Download presentation
1
Sedatives: Anxiolytics & Alcohol
Lesson 19
2
Sedative/Anxiolytic Drugs
GABAA agonists (Cl- channels) Barbiturates e.g., phenobarbitol, secobarbitol Benzodiazepines e.g., valium, librium Alcohol ethanol (ETOH) Buspirone (Buspar) 5HT1A partial agonist ~
3
ALCOHOL Family of structurally similar substances Methyl: Methanol
Isopropyl: Isopropanol (rubbing) Ethyl: Ethanol (ETOH); beverage Ethanol Synthesis Starch + Sugar + YeastCO2 + ETOH Self-limiting concentration: 12-14% No accepted medical use high abuse potential ~
4
Pharmacokinetics Routes: All routes effective
Inhalation - effective but risky P.O. most common route ~ Solubility highly water soluble somewhat lipid soluble Small & un-ionized crosses all membrane barriers Distributes to all tissues ~
5
Pharmacokinetics: Metabolism
Per os absorption 20% stomach / 80% small intestine Metabolized in liver (90-98%) Rate slow, fixed: 1/2 oz./hr Regardless Blood Alcohol Level (BAL) also coffee, cold shower, etc. BAL reduced by time or dialysis only No antidote for overdose ~
6
Ethanol Metabolism ETOH CO2 H2O Energy Acetaldehyde Acetate Alcohol
Dehydrogenase Aldehyde Dehydrogenase Acetyl CoA CO2 H2O Energy ETOH Acetaldehyde Acetate
7
Metabolism: Sex Differences
Same dose greater effects in females Weight Muscle / Fat New evidence: enzymes males: ETOH dehydrogenase in stomach higher 1st pass metabolism ~
8
Alcohol Dose Response Chart
BAL Effect Bottles of beer in 1 hr M F .05 euphoria, disinhibition, ¯ coordination .10 *legally drunk, ¯ coordination, drowsiness .15 significantly ¯ reaction time .25 “smashed”, staggering, severe motor ¯ .35 surgical anesthesia, possible death 5-10 hrs .4-.6 lethal dose 1 quart whiskey .08
9
Undesirable Effects General Depression Interferes with REM sleep
Withdrawal & Seizures Blackouts Wernicke-Korsakoff Syndrome Severe memory loss Thiamine deficiency Fetal Alcohol Syndrome morphological & cognitive effects ~
10
Effects on Liver Fatty Liver free fatty acids enlarged reversible
Normal Fatty Liver free fatty acids enlarged reversible Hepatitis cell damage regeneration w/ abstinence Cirrhosis: irreversible cell death fibrous scar tissue decreased metabolism toxicity ~ Fatty Cirrhosis
11
Other Effects Effects on Muscle cells Impairment Degeneration
Depressed immune function increased probability of sickness Reproductive function males decreased testosterone sperm females disrupts ovarian cycling ~
12
High Dependence Liability
Alcohol Dependence High Dependence Liability Positive & Negative Reinforcer Aversive Aftereffects Available/Inexpensive Socially Acceptable Easily Administered Rapid Onset of Effects ~
13
Dependence: Genetic Component
Sons of Male Alcoholics at > risk P3 R. Cloniger (1989) Statistical Evaluation Type I - Environmental Late developing - Age = 20-30 Type II - Genetic Early onset (teens & younger) Impulsive risk takers/Suicidal Violent/Agressive/Crime ~
14
Liquor-loving Mice Knockout mice delete single gene
Increased ETOH appetite Drank twice as much ETOH fewer motor effects 5-HT1B receptor autoreceptor ~
15
Treatment No best program Success rates: Higher rates:
1 year: up to 50% 2 years: 25% Higher rates: select populations & short follow-up Treatment approaches 12-step programs Behavioral-Cognitive Pharmacological ~
16
Antabuse Disulfiram Aversive therapy Interferes with ETOH metabolism
inhibits aldehyde dehydrogenase Acetaldehyde toxic ~
17
Antabuse nausea cramps sweating ~ ETOH Disulfiram (Antabuse)
Alcohol Dehydrogenase Aldehyde Dehydrogenase nausea cramps sweating ~ ETOH Acetaldehyde
18
New Treatments Naltrexone (opioid antagonist) Blocks rewarding effects
Relapse prevention binge after slipping: 50% Acamprosate (Campral) Blocks withdrawal effects NMDA antagonist / GABA agonist Naltrexone + Acamprosate? under investigation ~
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.