Toxicology of Antidepressant Drugs

As many pharmacodynamic effects carry over from animals to man, many toxic effects may also be predicted from observations made in animals. However, some important toxic effects are not predictable from animal studies (WHO, 1966) and this limitation may apply particularly to drugs acting on the central nervous system, such as the antidepressants. Nevertheless, the recognition of species differences and similarities in responses is considered as an important means of predicting toxic effects in man. In the following, some degree of correlation is attempted by the comparison, whenever feasible, between toxicity in laboratory animals and adverse effects described in man, particularly in cases of acute intoxication. However, due to the differing amount of data that was available on various drugs and the widely varying experimental conditions employed, such a comparison may not always prove to be reliable. The following review has been restricted to antidepressants in clinical use and, as far as evidence was available from the literature, concentrated on two main categories of antidepressants, the monoamine oxidase (MAO) inhibitors and the tricyclics. The lithium salts are considered in a separate chapter of this volume. Read more […]

A Point of View Concerning Treatment Approaches with Narcotic Antagonists

When narcotic antagonists were first introduced into the treatment of drug addiction, patients were placed on the medication without regard to selection criteria and assessments of “successes” or “failures” were made only on the basis of their retention in the program. Since that time, however, our evaluation criteria have become more refined and we have begun to look at more complex questions such as: Are these compounds “helpful” and if so, “for whom” and by what treatment techniques can we augment their usefulness? A salient aspect of our naltrexone studies, for example, is addressed to the question of “for whom?” Hopefully when our data analysis is completed, it will contribute to either affirming or negating the conceptual model that we have formulated to aid us in the differential diagnosis and treatment of opiate dependent individuals. For my presentation today I have chosen to share with you some aspects of our point of view concerning treatment approaches based on our clinical experience. As investigators, we are all committed to the rigors of science with its demand for carefully controlled data. However, I am not addressing myself to specific research data, but rather to some issues concerning the application Read more […]

Adverse Effects of Cocaine Abuse

Specific, consequences of cocaine abuse on health and psycho-social functioning were assessed in 55 cocaine-abusing subjects who called a telephone “helpline.” Results showed a high incidence and wide range of adverse consequences including: (a) impairment of job functioning, interpersonal relationships, and financial status; (b) disturbances of mood and cognitive functioning; (c) psychiatric symptoms of depression, paranoia, and increased suicidal/violent tendencies; and (d) physical symptoms of exhaustion, weight loss, sleep problems, and seizures. Cocaine-related automobile accidents, suicide attempts, and violent acts, including a cocaine-related homicide, were also reported. Intranasal users reported no fewer and no less severe adverse consequences than free-base smokers or intravenous users. Our findings challenge popular notions that cocaine is a benign “recreational” drug and that the intranasal route of administration guarantees protection against addictive patterns of use and adverse effects. Introduction Cocaine use has escalated to epidemic proportions in the U.S. in recent years. Nationwide surveys estimate that over 22 million American have used cocaine and the numbers continue to soar at an alarming Read more […]

Benzodiazepines in the Treatment of Alcoholism

This post comprises three sections that cover the main aspects of benzodiazepines and alcohol: (1) the basic pharmacology of benzodiazepines; (2) use of benzodiazepines in the treatment of withdrawal; and (3) the use of benzodiazepines in treating alcoholics. The basic studies suggest that a major site of action of alcohol may be the GABA/benzodiazepine receptor complex and that compensatory alterations in this complex may underly withdrawal. In the section on alcohol withdrawal, interactions between the GABA/benzodiazepine receptor complex, sympathetic nervous system, and hypothalamic-pituitary-adrenal axis are discussed. Use of benzodiazepines in the treatment of the alcohol withdrawal syndrome are reviewed, including the possibility that the benzodiazepines may prevent withdrawal-induced “kindling”. Lastly, we review indications for, and efficacy of, benzodiazepines in long-term treatment of patients with alcoholism. Benzodiazepines are not indicated for the treatment of alcoholism. Furthermore, they have very few indications in alcoholics and their dependency-producing potency has to be appreciated when they are used in patients with alcoholism. The benzodiazepines () are a group of compounds that were first Read more […]

Drug Impairment Reviews: Opiates and Minor Tranquilizers

STUDY: Gordon, N.B. Reaction Times of Methadone-Treated Heroin Addicts. Psychopharmacologia, 16:337-344. 1970. Site: Rockefeller University and Yeshiva University, New York City, New York. Subjects: The subjects were divided into six groups. Groups 1 and 3 both had been maintained for at least 1 year on methadone for the treatment of heroin addiction. Group 1 had 18 males whose average age was 32.5 years; group 3 had 9 females whose average age was 33.5 years. Group 2 consisted of 20 unpaid male volunteers who did not use drugs; they averaged 32.5 years. The participants in groups 4 and 5 had recently withdrawn from narcotic drugs. The 20 males in group 4 averaged 31.5 years and had withdrawn 14 days earlier. The 19 males in group 5 averaged 30 years and had withdrawn 4 days earlier. Group 6 consisted of 9 females whose average age was 23 years. They were paid volunteers from the nonprofessional hospital staff, and did not use drugs. Method: Measurements were taken under controlled laboratory conditions; urines were tested (details were not given) for drugs to assure conformity to group. Variations of reaction time were tested in a button-pressing situation: (a) simple reaction time (one of six stimuli); (b) Read more […]

Effect of Treatment With Diazenam or Lithium and Alcohol on Psychomotor Skills Related to Driving

STUDY: Linnoila, M., I. Saario, and M. Maki. Effect of Treatment With Diazenam or Lithium and Alcohol on Psychomotor Skills Related to Driving: European J. of Clinical Pharm., 7:337-342. 1974. Site: Department of Pharmacology, University of Helsinki, Helsinki, Finland. Subjects: Twenty male students, 20 to 23 years old, volunteered. All used alcohol occasionally, none was obese, took drugs, or had any psychiatric disorders. Method: The double-blind, crossover, 2-week studies under controlled laboratory conditions measured the subacute effects of diazepam alone and in combination with alcohol, and those of lithium alone and in combination with alcohol. The test groups were coded as follows: Placebo drug, placebo drink P group Diazepam, placebo drink D group Lithium, placebo drink L group Placebo drug, alcohol A5 group Diazepam, alcohol DA5 group Lithium, alcohol LA5 group Testing took place on 7th and 14th days of the treatments. Effects of learning were excluded by allocating subjects at random according to Latin square design. Subjects were trained on apparatus used before the experiments. Each testing period consisted of three sets of tests 30, 90, and 150 minutes Read more […]

Cocaine Abuse: A Review of Current and Experimental Treatments

Cocaine abuse is a recently revived drug problem that is again generating great popular concern. Unfortunately, scientific evaluation of cocaine abuse treatment has been surprisingly sparse kind no consensus exists regarding optimal treatment strategies. This review summarizes current treatment issues and regimens. as well as preliminary data on new, approaches to cocaine abuse treatment. Since this chapter will deal with treatment of the cocaine abuser, it is important from the outset to define what is meant by that term. Although in some settings any use of illegal drugs equals abuse such a definition is more legal than medical and will not he used here. Instead the definition of drug abuse found elsewhere in the field will be employed namely…“the nonprescription use of psychoactive chemicals by an individual to alter his her psychological state in a situation in which the individual or society incurs some harm” (). The great majority of cocaine users applying for treatment fit into this definition. The most common exception is the individual who defines his use as recreational controlled and nonharmful but is brought to treatment by another (e.g. spouse, parent), while the significant other views the cocaine Read more […]

Cocaine abuse treatment strategies

Strategies devised to treat cocaine abuse have existed since its intractable lure for some first became obvious almost a century ago. During this period no generally accepted or successful treatment has emerged. Chronic cocaine abuse has been assumed to cause no physiologic withdrawal state on discontinuation because of insufficient evidence for an abstinence syndrome of major physiological changes like the classic sort characterizing sedative or opiate withdrawal (). Cocaine abuse has thus been assumed to be a “psychological dependence” rather than one involving neurophysiological adaptations, and currently used treatments consist of psychological strategies aimed at modifying addictive behaviors. Issues related to current psychological strategies will be discussed first, followed by a summary of evidence indicating cocaine abuse may cause neuroadaptation. The latter includes a review of pharmacological strategies, aimed at reversal of such adaptation, which may hold future potential as adjuncts in cocaine abuse treatment. Cocaine abuse treatment strategies: Current treatments Potential New Directions in Treatment Despite the past assumption that cocaine abuse is a “psychological addiction,” it is plausible Read more […]

Treatment of Behavioral and Psychiatric Problems Associated With Opiate Dependence

Diverse problems and challenges confront the staff members of programs/clinics intended to treat individuals with histories of opiate use and associated problems. The clinic sponsored and staffed by the Philadelphia Veterans Administration Medical Center and University of Pennsylvania provides numerous examples of the merits and problems of such treatment programs. The clinic’s patient population over the past decade has varied from two to four hundred patients. A range of services is provided along with pharmacological interventions including opiate-specific treatments such as methadone, LAAM, naltrexone, and a variety of psychotherapeutic agents administered in treatment of diverse presenting disorders. It should be noted that the clinic differs in some respects from “standard” clinics insofar as it includes numerous associated ongoing basic and applied research projects. There may therefore be more options and staff available from time to time but there may also be considerable variability uncharacteristic of other clinics. In any case the clinic appears to have many of the problems reported to prevail in other nonresearch clinics. It can therefore be used as a reference in the sorts of issues which do arise. Patients Read more […]

Drug-Drug Interactions of Amphetamines

Adrenergic neuron blocking drugs Amphetamines and other stimulatory anorectic agents, apart from fenfluramine, would be expected to impair the hypotensive effects of adrenergic neuron blocking drugs such as guanethidine. Not only do they release noradrenaline from stores in adrenergic neurons and block the reuptake of released noradrenaline into the neuron, but they also impair re-entry of the antihypertensive drugs. Alcohol Alcohol increases blood concentrations of amphetamines. Barbiturates Barbiturates can enhance amfetamine hyperactivity. Benzodiazepines Benzodiazepines can enhance amfetamine hyperactivity. Estradiol Preclinical studies (as well as anecdotal clinical reports) have shown that estrogens, through effects on the central nervous system, can influence behavioral responses to psychoactive drugs. In an unusual crossover study, the subjective and physiological effects of oral D-amfetamine 10 mg were assessed after pretreatment with estradiol. One group of healthy young women used estradiol patches (Estraderm TTS, total dose 0.8 mg), which raised plasma estradiol concentrations to about 750 pg/ml, and a control group used placebo patches. Most of the subjective and physiological effects of amfetamine Read more […]