Toxicology of Antidepressant Drugs: Tricyclic Antidepressants

Animal Toxicity General Toxicology The LD 50 values for a number of tricyclic antidepressants, when administered to mice and rats in single oral or parenteral doses, are listed in Table Acute LD50 valuesa of some tricyclic antidepressants. Acute poisoning by tricyclic antidepressants usually leads to symptoms of central excitation followed at the higher and lethal dose levels by central inhibition. The symptomatology includes muscular weakness, twitching, stupor, respiratory disorders, ataxia, and tonic-clonic convulsions. Table Acute LD50 valuesa of some tricyclic antidepressants Imipramine Doxepine Nortriptyline Viloxazine Maprotiline Mouse i.v. p.o. 35 666 15- 20 148-178 26 327 60 1000 31 660- 900 Rat i.v. p.o. 22 625 13- 19 346-460 22 502 60-77 2000 38- 52 760-1050 a The values given are for LD50, single administration, in mg/kg body weight It is evident from Table Acute LD50 valuesa of some tricyclic antidepressants or from the reports of Pluviage () and of Ueki et al. () that no major differences in the acute toxicity of tricyclic antidepressants are apparent. Information on animal studies relating to the tolerance of tricyclic antidepressants 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 […]

Multimodality Treatment of Narcotic Addiction: Pharmacologic Therapies

Narcotic substitution The single therapy that has had the greatest impact on narcotic addiction appears to be methadone maintenance. Unlike drug-free approaches, it is acceptable to a large number of addicts (). It is medically safe, has minimal side effects and no toxicity when given to tolerant individuals, even for long periods of time (). Though the results of methadone treatment vary among programs, there is strong evidence that it provides a way to control narcotic addiction. Most patients who remain in methadone treatment have a marked decrease in heroin use, an increase in employment rates, and demonstrate improved personal adjustment (). At present there are approximately 80,000 people being treated with methadone in the United States (), but despite methadone’s wide applicability and effectiveness, it leaves much to be desired. It has been controversial since the beginning, and many aspects of methadone programs have been criticized (). One problem has been an inability to demonstrate that methadone treatment increases the long term cure rate for addiction. This is a disappointment, as many had hoped that the social rehabilitation obtained via methadone maintenance would lay the groundwork for successful Read more […]

Nicotine-Related Disorders

Nicotine-Related Disorders Tobacco addiction is the most preventable health problem in the United States. In 1993, approximately 60 million Americans smoked tobacco, and 400,000 deaths and $50 billion in direct medical-care expenditures were attributable to tobacco (Medical-Care Expenditures Attributable to Cigarette Smoking 1994). In the United States, approximately 30% of men and 26% of women smoke cigarettes. The percentage of young adults smoking cigarettes significantly increased between 1994 (35%) and 1998 (42%) (Office of Applied Studies 1999). Since 1965, the prevalence of cigarette smoking among adults in the United States has declined almost half. Cigarette smoking prevalence declined in the late 1970s, leveled off in the 1980s, and increased in the 1990s. Similar trends have occurred in other Western countries, but the prevalence of smoking has been increasing in Asia. Nicotine is a psychoactive substance with euphoric and positive reinforcement properties, similar to those of cocaine and opiates. The individual develops tolerance to nicotine and experiences significant withdrawal symptoms, including craving for tobacco, irritability, anxiety, difficulty concentrating, restlessness, decreased heart rate, Read more […]