Finally, the limitations of the databases used should be acknowledged. The epidemiological data used in these studies have typically been gathered for other purposes. For example, ims collects data on total sales of drugs in Canada. Drugs sold are not necessarily ingested, thus drug utilization data provide only crude estimates of the extent of drug use and do not indicate the appropriateness of such use. Furthermore, the ddd is a technical unit of measurement used to permit comparisons which may not accurately reflect the average prescribed daily dose in Canada.
However, while benzodiazepine kinetics are among the factors influencing abuse, intrinsic pharmacological activity of a drug is probably as important. Recent work in the benzodiazepine receptor area has postulated the existence of multiple high-affinity receptors for these benzodiazepines, one mediating the anxiolytic effect and the other the sedative and muscle relaxant effects . Continue reading
Our data support the hypothesis that a drug’s kinetics partially determine drug abuse. At least two kinetic characteristics, when present together (rapid absorption and intermediate half-life) were associated with higher abuse of benzodiazepines. It is not surprising that absorption seems to play a more important role than lipophilicity in determining abuse potential since time to enter the systemic circulation is in the order of several minutes to hours for most benzodiazepines while time to enter the brain is only in the order of a few minutes at most . Thus, absorption of the drug is the rate-limiting step. It is interesting, however, to speculate on the influence ofmicrokinetics at the receptor level on the abuse liability ofthe benzodiazepines. Asynchrony between plasma concentrations and receptor effects has been described for several drugs . Certainly a better understanding of benzodiazepine microkineti cs at the recept or level would enable a more refined testing of the hypothesis that the rapid availability of the drug at the receptor level, rather than rapid absorption, is the factor that provides the optimal condition to encourage drug self-administration. buy flovent inhaler
The only other comparative study ofbenzodiazepine abuse was a German study which showed that 7% of all inpatients in a p sy chiatric ward met the World Health Organization criteria for drug abuse and dependence and 77% of them abused benzodiazepines; 30% abused only benzodiazepines and diazepam, bromazepam and lorazepam (in that order) were preferred. These data, however, were not corrected for availability of the drugs. Continue reading
Our data support experimental data in humans and animals suggesting that there is differential abuse of benzodiazepines among drug abusers. It shows that, accounting for availability and mar ket penetra tion, some ben zo diazepines (such as diazepam) are more likely to be abused than others (eg, flurazepam). Although alprazolam had the highest abuse risk in this study, the data for this drug should be cautiously interpreted since both the number of years on the market and the observed abuse of alprazolam were so low during this period. Also, kinetic factors, such as absorption and elimination rate, play a role in determining which benzodiazepine will be preferred by abusers. ventolin inhalers
A different picture of relative benzodiazepine abuse emerges when abuse data are adjusted for total market exposure and compared with expected abuse (Figure 2). A ratio of observed abuse to expected abuse of 1:1 indicates that proportion of abuse parallels proportion of use. Some benzodiazepines, such as diazepam, have ratios much higher than 1:1, while others have ratios much lower (eg, flurazepam). Continue reading
Benzodiazepine use data
Between 1978 and 1984, total benzodiazepine use was 248 ddd/ 1000 inhabitants/ day. Diazepam represented 38%ofto-taluse, followed by flurazepam (19%). Diazepam had been on the Canadian medications market for 21 years. In contrast, triazolam represented 10% of total use although it had been on the market for only six years (Table 1).
With the risk rankings of benzodiazepines with equivalently long half-life so that the benzodiazepines with intermediate half-life were given higher dependence risk ratings. Also, the authors wanted to explore the role of the dose on abuse liability and postulated that abuse behaviour would increase with dose. Before ranking, benzodiazepine dose was expressed as the recommended maximum daily dose relative to the affinity for the benzodiazepine receptor in order to control for differences in affinity and thus standardize the doses for the potencies of the cheap drugs.
The influence of three kinetic variables – absorption rate, lipid solubiltty and elimination half-tife – on abuse and dependence potential were tested as follows.
Absorption rate (expressed as time to peak plasma concentrations) was postulated to be inversely correlated to abuse risk. Therefore, absorption rates of different benzodiazepines were obtained from the literature and used to estimate the abuse risk rank for each drug from 1 (highest abuse risk) to 10 (lowest abuse risk). In cases where absorption rates differed among publications, the mean of all available absorption rates was used. For benzodiazepines that are pro-drugs(eg, clo-razepate, flurazepam), the rate of appearance of the main metabolite was used for the ranking. A specific example of how the ranking was done is shown in Figure 1. Buy Asthma Inhalers Online Continue reading
Benzodiazepine abuse data
Data on benzodiazepine and other drug use and abuse were systematically collected for all patients admitted into the Clinical Institute of the Addiction Research Foundation (arf) with the diagnosis of benzodiazepine abuse and dependence. The arf receives referrals from Toronto and suburbs. Demographic characteristics of patients including age and sex as well as data on drug(s) of abuse, including drug name(s), dose, frequency, duration, source and withdrawal symptoms, are systematically recorded on specially designed forms. All patients included in this database met the Diagnostic and Statistical Manual (dsm-iii-r) criteria of psychoactive substance dependence for benzodiazepines .