Frequency of ABCB1 C3435T and CYP3A5*3 Genetic Polymorphisms in the Lebanese Population.

OBJECTIVES: CYP3A5 and ABCB1 are highly implicated in the pharmacokinetics and pharmacodynamics of immunosuppressive agents, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. The polymorphisms of their coding genes play important roles in the interindividual and intraindividual differences of bioavailability of these drugs. In this study, our objective was to investigate, in a Lebanese population,the frequency of ABCB1C3435T (rs1045642) and CYP3A5*3 (rs776746) polymorphisms and to compare the results to preexisting data from other populations. MATERIALS AND METHODS: We determined the frequencies of the allelic variants of interest for 1824 Lebanese participants, and we compared these results with those from other major ethnic groups. RESULTS: The allelic frequencies were 91.4% (C) and 8.6% (T) for CYP3A5*3 and 50.8% (T) and 49.2% (C) for ABCB1 C3435T. Our results were significantly different from most other world populations, except the European population. CONCLUSIONS: The frequencies of gene variants of interest in our Lebanese population were similar to those found in European populations. Most of our study population were CYP3A5*3 carriers, and more than half may have a lower P-glycoprotein efflux pump. These characteristics might render Lebanese transplant recipients more prone to the development of drug toxicity and in need of lower drug doses.

Asthma and COPD Patients' Perception of Appropriate Metered-Dose Inhaler Technique.

OBJECTIVES: Asthma and chronic obstructive pulmonary disease (COPD) are chronic illnesses of the airways affecting a good number of people in Lebanon and the Middle East. Pressurized metered-dose inhalers (pMDIs) are important drug delivery systems used to treat such pulmonary diseases. Drugs proven to be valuable and effective may fail to act effectively if such inhalers are used incorrectly. The purpose of this study was to assess the technical use of pMDIs by patients with pulmonary diseases presenting to the community pharmacies in Lebanon. METHODS: A structured questionnaire was developed to collect data. A total of 601 patients using drugs delivered through pMDIs and presenting to 12 Lebanese community pharmacies were recruited to participate in the research project. The questionnaire items were divided into 3 subscales: subscale 1-assessing the device preparation; subscale 2-investigating the device use; and subscale 3-examining the knowledge and use of spacers. After confirming the reliability and validity of the survey tool, patients' responses were analyzed and compared according to many variables. RESULTS: Many patients answered inaccurately to questions assessing both the device preparation and use. Around 40% of patients said they do not coordinate the inhalation with pressing the canister down. The mean scores were 1.72 (± 0.73) over 6 and 5.67 (± 1.44) over 7 for subscales 1 and 2, respectively. The mean total score on all questions was 7.39 over 13, with a standard deviation of 1.75. While patients' age did not impact the results, asthmatic, well-educated, male patients had fewer wrong answers when it comes to preparing and using the device (P < .01). CONCLUSIONS: Our study showed that many patients with asthma and COPD might not be properly using their pMDIs. Appropriate inhaler use is crucial for successful pulmonary disease management. As pMDIs are one of the most difficult devices to use, proper and tailored instructions should be given to patients.

Patterns of use of dry powder inhalers versus pressurized metered-dose inhalers devices in adult patients with chronic obstructive pulmonary disease or asthma: An observational comparative study.

Numerous patients with chronic obstructive pulmonary disease (COPD) and asthma do not use inhaler devices properly, which can contribute to poor disease control. The objective of this study is to assess the technical and safety use of dry powder inhalers (DPIs) versus pressurized metered-dose inhalers (MDIs) in adult patients with COPD or asthma in Lebanon. A concurrent, prospective comparative observational study was conducted at one hospital and 15 community pharmacies in Lebanon. Over a period of 18 months, 246 questionnaires were filled. Patients included were adults with COPD or asthma. Answers were entered into the Statistical Package for Social Sciences software and excel sheet. T-test and correlation were used to analyze the results; 67.8% and 38.4% of those using DPIs and MDIs, respectively, performed the exact technical steps adequately ( p = 0.003, relative risk: 2.134, 95% confidence interval: 0.910-4.842). When compared to MDI, a higher percentage of DPI users found their devices easy to use. Moreover, 81.4% of the MDI users found difficulty in coordinating between pressing the canister and inhaling. Rates of exacerbations were significantly higher in MDIs vs. DPI users (59.4% vs. 21.7%). Overall, 44.31% of patients did not receive education from their healthcare professionals about the devices. A significant number of COPD/asthma adult patients do not use their devices properly. Even though DPIs were significantly easier to use, proper education on the technical use of all types of inhalers is needed.

Acute and Fatal Isoniazid-Induced Hepatotoxicity: A Case Report and Review of the Literature.

This paper describes a case of an acute and fatal isoniazid-induced hepatotoxicity and provides a review of the literature. A 65-year-old female diagnosed with latent Mycobacterium tuberculosis infection was receiving oral isoniazid 300 mg daily. She was admitted to the hospital for epigastric and right sided flank pain of one-week duration. Laboratory results and imaging confirmed hepatitis. After ruling out all other possible causes, she was diagnosed with isoniazid-induced acute hepatitis (probable association by the Naranjo scale). After discharge, the patient was readmitted and suffered from severe coagulopathy, metabolic acidosis, acute kidney injury, hepatic encephalopathy, and cardiorespiratory arrest necessitating two rounds of cardiopulmonary resuscitation. Despite maximal hemodynamic support, the patient did not survive. A review of the literature, from several European countries and the United States of America, revealed a low incidence of mortality due to isoniazid-induced hepatotoxicity when used as a single agent for latent Mycobacterium tuberculosis infection. As for the management, the first step consists of withdrawing isoniazid and rechallenge is usually discouraged. Few treatment modalities have been proposed; however there is no robust evidence to support any of them. Routine monitoring for hepatotoxicity in patients receiving isoniazid is warranted to prevent morbidity and mortality.