution algorithms for evaluation of drug-related liver abnormalities are described and their characteristics and differences are illustrated with true patients from our clinical experience.

Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain.

Background/aims: Morphine has been contraindicated for pain treatment in acute pancreatitis because of its presumed opioid-induced sphincter of Oddi dysfunction. However, scientific evidence supporting a deleterious influence on the clinical course is absent. This pilot study was undertaken to evaluate the efficacy and adverse events of metamizole versus morphine in acute pancreatitis.

Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.

Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included.

Pharmacokinetic variations of acetaminophen according to liver dysfunction and portal hypertension status.

Aim: To study the pharmacokinetic and metabolism profiles of a single dose of acetaminophen in patients with cirrhosis.

Methods: Oral acetaminophen (1000 mg) was administered to seven healthy subjects and 14 patients with cirrhosis (nine Child-Pugh A or B and five Child-Pugh C grade), being five without and nine with oesophageal varices. Plasma levels of acetaminophen and its metabolites were determined by HPLC.

Risk of drug-induced agranulocytosis: the case of calcium dobesilate.

Background: In the last 20 years, some cases of agranulocytosis associated with calcium dobesilate consumption in Spain have been reported. A high risk of dobesilate-associated agranulocytosis (121 cases per million per year) calculated using both a case-control and a case-population strategy has been published. However few spontaneous reports have been noted in the same period of time.

A prospective study of the clarithromycin-digoxin interaction in elderly patients.

The study was a prospective observational trial carried out to assess the clarithromycin-digoxin interaction in elderly patients chronically taking digoxin. Digoxin concentrations were determined before and after concomitant treatment with clarithromycin. A Bayesian approach was used to calculate digoxin pharmacokinetics.

A new Poisson and Bayesian-based method to assign risk and causality in patients with suspected hepatic adverse drug reactions: a report of two new cases of ticlopidine-induced hepatotoxicity.

Objective: The diagnosis of drug-induced hepatotoxicity is based on circumstantial evidence and is often inaccurate. We have designed a method based on published data to assign causality to suspected cases of drug-induced hepatotoxicity.

Design: Forty-seven published cases of ticlopidine-induced hepatotoxicity were identified by a Medline-based literature search.

[Toxic hepatitis associated with tamoxifen use. A case report and literature review].

Tamoxifen is an antiestrogenic drug that acts by binding to the estrogen receptor. The drug is used as a co-adjuvant treatment in advanced breast cancer expressing the oestrogen-receptor protein. Clinical trials of tamoxifen have shown its efficacy in reducing mortality and recurrence rates over a five-year treatment.

A beta-2-adrenergic receptor activates adenylate cyclase in human erythrocyte membranes at physiological calcium plasma concentrations.

More information is needed about the subtype of the beta-adrenergic receptor coupled to the G-protein-adenylate cyclase (AC) system in human erythrocytes and about the optimal experimental conditions to study this system. In this study we describe the characteristics of spontaneous and beta-agonist-activated AC in human erythrocytes. Human erythrocyte membranes were isolated and AC activity was utilized to assess the quantity of cAMP.

Genetic variability in morphine sensitivity and tolerance between different strains of rats.

The development of tolerance, the sensitivity to morphine and the effective morphine plasma concentrations have been studied in Sprague-Dawley (SD-U) and Wistar (W) rats. Daily administration of morphine (10 mg/kg/12 h for 9 days) in W rats produced a reduction in morphine antinociception from day 1 (12+/-0 s) to day 9 (6.7+/-1.