Chapter 10 - SedativesChapter 10 - Sedatives

Sedative-Hypnotics: calm us down and Sedative-Hypnotics: calm us down and produce sleepproduce sleep

Antianxiety Drugs: tranquelizersAntianxiety Drugs: tranquelizers

Acute EffectsAcute Effects

From normal to coma and deathFrom normal to coma and death Low doses: relaxation; euphoria; Low doses: relaxation; euphoria;

disinhibition of cerebral cortex (like having a disinhibition of cerebral cortex (like having a few drinks)few drinks)

As dose levels increase: lower brain regions As dose levels increase: lower brain regions are affectedare affected

Therapeutic doses: sedated and drowsy; Therapeutic doses: sedated and drowsy; impairs motor performanceimpairs motor performance

Main use: was to treat insomnia; Main use: was to treat insomnia; significantly depresses REM; REM reboundsignificantly depresses REM; REM rebound

With alcohol-synergistic effectsWith alcohol-synergistic effects All barbs: agonists of GABAAll barbs: agonists of GABA

Chronic EffectsChronic Effects

Tolerance develops-may experience anxiety Tolerance develops-may experience anxiety and insomnia at original doseand insomnia at original dose

Both phramacodynamic and metabolic Both phramacodynamic and metabolic tolerancetolerance

Withdrawal: tremors, nausea & vomiting, Withdrawal: tremors, nausea & vomiting, sweating, general confusion, convulsions, sweating, general confusion, convulsions, hallucinations, fever, elevated heart ratehallucinations, fever, elevated heart rate

May be life-threatening-approx. 5% chance May be life-threatening-approx. 5% chance of death without med supervisionof death without med supervision

Current medical uses: epileptic seizures; Current medical uses: epileptic seizures; convulsionsconvulsions

Dependence potential: lab animals-self-Dependence potential: lab animals-self-administer at rates equal to cokeadminister at rates equal to coke

Use peaked in 1950s & 1960sUse peaked in 1950s & 1960s U. of Mich survey-hs seniors-2008-9% U. of Mich survey-hs seniors-2008-9%

lifetime; 1975-17% lifetime; 2008-6% within lifetime; 1975-17% lifetime; 2008-6% within past year; 1975-11% within past yearpast year; 1975-11% within past year

Nonbarbiturate Sedative-HypnoticsNonbarbiturate Sedative-Hypnotics

Chloral hydrate-1832-a depressant used for Chloral hydrate-1832-a depressant used for treating insomniatreating insomnia

Not as great an effect on REM as barbsNot as great an effect on REM as barbs Very irritating to stomachVery irritating to stomach Synergistic effects with alcoholSynergistic effects with alcohol ““Mickey Finn”-a few drops in glass of Mickey Finn”-a few drops in glass of

whiskeywhiskey

Methaqualone: Quaalude; Sopor 1965Methaqualone: Quaalude; Sopor 1965 1970s-recreational use spread1970s-recreational use spread 1984-Schedule I1984-Schedule I Still available-underground labs; importedStill available-underground labs; imported

Anxiety DisordersAnxiety Disorders

Six major types: panic disorder, obsessive-Six major types: panic disorder, obsessive-compulsive disorder, post-traumatic stress compulsive disorder, post-traumatic stress disorder, specific phobias, social phobias, disorder, specific phobias, social phobias, generalized anxiety disordergeneralized anxiety disorder

First antianxiety drug-meprobamate (Miltown)-First antianxiety drug-meprobamate (Miltown)-19551955

Became a household wordBecame a household word First drug in history to be marketed as an First drug in history to be marketed as an

antianxiety drug; actually produces sedation; both antianxiety drug; actually produces sedation; both physical and psych dependence; Schedule IV –physical and psych dependence; Schedule IV –very infrequently prescribedvery infrequently prescribed

BenzodiazepinesBenzodiazepines

Acute EffectsAcute Effects

Relatively slow absorption-effects more Relatively slow absorption-effects more gradual than barbs (absorbed through small gradual than barbs (absorbed through small intestine; barbs through stomach)intestine; barbs through stomach)

Do not affect respiratory centers in medulla; Do not affect respiratory centers in medulla; 50-60 times the normal dose won’t stop 50-60 times the normal dose won’t stop breathingbreathing

Dangerous with alcoholDangerous with alcohol

Elderly-slowed elimination-dangerous build-up: Elderly-slowed elimination-dangerous build-up: drug induced dimentia: confusion and loss of drug induced dimentia: confusion and loss of memorymemory

All ages: drowsiness and poor coordination-All ages: drowsiness and poor coordination-driving is dangerousdriving is dangerous

Problems learning; can prevent brain from Problems learning; can prevent brain from recording and adapting to new informationrecording and adapting to new information

Amnesia-Rohypnol (roofies)-much more potent Amnesia-Rohypnol (roofies)-much more potent than valium-2 mg in drinkthan valium-2 mg in drink

Chronic EffectsChronic Effects

Tolerance to sedative effectsTolerance to sedative effects No tolerance to antianxiety effects at No tolerance to antianxiety effects at

therapeutic dosestherapeutic doses Withdrawal-high anxiety, insomnia, Withdrawal-high anxiety, insomnia,

restlessness, agitationrestlessness, agitation Psychological dependence-the real problemPsychological dependence-the real problem

Effects on BrainEffects on Brain

Agonist of GABAAgonist of GABA 3 binding sites: sedative-hypnotics; barbs; 3 binding sites: sedative-hypnotics; barbs;

benzodiazepines; benzodiazepines and benzodiazepines; benzodiazepines and alcoholalcohol

GABA attaches to binding site; if GABA attaches to binding site; if benzodiazepines are occupying the site; benzodiazepines are occupying the site; greater inhibitiongreater inhibition

Receptors: primarily in limbic system and Receptors: primarily in limbic system and cerebral cortexcerebral cortex

Limbic system: antianxiety actionLimbic system: antianxiety action Cerebral cortex: sedationCerebral cortex: sedation

Drugs Designed Specifically to Drugs Designed Specifically to Induce SleepInduce Sleep

Ambien: 1993Ambien: 1993 Chemically unrelated to benzodiazepines; Chemically unrelated to benzodiazepines;

but act on a benzodiazepine receptor that but act on a benzodiazepine receptor that induces sleepinduces sleep

Doesn’t reduce anxiety; little or no relaxationDoesn’t reduce anxiety; little or no relaxation Short half-life: 2 hoursShort half-life: 2 hours Should be used 7-10 daysShould be used 7-10 days Lower abuse potential than benzos.Lower abuse potential than benzos.

Sleepwalking, binge eating, and driving Sleepwalking, binge eating, and driving without rememberingwithout remembering

Lunesta: 2005Lunesta: 2005 Also not a benzodiazepine but acts on Also not a benzodiazepine but acts on

receptors to induce sleepreceptors to induce sleep Lower abuse potential than Lower abuse potential than

benzodiazepinesbenzodiazepines

GHBGHB

gamma –hydroxybutyrategamma –hydroxybutyrate Odorless, colorless liquidOdorless, colorless liquid Europe: general anestheticEurope: general anesthetic Used by bodybuilders; sales banned in 1990Used by bodybuilders; sales banned in 1990 Still available by prescription-narcolepsyStill available by prescription-narcolepsy Pharmacologists think GHB may be a Pharmacologists think GHB may be a

neurotransmitter; synthesized in brain; has neurotransmitter; synthesized in brain; has specific receptor sites; effects can be blocked by specific receptor sites; effects can be blocked by antagonistsantagonists

Produces relaxation, mild euphoria, then Produces relaxation, mild euphoria, then headache, nausea, drowsiness, loss of headache, nausea, drowsiness, loss of consciousness, seizures, coma, deathconsciousness, seizures, coma, death

Not addictive at therapeutic doses; problems at Not addictive at therapeutic doses; problems at higher doseshigher doses

Routine tox screens in Ers-not set up to detect Routine tox screens in Ers-not set up to detect GHB; tell medical personnel if takenGHB; tell medical personnel if taken

Very dangerous with alcohol; additive; lower Very dangerous with alcohol; additive; lower blood pressure and decrease blood oxygenblood pressure and decrease blood oxygen

Tolerance and WithdrawalTolerance and Withdrawal

very serious problem: users learn that you very serious problem: users learn that you get a high like alcohol; sedation at higher get a high like alcohol; sedation at higher dosesdoses

Use recreationally for euphoria; uses as Use recreationally for euphoria; uses as sedative for falling asleep; may reach point sedative for falling asleep; may reach point where using every few hours, 24 hrs a daywhere using every few hours, 24 hrs a day

Withdrawal: very severeWithdrawal: very severe

Insomnia, anxiety, psychosis; like alcoholInsomnia, anxiety, psychosis; like alcohol Tremors, high heart rate, high blood Tremors, high heart rate, high blood

pressurepressure Should be done under medical supervisionShould be done under medical supervision