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PubMedDate not supplied

Prescription drug abuse in Canada and the diversion of prescription drugs into the illicit drug market.

Prescription drug abuse has received considerable attention in media reports in recent years. The purpose of this article is to describe the Canadian situation and context with regards to prescription drug abuse and the diversion of psychotropic prescription drugs into the illicit drug market, with a focus on the need for more data and interventions. Canada ranks within the top 10% of countries in the use of benzodiazepines, opioid prescriptions and stimulants. There are many ways that prescription drugs are diverted into the illicit market and varied reasons for use and abuse. Prescription drug abuse is further related to a number of negative consequences, including overdose. While seniors and women have been the primary focus for research in Canada on prescription drug abuse, adolescents and young adults have received less attention. Systematic epidemiological data specifically on prescription drug abuse in the Canada context are lacking and are needed in order to more clearly understand the reasons for the phenomenon and to develop and implement appropriate interventions.

Adolescent↗
PubMed1989

[Diagnostic and therapeutic applications of intracavernous injection of vasoactive drugs in impotence. Defense for the use of facilitating drugs. Part I--Pharmacology, classification and complications of active drugs].

The article discusses drugs which promote erection when injected via the intracavernous (IC) route during consultation. The diagnostic and therapeutic applications in the treatment of impotence are discussed also. 25% of impotent patients noted an improvement after this treatment while 50% of patients suffering from impotence of psychological origin noted an improvement. Auto-injection is also discussed. IC treatment now seems justified in most cases which have not responded to traditional therapeutic approaches and this includes cases of psychological origin. Vasoactive drugs can be described as being inducers (use of these drugs induces a rigid erection, even in the presence of the doctor), facilitating drugs (which produce a rigid erection only if sexual stimulation is present also) and inhibitors (which stop the erection). The former group (which has papaverine as leader) produces a significant number of side effects, not least of these being priapism; there is a risk of lasting iatrogenic impotence which is not negligible. These risks are reduced considerably when one uses facilitating drugs which, although less powerful, suffice in treating a large proportion of cases of impotence. Papaverine can not be replaced as a diagnostic drug but facilitating drugs should be used first in therapy and inducers should be used only if these facilitating drugs have failed.

Adrenergic alpha-Antagonists↗
PubMed2000

Fully intermittent dosing with drugs for tuberculosis.

BACKGROUND: The number of people infected with tuberculosis continues to rise world-wide. Rifampicin-containing treatment regimens can achieve high cure rates. Intermittent drug treatment delivered in the community has the potential to improve adherence to treatment. OBJECTIVES: The objective of this review was to compare the effectiveness of rifampicin-containing short-course chemotherapy regimens, given two or three times a week, with similar regimens given daily in patients with pulmonary tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of any multi-drug regimen containing rifampicin in patients with confirmed pulmonary tuberculosis. Treatment had to be given up to three times a week for up to nine months, with any initial daily dosing period not more than one month, and was compared to daily dosing throughout for the same period. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: One trial involving 399 patients was included. The trial compared treatment three times per week with daily treatment for six months. There was no difference in cure rate (198 out of 199 people in the intermittent group compared to all 200 in the daily group), but 5 patients relapsed in the group receiving intermittent therapy compared to one in the group receiving the daily regimen. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the equivalence of effect between fully intermittent, rifampicin-containing short-course chemotherapy and similar daily therapy in patients with pulmonary tuberculosis. Larger randomised studies are required to establish the effectiveness of fully intermittent, short-course chemotherapy.

Antitubercular Agents↗
PubMed1979

Drug effects on the liver: a tabular compilation of drugs and drug-related hepatic diseases.

Geneic and chemical names of drugs and the possible adverse effects of these drugs on the human liver were tabulated. All drugs compiled in these tables have been approved by the Federal Drug Administration. They are currently available in the United States, and they are listed in the 1979 Physicians' Desk Reference. The tables include: (1) names of drugs that have caused a characteristic morphologic change, such as cholestatic lobular hepatitis; (2) morphologic diagnoses that have been documented after administration of each drug; and (3) references that can be matched to each drug and to its effects on the liver.

Chemical and Drug Induced Liver Injury↗
PubMed1999

AND and AND-OR drug mixture discriminations in rats: generalization to single drugs and drug mixtures.

RATIONALE: Studies of the discriminative stimulus effects of drug mixtures provide an approach to polydrug abuse and studies on single drugs with multiple effects. OBJECTIVE: This study was designed to investigate whether the use of the AND-OR procedure increases the specificity of drug mixture discriminations. METHODS: Rats were trained to discriminate a mixture of amphetamine (0.4 mg/kg) plus pentobarbitone (10 mg/kg) from saline (AND-discrimination, n = 8) or to discriminate the same mixture from its component drugs alone (AND-OR discrimination, n = 9). The studies used two-lever operant procedures with a tandem variable interval 1-min fixed ratio 10 schedule of food reinforcement. RESULTS: Under AND-discrimination conditions, there was partial generalization to nicotine and midazolam when each drug was administered singly, and there was no generalization to cocaine, caffeine or ethanol. With the AND-OR discrimination, there was no generalization to any of the preceding drugs administered singly. In "single substitution" tests, nicotine or midazolam was co-administered with the training doses of pentobarbitone and amphetamine, respectively; there was full generalization in the AND-discrimination and partial generalization under AND-OR conditions. Cocaine co-administered with pentobarbitone generalized fully under both procedures, but the dose of cocaine needed was much larger in the AND-OR than in the AND-discrimination. In "dual substitution" tests, mixtures of two novel substances were tested. Mixtures of either nicotine plus midazolam or caffeine plus ethanol produced very marked generalization under AND-discrimination conditions, but were without significant effect in the AND-OR procedure. Throughout the studies, in every instance where comparisons were made, generalization was greater or occurred at lower doses under AND- than under the AND-OR discrimination. CONCLUSIONS: The study yielded extensive evidence supporting the hypothesis that the AND-OR discrimination procedure increases the specificity of discriminations based on drug mixtures.

Animals↗
PubMed1992

Spectrum of drugs against atypical mycobacteria: how valid is the current practice of drug susceptibility testing and the choice of drugs?

The in vitro activity of 13 drugs against 552 clinical isolates of atypical mycobacteria representing 12 species was performed in 7H11 agar medium at the National Reference Laboratory for Mycobacteria, using the 1% proportion method. All the species tested were resistant to isoniazid and pyrazinamide. In general, clofazimine and D-cycloserine showed the widest spectrum of activity except in the case of Mycobactrium fortuitum and M. chelonei which were resistant to both drugs, and the M. szulgai and M. terrae complex which was resistant to D-cycloserine. The next broad-spectrum drug was ethionamide, followed by ansamycin, rifampin, capreomycin, kanamycin, streptomycin and ethambutol. Among the fluoroquinolones, both ciprofloxacin and ofloxacin were active against M. xenopi, M. gordonae and M. fortuitum whereas M. kansasii and M. gastri were sensitive to ofloxacin only. When the species were listed in respect of the number of drugs to which they were susceptible (less than 10% of resistant strains), they were classified as follows; 7/13 drugs for M. kansasii, M. gastri and M. xenopi; 6/13 for M. gordonae; 5/13 for M. marinum; 3/13 for M. szulgai; 2/13 for M. fortuitum; 1/13 for the M. avium, M. scrofulaceum, M. simiae, and M. terrae complex, and none of the 13 in the case of M. chelonei. These results are discussed in relation to the multiple drug resistance of atypical mycobacteria. We conclude that the critical concentrations of drugs established for M. tuberculosis are not appropriate for atypical mycobacteria.

Antitubercular Agents↗
PubMed1996

Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS).

Since the first description by Saltzstein in 1959, the denomination of drug-induced pseudolymphoma was used to describe two cutaneous adverse drug reactions with a histological picture mimicking malignant lymphoma. On the basis of clinical presentation, this term includes two different patterns: (1) hypersensitivity syndrome which begins acutely in the first 2 months after the initiation of the drug and associates fever, a severe skin disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (hypereosinophilia, atypical lymphocytes) and organ involvement such as hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis. The cutaneous histological pattern shows a lymphocytic infiltrate, sometimes mimicking a cutaneous lymphoma, and the mortality rate is about 10%. When organ involvement exists, corticosteroids are often prescribed with dramatic improvement. Relapses may occur. (2) drug-induced pseudolymphoma which has a more insidious beginning with nodules and infiltrated plaques appearing several weeks after the beginning of the drug without constitutional symptoms. A pseudolymphoma pattern is seen on cutaneous histological slides. Complete improvement is usual after drug withdrawal, but a delayed lymphoma is possible. To decrease the ambiguity of the denomination of hypersensitivity syndrome, we propose the term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).

Anticonvulsants↗
PubMed2006

Drug-drug interaction between pitavastatin and various drugs via OATP1B1.

It has already been demonstrated that pitavastatin, a novel potent HMG-coenzyme A reductase inhibitor, is taken up into human hepatocytes mainly by organic anion transporting polypeptide (OATP) 1B1. Because OATP2B1 is also localized in the basolateral membrane of human liver, we took two approaches to further confirm the minor contribution of OATP2B1 to the hepatic uptake of pitavastatin. Western blot analysis revealed that the ratio of the band density of OATP2B1 in human hepatocytes to that in our expression system is at least 6-fold lower compared with OATP1B1 and OATP1B3. The uptake of pitavastatin in human hepatocytes could be inhibited by both estrone-3-sulfate (OATP1B1/OATP2B1 inhibitor) and estradiol-17beta-D-glucuronide (OATP1B1/OATP1B3 inhibitor). These results further supported the idea that OATP1B1 is a predominant transporter for the hepatic uptake of pitavastatin. Then, to explore the possibility of OATP1B1-mediated drug-drug interaction, we checked the inhibitory effects of various drugs on the pitavastatin uptake in OATP1B1-expressing cells and evaluated whether the in vitro inhibition was clinically significant or not. As we previously reported, we used the methodology for estimating the maximum unbound concentration of inhibitors at the inlet to the liver (I(u,in,max)). Judging from I(u,in,max) and inhibition constant (K(i)) for OATP1B1, several drugs (especially cyclosporin A, rifampicin, rifamycin SV, clarithromycin, and indinavir) have potentials for interacting with OATP1B1-mediated uptake of pitavastatin. The in vitro experiments could support the clinically observed drug-drug interaction between pitavastatin and cyclosporin A. These results suggest that we should pay attention to the concomitant use of some drugs with pitavastatin.

Cell Line↗
PubMed2004

Drug-drug interactions between antiarrhythmic drugs in chick embryos.

The drug-drug interactions between antiarrhythmic drugs were studied in chick embryos. Fertilized eggs of White Leghorns were incubated and investigated. Procainamide or flecainide with and without propranolol was injected into the air sac of a fertilized egg. Electrocardiograms (ECGs) were recorded 0 to 60 min after the injection. After each drug injection alone, the heart rate was not different compared with the control. However, the heart rate was significantly decreased by combinations of procainamide and propranolol or flecainide and propranolol. In addition, arrhythmia was produced in combination with propranolol. These findings indicate that the drug-drug interactions between antiarrhythmic drugs have a marked influence on the heart rate in chick embryos.

Animals↗
PubMed1988

Familial, interpersonal, and intrapersonal correlates of drug use: a longitudinal comparison of adolescents in treatment, drug-using adolescents not in treatment, and non-drug-using adolescents.

This study examined familial, interpersonal, and intrapersonal factors associated with adolescent drug use from both developmental and etiological perspectives. Retrospective case-control and prospective longitudinal designs were used. A multivariate analysis of variance with repeated measures design was conducted to examine changes over time and differences between groups of adolescents in treatment for alcohol and drug problems, drug-using adolescents not in treatment, and non-drug-using adolescents, on 16 measures of familial, interpersonal, and intrapersonal variables. Significant differences were found between adolescents using drugs (clinical or nonclinical) and those not using drugs and alcohol. No differences were found in any of the variables between clinical adolescents and those using drugs but not in treatment.

Adolescent↗
PubMed1991

[Electropharmacological test with class-I C drugs in paroxysmal supraventricular re-entrant tachycardia: is a negative result with a drug predictive of the ineffectiveness of other drugs of the same class?].

UNLABELLED: Propafenone and flecainide, both I C class drugs, are first choice in the treatment of paroxysmal supraventricular reciprocating tachycardia. The aim of this study was to check whether a negative or paradoxical electropharmacological test with one of the two drugs was predictive of an equally negative or paradoxical test with the other drug. Thirty patients with disabling paroxysmal supraventricular reciprocating tachycardia, 16 M, 14 F, mean age 30.6 +/- 16 years, were studied with serial electropharmacological tests using esophageal approach. The reentry circuit was sustained by an anomalous pathway in 25 patients (83.5%) whereas it was idionodal in the other 5 (16.5%). Propafenone was tested in 13 patients (43.5%, group A) after flecainide had resulted negative or paradoxical in the first test. In 17 patients (56.5%, group B) flecainide was tested after propafenone had resulted negative or paradoxical. The second drug tested was also ineffective in 14 of the 30 patients (group A + group B) while it had positive results in 16 patients. Specifically, propafenone was positive in 6 of the 13 patients (group A) in whom flecainide had been negative, and flecainide was positive in 10 of the 17 patients (group B) with acute negative or paradoxical propafenone test. These "acute" results were confirmed in steady-state with esophageal study and in the follow-up (21.9 +/- 9.3 months). CONCLUSIONS: 53.5% of the patients who are "non responders" to the electropharmacological test with one of the two drugs (propafenone or flecainide) may be "responders" to the other drug. Thus the ineffectiveness of one of the two drugs is not predictive of ineffectiveness of the other.

Adolescent↗
PubMedDate not supplied

Review of drug abuse and measures to reduce the illicit demand for drugs by region. Division of Narcotic Drugs of the United Nations Secretariat.

This article, which was prepared on the basis of two documents (E/CN.7/1987/9 and E/1987/17-E/CN.7/1987/18) of the Commission on Narcotic Drugs, summarizes information on drug abuse and measures to reduce the illicit demand for drugs at the global level and by region. The Commission on Narcotic Drugs noted at its February 1987 session that the drug abuse situation continued to deteriorate in most parts of the world. The most striking feature of the problem was the escalation of heroin and cocaine abuse, but the abuse of other substances also continued to spread. The injection of drugs had contributed significantly to the increasing spread of acquired immunodeficiency syndrome (AIDS) and hepatitis B. The age of first users was falling from adolescence to preadolescence and even earlier. Young users were experimenting with a variety of substances, most often with those that were easy to obtain. In most countries, drug abuse had spread to all social strata. The majority of abusers were males, but the proportion of female abusers was growing.

Adolescent↗
PubMed1988

Monitoring of drug-drug and drug-food interactions.

A program for detecting and preventing potentially serious drug-drug and drug-food interactions is described. Two clinical pharmacists developed drug interaction alert (DIA) cards for each potential interaction to be monitored. The cards contain information about the proposed mechanism and potential result of the interaction, as well as information about how to monitor or circumvent the interaction. Staff pharmacists check for the occurrence of potential interactions daily as they verify the filling of the patient-medication cassettes; a poster of all the interactions that are included in the program is posted in each satellite pharmacy to serve as a quick reference for the pharmacists. When a pharmacist detects a potential interaction, he or she completes a DIA card and places it in the medication cassette drawer (if the notice is directed to the nurse) or on the front of the patient's chart (if the notice is directed to the physician). The program was introduced to hospital personnel through inservice education programs and departmental newsletters. The results of a quality assurance review indicated that 95 of 279 (34%) cards dispensed to nurses and 40 of 49 (82%) cards dispensed to physicians resulted in some form of action. The program to detect and prevent potentially serious drug-drug and drug-food interactions has been successful.

District of Columbia↗
PubMed2006

Liposomal drugs dispersed in hydrogels. Effect of liposome, drug and gel properties on drug release kinetics.

Release of calcein and griseofulvin (GRF) from control (gels in which solutes are dissolved in) and liposomal gels was studied using agarose-assisted immobilization as a technique to separate gels from drug-receptor compartments. Liposomes composed of phosphatidylcholine (PC) or distearoyl-glycero-PC and cholesterol (DSPC/Chol), and incorporating calcein or GRF were prepared by thin film hydration. After cleaning the liposomes they were dispersed in different hydrogels (carbopol 974 [1, 1.5 or 2% (w/w)], hydroxylethyl-cellulose (HEC) [4% (w/w)], or a mixture of the two), and release of calcein or GRF was followed by fluorescence or photometric technique, respectively. Results show that calcein release from liposomal gels is slower compared to control gels, and can be further retarded by using rigid-membrane liposomes (faster release from PC-liposome compared to DSPC/Chol-liposome gels). Additionally, calcein release is not affected by the lipid amount loaded (in the range from 2 to 8 mg/ml), therefore solute loading can be controlled according to needs. Oppositely, GRF release from liposomal gels is determined by drug loading. At high drug loading levels (compared to GRF aqueous solubility), GRF is released with constant rate from liposomal gels irrespective of liposome type (PC or DSPC/Chol). Thereby, for amphiphilic/lipophilic drugs, drug properties (solubility, log P) determine the system behavior. Calcein and GRF release from control carbopol gels is faster compared to HEC and mixture gels. The same is true for calcein in liposomal gels. Carbopol gel rheological properties were found to be significantly different (compared to the other gels), implying that these characteristics are important for drug diffusion from gels.

Drug Carriers↗
PubMed2000

[Drug advertising--users want information. Report of telephone survey conducted by North-Rhine Westphalia Public Health Service on the topic of drug advertising and drug information for users].

In Germany, drug advertising of non-prescription drugs is a controversial subject. On the one hand, consumer organisations plead for placing a ban on advertising or at least to offer a detailed description of medical risks in respect of protection. On the other hand, the pharmaceutical industry is keen on liberalizing the specific advertising law for drugs. A representative telephone survey among the population of North Rhine-Westphalia was conducted in April and May 1999. It showed consumer interest in advertising, the value of information on risks, the institution with maximum credibility in drug information for consumers, the importance of the now obligatory sentence after every advertisement: Regarding risks and side effects read the leaflet in the package and ask your physician or pharmacist, and to what extend the consumer would take advice from independent experts over the telephone about drugs. It was found that, in particular women, about 30% are occasionally interested in advertising, younger people are more open-minded about advertising than older people; and that doctors and pharmacists have the most credibility and are consulted for further information. It was also found that more than 80% of the population demanded precise information on the side effects of drugs. One-third of the consumers declared that the obligatory sentence (see above) led to greater demand for information from doctors or to read attentively the instruction leaflet. Nevertheless, there is a need for more information from more than half of the consumers, who would take advantage of an independent advice centre if this should exist.

Adult↗
PubMed2005

Drug interactions between lamotrigine and psychoactive drugs: evidence from a therapeutic drug monitoring service.

We present a systematic study on the interaction potential of lamotrigine, with focus on psychoactive drugs. A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 1733 serum samples from 829 patients (530 women, 299 men) suitable for statistical analysis. Main results for the whole study population were (median; interquartile range in parentheses): dose, 200 (100-300) mg; serum concentration, 2.97 (1.82-4.74) microg/mL; Lamotrigine serum concentration-to-dose ratio (LTG-CDR), 14.8 (9.9-24.6) (ng/mL)/(mg/d). A linear mixed model, allowing multiple observations from the same patient, was used to identify and quantitate the effect of factors influencing the LTG-CDR. In addition to age and gender, a total of 35 different comedications (25 drugs used in psychiatry as well as 10 other drugs) were evaluated. With women younger than 70 years as the reference group, factors found to lower the LTG-CDR significantly were: male gender and comedication with carbamazepine, ethinylestradiol, fluoxetine, lithium, phenytoin, phenobarbital, or topiramate. Factors associated with a significantly higher LTG-CDR were: age > or =70 years, and cotreatment with valproate. No antidepressants other than fluoxetine and none of the antipsychotic drugs included were associated with an altered LTG-CDR. Concerning pharmacokinetic drug interactions, we conclude that lamotrigine can be safely combined with most psychotropic drugs.

Adolescent↗
PubMed2004

Legal implications of pharmacogenomics regarding drug trials, drug labeling, and genetic testing for drug prescription: an international approach.

Pharmacogenomics applies genomic technology to discover and develop drugs as well as to treat patients more effectively. This article addresses legal questions raised by pharmacogenomics, from drug development to drug use. Part II defines pharmacogenomics in further detail and explains the use of pharmacogenomics in drug development. Part III identifies potential legal questions raised by this approach to drug development and delivery. Parts IV to VIII offer possible solutions to these potential problems, analyzing the law in both the United States and the European Union (EU).

Clinical Trials as Topic↗