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PubMed1992

Determination of Zy 17617B in plasma by solid-phase extraction and liquid chromatography with automated pre-column exchange.

An automated chromatographic system, combining solid-phase extraction and automated pre-column exchange, is described for the routine determination of Zy 17617B at the pmol/ml level in human plasma. The sample extraction and elution onto the analytical column were performed automatically and concomitantly using a conventional liquid chromatographic apparatus equipped with a Merck OSP-2 on-line sample preparator. Validation data demonstrate the reliability of the method.

Antidiarrheals↗
PubMed1987

Opioid action of the intestine: the importance of the intestinal mucosa.

Drug effects on the intestine are traditionally explained in terms of action on the muscle layers and the nerves that control them. This is particularly true in the case of the opioids but research starting two decades ago has identified the intestinal mucosa as the site of action of the antidiarrhoeal opioids. Continued research using the intestinal mucosa offers a fresh approach to solving some old problems. For example it could lead to more confident predictions to be made about the wanted and unwanted effects of opioid drugs on the intestine and may help to find better drug treatments for alleviating withdrawal diarrhoea in addicts. Eventually it may help to explain how the general process of opioid dependence occurs at a cellular level.

Antidiarrheals↗
PubMed1996

Insights into opioid action in the intestinal tract.

Opioids have been used for centuries as antidiarrhoeal drugs. In recent years, their mechanism and sites of action in exerting their antidiarrhoeal effect have been studied intensely. Attempts have been made to propose their general mode of action. Whilst there are numerous similarities in their general effects on motility, fluid secretion, and neuroeffector transmission, the differences between species, in some cases, can be remarkable. We highlight and contrast the similarities and differences in the commonly examined species and compare them to humans. Insights into mechanisms of opioid antidiarrhoeal action now also provide some new perspectives of opioid action in the intestine.

Analgesics, Opioid↗
PubMed1996

Regulatory actions to enhance appropriate drug use: the case of antidiarrhoeal drugs.

Inappropriate drug use is a serious problem in the control of diarrhoeal diseases. To address this problem, the World Health Organization's Programme for the Control of Diarrhoeal Diseases reviewed the literature on the most commonly used antidiarrhoeal agents, and distributed the resulting document widely in 1990. Antidiarrhoeal drugs received simultaneous attention in the popular media as groups and individuals campaigned against their registration and use. This article evaluates the actions against antidiarrhoeal drugs taken by national drug regulators in the period during and after these events (January 1989 until December 1993). Information on regulatory actions was requested from countries and extracted from published and unpublished sources. Sixteen countries reported regulatory actions on 21 occasions during the period of study. The majority of actions concerned antimotility drugs; few were against adsorbents, antidiarrhoeal drugs containing antimicrobials, or adult formulae. Six countries took action against large and heterogenous groups of antidiarrhoeal drugs. Most actions occurred in the two-year period immediately following the distribution of the WHO review and the attention in the media. The sequence of distribution of the review, media coverage, and activities of dedicated groups and individuals, followed by a noticeable cluster of regulatory actions suggests a clear relationship. Further research is necessary to determine the relative role of each activity. There are several constraints to deregistration of profitable drugs and some drug regulators may have chosen to delay action until the end of the drug's registration cycle. Many more antidiarrhoeal drugs may lose their register in the future through a passive deregistration process. Deregistration of inappropriate drugs will probably take much time and widespread deregistrations are not likely. Furthermore, regulatory actions alone are probably insufficient to achieve a more appropriate use of drugs. More effect can be expected from simultaneous regulatory, managerial, and educational interventions directed at providers, combined with communication to the general public.

Adult↗
PubMed1996

Drug prescribing practices of general practitioners and paediatricians for childhood diarrhoea in Karachi, Pakistan.

Observations were made of 996 encounters between children with diarrhoea and practitioners (28 paediatricians, 62 general practitioners) in Karachi, Pakistan. Oral rehydration salt (ORS) was prescribed in more than 50% of encounters by 53% of general practitioners (GPs) and 61% of paediatricians. Sixty-six percent of GPs and 50% of paediatricians prescribed antibacterials, 60% of GPs and 28% of paediatricians prescribed antidiarrhoeals and 39% of GPs and 32% of paediatricians prescribed antiamoebics in more than 30% of their encounters. Looking at all the encounters, we observed that ORS was prescribed in 52 and 51%, antibacterials in 41 and 36%, antidiarrhoeals in 48 and 29%, and antiamoebics in 26 and 22% of encounters by GPs and paediatricians, respectively, Cotrimoxazole was the most frequently prescribed antibacterial by both types of practitioners. Antidiarrhoeals were prescribed more often by GPs than by paediatricians. In 77% of their encounters, GPs dispensed drug formulations known as "mixtures' made in their own dispensing corners. The mean duration of encounters between patients and GPs was 3 +/- 2 minutes and between patients and paediatricians was 9 +/- 4 minutes. These results indicate inadequate prescription of ORS and excessive prescription of antibacterials, antidiarrhoeals and antiamoebics. Intervention strategies need to be planned to improve the prescribing practices of both groups.

Amebicides↗
PubMed1996

Factors influencing physicians' prescribing behaviour in the treatment of childhood diarrhoea: knowledge may not be the clue.

Proper diarrhoea treatment has received greater attention during the last 10 years. However, the unjustified use of medicines to treat simple episodes of acute diarrhoea continues to divert attention and available resources away from appropriate treatment. A study to identify the factors determining prescribing practices for diarrhoea treatment was carried out in a peri-urban part of Lima, Peru in 1991. Physicians were interviewed, and then their practice was assessed by visits of confederates with healthy children described as ill, by interviews with mothers of sick children leaving the clinic, or by both of these methods. Physicians' reported practices in treating diarrhoea cases were compared to their actual practices. Although physicians' knowledge of drug management seemed to influence the low frequency of prescription of antidiarrhoeal drugs, it did not have the same influence on prescription of antimicrobials. Our results suggest that the diagnostic process and consequently the treatment decision do not follow a scientific rationale for this illness. The physicians' prescribing practices seemed to be more related to agreement with social expectations and the caretakers' perception of the physicians' role than they were to the standard biomedical rules of diarrhoea management.

Advertising↗
PubMed1996

Retail pharmacies in developing countries: a behavior and intervention framework.

Retail pharmacies in developing countries are one of the most important sources of advice on pharmaceuticals. Among the reasons the clients give are ease of access; availability of medicines; quality of service (no waiting and convenient hours of operation); and cheaper products, availability of credit, or the option to buy drugs in small amounts. However, the appropriateness of prescribing by retail pharmacy staff has been found to be far from acceptable. In childhood diarrhea, for example, oral rehydration salts (ORS), the appropriate diarrhea treatment, are recommended much less than pharmaceuticals of limited value, such as antimotility agents, adsorbents, etc. Little information is available for reasons underlying such behaviors. In this paper, we present a conceptual framework in which to analyze factors that may affect retail pharmacy prescribing, and we suggest strategies for behavior change. We developed this framework after examining relevant literature on retail pharmacy prescribing. We propose that pharmacy factors, client factors, physician practice and regulatory factors are the four sets of important factors for understanding pharmacy prescribing behavior. For intervention, we present four types of interventions which could be used for changing the behavior of pharmacy staff: information alone, persuasion, incentives and coercion. The behavior and intervention frameworks presented in this paper should also help in guiding further research in this area. For example, new information on the effects of ownership type, availability vs actual role of professional staff and authority structure on pharmacy treatment behaviors would be useful areas for future research. Similarly, additional research is needed on the comparative effects of coercive, persuasive and incentive strategies on pharmacy treatment behaviors.

Adult↗
PubMed1996

Small group intervention vs formal seminar for improving appropriate drug use.

In an attempt to evaluate the efficacy of different methods of interventions to improve the appropriate use of drugs for acute diarrhoea, a controlled study has been carried out in 6 districts in Yogyakarta and Central Java provinces, Indonesia. This study was designed to investigate the impacts of two different methods of educational intervention, i.e. a small group face-to-face intervention and a formal seminar for prescribers, on prescribing practice in acute diarrhoea. The districts were randomly assigned into 3 groups and 15 health centers were selected from each district. Prescribers in Group 1 underwent a small group face-to-face intervention conducted in the respective health center. Those in Group 2 attended a formal seminar conducted at the district level. Prescribers in Group 3 served as the control group. Both interventions were given on a single occasion without follow-up supervision or monitoring. Written information materials on the appropriate management of acute diarrhoea were developed and were provided to all prescribers in the intervention groups. Focus group discussions (FGDs) involving prescribers and consumers in the 6 districts were carried out to identify various underlying motivations of drug use in acute diarrhoea. The findings of the FGDs were used as part of the intervention materials. To evaluate the impacts of these interventions on prescribing practice, a prescribing survey for patients under five years old with acute diarrhoea was carried out in health centers covering 3-month periods before and after the intervention. The results showed that both interventions were equally effective in improving the levels of knowledge of prescribers about the appropriate management of acute diarrhoea. They were also partially effective in improving the appropriate use of drugs, reducing the use of non-rehydration medications. There was a highly significant reduction of antimicrobial usage either after small-group face-to-face intervention (77.4 +/- 2.7% to 60.4 +/- 2.9%; P < 0.001) or formal seminar (82.3 +/- 3.0% to 72.3 +/- 3.6%; P < 0.001), and the former caused significantly (P < 0.001) greater reduction than the latter. There was also a significant (P < 0.01) reduction in the usage of antidiarrhoeals after both interventions, i.e. from 20.3 +/- 3.7% to 12.5 +/- 3.3% (P < 0.01) after face-to-face intervention and from 48.5 +/- 4.1% to 27.0 +/- 4.3% (P < 0.01) after seminar. However, the formal seminar had a significantly (P < 0.01) greater impact than the small group face-to-face intervention. There was also a trend toward increased oral rehydration solution (ORS) usage after both interventions, but this did not achieve the level of statistical significance (P > 0.05). No changes were observed in the control group. Although the small group face-to-face intervention did not appear to offer greater impacts over large seminars in improving the appropriate use of drugs in acute diarrhoea, since the unit cost of training is far less costly than the seminar, it might be feasibly implemented in the existing supervisory structure of the health system.

Acute Disease↗
PubMed1996

Assessing the impact of a regulatory intervention in Pakistan.

In 1990 paediatric formulations of antimotility drugs were deregistered in Pakistan. Although preliminary research data suggests the incidence of paralytic ileus in children suffering from acute diarrhoea has fallen, cases continue to be recorded. A small-scale survey conducted in 1993 to assess the effectiveness of the regulatory intervention conclusively proved that while the deregistered products had been successfully withdrawn from the overwhelming majority of retail outlets, blackmarketing of a paediatric antimotility drug was taking place in one city. The results also indicated that throughout the country the deregistered formulations were being substituted by other irrational therapies, including the misuse of adult formulations. As a regulatory intervention, therefore, deregistration needs to be accompanied by efforts to change patient attitudes and physician prescribing habits.

Adult↗
PubMed1989

Study of Rwandese medicinal plants used in the treatment of diarrhoea I.

A series of 20 medicinal plants used in the Rwandese traditional medicine to treat diarrhoeal diseases has been screened for antibacterial activity against several Salmonella and Shigella and for antidiarrhoeal activity on mice. Fifty percent of the plants tested showed antibacterial activity against one or more microorganisms and 65% showed antidiarrhoeal activity.

Antidiarrheals↗
PubMed1992

Inhibition of Microlax-induced experimental diarrhoea with narcotic-like extracts of Psidium guajava leaf in rats.

Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera.

Animals↗
PubMed1994

Biochemical evaluation of the antiulcerogenic effect of Cauvery-100 (an ayurvedic formulation) in rats.

Due to the varied pathogenesis of ulcers, a number of pharmacologically different antiulcer drugs are now used in the treatment of the condition. The suitability of certain of these drugs is still to be established. Cauvery-100 is an ayurvedic formulation consisting of plant ingredients, and has been suggested to be useful in the treatment of gastrointestinal disorders. In the present study this drug was tested for its antiulcerogenic effect. The number of lesions on gastric mucosa decreased markedly after 15 days oral treatment with Cauvery-100 in rats with indomethacin-induced ulcers. The volume and total acidity of the gastric juice also decreased in the treated rats. The hexose, hexosamine and sialic acid levels of gastric contents, which were increased in untreated rats returned to near normal levels after 15 days of treatment. Protein in the gastric juice was elevated in untreated rats but returned to near normal levels after 15 days of treatment. Cauvery-100 acts both to decrease the acidity and to increase the mucosal defence in the gastric areas, thereby justifying its use as an antiulcerogenic agent.

Animals↗
PubMed1996

Evaluation of the calcium-antagonist, antidiarrhoeic and central nervous system activities of Baccharis serraefolia.

Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican traditional medicine. Although the methanolic extract of this plant has shown an important dose-dependent spasmolytic activity, its underlying mechanism has not been studied. In the present work, the methanolic extract of B. serraefolia significantly delayed the onset of tonic seizures induced by strychnine and pentylenetetrazol; besides, it diminished the death rate and number of animals that exhibited convulsions. It produced potentiation of the hypnotic effect of pentobarbital. Oral administration produced an inhibition of gastrointestinal transit in mice as effective as that produced by loperamide. As to the effect on smooth muscles, the active extract produced an inhibition of contraction induced electrically, which could not be reversed by naloxone. The calcium concentration-contraction curve showed a rightward displacement when the extract was added to isolated guinea pig ileum depolarized with high K+ and cumulative concentrations of Ca2+. The results suggest that the methanolic extract does not interact with classical opiate receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intra-cellular store.

Administration, Oral↗