Most developing countries suffer from lack of adequate drug information due to limited availability of current literature and also poor documentation and dissemination of what little information is available. Existence and proper functioning of independent drug information centres can greatly contribute to the provision of unbiased drug information that is much needed in these countries. A teaching hospital-based drug information centre can be of assistance not only in patient care but also in educational activities.The centre can benefit from the material, monetary and multidisciplinary human resources that are usually available in such an institution. A three-year experience of providing drug information service at the Tribhuvan University Teaching Hospital in Kathmandu shows that it is possible to initiate such an activity at the local level with modest resources and that such a service is utilised if available.

Objective: The modulatory role of (-aminobutyric acid (GABA)-benzodiazepine-Cl- channel, neuronal Ca 2+ channels, N-methyl-D aspartate (NMDA) and mitochondrial diazepam binding inhibitor receptors in the neurosteroid-induced attenuation of morphine tolerance and dependence was investigated. Methods: Mice were rendered dependent on morphine (10 mgkg, twice daily for 9 days) and the development of tolerance was assessed by tail-flick test. The abstinence behaviour was evaluated by naloxone (2 mg/kg)-induced jumping. Results: Concomitant treatment with neurosteroid pregnenolone sulfate (2 mg/kg), progesterone (5 mg/kg) or 4'-chlordiazepam (0.5 mg/kg) significantly prevented the development of tolerance and also inhibited the naloxone (2 mg/kg)-induced withdrawal jumping in morphine-dependent mice. The effect of 4'-chlordiazepam was blocked by the mitochondrial diazepam binding inhibitor receptor antagonist PK11195 (2 mg/kg), but not by flumazenil (2 mg/kg), a selective benzodiazepine receptor antagonist. In contrast, the effect of progesterone was not affected by PK11195 or flumazenil. As expected, the development of tolerance and dependence observed upon chronic morphine was inhibited by the Ca2+ channel blocker nifedipine or an NMDA receptor antagonist dizocilpine. Further, a combined chronic administration of nifedipine together with neurosteroids pregnenolone sulfate, progesterone or 4'-chlor-diazepam led to an additive inhibitory effects on morphine tolerance or dependence, whereas the dizocilpine effect could not be increased by coadministration of the neurosteroids. Conclusion: The results indicate a role for dihydropyridine-sensitive Ca2+ channels in the action of neurosteroids and mitochondrial diazepam binding receptors in the 4'-chlordiazepm on the development of tolerance and dependence on morphine. Further, the direct involvement of GABAA/benzodiazepine receptor-mediated chloride channel control in the observed neurosteroid effects cannot be unequivocally ruled out.

Objective: To study the effect of Ocimum sanctum (Tulsi) on experimental cataract in rats and rabbits. Methods: Two models of experimental cataract were induced: (1) Galactosaemic cataract in rats by 30% galactose, (2) Naphthalene cataract in rabbits by 1 gm/kg naphthalene. Ocimum sanctum (O.S.) was administered orally in both models at two dose levels 1 and 2 gm/kg of body weight for curative and prophylactic effects. The study was conducted for 40 days. Results: O.S. delayed the onset of cataract as well as the subsequent maturation of cataract significantly in both models. In addition to delay in reaching various stages of development of cataract, IV stage did not develop with high doses till completion of 40 days of experimental period. Conclusion: O.S. delayed the process of cataractogenesis in both models. The higher doses are more effective and have not promising prophylactic role rather than curative one. This effect is more clear in galactosaemic catract.

Objective: The efficacy of thiamine, methionine or zinc and few chelators either individually or in combination, to prevent acute cadmium toxicity in mice, was investigated. Methods: Mice were administered intraperitoneally (i.p.) a single lethal dose of cadmium and within few minutes were treated i.p. with either one of the chelators, thiamine, methionine or zinc either individually or in combination. Mortality was observed for next 3 days. In another set of experiment, mice were administered an acute dose of cadmium and were again treated with the above stated chemicals either individually or in combination. Distribution of cadmium in blood, liver and kidneys was determined after 48 hours. Results: Combined administration of zinc and sodium 2,3- dimercaptopropane 1 -sulfonate (DMPS) was more effective than any other treatment in preventing lethal effects of cadmium and accumulation of cadmium in blood and liver. Conclusion: Thiol chelators when administered in combination with zinc or methionine were more effective than Ca trisodium diethylenetriamine pentaacetic acid (CaNa3DTPA) in preventing appearance of toxic signs of acute cadmium toxicity.

Objective: To study the relationship of changing Ca2+levels, to the inotropic responses of amphibian and mammalian myocardium, to phosphodiesterase (PDE) Ill inhibitors, milrinone and trequinsin hydrochloride (HL725). Methods: The inotropic effects of milrinone and HL725 were investigated, on the isolated perfused frog heart and the isolated electrically - paced guinea pig left atrium at different perfusate calcium levels. Results: HL725 and milrinone produced a dose-dependent positive inotropy effect. The mammalian myocardium exhibited greater magnitude of positive inotropic response as compared to the isolated frog heart. Conclusion: The responses to HL725 and milrinone are species specific; due to the inherent ultrastructural variations and the resultant changed intracellular Ca2+ mileu.

0bjectives:To examine the role of blood glucose changes (biochemical) and the ATP sensitive potassium channels (cellular) on clonidine induced antinociception in normal (non-diabetic) mice. Methods: Swiss male albino mice (20-25 g) were employed. Blood glucose was estimated by AMES Glucometer and the antinociception by acetic acid induced abdominal constrictions assay. The effect of clonidine (1 .10 or 20 'g/kg; i.p 15 min. prior) on these parameters was measured. The effect of glibenclamide per se (10 mg/kg; i.p) and on clonidine (1 or 10 'g/kg) induced changes (given 10 min. prior to clonidine) was recorded. Further, the effect of either yohimbine (1 mg/kg; i.p.) or naloxone (10 mg/kg; i.p.) per se and on the effect of combined exposure with glibenclamide and clonidine induced changes on the above parameters were also recorded. Results: Clonidine produced hyperglycemia almost uniformly irrespective of the doses tested. However, its antinociceptive response was dose related. Glibenclamide perse (10 mg/kg; i.p) induced hypoglycemia without any antinociceptive response. Its pretreatment reversed the hyperglycemic effect and enhanced the antinociceptive response of clonidine. Yohimbine but not naloxone attenuated glibenclamide induced enhancement of clonidine induced antinociceptive response. Conclusion: The findings indicate that clonidine induced antinociception is independent of its hyperglycemic action. In contrast to morphine, clonidine induced antinociception seems not to involve ATP sensitive potassium channels, rather its antinociception is enhanced by the blockade of these channels. This enhancement is attributed partially to (2 adrenergic mechanisms excluding the opioid pathways. The results favour the contention that the mecanisms involved in the antinociception induced K by clonidine and morphine are different.

Objective: To comprehend the differential effects of phenobarbitone (PB) on the hepatic and renal glutathione-Stransferases (GSTs). Methods: Male rhesus monkeys were administered PB intraperitoneally at a dose of 50 mg/Kg body weight/day for four days. Livers and kidneys were homogenized and 100,000 x g supernatant were prepared. The assays of GSTs using 1 chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitro-benzene (DCNB) and ethacrynic acid (EA) were performed in the supematant obtained from control and PB pretreated macaques. Results: PB caused a statistically significant decrease in the specific activity of hepatic GST towards CDNB (49%) and DCNB (64%) and a nonsignificant decrease towards EA (22%). In the kidney, the specific activities of GSTs towards these substrates were decreased by PB to a lesser extent (CDNB, 28%; DCNB, 11%; and EA, 18%) and were statistically nonsignificant. Conclusion: PB decreases the activity of hepatic GSTs significantly and that of renal GSTs non-significantlv in the rhesus monkev. These observations are surprising in the context that PB is a well known inducer of GSTs in the rodents.

Objective: The methanol extract (MLE) and fractions (MLFX2 and MLFX5) isolated from Morinda lucida were studied for some pharmacological properties in animal models. Methods: Carrageenan-induced rat paw oedema model was used to test anti-inflammatory activity; the acetic acid-induced writhings and tail immersion test were used to evaluate analgesic effect; while antipyretic activity was evaluated by inducing pyrexia with lipopolysaccharide, and measuring the rectal temperature. The effect of MLE on phenobarbitone sleeping time was also tested. Results: MLE (6.25-50 mg/kg), and MLFX2 the carrageenan-induced rat paw oedema. FG and MLFX 5 (5 and 10 mg/kg) produced inhibition of MLE(50-200 mg/kg) significantly reduced the number of writhings induced by acetic acid and elevated pain threshold in hot water test. MLFX5 significantly (P<0.05) reduced lipopolysaccharide-induced hyperpyrexia in rats while MLFX2 exhibited no such effects. MLE was also found to potentiate phenobarbitone induced sleeping time. Conclusion: MLE, MLFX2 and MLFX5 exhibited anti-inflammatory activity; MLE also showed analgesic, antipyretic effects and potentiated phenobarbitone sleeping time. However, MLFX2 showed analgesic activity in the acetic acid test while MLFX5 exihibited antipyretic effect.

Objective: To study the prescribing patterns of doctors in Allahabad district for evaluation of their rationality. Methods: Prescriptions written by the consultants in Private (P.S.) and Service Sectors (S.S.) were collected and studied retrospectively under two heads: (a) whether the prescriptions written by the Doctors are in conformity with the general format (b) whether the drugs prescribed by them are rational. The study was conducted on the 200 prescriptions comprising of 92 prescriptions of PS and 108 prescriptions of SS. Results: Audit of the prescription pattern revealed that most of the prescriptions did not conform to the pattern of a typical prescription. Eighty five percent of them were without the age of the patient, which includes 30% of the paediatric prescriptions. Superscription was not mentioned in 71% of the prescriptions. Inscription, subscription and signature were inadequate in 50%, 18% and 35% of the prescriptions, respectively. In these 200 prescriptions drugs were inappropriately administered in more than half (52 %) and it was more common among the consultants in P.S. (65%) than in S.S. (41%). Forty percent of the prescriptions showed over prescribing. The tendency of polypharmacy was more in P.S. (5.05 medications per prescription) than S.S. (3.52). Interacting drugs were prescribed in 10% cases and banned drug formulations were prescribed in 3% cases. Conclusion: Large number of prescriptions do not conform to ideal pattern and lack in their rationality.

Objective: To determine the disposition kinetics and urinary excretion of gentamicin following a single intravenous dose (10 mg/kg) and to workout the suitable dosage regimen for the goats. Methods: The studies were conducted on five male goats. Blood samples were collected at different time intervals following a single intravenous dose of gentamicin (10 mgkg) and plasma concentrations of drugs were determined using the radioimmunoassay kits. The pharmacokinetics parameters were calculated by using the curve stripping and non-linear least square regression computer programmes and the dosage regimen calculated. Seventy two hours cumulative urinary excretion of gentamicin was also determined following drug administration. Results: The plasma disposition of the drug could best be described by two compartment open model. The distribution and elimination half life values of gentamicin were found to be 0.05 and 2.05 h, respectively. The mean ñ SEM values of apparent volume of distribution at steady state (Vdss) and the total body clearance (CIB) were calculated to be 0.23 ñ 0.04 L/kg and 1.37 ml/kg.min, respectively. The cumulative urinary excretion data revealed that urinary excretion during the first 24 h following drug administration was fast, as 67.7 ñ 0.44 per cent of the total administered drug was excreted in the urine. Conclusion: To maintain the plasma concentrations of gentamicin within the safe therapeutic range, a rational dosage regimen for goats would be 1.8 and 1.5 mg/kg as the loading, and the maintenance doses, respectively, to be repeated at 6 hourly interval by intravenous route

Objective: To evaluate the antimalarial activity of Morinda Lucida leaf extract, using a rabbit in vitro model. Methods: The petroleum ether extract and fractions of the leaf samples of Morinda lucida were evaluated for antimalarial effects against Plasmodium falciparum using the rabbit in vitro technique. The sera collected from rabbits administered with the extract, fractions, chloroquine (Standard) and normal saline. These were used to evaluate their activity in inhibiting growth of the parasites in vitro. Results: The petroleum ether extract, chloroquine and fractions A and C at the employed doses inhibited the P. falciparum growth. Conclusion: Petroleum ether extract and some fractions of M. lucida inhibited the maturation of drug sensitive strain of P falciparum in-vitro.

. Forty healthy individuals and 70 psychiatric patients aged 25 to 45 years without previous history of TAB inoculation or enteric fever during last one year and serum negative for S. typhi and S. paratyphi (A & B) antibodies (titre<40) were selected. Group of 40 healthy individuals served as control. The psychiatric patients were started on chlorpromazine 2.5 mg three times a day orally. On 7th day 1 ml of formalised TAB vaccine (Glaxo) was injected subcutaneously. Blood was with-drawn on 15th and 30th days of inoculation and serum was tested for antibody titre by agglutination. The antibody titre was significantly lower in the chlorpromazine treated group against TO and TH on 15th day and against PA (H) and PB (H) also on 30th day. The parallel shift of the curves in the treated group as compared to the control suggests that only one mechanism is likely to be responsible for the reduction in antibody titre. It is concluded that chlorpromazine produces a significant immunological inhibition when administered for 7 days prior to TAB vaccine.

. Forty healthy individuals and 70 psychiatric patients aged 25 to 45 years without previous history of TAB inoculation or enteric fever during last one year and serum negative for S. typhi and S. paratyphi (A & B) antibodies (titre<40) were selected. Group of 40 healthy individuals served as control. The psychiatric patients were started on chlorpromazine 2.5 mg three times a day orally. On 7th day 1 ml of formalised TAB vaccine (Glaxo) was injected subcutaneously. Blood was with-drawn on 15th and 30th days of inoculation and serum was tested for antibody titre by agglutination. The antibody titre was significantly lower in the chlorpromazine treated group against TO and TH on 15th day and against PA (H) and PB (H) also on 30th day. The parallel shift of the curves in the treated group as compared to the control suggests that only one mechanism is likely to be responsible for the reduction in antibody titre. It is concluded that chlorpromazine produces a significant immunological inhibition when administered for 7 days prior to TAB vaccine.