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 […]

Medical Consequences of the Use of Cocaine and Other Stimulants

Once thought to be a benign, nonaddicting drug, cocaine now has well-recognized adverse effects. These adverse effects are manifested in nearly all organ systems of the body. It is important to realize that an organ system breakdown in classifying the adverse effects of cocaine is artificial and that multiple organs are often affected by similar mechanisms. In particular, the effects of cocaine on the cardiovascular system help to explain many of the effects on other organs throughout the body. In addition, certain adverse effects may be dependent on the route of administration, or dose of cocaine. The adverse effects of two other stimulant drugs, methamphetamine and phenylpropanolamine, will be summarized at the end of this post. History The history of cocaine use has been well described by a number of authors. Peruvian Indians have a long history of chewing coca leaves to achieve euphoria, combat fatigue, and increase stamina. Sigmund Freud used cocaine and also prescribed it as treatment for alcohol or opiate addiction. At one time, cocaine was a common ingredient in many commercial products, including teas and patent medicines. Although no longer the case, when first introduced, Coca-Cola was formulated using Read more […]

Drug-Drug Interactions of Cocaine

Alcohol Cocaine abusers have reported that alcohol prolongs the euphoriant properties of cocaine, while ameliorating the acutely unpleasant physical and psychological sequelae, primarily paranoia and agitation. It may also lessen the dysphoria associated with acute cocaine abstinence. It has also been proposed that concurrent alcohol abuse may be an integral part of cocaine abuse. The combination of cocaine with alcohol can cause enhanced hepatotoxicity and enhanced cardiotoxicity. Trauma in patients who use cocaine plus alcohol has been reported. Those who use cocaine plus alcohol are 3-5 times more likely to have homicidal ideation and plans; this is particularly prominent in patients with antisocial personality disorder. A large high school survey by the Centers for Disease Control and Prevention showed that illicit substance abuse, prevalence of weapon carrying, and physical fighting were higher among the adolescents who reported recent use of cocaine, marijuana, alcohol, and corticosteroids. Among 215 female homicide offenders, 70% had been regular drug users at some time before imprisonment. Alcohol, crack, and powdered cocaine were the drugs most likely to be related to these homicides. In a double-blind Read more […]

Amphetamines and the Law

Jimmy, 17, was riding his skateboard home on the sidewalk when suddenly, a few hundred feet ahead of him, six police cars rushed in and came to a stop surrounding a small house set back from the street. Jimmy stopped in amazement and watched as the police raced from their squad cars, banging on the door of the house and shouting at the top of their lungs. No one answered, and the police used a battering ram to break down the door and then rushed in. Jimmy and others who were passing by wanted to wait and see what happened next, but a local police officer chased everyone away, telling them to go home, the show was over. On the news that night, Jimmy heard that the house the police had raced into was a clandestine methamphetamine lab. The landlord had apparently grown suspicious and contacted the cops. Amphetamines that are abused may be diverted from legal sources, whether the drug is obtained from people with prescriptions for the drug because they have been diagnosed with attention-deficit/hyperactivity disorder or the drug is stolen from others. It may also be purchased from drug dealers or through an illicit site on the Internet. This is also the case for methylphenidate (Ritalin) that is abused. In contrast, most Read more […]

Drug Testing

Many organizations require individuals to undergo drug testing if they wish to be considered for a job and sometimes if they wish to stay on the job. In addition, individuals on probation for crimes often must undergo random drug tests and a failure — a positive drug test — is a violation of their probation and must be adjudicated in a court to determine if the individual should be given more probation or serve the jail or prison sentence that was foregone in lieu of probation. Parolees — individuals newly released from prison — often must also undergo random drug tests and a failure is grounds for return to prison. The Department of Health and Human Services recommends testing for five substances, including amphetamine, marijuana, cocaine, opiates, and phencyclidine (PCP, angel dust). Amphetamines can be tested for up to 48 hours after the drug was ingested. According to pharmacologist Karen E. Moeller and colleagues, many drugs can give a false reading for amphetamines, such as the antidepressants bupropion (Wellbutrin), desipramine (Norpramin), or fluoxetine (Prozac), as well as pseudoephedrine (an ingredient in many cough and cold remedies), the blood pressure medication labetalol (Normodyne), the Parkinsons Read more […]

Methamphetamine Misuse in Sociocultural Context

In the late twentieth and early twenty-first century United States, the production and misuse of methamphetamine was a growing and urgent public health, criminal justice, and child welfare problem affecting whole families and communities. Methamphetamine, also known as crank, crystal, glass, ice, speed, hillbilly crack, and yaaba, among other names, is a form of amphetamine with strong central nervous system effects. It gained popularity as a less expensive, more easily available and longer-lasting stimulant than cocaine. It is highly addictive, and regular use is associated with a variety of serious health and mental heath problems. Methamphetamine use also contributes to a rising rate of violent crime (Federal Bureau of Investigation). Initially limited to the western states and Hawaii, by the late twentieth century, methamphetamine misuse and production had spread throughout the United States, particularly into rural areas. At the time of our study, a combination of factors fueled the rapid growth of methamphetamine misuse and production in the rural Midwest. Rural poverty contributed to the despair that led some to escape through substance misuse and provided financial incentives for methamphetamine production, Read more […]

A Brief Overview of Cultural and Historical Contexts

The persistent and widespread problem of methamphetamine misuse is shaped not only by the biology of addiction, but by historical and cultural contexts. Methamphetamine is a methylated derivative of amphetamine, which was first synthesized in 1887, by a German chemist. It was first synthesized from ephedrine in 1893, by a Japanese chemist. In 1919, methamphetamine was synthesized in Japan via reduction of ephedrine using red phosphorous and iodine. The first medical use for methamphetamine was marketed by Smith-Kline-French in 1928 as Benzedrine, used in inhalers sold over-the-counter for treating asthma. (Benzedrine led to the street name of “bennies.”). Amphetamines were subsequently found to be effective in treating narcolepsy, nasal congestion, weight gain, and attention deficit disorder, and for providing extended periods of wakefulness (Bender & Cottington, 1942). In the 1930s and 1940s, amphetamines were prescribed for schizophrenia, morphine addiction, and low blood pressure. During World War II, the armies of Japan, Germany, and the United States all provided amphetamines to military personnel to fight fatigue and enhance performance. Amphetamines also were used in Japan to improve the productivity of civilian Read more […]

The U.S. Case

The interaction among the biology of addiction, market economics, and other aspects of cultural context also has been observed repeatedly in the United States. In the years after World War II, over-the-counter drugs containing methamphetamine were widely available in the United States. Amphetamine tablets were available without prescription until 1951, and amphetamine-containing inhalers were available over the counter until 1959- During the 1950s, persons in various walks of life including college students, long-haul truck drivers, individuals trying to lose weight, and athletes trying to enhance their performance used methamphetamine in legal tablet form for nonmedical purposes. Amphetamines were extremely popular with the general public as dieting and “pep” pills. Benzedrine was available without a prescription and was regarded as harmless. Famous musicians, film stars, and writers believed that their talents would be enhanced with amphetamine use. WH. Auden, James Agee, Graham Greene, Philip K. Dick, John-Paul Sarte, and Jack Kerouac all used stimulants to improve their stamina and literary output. As the use of the drugs expanded, so did the number of people who became addicted. The relaxed cultural attitude Read more […]

The Redemptive Community

Chris was released from jail. His friend and his friend’s wife came to court, and the judge released him to their custody. His parents also had shown up at court that day and were there to greet him when he was released from jail. He sat on the street curb and cried because he could not believe he was released. The next morning his friend took him over to another friend’s house. Before he did, he told Chris something he would never forget, that his recovery would be based on the type of community Chris created around himself. Chris visited their friend’s home every day the first week he was out of jail. Chris’s friend took him to numerous homes and have Chris tell his story of where he had been. Chris always experienced a sense of acceptance. While staying with his friend, Chris was responsible for things around the house, weeding, painting, and sheetrocking. Everything was on the right path. However, his change was not completely without incident. Shortly after he was released from jail and while he was still living with his friends, they had to leave town, and they left Chris in their home alone for several days. The freedom was a little too much for Chris to handle in these early stages of his recovery. Almost Read more […]

Diagnosis of Methamphetamine Use

The Symptomatic Patterns The clinical symptoms of methamphetamine use are primarily sympathomimetic in nature and are well documented in the literature on humans and animals. At low doses, methamphetamine causes generally positive effects, such as increased alertness, energy, euphoria, elevated self-confidence, persistent activity and work, increased talkativeness, increased sexual pleasure and hypersexuality, a sense of well-being, increased strength, and a loss of appetite. The ego-syntonic, pleasurable nature of methamphetamine intoxication explains its persistence as well as the addictive cycle that usually emerges. Table Impact of Changing Dose of Methamphetamine Across Several Dimensions depicts methamphetamine intoxication and its general effects on violence potential and reality testing. The increase in violence potential and the decrease in reality testing are associated with increasing dosages. Note that reality testing in homicides may be preserved under mild effects of methamphetamine, but that delusional homicides are the hallmark of severe impairment as a result of this drug. Higher doses of methamphetamine may result in negative symptoms such as disorganized or purposeless physical activity, tremors, Read more […]