Effect of vitamin D on vascular health in hypertensive patients with vitamin D deficiency

Background: Many observational studies have shown association of cardiovascular disease and vitamin D deficiency. However, there is a need for prospective studies to show causal effect of vitamin D and cardiovascular diseases in India. Hence the present study was designed to study the effect of vitamin D on markers of vascular health in hypertensive patients with vitamin D deficiency. The objective of the study was to assess the effect of vitamin D supplementation on markers of vascular health in hypertensive patients with vitamin D deficiency.Methods: Hypertensive patients were screened for vitamin D deficiency defined as 25 OH vitamin D less than 20 ng/mL after written informed consent. Hypertensives deficient with 25 OH vitamin D were recruited for the study to receive cholecalciferol 60000 IU/ week for 8 weeks. The vascular parameters such as blood pressure, pulse wave velocity, arterial stiffness index, malondialdehyde and total antioxidant status were assessed at baseline and after 8 weeks of cholecalciferol. The results were analysed using paired‘t’ test.Results: A total of 119 hypertensive patients were screened for vitamin D status. Among them 57 patients were found to be vitamin D deficient (48.7%). Thirty two patients completed the study. The baseline serum 25 OH vitamin D3 was 12.55 ± 5.7 ng/mL and it increased to 40.06 ± 10.53 ng /mL after 8 weeks.Conclusions: The vascular parameters didn’t show any statistically significant difference between baseline and at 8 weeks. However trend for decline was observed for malondialdehyde, right brachial pulse wave velocity

Medication error – Inadvertent high dose intradermal cloxacillin induced skin necrosis

Medication error is one of the important causes of preventable adverse drug reactions. It can occur in the form of administration of a wrong drug, in the wrong dose, to the wrong patient, in an unsuitable dosage form, for the wrong duration or by using an inappropriate route of administration. Intradermal skin testing for cloxacillin hypersensitivity is done at low doses to check for drug allergy. In this report, three patients were given 50 times higher dose of cloxacillin than recommended for skin testing, resulting in pain and necrosis at the site of injection. The error occurred due to wrong dilution of the drug as done by a nursing intern. Some reasons for this could be overtime working, under trained staff, unsupervised nursing interns, complicated and unclear protocols, interpersonal communication gap between health care professionals and also poor availability of ideal resources. Pharmacovigilance centers must alert health care professionals about the significance of reporting medication errors through bulletins and journals

Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters - a review with Indian perspective

Phase I and II drug metabolizing enzymes (DME) and drug transporters are involved in the absorption, distribution, metabolism as well as elimination of many therapeutic agents, toxins and various pollutants. Presence of genetic polymorphisms in genes encoding these proteins has been associated with marked inter-individual variability in their activity that could result in variation in drug response, toxicity as well as in disease predisposition. The emergent field pharmacogenetics and pharmacogenomics (PGx) is a promising discipline, as it predicts disease risk, selection of proper medication with regard to response and toxicity, and appropriate drug dosage guidance based on an individual′s genetic make-up. Consequently, genetic variations are essential to understand the ethnic differences in disease occurrence, development, prognosis, therapeutic response and toxicity. For that reason, it is necessary to establish the normative frequency of these genes in a particular population before unraveling the genotype-phenotype associations. Although a fair amount of allele frequency data are available in Indian populations, the existing pharmacogenetic data have not been compiled into a database. This review was intended to compile the normative frequency distribution of the variants of genes encoding DMEs (CYP450s, TPMT, GSTs, COMT, SULT1A1, NAT2 and UGTs) and transporter proteins (MDR1, OCT1 and SLCO1B1) with Indian perspective

Association of ADH1C and ALDH2 genes with alcohol dependence in south Indian Tamilian population: A case control approach

Objectives: Alcohol dependence (AD) poses a serious medical problem and significant public health issue contributing to morbidity and mortality throughout the world. The aim of the study was to establish the allele and genotype frequencies and to test the association of rs698 (ADH1C) and rs671(ALDH2) with the risk of alcohol dependence in south Indian Tamilian population. Methodology: A total of 150 alcohol dependent cases aged between 18- and 65-years fulfilling DSM-V criteria were recruited from the de-addiction centre. Blood donors (n=150) who had a history of alcohol intake with AUDIT score of less than eight were selected for the control group. The alleles were genotyped using TaqMan SNP genotyping assays by quantitative PCR. Association with alcohol dependence was evaluated with various genetic models using the Chi-square test. Multiple logistic regression analysis was performed to explore the effect of covariates. Results: The observed genotype frequency distributions of rs698 and rs671 were in agreement with Hardy Weinberg equilibrium (p>0.05).The dominant and allelic genetic model of ALDH2, rs671 between cases and controls showed a statistically significant association of the genetic variant with AD.&nbsp

Case Report - Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India

The authors report an Indian adult female patient with a history of generalized tonic clonic seizures who developed severe features of phenytoin (DPH) toxicity on therapeutic dosage of this antiepileptic drug. Administration of 300mg/day of DPH in this patient resulted in toxic symptoms associated with an excessive serum DPH concentration of 33μg/ml. The PCR-RFLP analysis revealed a homozygosity involving CYP2C9*3*3. This mutation results in a marked decrease in the enzymatic activity (CYP2C9) and leads to a decreased clearance of the drug which can lead to severe acute and chronic toxicity. On switching the antiepileptic therapy from DPH to sodium valproate, there was reversal of both