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Sedative-Hypnotics.docx

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Department
Psychology
Course Code
Psychology 2020A/B
Professor
Riley Hinson

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SEDATIVE-HYPNOTICS INTRODUCTION  Sedative-hypnotic: drug that depresses CNS activity, medical use of relieving anxiety & inducing sleep o Ameliorate effects of stress; escape feelings of discomfort, tension, anxiety, dysphoria  2-4% of population has had an anxiety disorder at one time  Anxiolytics: ideal anxiolytic alleviates stress w/o side effects, however most do o Side effects: depressed CNS (sedative action), induce sleep (soporific effect), dull awareness (hypnotic effect) o Alcohol: (ethanol) first common use as self-medication for anxiety; major component of “patent medicine” in late 1800s; not ideal- numerous side effects (physical dependence, liver disease, brain damage) EARLY SEDATIVE HYPNOTICS  Potassium bromide: calming & soothing effect o Popularity from mid 1800s-1900: treated epilepsy in 1857 because they believed it resulted from extreme masturbation- KBr is used to reduce sexual drive o Discontinued due to toxicity: bromide intoxication common due to its 12 day half-life and slow excretion by kidneys o Bromide intoxication: symptoms= impaired thought/memory, constipation, headache, dermatitis, drowsiness, irritability, delirium, hallucinations, mania, coma o “Bromoseltzer”: medication previously used as a hangover remedy  Chloral Hydrate: synthesized 1832, abused from late 1800s-present (ie: Marilyn Monroe, Anna Nicole Smith) o ‘Mickey Finn’ (knock-out drops): combined w/ alcohol; early version of date rape drug o Chloral hydrate is converted to active metabolite trichloroethanol in the body o Administration: syrup or capsule o **Sleep inducing drug (30 min onset of action; short duration) o Undesirable effects: gastric upset, flatulence, vomiting, nightmares, unsteady gait  Paraldehyde: used as sedative/anticonvulsive for 100+ yrs; control alcohol withdrawal/ agitated mental patients o Taste/ smell very bad (lungs produce unpleasant smell) o Addiction comes from initial exposure during alcoholism treatment; individuals prefer it to alcohol despite awful taste and odor o Causes little respiratory depression o Seldom used today: except rectal administration for seizures in young children (rarely used) BARBITURATES  Adolph von Baeyer (1864): synthesized parent compound for barbiturates from malonic acid (acid in apples) & urea (white, crystalline substance; chief component of blood; end product of protein metabolism): called Barbituric acid  Two theories on name origin… 1. Compound was 1 obtained from uric acid on St. Barbara Day 2. Named after Munich waitress who contributed her urine  Barbituric acid wasn’t effective, but produced hypnotic effects once modified  Fischer & Von Mering: completed 1 modification called diethylbarbituric acid; indicating 2 ethyl groups, 2H5, replaced hydrogen’s in position 5  Diethylbarbituric acid: 1. Generic name= Barbital 2. Trade name= Veronal (name chosen bc Von Mering was in Verona when he heard of it’s synthesis; also Verona is a town associated with peace and solace)  Barbital: very popular w/ sleep facilitations & had daytime anxiolytic properties; long onset; long duration of action o Known as barbitone in Britain (names end in –one instead of –al; but they are the same compounds!)  2500 different barbiturates have been synthesized today; 50 are currently marketed  the goal is to find compounds with shorter duration of action; therefore long acting barbiturates are unsuitable for insomnia treatment as user wakes up still drowsy  Barbiturates: today, are not drug of choice for anxiety/insomnia treatment o In past- managed epilepsy (acute/chronic) but other drugs have replaced barbiturates for this purpose o Sometimes given for severe head injury- protect brain during acute phase of trauma by decreasing neuronal activity o Classified according to speed of onset and duration of action which is influence by lipid solubility  High lipid solubility: readily get in/out of brain by diffusing down [ ] gradient; useful for sleep induction or emergency seizures  Low lipid solubility: don’t readily get in/out of brain; used in chronic anxiety/epilepsy  Long-acting barbiturates o Onset of 1 hr o Duration of 6 hrs o Prototypical compound: Phenobarital (luminal)-synthesized 1912  Available in tablets, capsules, liquid  Intermediate-acting barbiturates o Onset of 30 min o Duration of 4-6 hrs o Prototypical compound: Amobarital (amytal)-synthesized 1923 o Amytal= “truth serum”, although can’t guarantee info given is true as people who are under the influence may just be very talkative  1st use of term, ‘psychopharmacology’ in paper published by Thorner called “The Psycho-Pharmacology of Sodium Amytal”  Short-acting barbiturates o Onset of 15 min o Duration of 1-4 hrs o Common compounds: Pentobarbital (Nembutal), Secobarbital (Seconal)- both synthesized 1930  Ultra short-acting barbiturates o Onset of seconds o Duration of 5 min o Common compounds: Hexobarbital, Thiopental (Pentothal): introduced as intravenous anesthetics in 1930s  Barbiturate Abuse o Hygeia health magazine  1942 article: “1 250 000 000 doses a year”  1945 article: “Waco was a barbiturate hotspot”  Hygeia was the lay publication of American Medical Association with the intent of articles to advise barbiturate use only under Dr’s prescription o Collier’s magazine  1949 article: “Thrills pills can ruin you” o Barbiturates made illegal: which developed illegal market in late 1950s to early 1960s  In 1950s, became most widely abused drug because doctors were prescribing too easily in US  Abuse decline resulted by introduction of benzodiazepines  **Even after prescriptions declined, it is estimated 10 trillion doses of barbiturates produced annually in US during 1970s (enough for 40-50 doses for every man, woman, child in US) o Typical abuser: Caucasian female; 30-50 yrs; middle/upper class
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