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This study was conducted to determine the prevalence of drug-related hospital admissions in southern Tasmania, Australia. The causes of consecutive admissions to medical wards of the Royal Hobart Hospital were reviewed. Comprehensive data were collected over a 10-week period on 691 admissions (median age: 67 years and range: 11-97 years; 50.8% males). Sixty-eight (9.8%) of the admissions were classified as being either probably or definitely drug-related. Most of these admissions were attributable to intentional overdose (38.2%) or an adverse drug reaction (30.9%). The overdoses often involved benzodiazepines or antipsychotics. Gastrointestinal bleeding related to the use of nonsteroidal anti-inflammatory drugs was the most common adverse drug reaction (38.1% of all reactions). Other drug-related admission categories were poor compliance (14.7%), dosage decrease or therapy cessation by a doctor producing an exacerbation of symptoms (7.4%), substance abuse (4.4%) and drug interaction (4.4%). Patients with a drug-related admission were, on average, younger than the other medical admissions, with no significant difference in gender. Patients admitted due to an overdose or substance abuse were younger than other drug-related admissions and non-drug related admissions. In conclusion, this study has determined that almost 10% of medical admissions to the hospital are drug-related and it is estimated that 40 to 50 elderly people are admitted each year suffering from gastrointestinal bleeding related to nonsteroidal anti-inflammatory drugs.

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OBJECTIVE: To gather data on the prescribing of psychoactive drugs (benzodiazepines, antidepressants and antipsychotics) using a network of Tasmanian community pharmacies. DESIGN SETTING AND PARTICIPANTS: The prescribing of psychoactive drugs in the community was studied during 1989 using data retrospectively obtained from computerised dispensing systems in 11 community pharmacies in Tasmania. The data collection procedure included all prescriptions dispensed in the pharmacies, irrespective of supply under the Pharmaceutical Benefits Scheme, the Repatriation Pharmaceutical Benefits Scheme or as a private prescription. MAIN OUTCOME MEASURES: Results of the pooled data were quantified by both the number of prescriptions and the defined daily doses (DDDs) dispensed for the psychoactive drugs. RESULTS: When extrapolated to the population of Tasmania, the estimated annual prescribing rates for the benzodiazepines, antidepressants and antipsychotics (including lithium) were 853.3, 316.2 and 54.8 prescriptions per 1000 persons, respectively. Prescriptions for the psychoactive drugs accounted for 13.2% of all prescriptions dispensed. In terms of DDDs, the estimated prescribing rates for the total Tasmanian population for the benzodiazepines, antidepressants and antipsychotics were 47.8, 12.5 and 2.1 DDDs per 1000 persons per day, respectively. The rate of benzodiazepine prescribing appeared to be high in comparison with the limited Australian data available. The relative prescribing rates of the long acting benzodiazepine hypnotics, flunitrazepam and nitrazepam, were also disturbingly high. CONCLUSIONS: This study has demonstrated the potential value of comprehensive pharmacoepidemiological data obtained from a network of community pharmacists and will form the basis for future studies using an expanded collection procedure.

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The time course of the sorption of drugs by polyvinylchloride infusion bags has been approximated using a diffusion model in which the plastic is assumed to act as an infinite sink. This model appears to be suitable for estimation of storage times relevant to clinical usage and enables the magnitude of the uptake in a specific time to be described by a single parameter, referred to as the sorption number. This parameter is defined by the plastic-infusion solution partition coefficient, the diffusion coefficient in the plastic, the fraction un-ionized in solution, the volume of the infusion solution, and the surface area of the plastic. An approximation of the model allows a ready estimation of the sorption number from the fraction remaining in solution at a given time. The sorption number can be extrapolated to allow prediction of the effects of time, plastic surface area, solution volume, and solution pH on fractional solute loss. A reasonable correlation was established between the logarithm of this parameter and the logarithm of the octanol-water partition coefficients of various solutes. The model allows the fraction of a solute remaining in a plastic infusion bag at a given storage time to be estimated from the octanol-water partition coefficient of the solute and other readily available data.

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The permeation of triamcinolone, hydrocortisone, prednisolone, corticosterone, triamcinolone acetonide, testosterone, and betamethasone-17-valerate through excised human stratum corneum was quantified. The time course of permeation could be adequately described by a simple diffusion model suggesting that shunt transport may not be important. The disappearance of these steroids from aqueous solutions applied to human and rat dermis was also monitored. The concentrations of unbound steroid in the viable epidermis appeared to be mainly related to the blood perfusion rate in the dermis and, more importantly, to the lipophilicity of the steroid. The most lipophilic steroids penetrated the human epidermis at the fastest rates but are cleared from the viable epidermis at rates comparable to those found for more polar steroids.

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The effect of iontophoresis on the rate of permeation of a number of therapeutically active weak acids and bases through excised human stratum corneum has been examined, over a range of pH values. It has been shown that the amount of ionized drug species present in the drug solution is an important factor in the delivery of acids and bases by this route and that the molecular weight of the drug does not influence the rate of delivery by iontophoresis.

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Aqueous solutions of several ionizable substances were stored in plastic infusion bags and the sorption of the substances monitored with time. The substances used were p-nitrophenol, p-toluidine, warfarin sodium [3-(alpha-acetonylbenzyl)-4-hydroxycoumarin sodium salt] and trifluoperazine hydrochloride (10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazine dihydrochloride). The rate and extent of sorption for each substance varied with pH and was consistent with a preferential uptake of the un-ionized species. The uptake of p-nitrophenol and p-toluidine was adequately described by a diffusion model derived assuming that sorption is rate-controlled by the diffusivity of the solute in the plastic matrix, and that only the un-ionized species was sorbed by the plastic matrix. However, the uptake of warfarin sodium and trifluoperazine hydrochloride was described more accurately by a diffusion model in which the diffusional resistance of the plastic matrix and of an interfacial resistance barrier both contributed to the diffusional resistance encountered in the sorption process. It appeared that the rate of uptake of the un-ionized form of these solutes was diminished due to the influence of interfacial or aqueous diffusional barriers. Solute lipophilicity and degree of ionization appeared to be important factors determining the relative contribution of the respective barriers to the overall diffusional resistance.

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The effect of iontophoresis and the pH of aqueous vehicles on the rate and extent of permeation of lignocaine through excised human stratum corneum was investigated. In the absence of iontophoresis, the rate of penetration was greatest at the higher pH values where lignocaine exists mainly in the unionized form; iontophoresis was most effective at the lower pH values where lignocaine is mainly ionized. At pH 3.4, and 5.2, the flux increased during iontophoresis, by approximately 8.5 and 4 times, respectively, relative to that occurring without iontophoresis. The present results suggest that some weak electrolytes which show poor percutaneous penetration may be administered topically using iontophoresis provided the drug is kept in a highly ionized form.

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The time course of sorption of diazepam and nitroglycerin from aqueous solutions into plastic materials has been represented by the diffusion and compartmental models for a variety of storage conditions. The diffusion model seemed to be the more satisfactory model in respect to both description and prediction of the drug uptake for all conditions. The compartment model appeared to be useful for describing the drug uptake at earlier times, giving a satisfactory fit to the data and reliable final parameter estimates. However, that model was not able to describe the loss as equilibrium was approached or accurately predict the disappearance profiles for these solutes with alterations in solution volume or infusion bag size. Approximations of the diffusion model gave parameter estimates consistent with those obtained by nonlinear regression using the full equations.

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The teaching of pharmacy computerisation to final year students in an Australian University is described. A practical segment follows a classroom introduction to the subject and is itself followed by a review and discussion. A flow chart of the program is presented. The development of this system demonstrates that pharmacists, with a minimal background in programming, are capable of generating software best suited to their own individual needs.

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The disappearance of chlorbutol from aqueous solutions stored in polyethylene containers under various experimental and simulated patient use conditions is described. Chlorbutol is lost by sorption into the container wall, container insert and by permeation into the external environment. The extent of chlorbutol loss from solution and uptake by the container components is dependent on temperature, chlorbutol concentration and the closure used. Aqueous chlorbutol solutions stored in the polyethylene container evaluated have a predicted shelf-life (time for 10% loss) of about 4 months at 25 degrees C and 8 months at 20 degrees C. Negligible loss is found during simulated patient use over 1 month.

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The dynamics of the interaction of clomethiazole edisylate (1) with polyvinyl chloride and cellulose propionate, the main plastics used in the manufacture of infusion bags and sets, was examined. An experimental system in which the plastic was either open or closed to the environment was used to determine the relative contribution of the sorption and permeation processes to loss from solutions of clomethiazole edisylate (I) in contact with the plastic infusion systems. Sorption by the plastic infusion materials accounted for most of the drug loss, while permeation into the external environment accounted for the remainder. The sorption and permeation into and through polyvinyl chloride was temperature dependent. The diffusion coefficient and permeation rate constant both increased with temperature, while the polyvinyl chloride-water partition coefficients were independent of temperature. The activation energy for the diffusion in polyvinyl chloride was 13.5 kcal/mol. The permeability of the infusion bag plastic and the evaporation across an unstirred air boundary layer adjacent to the external surface of the plastic both appeared to contribute to the overall diffusional resistance encountered in the permeation process. The plastic-water partition coefficients are independent of initial concentration, suggesting that the concentration-dependent loss of the drug from solutions stored in plastic infusion bags and burets is a result of the greater diffusivity of the drug in the plastic at the higher initial concentrations. Plasticization of the polymers by the drug is indicated by the increase in the diffusivity of the drug in polyvinyl chloride and cellulose propionate, the increase in the rate and extent of sorption of a radiolabeled marker (diazepam) by the plastic, and the decreased stiffness of polyvinyl chloride exposed to higher concentrations of the drug.

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Factors affecting the loss of diazepam from i.v. admixtures to flexible polyvinyl chloride (PVC) bags and to various administration sets were studied. Admixtures containing diazepam and 0.9% sodium chloride injection were stored for up to 550 hours in flexible PVC bags and in glass vials at various temperatures. Diazepam injection containing two different solvents was used. Initial diazepam concentrations in storage studies ranged from 25 to 100 micrograms/ml and pH ranged from 4.2 to 7.5. To determine availability of diazepam after infusion through administration sets, solutions (50 micrograms/ml) from glass containers were run through six different sets at 1 ml/min for seven hours. In storage studies, the difference in composition of the solvent was found to have only a slight effect on the rate and extent of diazepam loss. Diazepam loss was unaffected by pH. For admixtures stored in 1000-ml flexible PVC bags, the fractional loss of diazepam was greater at small volumes. The diazepam concentration of solutions in flexible PVC bags decreased more rapidly during infusion than during storage of the total original volume. The fraction of diazepam remaining in stored solutions was independent of the initial concentration, but the rate and extent of diazepam loss was greater at higher temperatures. Diazepam loss was dependent on length of flexible PVC tubing, and diazepam availability was greater with faster flow rates. In solutions infused through the polyolefin Tridilset, 100% of the diazepam remained. When storage of diazepam admixtures in PVC bags or administration through PVC tubing cannot be avoided, measures to minimize the rate and extent of diazepam loss include decreasing the temperature and the storage time and increasing the surface-area-to-volume ratio and the flow rate. Equations are presented for calculating the amount of diazepam delivered.

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The loss of 45 drugs from intravenous solutions during simulated infusions through plastic infusion sets; factors affecting such losses; and ways to minimize these losses are investigated. A total of 43 drugs was studied in 0.9% sodium chloride solution; one drug was in 5% dextrose solution and one in a solvent supplied by the manufacturer. Drug loss was studied in plastic infusion sets, with and without burette chambers, and glass infusion bottles; polyethylene and silastic tubing with glass syringes on an infusion pump; and single-use all-plastic syringes. Variables studied were flow rates, infusion times, drug concentrations, pH, and tubing lengths and radii. Clomethiazole edisylate, chlorpromazine hydrochloride, diazepam, promazine hydrochloride, promethazine hydrochloride, thiopental sodium, thioridazine hydrochloride, and trifluoperazine dihydrochloride were lost from solution during infusions through at least one system. The loss of most drugs during infusion was slow, time-dependent, and concentration-independent, indicating a diffusion-controlled sorption process rather than a binding, adsorptive process. Drug loss was lowest in short lengths small-diameter tubing with low permeability constants. None of the drugs was lost stored in all-plastic single-use syringes. It is concluded that loss of drugs through sorption processes can be minimized by administering infusions through short lengths of small-diameter tubing made of inert plastics.

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Forty-six injectable drug products, many of which are administered by i.v. infusion, were studied for loss from aqueous solutions stored in polyvinyl chloride infusion bags for various periods of time. The polyvinyl bags were stored in the dark at room temperature for up to three months. Drugs stored in glass vials served as controls. The solutions were assayed spectrophotometrically at regular intervals. The effects of drug concentration and pH on the loss of drug from solution were studied. Octanol-water partition coefficients were used as a gauge of lipid solubility of the drugs. Five of the drug products-clomethiazole edisylate, diazepam, hydralazine hydrochloride, thiopental sodium, and warfarin sodium-were found to be lost to a substantial extent after one week. For all drugs studied, the effects of the initial concentration on drug loss varied. The amount of drug lost over a given time was a function of the pH of the solution. The main physico-chemical determinants controlling drug sorption appeared to be the extent of ionization and the lipid solubility of the drug. For most of the drugs studied, minimal losses from the aqueous solutions were observed over short periods of storage time. Disappearance was slow and time dependent, indicating a diffusion-controlled sorption process. The losses of clomethiazole edisylate, thiopental sodium, and diazepam may be clinically important.

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