Chapter 7. Depressants and Inhalants. Depressants & Inhalants. History: Before Barbiturates 10/1/2012
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1 Chapter 7 Depressants and Inhalants Depressants & Inhalants Depressants = drugs that slow activity in the central nervous system Include prescription drugs that treat anxiety (sedatives) and insomnia (hypnotics) As a group, also called sedative-hypnotics Alcohol is the most widely used depressant Benzodiazepines are the most widely prescribed depressants Inhalants: Volatile solvents and other compounds used for intoxicating purposes Have depressant effects similar to sedative-hypnotics History: Before Barbiturates Chloral hydrate ( knockout drops, Mickey Finn ) Synthesized in 1832; used clinically in 1870 Induces sleep in less than an hour Abuse 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; appeared in OTC drugs through the 1960s Can accumulate in the body and cause toxic effects 1
2 Barbiturates Discovery/Introduction 1903: Barbital (Veronal) became the first barbiturate to be used clinically Other popular barbiturates include phenobarbital, amobarbital and secobarbital Grouped on the basis of the time of onset and duration of activity Low-dose, long-acting forms used for daytime relief of anxiety Higher-dose, shorter-acting forms used to induce sleep Barbiturates Short-acting (pentobarbital, secobarbital) Time of onset: 15 minutes Duration of action: 2 to 3 hours Intermediate-acting (amobarbital, butabarbital) Time of onset: 30 minutes Duration of action: 5 to 6 hours Long-acting (mephobarbital, phenobarbital) Time of onset: 1 hour Duration of action: 8 hours or longer Sodium Pentathol Ultra-short acting barbiturate Administered intravenously Used as an anesthetic for brief surgical procedures Moves very rapidly into the brain Also used to make people relaxed and talkative (truth serum) Thiopental is currently the first of the three drugs administered for the death penalty 2
3 Methaqualone ( ludes or sopors ) 1965: Despite problems in other countries, methaqualone (Quaalude, Sopor) was introduced in the United States No initial monitoring- Package insert read Addiction potential not established Overprescribed; quickly became widely misused and abused 1973: Put on Schedule II 1985: Put on Schedule I Benzodiazepines 1960: Introduction of Librium (chlordiazepoxide), the first commercially marketed benzodiazepine Reduces anxiety without inducing sleep Much larger safety margin than barbiturates Physical dependence rare Overdose rare and usually only when combined with other depressants like alcohol 1970s: Valium (Diazepam), a lower-dose benzodiazepine, became for a time the best seller among all prescription drugs Benzodiazepines Dependence and overdose can occur; dosage and time course are critical factors Overdose deaths more likely 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 action Perhaps there are more differences among the barbiturates and among the benzodiazepines than there are between these two classes of drugs 3
4 Benzodiazepines: Rohypnol Rohypnol R2, rib, roofies, rope is a 1990s version of a Mickey Finn Produces profound intoxication when mixed with alcohol Reports surfaced of the drug being slipped into drinks and used as a date-rape drug Changes in laws and in the formulation of the pills should reduce its abuse Mechanism of Action Benzodiazepines and barbiturates Bond with brain receptors Enhance the normally inhibitory effects of GABA Nonbenzodiazepine hypnotics Selectively target the GABA-A receptor Seem to work better as sleeping pills than as antianxiety drugs Include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta) : Summary Anxiolytics As sleeping agents As anticonvulsants 4
5 Anxiolytics (anxiety-reducers) Sedatives often prescribed to reduce anxiety Four benzodiazepines (Xanax, Ativan, Klonopin, Valium) are among the top 100 most commonly prescribed medications in the United States Concerns about use of sedatives as anxiolytics: Some anxiety disorders respond to anxiolytics while others seem to be treated more effectively by antidepressants or behavior therapy Patients may take the drugs for long period Anxiolytics may be overprescribed Is a person taking the drug to treat a disorder or to feel better in a general way? As sleeping pills Taking a large enough dose of a hypnotic drug helps a person get to sleep more quickly Insomnia is a common complaint, although people sometimes overestimate its severity Today, fewer hypnotics are prescribed than in the past, and they are usually taken for only a few nights at a time 5
6 Concerns about use as sleeping agents Hypnotics may induce tolerance, dependence, rebound insomnia, and hangover effects After 1976, benzodiazepines displaced barbiturates in the sleeping-pill market Safety issues raised that Halcion produces adverse psychiatric reactions in some patients Nonbenzodiazepine hypnotics Zolpidem (Ambien) binds selectively to GABA-A receptors Rapid onset and short duration of action Concern about people driving while still under the influence (from not allowing 8 hours of sleep after taking drug) Eszopiclone (Lunesta) Approved for long-term use Falling Asleep Without Pills Have a regular sleep schedule When you go to bed, turn out the lights and relax Exercise regularly but not late in the evening Prepare a comfortable sleep environment in terms of temperature and noise Eat a light snack before bed Avoid tobacco use If you don t fall asleep within 30 minutes, get up and do something relaxing before trying to fall asleep again Do not nap during the day Avoid chronic use of sleeping pills 6
7 As anticonvulsants Barbiturates and benzodiazepines, in low doses or combined with other anticonvulsants, may be prescribed for seizure disorders (epilepsies) Potential problems Tolerance can make it difficult to find a dose that is effective but doesn t cause excessive drowsiness Abrupt withdrawal is likely to cause seizures Depressants: Causes for Concern Dependence Psychological dependence especially associated with short-acting barbiturates Physical dependence potentially life-threatening withdrawal syndrome linked to large doses of sedative-hypnotics Barbiturate withdrawal: anxiety, insomnia, tremulousness, weakness, nausea and vomiting, seizures, disorientation, agitation, delusions, and visual and auditory hallucinations Benzodiazepine withdrawal is less severe: anxiety, irritability, or insomnia Cross-dependence occurs among the barbiturates, the benzodiazepines, and alcohol Depressants: Causes for Concern Toxicity Behavioral Alcohol-like intoxication with impaired judgment and coordination Increased risk of injury while driving or engaging in other activities Additive effects if combined with alcohol Physiological Respiratory depression Especially dangerous if combined with alcohol 7
8 Depressants: Causes for Concern Patterns of abuse Most abuse associated with oral use of legally manufactured products Two types of typical abusers Older adults using prescription drug who develop tolerance and increase their dosage Younger people who obtain drugs to get high; may take high doses and/or mix with alcohol Inhalants: Introduction High-dose exposure causes intoxication, with effects similar to alcohol Products that can be abused by inhalation include gasoline, glue, paint, lighter fluid, spray cans, nail polish, correction fluid Inhalants: Examples Volatile solvents (petroleum, acetone, toluene) Paint, paint thinner and remover, nail polish remover, correction fluid, glues, cements Aerosols, propellants, gases (butane, propane) Spray paint, hair spray, lighters, whipped cream Anesthetics (nitrous oxide, ether) Current and former medical anesthetics Nitrites (isoamyl, isobutyl) Locker room, Rush, poppers 8
9 Inhalants: Gaseous Anesthetics Nitrous oxide ( laughing gas ) was first used in the early 1800s Still used for light anesthesia, especially by dentists Used as a propellant for commercial and home whipping-cream dispensers Inhalants: Nitrites Relaxes blood vessels which increases blood flow, but also lowers blood pressure. Used as a treatment for cyanide poisoning. With high doses there maybe lightheadedness or faintness Consumer Product Safety Commission has taken steps to remove poppers and other nitrites from the market since 1988 Inhalants: Volatile Solvents Overly informative news articles and education programs actually demonstrated how to abuse volatile solvents Abuse tends to occur as localized fads Most abusers are very young solvents are readily available and inexpensive 9
10 Inhalants: Dangers Kidney damage Brain damage Peripheral nerve damage Irritation of the respiratory tract Severe headache Death by suffocation Gamma Hydroxybutyric Acid Naturally-occurring chemical found in the brain and body Structurally similar to the inhibitory neurotransmitter GABA Causes CNS depression, especially when combined with alcohol Gamma Hydroxybutyric Acid Has been used as an anesthetic Behavioral effects similar to alcohol Lack of coordination and slurred speech Considered a date-rape drug Except for a specific formulation used to treat cataplexy, GHB is listed on Schedule I 10
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