Drugs Side Effects in Pregnant Women Infected with HIV Referred to Imam Khomeini Hospital, Voluntary Counseling and Testing Center Tehran, Iran 2009 – 2013

Objective: To have enough information about the prevalence of the ARV side effects in pregnant women infected with HIV and their infants and also evaluate drug efficacy in decreasing HIV infection in their children.Method: This descriptive study was based on information of 40 pregnant women infected with HIV files at voluntary and counseling center, Imam Khomeini Hospital, Tehran, Iran during 2009 -2013. In this study, we evaluated epidemiologic, demographic, clinical, laboratory data and drugs side effects,.Results: The most commonly used drug group was AZT/3TC/EFV; about 75.5% of patients received mother to child prevention and 27.5% received ARV Antiretroviral therapy treatment. 5% anemia, 2.5% rash and 2.5% pre rupture of membranes were reported and no preeclampsia or gestational diabetes were reported in patients files. Only one abortion (2.5%) was occurred in late first trimester. Except rash, other adverse effects were solely reported in ARV treatment group. All neonates had normal Apgar score. Fetal defects were not reported at birth.Conclusion: In this evaluation, safety of ARV in pregnancy period and at birth was observed especially in the group received prevention of mother to child transmission (PMTCT). So we advise ARV treatment or PMTCT in pregnancy period

Risks to health professionals from hazardous drugs in Iran

Ongoing concerns exist regarding the dangers inherent when handling cytotoxics, particularly drugs which are in parenteral formulations. On occasions, nurses and medical doctors have been preparing and administrating these drugs in the open spaces of wards in the absence of suitable personal protective equipment (PPE) and safety cabinets. To explore further into the severity of occupational hazards, we conducted our research in order to evaluate the healthcare’s understanding of occupational exposure to cytotoxics and occurrence of any side effects. A cross-sectional study using a self-administered questionnaire was distributed amongst oncology nurses in nine specialized cancer centers in Tehran. The questionnaire was based on most reputable international guidelines, aiming to evaluate the attitude, knowledge and safe practices of nurses' handling cytotoxic drugs. The gathered data and reported side effects were compared between “oncology/hematology” and “non-oncology” participants. The majority of nurses from oncology wards were aware of the potential hazards associated with handling of chemotherapy and reported high levels of compliance with the use of PPE during reconstitution of antineoplastic agents. Almost all nurses reported the use of a safety cabinet during preparation, however only 55 % reported that they have annual medical check-ups and 45 % reported having received specialized training. This work was also to evaluate the experimental procedures as well as cleaning solutions used to reduce the level exposure. While the level of knowledge about antineoplastic agents is high among nurses, along with the level of PPE use, medical surveillance and employee training seems to be lagging behind

Validated capillary electrophoresis assay for the simultaneous enantioselective determination of propafenone and its major metabolites in biological samples

A robust, inexpensive, and fully validated CE method for the simultaneous determination of the enantiomers of propafenone (PPF), 5-hydroxy-propafenone (5OH-PPF) and N-despropyl-propafenone (NOR-PPF) in serum and in in vitro media is described. It is based upon liquid-liquid extraction at alkaline pH followed by analysis of the reconstituted extract by CE in presence of a pH 2.0 running buffer composed of 100 mM sodium phosphate, 19% methanol, and 0.6% highly sulfated beta-CD. For each compound, the S-enantiomers are shown to migrate ahead of their antipodes, and the overall run time is about 30 min. Enantiomer levels between 25 and 1000 ng/mL provide linear calibration graphs, and the LOD for all enantiomers is between 10 and 12 ng/mL. The assay is shown to be suitable for the determination of the enantiomers of PPF and its metabolites in in vitro incubations comprising human liver microsomes or single CYP450 enzymes (SUPERSOMES). Incubations with CYP2D6 SUPERSOMES revealed, for the first time, the simultaneous formation of the enantiomers of 5OH-PPF and NOR-PPF with that enzyme. CE data can be used for the evaluation of the enzymatic N-dealkylation and hydroxylation rates

Capillary electrophoretic investigation of the enantioselective metabolism of propafenone by human cytochrome P-450 SUPERSOMES: Evidence for atypical kinetics by CYP2D6 and CYP3A4

An enantioselective CE method was used to identify the ability of CYP450 enzymes and their stereoselectivity in catalyzing the transformation of propafenone (PPF) to 5-hydroxy-propafenone (5OH-PPF) and N-despropyl-propafenone (NOR-PPF). Using in vitro incubations with single CYP450 enzymes (SUPERSOMES), 5OH-PPF is shown to be selectively produced by CYP2D6 and N-dealkylation is demonstrated to be mediated by CYP2D6, CYP3A4, CYP1A2, and CYP1A1. For the elucidation of kinetic aspects of the metabolism with CYP2D6 and CYP3A4, incubations with individual PPF enantiomers and racemic PPF were investigated. With the exception of the dealkylation in presence of R-PPF only, which can be described by the Michaelis-Menten model, all CYP2D6-induced reactions were found to follow autoactivation kinetics. For CYP3A4, all NOR-PPF enantiomer formation rates as function of PPF enantiomer concentration were determined to follow substrate inhibition kinetics. The formation of NOR-PPF by the different enzymes is stereoselective and is reduced significantly when racemic PPF is incubated. Clearance values obtained for CYP3A4 dealkylation are stereoselective whereas those of CYP2D6 hydroxylation are not. This paper reports the first investigation of the PPF hydroxylation and dealkylation kinetics by the CYP2D6 enzyme and represents the first report in which enantioselective CE data provide the complete in vitro kinetics of metabolic steps of a drug

Validation and Uncertainty Estimation of an Ecofriendly and Stability-Indicating HPLC Method for Determination of Diltiazem in Pharmaceutical Preparations

A green, simple, and stability-indicating RP-HPLC method was developed for the determination of diltiazem in topical preparations. The separation was based on a C18 analytical column using a mobile phase consisted of ethanol: phosphoric acid solution (pH = 2.5) (35 : 65, v/v). Column temperature was set at 50°C and quantitation was achieved with UV detection at 240 nm. In forced degradation studies, the drug was subjected to oxidation, hydrolysis, photolysis, and heat. The method was validated for specificity, selectivity, linearity, precision, accuracy, and robustness. The applied procedure was found to be linear in diltiazem concentration range of 0.5–50 μg/mL (r2=0.9996). Precision was evaluated by replicate analysis in which % relative standard deviation (RSD) values for areas were found below 2.0. The recoveries obtained (99.25%–101.66%) ensured the accuracy of the developed method. The degradation products as well as the pharmaceutical excipients were well resolved from the pure drug. The expanded uncertainty (5.63%) of the method was also estimated from method validation data. Accordingly, the proposed validated and sustainable procedure was proved to be suitable for routine analyzing and stability studies of diltiazem in pharmaceutical preparations

The Evaluation of the possible effect of positive end expiratory pressure (PEEP) on pharmacokinetics of phenytoin in patients with acute brain injury under mechanical ventilation

Preliminary data suggests that vital physiologic support measures and free fraction of phenytoin are altered following head trauma. Therefore, we conducted a prospective, randomized controlled study to determine the correlation of albumin concentration and unbound phenytoin plasma concentration following head injury. Ten adult head trauma patients in the neurosurgical intensive care unit receiving phenytoin for the seizure prophylactic treatment were studied for their free and total plasma phenytoin concentration in peak and trough times and their respective albumin concentration. Free and total phenytoin levels were determined by both liquid chromatography and florescence polarization immunoassay (Eclair) of plasma samples after ultrafiltration and deproteinization. No significant difference was found in the plasma concentration measured with HPLC or FPIA while a marked correlation was noted between plasma albumin and free phenytoin concentration (r2=0.85). The total and free phenytoin concentrations were not significantly correlated (r2=0.60). A remarkable difference (P<0.05) was noticed when doses in patients were adjusted on the basis of total plasma phenytoin and calculated plasma phenytoin adjusted for serum albumin. Therefore, therapeutic monitoring in neurosurgical patients receiving phenytoin should be performed on the basis of pharmacologically active component (free fraction), rather than total phenytoin which is presently performed in the clinics.8 page(s

Philosophy of Medicine Exam in the Olympiad for Medical Sciences Students: Report of an Experience

Introduction: Academic Olympiad for medical sciences students focuses on areas that require reflection, reasoning and problem solving and that are generally neglected in the official education system and evaluation of medical students. Previously, it was administered in three areas of scientific thinking in basic sciences, clinical reasoning and health system management. In order to cover, philosophical reflection and analysis on health issues, Philosophy of Medicine was added to the previous areas. This paper explains the process of designing the theoretical framework and implementing the Philosophy of Medicine Exam. Methods: Philosophy of Medicine Exam was designed in four phases: developing the framework for designing the exam questions, selecting the topics of the exam, preparing the exam questions and running the exam. Philosophy of Medicine Exams were held for the first time in the seventh National Olympiad for Medical Sciences Students in the summer of 2015 in both individual and group competition phases. Results: With the contribution of faculties with relevant specialties for 12 months, the framework for designing the exam questions was developed; it aimed at evaluating philosophical knowledge, philosophical analysis and philosophical debate. The topics included ontology and epistemology of health and disease as well as diagnosis and treatment. For the individual competition, 75 questions in the philosophical knowledge exam and four questions in the philosophical analysis exam were asked; 106 medical sciences students participated in this phase nationwide. In the group phase, eight three-student teams competed by debating on three issues. Conclusion: The Philosophy of Medicine Exam in the Olympiad showed that initiating and promoting the philosophical view in the health domain is achievable. Large participation of students across the nation and cooperation of faculty members suggest that philosophy of medicine could be a crucial interdisciplinary filed in the health discourse, and research and education in this area should be taken into account