Adverse event reporting tools and regulatory measures in India through outcome of Pharmacovigilance Programme of India.

The primary care medical practitioners as well as common public must be made aware of the importance and benefits of reporting adverse drug reactions (ADRs). The reporting of ADRs through periodic safety update reports is a regulatory requirement in many countries including India, however, the importance of ADR reporting through spontaneous reporting system cannot be ignored. After the initiation of Programme for International Drug Monitoring, WHO-Uppsala Monitoring Centre (UMC), Sweden, succeeded in establishing a worldwide pharmacovigilance (PV) network in >150 countries. As a full member of this program, India also has developed a robust PV system through Pharmacovigilance Programme of India (PvPI) involving its various ADR Monitoring Centers and after due quality check of Individual Case Safety Reports (ICSRs), submits this information to UMC through a web-based tool VigiFlow®. This information is then stored into VigiBase® which is the repository of worldwide ICSRs. Based on the drug safety information collected, PvPI issues alerts, recommends label change (if any), and identifies signals thereby supporting National Regulatory Authority. At national level, PvPI has developed several tools for reporting of ADRs by the stakeholders. This article provides an overview of adverse events reporting tools in India vis-a-vis selected countries around the world, based on a comparative literature search. This article also throws light upon the regulatory aspects of PV in India, findings of PvPI and its recommendations to Central Drugs Standard Control Organization, collaboration of PvPI with Public Health Programmes, future prospects of reporting ADRs in India and how it will help enhance the quality of ADR-reporting by citizens of India.

The Influence of Statistical versus Exemplar Appeals on Indian Adults' Health Intentions: An Investigation of Direct Effects and Intervening Persuasion Processes.

In two separate investigations, we examined the persuasive effectiveness of statistical versus exemplar appeals on Indian adults' smoking cessation and mammography screening intentions. To more comprehensively address persuasion processes, we explored whether message response and perceived message effectiveness functioned as antecedents to persuasive effects. Results showed that statistical appeals led to higher levels of health intentions than exemplar appeals. In addition, findings from both studies indicated that statistical appeals stimulated more attention and were perceived as more effective than anecdotal accounts. Among male smokers, statistical appeals also generated greater cognitive processing than exemplar appeals. Subsequent mediation analyses revealed that message response and perceived message effectiveness fully carried the influence of appeal format on health intentions. Given these findings, future public health initiatives conducted among similar populations should design messages that include substantive factual information while ensuring that this content is perceived as credible and valuable.

Clinical Profile and Management of Poisoning with Suicide Tree: An Observational Study.

INTRODUCTION: The clinical features, management, and the associations of dosage in poisoning with the cardiotoxic plant Cerbera odollam (suicide tree), responsible for more than half of plant poisoning deaths in the South Indian State of Kerala alone, have not been evaluated. There are only few studies on its clinical features and none on the usage of cardiac pacing in its management, given its rarity in the Western world. We depend on data for similar toxins to form our management protocols. AIMS: Our aim was to describe the clinical features of C. odollam poisoning, dosage, and its relations to clinical features and pacemaker initiation therapy and to study the characteristics of temporary pacemaker therapy in its management. SUBJECTS AND METHODS: This study was conducted in fifty consecutive cases who presented with a history of C. odollam poisoning from whom clinical data were obtained. Cases initiated on temporary cardiac pacemaker therapy due to the toxin effects were also studied. Effect of dosage on various clinical manifestations and pacing was analyzed. RESULTS: All cases were due to suicidal ingestion. Vomiting (54%), thrombocytopenia (50%), and sinus bradycardia (32%) were the most common features. The need for cardiac pacing had a significant association with dosage in kernels ingested (P < 0.05) and with thrombocytopenia (P < 0.05). There was no association between hyperkalemia and death. Thirty-six percent of cases had to be paced, of which 16% died. In-hospital mortality of odollam poisoning was 12%. CONCLUSIONS: C. odollam poisoning cases merit monitoring and treatment in Intensive Care Unit with facilities for electrocardiographic monitoring and temporary cardiac pacing. The clinical features and the factors associated with mortality are different from other cardiac glycosides.

Effect of probenecid on kinetics of enrofloxacin in lactating goats after subcutaneous administration.

A comparative pharmacokinetic study of enrofloxacin (5 mg/kg, sc) was conducted in probenecid-pretreated (70 mg/kg, orally 1.5 h prior to enrofloxacin administration) lactating goats to assess the effect of probenecid on the kinetics of enrofloxacin. Concentration of enrofloxacin in plasma, milk and urine was estimated by microbiological assay using Escherichia coli (ATCC 25922). Minimum detection level of enrofloxacin was 0.01 microg/ml. The plasma log concentration versus time curve showed monophasic pattern and followed one compartment open model. Plasma drug concentration was significantly higher during 1-2 h in probenecid-pretreated group. Significantly higher drug concentration in milk was noted at most of the time points, while significantly lower urine drug concentration (0.083-1 h and 5-12 h) were obtained in probenecid-pretreated group. The kinetic parameters (A, B and 3) were significantly higher, while t(1/2)beta, MRT and Vd(area) were significantly lower in probenecid-pretreated group. Probenecid pretreatment decreased the urinary excretion of enrofloxacin, whereas enhanced excretion in milk which could be useful in cases of affections of udder in goats.

Effect of fever on pharmacokinetics and dosage regimen of intramuscularly administered amikacin in goats.

A comparative pharmacokinetic study of amikacin (10 mg/kg intramuscular) by microbiological assay method in normal and experimentally induced febrile goats revealed that the plasma drug concentrations were significantly higher in febrile condition at most of the time intervals. Various pharmacokinetic parameters like t(1/2), AUC, AUMC, MRT and Vd(area) were significantly higher whereas total body clearance (Cl(B)) was significantly lower in febrile goats as compared to normal goats. Absorption half-life (t(1/2) ka) value differed non-significantly. For maintaining mean therapeutic level of 2 mg/ml, a priming dose (D*) of 14.73+/-2.28 mg/kg, followed by maintenance dose (D(o)) of 13.95+/-2.28 mg/kg at shorter dosage interval (t) of 8 hr may be useful in case of normal goats whereas lower doses (D* of 13.58+/-1.61 mg/kg followed by D(o) of 12.65+/-1.60 mg/kg) at longer tau of 12 hr may be advised in case of febrile goats.

Immunity in children with exposure to environmental lead: I. Effects on cell numbers and cell-mediated immunity.

Studies conducted in animal systems have shown that lead is an immunosuppressive agent at levels far below those causing overt toxicity. Children less than six years of age are the population at highest risk for exposure to environmental lead; however little data were available to assess effects on the developing immune system in this age group. Reported here is the completed Phase I study on 193 children, ages 9 months to 6 years, with blood lead levels from 1 to 50 (µg dL(-1), recruited from the urban population of Springfield-Greene County, Missouri, through their participation in the WIC (Women, Infants, and Children) and Lead Poisoning Prevention Programs. This portion of the study dealt with enumeration of cells involved with the immune response andin vitro mitogenic stimulation of lymphocytes. The percent lymphocytes, monocytes, granulocytes, T cells (total), B cells, CD4+T's and CD8+T's and CD4+/CD8+ ratios were determined and the data were analysed. No consistent significant differences were seen among the various risk categories currently identified by the CDC. Though two age groups showed some possible effect of lead, none of the various cellular parameters within these age groups showed significant correlation with blood lead. The lymphocyte response toin vitro mitogenic stimulus was studied on 42 children (including 17 in risk classifications IIA and higher) using the mitogens phytohemagglutinin (PHA), Concanavalin A (Con A), and Pokeweed mitogen (PWM). No consistent statistically significant differences were seen among the various risk categories; the effects of lead, if present, are most likely subtle and obscured by the interindividual and time-dependent variation inherent in this type of study.

Ventilation-perfusion scintiscanning in tropical pulmonary eosinophilia.

We report the findings of ventilation and perfusion scintiscanning performed in three untreated patients with acute tropical pulmonary eosinophilia (TPE). In a 26-year-old man whose arterial blood gas values were normal, the lung scan showed normal radioactivity. The scintigrams of a 20-year-old woman who had hypoxemia and hypercapnea showed gross ventilation defects of both lungs that were mainly mismatched; changes in the perfusion scan were minimal. Scintiscanning in a 14-year-old girl who had moderate arterial hypoxia and mild hypocapnea, on the other hand, showed ventilation defects in both lungs, more marked in left lung; multiple matching ventilation-perfusion defects were also seen; however, the V/Q defects did not appear to be equally matched. The scintigraphic findings were compatible with arterial blood gas status of the individual patients and consistent with the notion that a disturbed ventilation-perfusion relationship may be responsible for hypoxemia in some of the patients with TPE.

Perfusion lung scan in tropical pulmonary eosinophilia.

Perfusion lung scan using macroaggregate of human serum albumin tagged with I131 was done in 7 patients with tropical pulmonary eosinophilia (TPE). In the 3 untreated patients perfusion defect of varying degree could be noticed, whereas in 4 other patients with history of chronic illness and previous treatment with multiple courses of diethylcarbamazine the lung scan was normal. Possible pathophysiology in light of above findings in TPE is discussed.

Internationalization of multi hospital systems.

Much like the manufacturing multinationals of yore, professional service establishments are now going abroad in large numbers. Two factors drive their expansion overseas--the increasing restrictions on their operations domestically, and the inviting opportunities in some of the global markets. A survey of multi hospital corporations both with and without experience in foreign markets was conducted regarding the expansion of their operations overseas. Examined were factors central to the decision-making process including: the various types of foreign health care systems; the entry strategies in penetrating foreign markets (fully owned, joint ventures, etc.); favorable factors and barriers considered in choosing foreign markets; the ability to transfer standardized systems from operations in the U.S.; and the profits from such operations. Respondents provided information regarding the above factors that are critical in determining an overseas expansion strategy.

Pharmacokinetics and distribution of ampicillin in plasma, milk and uterine fluid of female buffaloes.

A pharmacokinetic study of ampicillin (6 mg/kg intravenous) revealed that the peak concentrations of 17.81 +/- 1.25, 5.64 +/- 2.24 and 1.09 +/- 0.10 micrograms/ml of the drug were attained at 15 min, 30 min and 2 h in plasma, milk and uterine fluid respectively. A therapeutic concentration of greater than or equal to 0.1 microgram/ml was maintained from 15 min-8 h, 15 min-6 h and 30 min-6 h in plasma, milk and uterine fluid. Hence, the drug may be used effectively in mammary gland and uterine infections apart from its use in other systemic infections.

Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats.

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70 +/- 4.06, 2.67 +/- 0.23, 5.65 +/- 0.45 and 82.23 +/- 10.06 micrograms/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of greater than or equal to 0.5 micrograms/ml was maintained from 5 min-36 h, 30 min-30 h, 1-36 h and 5 min-48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t1/2 alpha) of 0.44 +/- 0.04 h and a high elimination half life (t1/2 beta) of 19.24 +/- 1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K12:(K21-beta)] of 5.12 +/- 0.97 during the elimination phase and a Vdarea of 1.59 +/- 0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (Cp infinity min = MIC) of 0.5, 1.0 and 1.5 micrograms/ml at selected dosage intervals of 12 and 24 h was also calculated.

Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats.

A pharmacokinetic study of doxycycline after intravenous administration at 5 mg/kg body weight in goats revealed that a concentration of greater than or equal to 0.5 microgram/ml was maintained for 5 min-2 h, 4-12 h, 2-12 h and 5 min-greater than 48 h in plasma, interstitial fluid, milk and urine respectively. The low t1/2 alpha of 0.73 +/- 0.11 h and high t1/2 beta of 16.63 +/- 1.58 h show that the drug is rapidly distributed but slowly eliminated from the body. The tissue:plasma concentration of 4.86 +/- 1.06 during the elimination phase [K12/(K21-beta)] indicates a high expected tissue concentration, which is supported by similarly increased drug concentration in interstitial fluid and milk. The high Vdarea of 9.78 +/- 0.86 L/kg observed denotes that, apart from its wide distribution, the drug may be stored in fat depots as it is known to be highly lipophilic. As the drug maintained a therapeutic concentration for a shorter time in plasma, and the calculated dose rate for maintaining a minimal plasma concentration of 0.5-1.5 micrograms/ml is relatively high, it may not be of much use in treating septicaemia in this species. Since the observed tissue:plasma concentration was higher and a therapeutic concentration was maintained in interstitial fluid and milk for longer, the drug can be used for other systemic infections at a lower dose rate than that required for treating septicaemia. As the drug maintained a very high concentration in urine, it may be of particular value in treating urinary tract infections caused by sensitive micro-organisms.

Pharmacokinetics and distribution of sulphadimidine in plasma, milk and uterine fluid of female buffaloes.

The pharmacokinetics of sulphadimidine after a single dose (200 mg/kg i.v.) was studied in five healthy lactating buffaloes. The study revealed that the drug attained its peak concentration of 314.0 +/- 13.0, 242.4 +/- 3.0 and 100.2 +/- 2.5 micrograms/ml at 15 min, 30 min and 12 h in plasma, milk and uterine fluid, respectively. The pharmacokinetic parameters calculated by a 2-compartment open model gave values for t1/2 alpha, t1/2 beta and vdarea of 2.10 +/- 0.36 h, 12.36 +/- 0.57 h and 1.23 +/- 0.07 L/Kg, respectively. A high vdarea as well as a value of 0.74 +/- 0.08 for K12:K21-beta (tissue approximately equal to Plasma) indicates better penetration of the drug into the different body fluids and tissues, which is further supported by a high concentration obtained in milk and uterine fluid. The therapeutic concentration (greater than or equal to 50 micrograms/ml) was maintained for around 24 h in plasma and milk and 12 h in uterine fluid. The results suggest that, apart from its use in systemic infections, the drug can be effectively used by the i.v. route in uterine and mammary gland infections. The dosages for maintaining concentration of 50 micrograms/ml, 100 micrograms/ml and 150 micrograms/ml at convenient dosage intervals of 12 and 24 h were also determined.

Pharmacokinetics of streptomycin with particular reference to its distribution in plasma, milk and uterine fluid of she-buffaloes.

The study elucidated the pharmacokinetics of streptomycin in healthy lactating she-buffaloes after a single intramuscular (IM) injection (10 mg/kg). The drug attained its peak concentrations of 24.39 +/- 2.67, 0.45 +/- 0.05 and 5.06 +/- 0.18 micrograms/ml at 1, 4 and 1 hour in plasma, milk and uterine fluid respectively. Calculations based on the assumption of a 2-compartment model gave a plasma t1/2 (beta) of 4.01 +/- 0.44 h and an apparent volume of distribution [Vd(area)] of 0.47 +/- 0.06 1/kg. The drug was detectable in the plasma, milk and uterine fluid for 30, 8 and 12 hours, respectively. A therapeutic concentration of the drug was maintained for 6 to 7 hours in the plasma and for around 1 hour only in the uterine fluid. However, a therapeutic level could not be achieved in milk at any time. The results suggest that the drug can be used clinically by the IM route against streptomycin susceptible systemic infections but not those in the uterus and mammary gland.

Effect of some beta-adrenoceptor blockers and of (+) propranolol on adrenaline-induced pulmonary edema in mice.

(+) Propranolol is considered to prevent adrenaline-induced pulmonary edema (A.P.E.) due to the beta-adrenoceptor blockade. However, local anaesthetics also are known to prevent pulmonary edema. To assess the role of beta-adrenergic blockade in A.P.E., the effect of a beta 1-blocker possessing local anaesthetic action (+/- Metaprolol) and a beta 1-blocker possessing no local anaesthetic action (+/- practolol) was studied along with propranolol derivatives. The study revealed that (+), (-), (+/-) propranolol and (+/-) metaprolol completely prevented A.P.E. whereas (+/-) practolol did not. This shows that local anaesthetic action but not the-beta adrenergic blockade may be responsible for prevention of A.P.E.

Pulmonary surfactants in pulmonary oedema induced by head injury in mice.

A study has been carried out to examine the role of pulmonary surfactants in pulmonary oedema induced by head injury. Pulmonary oedema was induced by head injury in mice by the method of Mackay (5). There was no change in surface tension as well as total phospholipid concentration of the lung between control and test groups suggesting that there was no involvement of lung surfactant sytem in pulmonary oedema induced by head injury. Since the animals in the test group died within a few minutes, possibly there may not have been sufficient time for alteration of lung surfactant system.