Adverse drug reaction risk assessment with prescribed renal risk drugs among hospitalized patients attending a teaching hospital in South India

Background: Renal impairment is the primary cause of mortality and morbid conditions in patients. Inappropriate drug use in patients who are with risk of renal damage causes harmful and deleterious effects. Adjusting doses based on renal function is necessary for renal risk drugs, primarily to avoid adverse reactions of medications. Aim of the present study was to assess the risk of incidence on ADRs with drugs lowering the renal function.Methods: This is a cross-sectional observational study conducted in General Medicine department. 230 Patients constituted the sample in the study. The study was conducted for a period of one year and prescriptions with renal risk drugs were evaluated. Changes in the renal functional tests were compared to the normal range and adverse drug responses were monitored.Results: A total of 230 patients who fulfilled the inclusion criteria were included in the study. The meanage of the study subjects were 50.9±15.2 respectively. 56.39% patients were men and 43.6% were women. Renal risk drugs included in the study are anti-hypertensive, antibiotics, and analgesics. Paracetamol (24.77%) followed by telmisartan (20.85%) are the predominantly prescribed renal risk drugs with high incidence of adverse drug reactions. Causality assessment by Naranjo ADR probability scale showed out of 211 ADRs, 51.6% were possible, 25.59% were doubtful, 21.8% were probable and 0.94% was definite.Conclusions: The current study signifies that patients under high risk of renal damage require continuous monitoring and optimized therapy for better disease management.

Clinical study of neurological presentation of diabetes mellitus in a tertiary care hospital

Background: A wide range of commotions affecting the central and peripheral nervous systems, either directly or indirectly, may be observed in patients with diabetes mellitus. The spectrum of neurological complications among diabetes are quite varied.Methods: Authors conducted a Cross-sectional prospective observational study to study different neurological manifestations of diabetes mellitus. at NRI General Hospital, Chinakakani, Guntur District, Andhra Pradesh. The selected patients were studied in detail with history and physical examination. The investigations included Fasting Blood Sugar (FBS), Postprandial Blood Sugar (PPBS), Glycosylated Hemoglobin (HbA1C).Results: A total of 100 subjects were included in the final analysis. Majority of participants were aged between 46 to 65 years, and 55% of them were males. Only 13% of the participants had HBA1c value below 7.5 gm%. Out of 100 participants, 82% participants had diabetic peripheral neuropathy. A total of 6 subjects had cranial neuropathy, with 5% participants having 3rd nerve and one participant had 6th nerve. Involuntary movements (Chorea) was present in 4% of patients. Among the people with Seizures, 6% participants had Hyperglycemic, and 2% participants had Hypoglycemic seizures. Out of 100 participants, 7 participants had dysautonomia.Conclusions: Peripheral neuropathy was the most common neurological manifestation among the diabetic population. The other key neurological abnormalities include cranial nerve palsy, dysautonomia, seizures and Chorea. Clinicians need to be aware the entire spectrum of neurological abnormalities among patients with type 2 Diabetes.

The impact of non-steroidal anti-inflammatory drugs use in elderly cardiovascular patients: an observational study from tertiary care in South India

Background: Long-term use of NSAIDs, by patients having cardiovascular conditions, has shown to increase the risk of cardiovascular events and increased risk of death. Hence, the study was conducted to determine the complications related to NSAID use by the elderly patients with cardiovascular disease (CVD).Methods: The study was a single-center prospective observational study conducted November 2017 to October 2018. Elderly patients (>60 years) suffering from various CVDs and reported NSAID intake daily for at least one month were included. A questionnaire included demographic, treatment related history and complete details of NSAIDs intake including nature, dose, indication, source etc. The same questionnaire was again filled at the end of one-year follow-up.Results: A total of 100 participants were included in the study. The mean age was 72±8.6 years. Majority of the patients (93%) had hypertension, and 69% of the patient had previous MI.  Five NSAIDs (diclofenac, ibuprofen, mefenamic acid, naproxen, and ketorolac) were used routinely. At least one over the counter NSAID used was reported by 86%, 57% were prescribed at least one NSAIDs by their orthopaedics and physicians. At the end of 1-year follow-up, authors found that 71% had MI (2% increase), 4% developed reinfarction, 20% had severe left ventricular failure (4% increase), 7% had atrial fibrillation (1% increase), and 2% patients died and 63% patients reported raise in systolic blood pressure by 5mmHg.Conclusions: High prevalence of concomitant NSAID use among elderly CVD patients, which might be contributing towards increase in CVS morbidity and mortality.

A study of clinical and etiological profiles of patients presenting with Pancytopenia in NRI General Hospital

Introduction: Pancytopenia is characterized by a decrease in the red blood cells, white blood cells along with the platelet count below the normal levels. It can be due to a number of pathologic mechanisms, depending on the geographic location. Early diagnosis and treatment are crucial in the management of pancytopenia. There are very few studies regarding the clinic-pathological profile of such patients. Materials and methods: A cross-sectional study was undertaken at NRI General Hospital, Chinakakani. All eligible participants more than 13 years of age were included. Data collection was done from August 2016 to August 2018. A thorough history taking along with clinical examination and laboratory investigations were performed among the study population. Data was analyzed using SPSS version 13. Results: The most common finding suggestive of etiology was megaloblastic anemia at 38.4%, which was more common among females. Aplastic anemia was the second most common finding at 24.6%. Other diagnoses included hypersplenism, myelodysplastic syndrome and acute leukemia. Fever and pallor were the most common presenting symptoms. Blood examinations demonstrated anisopoikilocytosis, hypersegmented neutrophils, erythroblasts, macrocytes and reticulocytes, which were found in differing proportions in the various etiological diagnoses. Conclusion: It is noteworthy that megaloblastic anemia, a reversible condition, is common in India compared to the higher occurrence of aplastic anemia and myelodysplastic syndrome in developed Vijaya Kumar Vasa, Sadhna Sharma, Rakesh Nukasani, Srivani Gulleli, Phani Kumar Reddy. A study of clinical and etiological profiles of patients presenting with Pancytopenia in NRI General Hospital. IAIM, 2019; 6(2): 114-120. Page 115 nations. Clinical alertness and suspicion can assure early diagnoses and treatment can prevent complications and reduce the burden. The need for more standard management protocols is immediate.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome.

Background & objectives: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. Methods: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD ) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. Results: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. Interpretation & conclusions: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action.

Purple urine bag syndrome- changing hue.

Purple Urine Bag Syndrome (PUBS) is a unique disease entity characterised by purple discoloration of urine secondary to recurrent urinary tract infections with indigo and indirubin producing bacteria and is predominantly seen in constipated, chronically debilitated and catheterised women with alkaline urine. This syndrome indicates underlying recurrent urinary tract infections (UTIs) associated with higher incidence of mortality and morbidity than urinary tract infection alone without this occurrence. This article is about an elderly hypothyroid woman with PUBS and reviews the need to be aware of this entity.

Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential.

BACKGROUND: Reduction in the dosing frequency of antituberculosis drugs (ATDs) by applying drug delivery technology has the potential to improve the patient compliance in tuberculosis (TB). Alginate (a natural polymer) based nanoparticulate delivery system was developed for frontline ATDs (rifampicin, isoniazid, pyrazinamide and ethambutol). METHODS: Alginate nanoparticles were prepared by the controlled cation induced gelification method and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated in M. tuberculosis H37Rv infected mice. RESULTS: High drug encapsulation efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days and in the organs (lungs, liver and spleen) for 15 days. In comparison to free drugs (which were cleared from plasma/organs within 12-24 h), there was a significant enhancement in the relative bioavailability of encapsulated drugs. In TB-infected mice three oral doses of the formulation spaced 15 days apart resulted in complete bacterial clearance from the organs, compared to 45 conventional doses of orally administered free drugs. CONCLUSIONS: Alginate nanoparticles appear to have the potential for intermittent therapy of TB.

Oral poly(lactide-co-glycolide) nanoparticle based antituberculosis drug delivery: toxicological and chemotherapeutic implications.

The present study reports on the detailed toxicological and chemotherapeutic evaluation of antituberculosis drug loaded nanoparticles in mice. A single oral dose administration of poly(lactide-co-glycolide) (PLG, a synthetic polymer) nanoparticles containing rifampicin+isoniazid+pyrazinamide+ethambutol could maintain drug levels in various tissues for 9-10 days and did not elicit any adverse response even when administered at several fold higher than the recommended therapeutic dose. However, dosing with conventional free drugs at the equivalent higher doses was lethal. Despite multiple oral dosing with the formulation at every 10th day, no toxicity was observed on the completion of subacute (28 days) or chronic (90 days) toxicity studies based on survival, gross pathology, histopathology, blood biochemistry and hematology. In mice harboring a high mycobacterial load (mimicking human tuberculosis), two independent chemotherapeutic regimens, i.e. 5 doses of PLG nanoparticles encapsulating (rifampicin+isoniazid+pyrazinamide+ethambutol) administered 10 days apart, or 2 doses of the 4-drug formulation followed by 3 doses of 2-drug formulation (rifampicin+isoniazid) resulted in undetectable bacilli. Further, the efficacy was comparable to 46 daily doses of oral free drugs. Therefore, the experimental evidence suggests that PLG nanoparticle-based antituberculosis drug delivery system is safe and well suited for prolonged and intermittent oral chemotherapy.

Lung specific stealth liposomes as antitubercular drug carriers in guinea pigs.

The problem of patient non-compliance in the management of tuberculosis (TB) can be overcome by reducing the dosing frequency of antitubercular drugs (ATD) employing drug carriers. This study reports on the intravenous (iv) administration of lung specific stealth liposomes encapsulating ATD (rifampicin and isoniazid in combination) to guinea pigs and the detailed pharmacokinetic/chemotherapeutic studies. Following a single iv administration of liposomal drugs, the latter were found to exhibit sustained therapeutic levels in plasma for 96-168 hr with half-lives of 24-70 hr, mean residence time (MRT) of 35-81 hr and organ drug levels up to day 7. The relative bioavailability (as compared to oral free drugs) was increased by 5.4-8.9 folds, whereas the absolute bioavailability (as compared to iv free drugs) was increased by 2.9-4.2 folds. Weekly therapy with liposomal ATD for 6 weeks produced equivalent clearance of Mycobacterium tuberculosis from organs as did daily therapy with oral free drugs. Hence, intravenous liposomal ATD offer the therapeutic advantage of reducing the dosing frequency and improving the patient compliance in the management of TB.