Quality medicines for the poor: experience of the Delhi programme on rational use of drugs.

Prior to 1994, most Delhi hospitals and dispensaries experienced constant shortages of essential medicines. There was erratic prescribing of expensive branded products, frequent complaints about poor drug quality and low patient satisfaction. Delhi took the lead in developing a comprehensive Drug Policy in 1994 and was the only Indian state to have such a comprehensive policy. The policy's main objective is to improve the availability and accessibility of quality essential drugs for all those in need. The Delhi Society for the Promotion of Rational Use of Drugs (DSPRUD), a non-governmental organization, worked in close collaboration with the Delhi Government and with universities to implement various components of the policy. The first Essential Drugs List (EDL) was developed, a centralized pooled procurement system was set up and activities promoting rational use of drugs were initiated. In 1997, the Delhi Programme was designated the INDIA-WHO Essential Drugs Programme by the World Health Organization. The EDL was developed by a committee consisting of a multidisciplinary group of experts using balanced criteria of efficacy, safety, suitability and cost. The first list contained 250 drugs for hospitals and 100 drugs for dispensaries; the list is revised every 2 years. The pooled procurement system, including the rigorous selection of suppliers with a minimum annual threshold turnover and the introduction of Good Manufacturing Practice inspections, resulted in the supply of good quality drugs and in holding down the procurement costs of many drugs. Bulk purchasing of carefully selected essential drugs was estimated to save nearly 30% of the annual drugs bill for the Government of Delhi, savings which were mobilized for procuring more drugs, which in turn improved availability of drugs (more than 80%) at health facilities. Further, training programmes for prescribers led to a positive change in prescribing behaviour, with more than 80% of prescriptions being from the EDL and patients receiving 70-95% of the drugs prescribed. These changes were achieved by changing managerial systems with minimal additional expenditure. The 'Delhi Model' has clearly demonstrated that such a programme can be introduced and implemented and can lead to a better use and availability of medicines.

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine.

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ) management of acute migraine. DESIGN AND METHODS: A double blind comparative study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) for treatment of acute migraine. In all, 114 episodes of acute migraine were evaluated. Patients graded symptoms on a four-point scale before and up to 4 hours after treatment. The primary efficacy parameters included headache resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary endpoints included improvement in quality of life (QOL). RESULTS: The percentage of patients reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache tended to recur in both the placebo and ERG groups after initial improvement. Buccal PCZ was well tolerated; no signs of local irritation were evident, and patients found the formulation easy to use. Mild but transient sedation and drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via the buccal route produced faster improvement and greater efficacy than placebo (oral as well as buccal) or oral ERG. The global QOL score 2 hours after treatment scores was higher in the PCZ group. Buccal PCZ may represent a particularly effective alternative for acute migraine treatment.

Effect of fluvoxamine and N-methyl-D-aspartate receptor antagonists on shock-induced depression in mice.

We have earlier demonstrated that NMDA receptor antagonists possess antidepressant effect and also they show a synergism with imipramine. The present study attempts to investigate whether NMDA receptor antagonists also interact with selective serotonin reuptake inhibitors. The study was conducted in albino mice using shock-induced depression model. The mice were placed on a grid floor and shock delivered were of 2 sec duration with a 9 sec interval for 1 h. Twenty four hours later depression was measured by an open field test followed by a forced swimming test. Presentation of inescapable foot shock significantly reduced ambulation (from 159.50 +/- 5.42 to 80.50 +/- 4.61) and rearing (from 22.10 +/- 2.15 to 11.30 +/- 1.32) in the open field arena and increased immobility duration in the forced swimming test (from 82.20 +/- 3.51 to 158.90 +/- 4.61). Pretreatment with fluvoxamine, MK-801, ketamine and the combination of fluvoxamine with either of the NMDA antagonists antagonised shock-induced depression. Haloperidol and ketanserin pretreatment modified the effect of these agents. These findings suggest an interaction of NMDA receptor antagonists with fluvoxamine, and an involvement of brain dopaminergic and tryptaminergic mechanisms in the behavioural suppression observed after inescapable foot shock.

Enigmatic relationship of Pleckstrin homology domain with phospholipid breakdown mediated signal transduction.

Research into phospholipid signaling continues to flourish, as more and more bioactive lipids and proteins are being identified and their actions characterised. The Pleckstrin homology (PH) domain is one such newly recognized protein module thought to play an important role in intracellular signal transduction. The tertiary structures of several PH domains have been determined, some of them complexed with ligands and on the basis of structural similarities between PH domains and lipid binding proteins it has been suggested that PH domains may be binding to lipophilic molecules. In fact many of the proteins that contain this domain can interfere with the membrane association. This review examines the specificity of this binding and illustrates the importance of charge-charge interactions in PIP2-PH domain complex formation. The precise physiological functions of PH domain in vivo remains to be explored therefore this review examines the biochemical aspects of the interaction of PH domains with phospholipid breakdown mediated products and proto-oncogenic serine-threonine kinase (Akt), protein tyrosine kinases, which have been found to be a target of phospholipid second messengers. Thus, number of cellular processes mediated by this way, ranging from insulin signaling and protein synthesis to differentiation and cell survival are regulated by this intracellular signaling protein module.

Interaction between N-methyl-D-aspartate receptor antagonists and imipramine in shock-induced depression.

In the past few years, literature has accumulated describing manifestation of seizures following administration of certain antidepressants. Such reports are of particular importance because depression is a frequent psychiatric problem associated with epilepsy. Therefore, in the view of the fact that NMDA receptor antagonists have been reported to reduce behavioural deficits and have been shown to be anticonvulsant, it was considered imperative to study their antidepressant effect using shock-induced depression model in mice. Presentation of inescapable foot shock significantly reduced ambulation and rearing in the open field arena and increased immobility duration in the FST. Pretreatment with imipramine, MK 801 and ketamine significantly prevented the effect of shock. Also, the combination of imipramine with either of the NMDA antagonists antagonised the effect of shock. Haloperidol, prazosin and ketanserin pretreatment modified the effect of these agents. These findings suggest an antidepressant effect of the NMDA receptor antagonists, and a complexity of neurotransmitter mechanisms, which are responsible for the occurrence of behavioural effects in shock-induced depression model.

Indoor air quality and acute lower respiratory infection in Indian urban slums.

The present prospective study was conducted at two urban slums of Delhi, Kusumpur Pahari and Kathputly Colony, in the peak winter season from November 1994 through February 1995. We studied 642 infants to determine the incidence of acute lower respiratory infection (ALRI) and its relationship to indoor air pollution due to fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317 children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene), there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p < 0.05). Controls were children without ALRI and were used as controls in different groups. The demographic data and risk factors, namely, nutritional and immunization status, were comparable in ALRI cases and controls in both study areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur Colony. Only one case of croup was reported from Kusumpur Pahari among wood users. The duration of illness was longer in the Kusumpur Pahari due to poor compliance, feeding, and child rearing habits. In conclusion, a higher incidence of ALRI was reported in kerosene users in Kathputly Colony, a high pollution area; however, the reasons for the differences observed need further elucidation.

Vasopressin induces dopamine release and cyclic AMP efflux from the brain of water-deprived rats: inhibitory effect of vasopressin V2 receptor-mediated phosphorylation.

The neurohypophyseal hormone vasopressin (AVP) is widely distributed throughout the central nervous system. It acts as an excitatory transmitter in the CNS and plays an important physiological role in water and electrolyte homeostasis. However, water deprivation has been shown to induce changes in the levels of monoamines, but there is little knowledge about the influence of AVP on monoamine levels after water deprivation. In this study, we investigated the effect of AVP and its receptor antagonists on alterations in dopamine (DA) release and cyclic adenosine 3',5' monophosphate (cAMP) efflux from rat brain slices following water deprivation. Striatal brain slices (500 microm thick) were incubated in a medium with or without AVP (0. 1-1.0 microM) for 30 min. After 2 h of washout in normal medium, high KCl (40 mM)-evoked DA release and cAMP efflux from the rat brain slices were examined. In the brain slices of euhydrated animals, treatment with AVP slightly altered DA release and cAMP efflux from the brain. This increase in DA release and cAMP efflux was not significantly affected by the addition of a calcium/calmodulin-dependent protein phosphatase, calcineurin (20 microM), to the incubation medium or either by a V1 or V2 AVP receptor antagonist. In contrast, AVP significantly increased the DA release and enhanced the cAMP efflux from the brain slices of water-deprived animals. The AVP-induced increase of brain response in the water-deprived animals was significantly attenuated by a V2 receptor antagonist, partially by calcineurin, but not by a V1 receptor antagonist. The present results suggest that AVP may play a role in water-deprivation-induced DA release and cAMP efflux, which is possibly mediated through the activation of the V2 receptor. The V2 receptor action is attenuated by calcium/calmodulin-dependent dephosphorlyation of some cellular proteins critical for signal transduction.

Treatment seeking behaviour in sexually transmitted diseases.

The present study has been conducted to assess social and behavioural factors predisposing individuals suffering from sexually transmitted diseases to seek treatment and the role of the health provider in them. Out results showed that the demographic, socio-economic and behavioural characteristics of patients seeking treatment at alternative places and those attending the referral hospital in the first instance were comparable. Inhibition, time and distance were important considerations for selecting a health facility. Private clinics were the most preferred (72.4%) source of treatment. In 60.3% of cases written prescriptions were not given and advice regarding treatment of sexual partner was not there in any of the cases. 98.3% of the patients lacked awareness about their disease and 91.4% patients about the treatment they were receiving.

PIP: The prospective study was conducted on 100 patients attending the Dermatology and Venereal Diseases Department of Lok Nayak Hospital, New Delhi, to investigate the socioeconomic and behavioral factors that may influence treatment-seeking behavior for sexually transmitted diseases (STDs). All the subjects were interviewed using a pretested, semistructured questionnaire. Results showed that socioeconomic factors affect the utilization of STD services in many individuals. Accessibility to health care services in terms of time and money were important determinants of treatment-seeking behavior of the patient. This present study clearly documents that the majority of patients (98%) were unaware of their diagnosis, treatment and the seriousness of their illnesses. Furthermore, the media failed to charge the treatment-seeking behavior of STD patients, though it was considered as an important source of public education on the various aspects of STD.

Neurobiological characterization of bipolar affective disorders : a focus on tardive dyskinesia and soft neurological signs in relation to serum dopamine Beta hydroxylase activity.

In this study, the prognostic determinants were investigated involving bipolar patients classified into two groups-one with favourable course and outcome, and the other with clearly unfavourable prognosis, based on certain recommended criteria, with intermediate prognosis were excluded. As compared to the poor prognosis group, the good prognosis group had lower social dysfunctions, lower ratings on psychopathotogy fewer indicators of neurodysfunction in form of neurological soft signs (NSS) and tardive dyskinesia (TD). The poor prognosis group was characterized by: (i) older age at onset; (ii) more manic than depressive episodes (5:1) and (HI) lower levels of serum dopamine-ß-hydroxylase activity (DBH). The association between poor prognosis bipolar disorder having neuroleptic intolerance (TD and NSS) with low serum DBH, suggests that it is genetically governed. Further research in this direction seems in order, particularly the follow up of first episode manic disorders.

Drug utilisation patterns in the Third World.

Drugs are not available to the majority of the population in developing countries. Aggravating factors include weak healthcare structure, inadequate financial resources, nonavailability of pharmaceuticals, lack of drug legislation and policy, ineffective drug utilisation and the prevalence of self-medication. Although most of the population lives in rural areas, available funds are mostly utilised for urban areas. The use of drugs by injection is common in developing countries. In addition, many patients self-medicate because most drugs are available without a prescription from a doctor. There is therefore a great need for prescriber education in rational drug use, and for public education in the use of commonly used drugs. National health and drug policies should be formulated which incorporate the essential drug concept, and drug legislation needs to be revamped and implemented effectively. These measures may be helpful in providing better healthcare to the majority of the population in developing countries.