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 […]

Tricyclic Antidepressants: Intoxication in Man

Effects of Acute Overdose Most of the numerous publications on acute intoxication with tricyclic antidepressants deal with attempted suicide in adults or with accidental selfpoisoning in children. Taking into account the difficulty in establishing the dose ingested – particularly in the case of children and of successful suicides – it is not surprising that it is difficult to predict the severity of an acute intoxication from the dose apparently taken. In children, fatalities have occurred with doses below 500 mg and survival with doses as high as approximately 1,700 mg. In adults, doses below 1,000 mg may already prove fatal but survival has been reported with doses up to 4,000 mg or higher (). In children, the critical dose level for imipramine seems to lie around 500 mg. Of a survey comprising 34 cases, only two children who had ingested less died whereas only three with larger doses survived (). Adults, who have ingested 1,000 – 2,000 mg still have a good chance of recovery whereas the risk of a fatality becomes far greater at levels of over 2,000 mg (). In relation to body weight, an LD50 value for imipramine has been determined for children at 40 – 50 mg/kg and for adults at 30 – 50 mg/ kg (). The symptoms 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 […]

Sedative-, Hypnotic-, and Anxiolytic-Related Disorders

Abuse and Dependence Sedative-hypnotic and alcohol intoxications are similar in symptoms and complications. Because sedative-hypnotic use is so frequent in hospitalized patients, the detection of sedative abuse can be difficult. Abuse rarely starts as a result of treatment of acute anxiety or insomnia in a hospitalized patient. The risk of sedative abuse in chronically medically ill outpatients is far greater. There are three major classes of benzodiazepine abusers: polysubstance abusers, pure sedative abusers, and therapeutic users who have lost control. Individuals prone to polysubstance abuse tend to use sedatives for their calming effects (i.e., to come down after use of a stimulant such as cocaine) and for their ability to decrease dysphoric affects, including anxiety, or to potentiate euphoric effects of other drug classes (e.g., benzodiazepines in combination with methadone to boost euphoria). Pure sedative abusers usually have significant underlying psychopathological conditions, and relapse is common. In a long-term follow-up study involving subjects with primary sedative-hypnotic dependence, 46% of the subjects continued to abuse drugs after in-hospital rehabilitation treatment. Anyone can develop physiological Read more […]