PSYC 222 1st Edition Lecture 22Outline of Last Lecture • The return of Methamphetamine• Present day Methamphetamine abuse• Amphetamine Pharmacology• Absorption and Elmination• Beneficial Uses• Medical Uses• Concerns: Acute Toxicity• Concerns: Chronic ToxicityOutline of Current Lecture • Depressants and Inhalantsi. Depressants ii. Barbituratesiii. Meprobamateiv. Mechanism of actionv. Beneficial uses: Anxiolytics and Hypnoticsvi. Concerns: Anxiolytics and Hypnoticsvii. Dependance liabilityviii.Methaqualoneix. BenzodiazepinesCurrent Lecturei. A class of drugs that decrease CNS activity. Have a widespread effect in the brain. As a group, also called sedative-hypnotics. Sedatives treat anxiety. hypnotics treat insomnia. Widely used Depressants include: Alcohol, and Benzodiazepines (prescription).ii. History before barbiturates: Chloral Hydrate: aka "knockout drops", "Mickey finn". Synthesized in 1832. Used clinically in 1870. Induces sleep in less than one hour. Repeated use leads to gastric irritation. Paraldehyde: synthesized in 1829. Used clinically in 1882. Effective with a wide safety margin. Noxious taste and odor. Bromides: widely used as a sleep agent in patent medicines. Remained in OTC drugs through the 1960s. Accumulates in the body and cause toxic effects. Barbiturates: First introduced in 1903. So popular and useful that over 2500 examples were synthesized. Popular barbiturates included phenobarbital, amobarbital, and secobarbital. Grouped based on the time of onset and duration of activity. Short-acting and rapid onset used to induce sleep and often prescribed in high doses. Long acting and delayed onset used to reduce anxiety and often prescribed in low doses. Concerns about barbiturates: Overdose deaths are either intentional and accidental or cause by respiratory depression. Abuse dependence;reinforcing effects of a drug are related to the rapidity of onset of effects. Short acting drugs are more likely to lead to psychological dependence. Concerns led to search for safer medications. iii. Widely prescribed in the 1950s. Used as an anxiolytic. Likely barbiturates, can produce psychological and physical dependance.iv. Benzodiazepines and Barbiturates bind with recceptors on GABA receptor complex. Seperate binding site for barbiturates and benzodiazepines. Enhance the normally inhibitory effects of GABA. Nonbenzodiazepine Hypnotics is an entirely new class of drugs that may selectively bind to different sites on the receptor complex. v. Anxiolytics: Sedatives often prescribed to reduce anxiety. 4 Benzodiazepines are among the top 100 most commonly prescribed medications in the U.S; 1) Xanax 2) Ativan 3) Klonopin 4) Valium. Hypnotics: Sleeping pills. Sedatives at large enough doses decrease sleep onset time. About 1/3 of American adults report trouble sleeping. vi. Anxiolytics: Sedatives are not applicable for all anxiety disorders. Example: OCD or specific phobias. Most sedatives are not prescribed by psychiatrists. Hypnotics: Concerns include sleepwalking, sleep eating, and driving while in a semi- waking state. In2008, all hypnotic drugs were required to carry a safety label. Zolpidem- related ER visits more than tripled between 2005 and 2010.vii. Physiological dependence especially associated with short acting sedatives. Physcial dependence; withdrawl syndrome is similar to alcohol and potentially life threatning. Still available as a prescription drug. Largely replaced by benzodiazepines.viii.Other names: Brand name= Quaalude or Sopor. Slang name= "ludes" or "sopors" Despiteproblems in other countries, drug was introduced in the U.S 1965. Package insert read "Addiction potential not established". Physicians overprescribed, thinking the drug was asafe alternative to barbiturates. Widely misused and abused.ix. 1st introduction in 1960. Chlordiazepoxide (librium), 1st commcercially marketed benzodiazepine. Reduces anxiety without inducing sleep. Much larger saftey margin than barbiturates. Physical dependence was rare. Overdose was rare. 1970s: Diazepam (Valium) became the best seller among all prescription drugs. Dependence and overdosecan occur. Dose level and time course are critical factors. Overdose deaths are more liekly for drugs sold in higher doses. Psychological dependence more likely with drugs that have a rapid onset of effects. Physical dependence more likely with drugs that have a short duration of