Pretreatment Drug Research Articles

Multiple substance use by alcoholics.

SummaryUse of drugs by 1,340 alcoholic clients of 17 New York alcoholism rehabilitation units was assessed for pre‐treatment and three and eight month post‐treatment periods. Drug use was reported by 44% of the clients before treatment and about 30% after treatment. Clients who were drinking greater amounts of ethanol before treatment tended to be drug users after treatment. Only a slight substitution of drug use for alcohol use was found from before to after treatment. Alcoholic substance users were more likely to be behaviourally and physiologically impaired than were alcohol users. Greater impairment for alcoholic and substance users was found both before and after treatment. Special categories of pre‐treatment drug use showed differential predictive relationship with alcohol use after treatment. Drug use by alcoholics was shown to be related to a number of dysfunctional behaviours indicating a need for improved assessment and treatment of substance users in alcoholism rehabilitation programmes.

Patterns of alcohol and drug use of adolescent students and adolescents in treatment.

use have become established in the lives of adolescents in many American communities. During the past decade patterns of use have undergone rapid and at times erratic changes (8-12), and their delineation has been hampered by practical constraints as well as methodological and theoretical differences and biases among investigators (13-15). An especially significant and continuing problem has been to identify adolescents who would benefit from programs of intervention and treatment. Studies (16-20) examining the pretreatment alcohol and drug use of adolescents enrolled in drug treatment programs suggest that their patterns of use may be more similar to those of adolescents in school populations than to those of adults receiving treatment for drug addiction or alcoholism. While alcohol is still the

Opiate antagonist-receptor interaction unchanged by acute or chronic opiate treatment

The apparent pA 2 of naloxone, a measure of the apparent receptor affinity for the antagonist, was estimated in naive rats, in rats after acute and various schedules of chronic morphine pretreatment, and in rats during abrupt withdrawal. The results were adjusted to compensate for the amount of pretreatment drug in the rat brains as, otherwise, such a drug could have inflated the apparent pA 2 values (see appendix). After this adjustment, a tendency of the apparent pA 2 values to be increased after chronic pretreatment disappeared. The apparent pA 2 of naloxone in acutely pretreated rats was also unchanged from that in naive rats, while the results in abruptly withdrawn rats were ambiguous. Thus, no change in the affinity of the antagonist for opiate receptors was found and theories suggesting that a conformational change takes place in the opiate receptors during the development of tolerance/dependence could not be supported.

Self-esteem patterns distinctive of groups of drug abusing and other dysfunctional adolescents.

Self-report measures on seven scales representing four broad processes of self-esteem were used to contrast three groups of drug abusers (pretreatment, in-treatment, and posttreatment), two other groups of institutionalized dysfunctional youth, and a "normal" public school sample, all from a population of White middle-class suburban adolescents. Multivariate analysis of covariance with adjustment for age and sex was used to compare the dysfunctional groups with the normal group. Discrimination analysis portrayed the dimensions of self-esteem separating all the groups. Pretreatment and in-treatment drug abusers had significantly lower scores on all seven measures of self-esteem; posttreatment abusers did not show these decrements, but reported greater ease in sharing feelings than normals did. The learning disabled adoles reported a lower sense of well being and greater ease in sharing feelings. These outcomes suggest that low self-esteem is not a general consequence of personal dysfunction per se, and may play a causal role in drug abuse.

PHARMACODYNAMIC STUDIES WITH A NEW PROGESTATIONAL SUBSTANCE ‐ ORG 2969 ‐ IN COMBINATION WITH ETHINYLOESTRADIOL

A new orally active progestin ORG 2969 (13-ethyl-ll-methylene-1819-dinor-17 alpha-pregn-4-en-20-yn-17-ol) was studied in combination with ethinyl estradiol (EE) to determine its ability to suppress ovulation and its effects on peripheral functions in human volunteers. .015 .03 .075 .1 and .125 mg of Org 2969 combined with .05 mg of EE; .05 mg of Org 2969 plus .03 mg of EE; or .15 mg of Org 2969 plus .02 mg of EE formulations were tested in 21-day cyclic regimens. In addition 2 normophasic regimens were tested. The 1st cycle in all dose groups served as control. Treatment cycles lasted up to 8 months. In 21 volunteers the 1st post-treatment cycle was also studied. During every cycle serum luteinizing hormone estradiol and follstimulating hormone were measured daily on Days 7-23 and serum progesterone on Days 14-23. Basal body temperature cervical mucus properties vaginal smears and endometrial biopsies were also observed routinely. Hormone determinations are presented in graphs; results suggested that all pretreatment cycles were ovulatory and all treatment cycles were anovulatory. In the majority of patients the 1st post-treatment cycle was ovulatory. Endometrial biopsies showed normal secretor pattern during pretreatment drug related changes during treatment and close to normal secretory pattern during post-treatment cycles. The other peripheral paramenters studied were also in accord with hormonal determinations.

Pretreatment Drug Use by Patients Entering Drug Treatment Programs during 1971–1973

Patterns of pretreatment drug abuse are described for 28,419 drug users who entered community-based treatment centers that participated in the national Drug Abuse Reporting Program during 1971–1973. Daily heroin use was reported by 60 per cent of the patients; one-third used daily heroin but no nonopioids, one-third used daily heroin and either cocaine, marihuana, or both, and the remainder used other nonopioids (particularly barbiturates) with daily heroin. Polydrug use (three or more nonopioids) was common among the patients who used no heroin or used it infrequently. As expected, polydrug use was most frequent among younger individuals, while daily heroin use (especially without other drugs) was increasingly prevalent among older age groups. Although alcohol use in at least moderate amounts was reported by only a third of the sample, it was most frequent among polydrug users, and was least frequent among daily users of heroin only. Within groups categorized by general patterns of illicit drug use, however, prevalence of alcohol use was higher among males than females, and increased with age.

The offset of morphine tolerance in rats and mice.

1. In rats and mice made tolerant to morphine by pretreatment with the drug, the shift to the right of the log dose/analgesic response line for in naive animals occurs without significant change in slope provided that sufficient time is allowed for elimination of pretreatment drug. 2. Responsiveness to the analgesic effects of morphine, given together with cycloheximide to prevent reinforcement of tolerance, was measured in rats (paw pressure method) and mice (hot plate method) at intervals during 1-23 days following cessation of a variety of regimens of tolerance-inducing drug treatments. 3. A biphasic pattern of recovery of responsiveness was observed, which was independent of the regimen or the drug (morphine, methadone or diamorphine) used to induce tolerance. Estimates of the rates of the first, fast phase are imprecise but the rate of the second phase of offset, from 4th day after cessation of pretreatment had, in rats, a mean half-time of 13.2 plus or minus 0.53 days-for all pretreatments combined, there being no significant differences between the various pretreatment regimens employed. In mice, similarly, a biphasic recovery of analgesic responsiveness was seen after morphine pretreatment, the mean half-time of the slower phase being 17.4 days. 4. Precipitation of an acute withdrawal syndrome in rats by naloxone HCl given 6 h after the final injection of a tolerance-inducing treatment with morphine did not affect the subsequent rate of recovery from tolerance. 5. During the period following a tolerance-inducing pretreatment with morphine in mice, the rate of attenuation of the naloxone-evoked jumping response was faster than the rate of offset of tolerance.

A study in Hong Kong to evaluate the role of pretreatment susceptibility tests in the selection of regimens of chemotherapy for pulmonary tuberculosis — Second report: A Hong Kong Tuberculosis Treatment Services/British Medical Research Council Investigation

The results up to 3 years have been presented for a controlled clinical trial in Hong Kong, undertaken to evaluate the role of pretreatment sensitivity tests to streptomycin, isoniazid and PAS in the selection of regimens of chemotherapy for patients with pulmonary tuberculosis, of whom 25 per cent had received previous chemotherapy for up to 4 months. The 3 policies studied at random were: • Policy A: Streptomycin, isoniazid and PAS, followed by isoniazid and PAS, ignoring the pretreatment sensitivity test results. • Policy B : The above standard chemotherapy, but introducing other drugs if the pretreatment strain was resistant in a standard indirect sensitivity test. • Policy C: A slide culture sensitivity test was performed before the start of treatment and appropriate regimens were selected in the light of the results. After exclusions, 527 patients remained in the analysis up to 3 years, 174 on Policy A, 182 on Policy B and 171 on Policy C, 32 per cent, 25 per cent and 33 per cent respectively having drug-resistant strains on standard indirect sensitivity testing on admission, the proportions resistant to 2 or all 3 drugs being 14 per cent, 10 per cent and 13 per cent. The proportions of patients with a favourable response throughout the 3 years were 88 per cent for Policy A, 87 per cent for Policy B and 90 per cent for Policy C, the findings for the patients with sensitive strains on admission being 97 per cent, 88 per cent and 91 per cent respectively and for patients with resistant strains on admission 69 per cent, 87 per cent and 88 per cent respectively. After changes of chemotherapy were made for the patients who failed on their first regimen, the final success rates achieved at 3 years were 95 per cent on Policy A, 95 per cent on Policy B and 96 per cent on Policy C, the results for the patients with sensitive strains on admission being 97 per cent, 95 per cent and 96 per cent respectively and for those with resistant strains 91 per cent, 93 per cent and 96 per cent respectively. On Policy A 24 of 31 patients with resistance to 1 drug had a favourable response throughout the 3 years, as did 12 of 17 with resistance to 2 drugs and 2 of 7 with resistance to all 3 drugs. After changes of chemotherapy the numbers with a favourable response increased to 29, 15 and 6 respectively. The failure rate in patients with fully sensitive organisms who were treated with the standard chemotherapy was 8.4 per cent, due to a failure to self-administer drugs in the continuation phase of chemotherapy. An estimated failure rate of 5.2 per cent resulted from the high (30 per cent) prevalence of pretreatment drug resistance in the patients on Policy A. More reserve drugs were prescribed and there was more drug toxicity in the patients on Policies B and C, which are also less simple to implement than Policy A and depend on the availability of accurate sensitivity testing. Two subsidiary investigations were also undertaken in the study. In one the patients were randomly allocated to 3 or 6 months of triple chemotherapy in the initial intensive phase. The results show no benefit from 6 months triple chemotherapy over 3 months. In the second the patients were randomly allocated to either 18 or 24 months treatment. The benefit obtained from 24 onths treatment was at most slight.

Effects of Δ 9-THC on food and water intake of deprivation experienced rats

Two groups of sixteen rats were placed on either a 23-hr food or water deprivation regimen for 150 days. For twelve days following this period of adaptation, half of the rats in each group were pretreated with an oral dose of 1.0 milligram Δ 9 -tetrahydrocannabinol per kilogram of body weight which was administered immediately after the daily 1-hr access to food and water. During the twelve-day treatment phase, all the rats were administered the drug dose two hours prior to the daily access period. Finally, the rats were returned to nondrug recovery conditions for eight days. The amount of food and water consumed during the 1-hr access period was increased by Δ 9 -tetrahydrocannabinol throughout the treatment phase, regardless of the rats' deprivation or pretreatment drug conditions.

Patterns of Multiple Drug Abuse: 1969-1971

Information concerning types and frequencies of pretreatment drug abuse, obtained by interview from 11,380 patients included in the first two years (June 1969-June 1971) of the NIMH-TCU Drug Abuse Reporting Program, were examined with respect to patterns of usage. Twenty-eight patterns were defined, involving various combinations of drugs used and frequencies of use. The results indicated that the most frequent drug-abuse pattern in this patient sample, accounting for 28% of the entire sample, was the daily or weekly use of heroin with no other drugs. The daily or weekly use of heroin with cocaine, with marihuana, and with both cocaine and marihuana were also frequently observed patterns, and combined with the heroin-only pattern, they characterized the majority of all the patients. The most common patterns reported by the remainder of the patients were of poly-drug use, typically involving marihuana, amphetamines, and barbiturates, as well as heroin and cocaine.

A controlled clinical trial of the role of thiacetazone-containing regimens in the treatment of pulmonary tuberculosis in Singapore

This report gives the findings over 1 year of an investigation into the role of thiacetazone-containing regimens in pulmonary tuberculosis in Singapore. Three regimens were allocated at random to newly-diagnosed patients with smear-positive disease. • SH/H Streptomycin 1 g. daily plus isoniazid 300 mg. daily for 6 months followed by isoniazid 300 mg. daily. • STH/TH Streptomycin 1 g. daily plus thiacetazone 150 mg. plus isoniazid 300 mg. daily for 6 months followed by thiacetazone 150 mg. plus isoniazid 300 mg. daily. • TH Thiacetazone 150 mg. plus isoniazid 300 mg. daily. A total of 114 SH/H, 94 STH/TH and 78 TH patients were eligible for the therapeutic comparison at 1 year. At 6 months 100% SH/H, 98% STH/TH and 76% TH patients were culture negative as were 97%, 99% and 69% respectively at 12 months. The proportions of patients with isoniazid-resistant strains at 12 months were 3% of the SH/H, 5% of the STH/TH and 27% of the TH regimen. There was practically no evidence of the emergence of streptomycin resistance in the SH/H or STH/TH regimens, but some evidence of lowered susceptibility to thiacetazone in the TH regimen. At 1 year 99% of the SH/H, 100%. of the STH/TH and 65% of the TH patients had a favourable bacteriological response to treatment. Age, extent of disease and thiacetazone sensitivity were related to response in the TH regimen. Side-effects were reported in 64% of the 131 SH/H, 91% of the 128 STH/TH and 72% of the 100 TH patients, a major interruption (of 7 days or more) occurring in 15%, 34% and 19% respectively and treatment was changed for side-effects in 1%, 9% and 4%. Rashes occurred in 27% of the SH/H, 57% of the STH/TH and 49% of the TH patients and dizziness or giddiness in 32%, 54% and 13% respectively. Most side-effects were reported in the first 3 months. The frequency of side-effects on the thiacetazone-containing regimens was similar in patients of Chinese, Malay and Indian origin. If all patients are considered at 1 year, assessing bacteriological response for patients who continued on the regimen and those with pretreatment drug resistance, but assessing patients who had treatment changed for toxicity as failures of the regimen, 6% of the SH/H, 8% of the STH/TH and 40% of the TH patients had an unfavourable response to treatment. It is concluded that neither of the thiacetazone-containing regimens has a role in the routine treatment of newly-diagnosed patients with pulmonary tuberculosis in Singapore, the STH/TH regimen because it is toxic, and the TH regimen because it is both therapeutically ineffective and toxic.

Treatment of patients with pulmonary tuberculosis classified according to the history of previous chemotherapy and without reference to pre-treatment drug sensitivity

Patients with pulmonary tuberculosis can be classified into groups according to the history of previous chemotherapy. One group includes patients who deny any previous treatment, those who admit to not more than 30 days treatment regardless of its quality, and those who admit to treatment of longer than 30 days but in whom the treatment has been of good quality. In such patients it is unnecessary to carry out sensitivity tests, for good results with an initially triple-drug regimen (streptomycin, isoniazid and PAS) can be achieved without them. In 106 patients in whom sensitivity tests were not done 100% sputum conversion on smear examination was obtained after five months. In a similar group of 103 with cultures reported sensitive to all three drugs 100% conversion was obtained after four months. In Rio de Janeiro 81% of 913 patients in this category treated by a simple standard regimen without sensitivity tests were classed as ‘bacteriologically favourable’ after one year. Relapse was rare -only 1·6% during a minimum of 22 years observation. Similar good results can also be obtained in underdeveloped areas, if the organization of treatment services is efficient. For instance, in an area of Bahia in which all the health centres could do smear examinations but few had x-ray facilities, 75% of 529 patients were classed after a year as `bacteriologically favourable' and only 7 % had defaulted from treatment.

Controlled clinical trial of 4-4 diisoamyloxythiocarbanilide in the treatment of pulmonary tuberculosis

A total of 100 Chinese patients suffering from open pulmonary tuberculosis were randomly allocated to treatment with either PAS and isoniazid or with 4-4 diisoamyloxythiocarbanilide (‘isoxyl’) and isoniazid. Twenty were excluded from further participation because of pretreatment drug resistance. Of the remaining 80 patients, one each from the 39 PH group and 41 IX group were withdrawn at the 16th week, the IX patient being withdrawn because of failure of treatment. There were no noticable toxic effects from treatment. After 24 weeks' treatment 71% of the PH group and 40% of the IX group had negative cultures. Isoniazid-resistance emerged in 7 of the 38 PH and in 20 of the 40 IX patients. Pretreatment resistance to ‘Isoxyl’ was reported in 37 of the 78 patients who completed the trial. This might well have had an effect on the results of treatment with ‘Isoxyl’ and isoniazid.