Chapter 10 - Sedatives

 Sedative-Hypnotics: calm us down and produce sleep  Antianxiety Drugs: tranquelizers

Acute Effects  From normal to coma and death  Low doses: relaxation; euphoria; disinhibition of cerebral cortex (like having a few drinks)  As dose levels increase: lower brain regions are affected  Therapeutic doses: sedated and drowsy; impairs motor performance

 Main use: was to treat insomnia; significantly depresses REM; REM rebound  With alcohol-synergistic effects  All barbs: agonists of GABA

Chronic Effects  Tolerance develops-may experience anxiety and insomnia at original dose  Both phramacodynamic and metabolic tolerance  Withdrawal: tremors, nausea & vomiting, sweating, general confusion, convulsions, hallucinations, fever, elevated heart rate  May be life-threatening-approx. 5% chance of death without med supervision

 Current medical uses: epileptic seizures; convulsions  Dependence potential: lab animals-self- administer at rates equal to coke  Use peaked in 1950s & 1960s  U. of Mich survey-hs seniors % lifetime; % lifetime; % within past year; % within past year

Nonbarbiturate Sedative-Hypnotics  Chloral hydrate-1832-a depressant used for treating insomnia  Not as great an effect on REM as barbs  Very irritating to stomach  Synergistic effects with alcohol  “Mickey Finn”-a few drops in glass of whiskey

 Methaqualone: Quaalude; Sopor 1965  1970s-recreational use spread  1984-Schedule I  Still available-underground labs; imported

Anxiety Disorders  Six major types: panic disorder, obsessive- compulsive disorder, post-traumatic stress disorder, specific phobias, social phobias, generalized anxiety disorder  First antianxiety drug-meprobamate (Miltown)  Became a household word  First drug in history to be marketed as an antianxiety drug; actually produces sedation; both physical and psych dependence; Schedule IV – very infrequently prescribed

Benzodiazepines

Acute Effects  Relatively slow absorption-effects more gradual than barbs (absorbed through small intestine; barbs through stomach)  Do not affect respiratory centers in medulla; times the normal dose won’t stop breathing  Dangerous with alcohol

 Elderly-slowed elimination-dangerous build- up: drug induced dimentia: confusion and loss of memory  All ages: drowsiness and poor coordination- driving is dangerous  Problems learning; can prevent brain from recording and adapting to new information  Amnesia-Rohypnol (roofies)-much more potent than valium-2 mg in drink

Chronic Effects  Tolerance to sedative effects  No tolerance to antianxiety effects at therapeutic doses  Withdrawal-high anxiety, insomnia, restlessness, agitation  Psychological dependence-the real problem

Effects on Brain

 Agonist of GABA  3 binding sites: sedative-hypnotics; barbs; benzodiazepines; benzodiazepines and alcohol  GABA attaches to binding site; if benzodiazepines are occupying the site; greater inhibition

 Receptors: primarily in limbic system and cerebral cortex  Limbic system: antianxiety action  Cerebral cortex: sedation

Drugs Designed Specifically to Induce Sleep  Ambien: 1993  Chemically unrelated to benzodiazepines; but act on a benzodiazepine receptor that induces sleep  Doesn’t reduce anxiety; little or no relaxation  Short half-life: 2 hours  Should be used 7-10 days  Lower abuse potential than benzos.

 Sleepwalking, binge eating, and driving without remembering  Lunesta: 2005  Also not a benzodiazepine but acts on receptors to induce sleep  Lower abuse potential than benzodiazepines

GHB  gamma –hydroxybutyrate  Odorless, colorless liquid  Europe: general anesthetic  Used by bodybuilders; sales banned in 1990  Still available by prescription-narcolepsy  Pharmacologists think GHB may be a neurotransmitter; synthesized in brain; has specific receptor sites; effects can be blocked by antagonists

 Produces relaxation, mild euphoria, then headache, nausea, drowsiness, loss of consciousness, seizures, coma, death  Not addictive at therapeutic doses; problems at higher doses  Routine tox screens in Ers-not set up to detect GHB; tell medical personnel if taken  Very dangerous with alcohol; additive; lower blood pressure and decrease blood oxygen

Tolerance and Withdrawal  very serious problem: users learn that you get a high like alcohol; sedation at higher doses  Use recreationally for euphoria; uses as sedative for falling asleep; may reach point where using every few hours, 24 hrs a day  Withdrawal: very severe

 Insomnia, anxiety, psychosis; like alcohol  Tremors, high heart rate, high blood pressure  Should be done under medical supervision