1. CHAPTER 5 Downers Ethanol

2. Ethanol Pharmacokinetics Miscible in water and fat Virtual complete absorption from mucosal linings and gut Time to blood peak ~60 – 90 min after last drink Empty Stomach: 20% of dose absorbed in stomach 80% - upper intestine Gastric emptying time Full Stomach Significantly longer in stomach, lower peak – see metabolism

3. Ethanol Distribution Equally distributed in all tissues and fluids Penetrates blood/brain barrier due to lipid solubility Freely crosses placental barrier giving fetus similar blood levels as mother FAS affects 30-50% of babies born to alcoholic mothers

4. Ethanol Metabolism/Excretion 95% metabolized by alcohol dehydrogenase – 85% in liver 5% excreted unchanged – mostly lungs - breath 15% metabolized by ADH in stomach lining cells 1 st Pass Metabolism Longer in stomach, more metabolism Women have 50% less gastric ADH metabolism Men have greater muscle/fat ratio (greater “volume of distribution”) – dilutes alcohol Women have higher body fat ratio (lower volume of distribution) – concentrates alcohol

5. Ethanol Metabolism/Excretion Alcohol converted to Acetaldehyde by ADH Acetaldehyde to Acetic acid by aldehyde dehydrogenase Acetic acid to CO2 and H2O, releasing energy

6. Ethanol Metabolism/Excretion Maximum metabolism: 170 g/day (100% EtOH) Rate limiting step: ADH, regulated by availability of NAD “Zero Order Metabolism”: rate of metabolism essentially independent of drug concentration “Average person” blood level drops ~0.015 g/dL per hour after complete absorption

7. Ethanol Legal Limits WA State – 0.08 g/dL (blood) or g/210L (breath) – DUI Federal DOT FMCSA – 0.02 – unfit for duty Federal DOT FMCSA – 0.04 – violation – evaluation and treatment required before return to duty

8. Ethanol

9. Pharmacodynamics Inhibits Glutamate receptors Reduces effectiveness of excitation mechanism Removal of alcohol after chronic use can lead to withdrawal symptoms including seisures Activates GABA receptor ion channels resulting in neuron inhibition (GABA agonist) Sedation Muscle relaxation Inhibition of cognitive and motor skills Relationship between alcohol problems and panic/anxiety disorders Positive reinforcement - dopamine related, mechanism unclear, may involve endorphins/enkephalins

10. Ethanol Serotonin Chronic alcohol use increases serotonin production May be link to dopamine producing neurons

11. Ethanol Pharmacological Effects Reversible CNS depression Respiration Transitory stimulation – low dose Depressed at high dose Anticonvulsant properties However withdrawal can CAUSE seizures peaking at 8-12 hr after last drink

12. Ethanol Circulatory system Dilates vessels – danger in cold weather Long-term use damages heart muscle Low dose daily (up to 2.5 oz – 1 drink) may reduce heart attack risk (increases HDL, reduces LDL) – except in smokers Light-moderate dose may reduce stroke risk Higher doses increase stroke risk Diuresis Interferes with sexual performance

13. Ethanol Psychological Effects Low dose Stimulant and depressant effects Disinhibition – highly variable reaction Expectations Environment Violent crime Particularly sexual assault/rape Loss of coordination but functional 50% of highway accidents alcohol related Higher doses – growing incapacitation

14. Ethanol Long term effects Moderate drinking Few changes Heavy drinking Brain Liver GI tract Malnutrition Lots of calories, no nutrition

15. Ethanol Tolerance/Dependence Metabolic Liver increases ADH – 25% of tolerance Tissue Neurons adapt – can function at 2X EtOH level as non- tolerant person Other

16. Ethanol Toxicity ReversibleDrug-Induced Brain Syndrome Clouded senses/disorientation Impaired reasoning/judgement Amnesia Diminished intelect Liver damage Cirrhosis - 75% of all deaths assoc. with EtOH Brain Neuron destruction leading to dementia

17. Ethanol Toxicity GI Pancreatitis Chronic gastritis Ulcers Carcinogen or co-carcinogen Tongue Mouth Throat Liver GI Breast? Immunosuppressant action

18. Ethanol Toxicity Teratogenic (damages fetus) Fetal Alcohol Syndrome - FAS CNS dysfunction Retarded body growth Facial abnormalities Heart defects Malformed eyes/ears Significant differences noted in children of mothers who drank only “social” amounts

19. Alcoholism Models Moral AA – 12 step – spiritual and behavioral – individual is powerless to help themselves, need help of outside Power Disease AMA – primary chronic disease, progressive, fatal – requires treatment Behavioral Drinking is behaviorally reinforcing, learned, maladaptive – pattern can be altered – genetics play a role

20. Alcoholism Types (Jellinek – 1960) Alpha – psychological dependence due to inability to cope Beta – social dependence, frequently heavy beer drinker Gamma – most severe – emotional, psychological impairment, progressing to physical dependence Delta – maintenance drinker, cannot abstain for even a day or two, but not drunk Epsilon – binge drinker Zeta – moderate drinker who becomes abusive and violent

21. Alcoholism Dual diagnosis 30-50% of alcoholics – major depression 33% anxiety disorder 36% addicted to other drugs 38% impulse control problem

22. Alcoholism Pharmacotherapies Reverse acute alcohol effects Treat/Prevent withdrawal Maintain abstinence/prevent relapse Treat coexisting psychiatric disorders Benzodiazepines – drugs of choice for acute withdrawal Alcohol sensitizing drugs – decrease consumption (Antabuse – Disulfiram) Naltrexone – reduce craving (opiate antagonist) Buproprion – dopaminergic help maintain abstinence

23. Inhalants Volatile chemical Inhaled, absorbed through lungs Anesthetics – nitrous oxide, halothane Household solvents Office supplies Gases – butane, propane, etc. Propellants Organic solvents e.g. nitrates

24. Inhalants WHO??? Mostly adolescents 20% of kids by end of 8 th grade 95% of deaths occurred in males

25. Inhalants Effects Acute Rapid intoxication – similar to alcohol Progresses through sedation, disinhibition, staggering, etc. Severe intoxication can lead to general anesthesia and/or death Can be treated by supportive therapy such as oxygen Chronic CNS dysfunction Liver/kidney failure Fetal Solvent Syndrome