Evaluation of Supportive Care Management Outcomes in Cancer Chemotherapy: A Prospective Observational Study in a Tertiary Care Teaching Hospital in South India.

AIMS: Evaluation of supportive care management of cancer patients experiencing drug-related problems (DRPs) is a challenge because it might increase the cost due to additional therapy. The main objectives of this study were to estimate chemotherapy-associated drug-related hospital admissions in the department of medical oncology and to estimate the cost of managing chemotherapy-associated DRPs. SETTINGS AND DESIGN: This study is a prospective observational study. SUBJECTS AND METHODS: Patients with chemotherapy-related DRPs were prospectively identified from the patient's medical records. The contribution of DRPs and cost incurred due to each hospitalization was assessed. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS® 20.0 version. RESULTS: Out of 55 patients analyzed for DRPs, 25 (45.5%) patients in the age group of 51-60 years experienced DRPs most frequently. Most commonly occurring DRP was adverse drug reactions 42 (76.4%), which were more frequent in females. DRPs were maximum with alkylating agents 15 (27.3%) and the least with hormonal agents 1 (1.8%). The mean length of hospitalization was 9.6 ± 6.5 days. The total direct medical cost was Rs. 31,540 ± 42,476, of which medicine cost accounted for Rs. 16,550 ± 25,404, constituting a major share of the total medical costs. CONCLUSIONS: Pharmacists can provide better patient care by identifying and preventing DRPs and reducing drug-related morbidity and mortality.

Demographics, clinical characteristics and management of herbicide poisoning in tertiary care hospital.

Herbicide poisoning is most common method of suicide in India and it is associated with high morbidity and mortality. Among different herbicidal poisonings the most predominantly found poisonings are paraquat and glyphosate. These compounds are highly toxic and their poisonings require proper management techniques. High fatality is seen in these cases which are mainly due to its inherent toxicity and lack of effective treatment. Common symptoms of these poisonings includes gastrointestinal corrosive effects with mouth and throat, epigastric pain and dysphagia, acid-base imbalance, pulmonary edema, shock and arrhythmia. Long term health effects include pulmonary fibrosis, renal failure, hepatic failure, heart failure, multi-organ failure or death. No proven antidote exists for these poisonings. So the treatment is mainly supportive. Initially gastric lavage or whole-gut irrigation using adsorbents such as Fuller's earth, bentonite or activated charcoal is recommended. In case of renal failure hemodialysis or hemoperfusion may be considered. However novel approaches like treatment with N-acetylcysteine, vitamin C, vitamin E, cyclophosphamide may also be helpful.

Antihypertensive prescribing preferences in three South Indian Hospitals: cost analysis, physicians perspectives and emerging trends.

OBJECTIVES: The objectives of this study were i) to analyze the prescription pattern of antihypertensive agents in three South Indian hospitals ii) to perform cost-analysis of various antihypertensive treatment regimens iii) to examine the physicians' perspectives of antihypertensive prescribing. METHODS: A cross-sectional study was done on patients with essential hypertension (n = 2,100) by analyzing the medical records of the patients for the drugs prescribed and patient demographics. Cost comparisons were made for the most frequently prescribed agents for each class at the most frequently prescribed dose and regimen. A questionnaire was developed containing questions on familiarity with guidelines, diagnosis of clinical hypertension, an evaluation of patients and choice of drug, and was distributed to physicians in the three hospitals. RESULTS: About one-half of the patients received monotherapy where the remaining received combination therapy for their hypertension. Calcium channel blockers (CCBs) were the most preferred agents used, either as monotherapy or combination therapy in hypertensive patients with or without comorbidities. At the most frequently prescribed dose and dosage regimen, thiazide was the least expensive antihypertensives, followed by CCBs. Physician's responses favored the use of CCBs as first-line agent for uncontrolled hypertension and a two-drug combination approach. CONCLUSIONS: The preference of CCBs and combination-therapy over the traditionally used diuretics or beta-blockers is consistent with the outcomes of recent clinical trials that underscore the benefits of using combination therapy with CCBs as initial therapy for uncomplicated hypertension.

Clinical pharmacokinetics of the diastereomers of arteether in healthy volunteers.

OBJECTIVE: To evaluate the pharmacokinetics of alpha- and beta-diastereomers of arteether in healthy male volunteers. PARTICIPANTS AND METHODS: The study was a single-centre clinical pharmacokinetic trial in healthy male subjects. A group comprising 13 subjects aged 25-50 years received a single intramuscular 150 mg individual dose of the arteether formulation containing alpha- and beta-isomers in a 30:70 ratio. Serial blood samples collected over a period of 0-192 hours were analysed by high-performance liquid chromatography-electrospray ionisation/tandem mass spectrometry and the plasma concentrations were subjected to compartmental and noncompartmental analyses. Pharmacodynamic parameters such as area under the inhibitory curve, ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC), maximum plasma concentration to MIC (Cmax/MIC) and time that plasma concentration exceeds the MIC (T>MIC) were calculated in vitro in four strains of Plasmodium falciparum to evaluate the in vivo effectiveness of the proposed dosage regimen. RESULTS: There were no adverse effects observed during the study. The extent of metabolism of arteether to dihydroartemisinin (DHA) was low (approximately 5%) so as to be therapeutically nonsignificant. The pharmacokinetic profiles of the arteether diastereomers were different, and the maximum plasma concentrations of alpha- and beta-isomers were reached at 4.77+/-1.21 hours and 6.96+/-1.62 hours, respectively, after which they showed biphasic decline with apparent terminal elimination half-lives of 13.24+/-1.08 hours and 30.17+/-2.44 hours, respectively. The plasma and renal clearances, as well as whole blood to plasma partition ratios of the isomers, were comparable, while the apparent volume of distribution during terminal phase of the beta-isomer was approximately 3-fold higher than that of the alpha-isomer. In vitro erythrocyte culture experiments with four strains of P. falciparum showed similar MICs for both isomers of arteether. The highest observed MIC of 8 microg/L was selected for estimating the pharmacokinetic and pharmacodynamic parameters, which showed excellent correlation with published data on the clinical efficacy of arteether. CONCLUSION: The pharmacokinetics of arteether isomers demonstrated stereoselectivity, which was reflected mainly in the volume of distribution and the terminal elimination half-life. The alpha- and beta-isomers of arteether appeared to compliment each other pharmacokinetically, with the alpha-isomer providing comparatively rapid and higher plasma concentrations resulting in immediate reduction in percentage parasitaemia, while the beta-isomer, with its longer terminal elimination half-life, mean residence time and sustained plasma concentrations, maintained the activity for longer periods. The extent of metabolic conversion of arteether to DHA was minimal, so as to have any therapeutic or toxic significance.

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 µg/mL pre dose to 4 µg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations.

Tobacco smoke exposure induces nicotine dependence in rats.

RATIONALE: Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents. OBJECTIVES: The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats. METHODS: The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central alpha7 nicotinic acetylcholine receptor (nAChR) and non-alpha7 nAChR levels (primarily alpha4beta2 nAChRs). RESULTS: The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the alpha7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-alpha7 nAChR density in the dentate gyrus. CONCLUSION: Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.

Preadolescent tobacco smoke exposure leads to acute nicotine dependence but does not affect the rewarding effects of nicotine or nicotine withdrawal in adulthood in rats.

Epidemiological studies indicate that parental smoking increases the risk for smoking in children. However, the underlying mechanisms by which parental smoking increases the risk for smoking are not known. The aim of these studies was to investigate if preadolescent tobacco smoke exposure, postnatal days 21-35, affects the rewarding effects of nicotine and nicotine withdrawal in adult rats. The rewarding effects of nicotine were investigated with the conditioned place preference procedure. Nicotine withdrawal was investigated with the conditioned place aversion procedure and intracranial self-stimulation (ICSS). Elevations in brain reward thresholds in the ICSS paradigm reflect a dysphoric state. Plasma nicotine and cotinine levels in the preadolescent rats immediately after smoke exposure were 188 ng/ml and 716 ng/ml, respectively. Preadolescent tobacco smoke exposure led to the development of nicotine dependence as indicated by an increased number of mecamylamine-precipitated somatic withdrawal signs in the preadolescent tobacco smoke exposed rats compared to the control rats. Nicotine induced a similar place preference in adult rats that had been exposed to tobacco smoke or air during preadolescence. Furthermore, mecamylamine induced place aversion in nicotine dependent rats but there was no effect of preadolescent tobacco smoke exposure. Finally, preadolescent tobacco smoke exposure did not affect the elevations in brain reward thresholds associated with precipitated or spontaneous nicotine withdrawal. These studies indicate that passive exposure to tobacco smoke during preadolescence leads to the development of nicotine dependence but preadolescent tobacco smoke exposure does not seem to affect the rewarding effects of nicotine or nicotine withdrawal in adulthood.