1. Depressant Drugs Part 1 Kim Edward Light, Ph.D.
Professor, College of Pharmacy
University of Arkansas for Medical Sciences

2. Objectives – part 1 Discuss general nature of depressant drugs.
Discuss origins and effects of ethyl alcohol.
Determine alcohol dosage of different beverages.
Discuss the ADME of alcohol.
Discuss alcohol pharmacology.
Relate alcohol effects with blood alcohol concentrations (BAC).
Discuss the nature of alcohol impairment.
Identify the time course of BAC and estimate the time for total alcohol elimination.
Discuss the impact of alcohol use on society.

3. Depress-ant® Drugs Alcohol Barbiturates Benzodiazepines
Non-benzodiazepines
Methaqualone
Meprobamate
Glutethimide
Chloral hydrate
Antihistamines (some)
Narcotics – opiates

4. Depressant Drugs - Depress
Cognition, judgment, self-control
Vision, hearing, touch, smell, taste
Coordination – speech, balance, movement
Awareness and wakefulness
Memory (amnesia)
Consciousness

5. Depressant Drugs Therapeutic Uses (does not apply to all)
Anxiety & nervousness.
Sedation.
Acute panic disorder.
Seizures.
Insomnia and related sleep disorders.
Acute and chronic pain (opiates).

6. Adverse Effects - Acute
Impaired ability to operate machinery or motor vehicles.
Social disinhibition
CNS depression
Increased risk of accidental injury or death
Amnesia
Coma
Respiratory arrest

7. Adverse Effects – Chronic
Synergistic effects when used in combination with other drugs
Prolonged CNS depression
Dependance and withdrawal

8. Ethyl Alcohol 2 carbon simple molecule.
Fermentation of sugar by yeast.
Alcohol concentration ~14%.
Distillation required for higher concentrations.

9. Proof Alcohol content expressed as “proof”
Ignition of gunpowder soaked with the beverage
Requires at least 50% alcohol.
Proof is twice the % of alcohol
100% alcohol = 200 proof
80 proof = 40% alcohol

10. Alcohol Availability Wide variety of products beverages
medications (cough syrups, cold medicines)
mouthwashes
Beverage alcohol ranges
3% → 150%
Size of a single “drink” is inverse proportion to alcohol content.

11. Alcohol Dose Cannot be standardized into a simple unit or “drink.”
Compute grams:
%alcohol (as a decimal) x total volume (in mL, 1 oz = 29.6 mL) x density of ethyl alcohol (0.789 g/mL).
Formula: (mL consumed) x (%alcohol) x = grams of alcohol consumed.

12. Dose Per Drink 1 can (12 oz or 360 mL) beer at 5% contains 14.2 grams
1 shot (1.5 oz or 45 ml) 80 proof spirits (40%) contains 14.2 grams
{(45mL*0.40)*0.789=14.2}
1 glass (5 oz or 150 mL) of 12% wine contains 14.2 grams
{(150mL*0.12)*0.789=14.2}

13. Absorption Primarily absorbed in the duodenum
Rate is extremely variable
Peak blood alcohol concentration (BAC) depends on:
Volume & %alcohol
Rate of drinking
Food consumption and composition
Gastric emptying (CO2 promotes)
Gastric metabolism
Hepatic first pass metabolism

14. Distribution Total Body Water
BAL or BAC (blood alcohol level or concentration) is expressed as grams alcohol per unit volume
g/100mL -- g% -- %

15. ♀ ♂ Total Body Water Total body water based on size and sex.
Males more water/pound than females ♂ ♀

16. Alcohol Concentration
[Alc] = (dose x 100) / (bw x r)
The “r” (Widmark's rho) represents the percent of body weight that is composed of water.
r=0.55 (SD +/ ) for females;
r=0.68 (SD +/ ) for males;
Dose and body weight (bw) in grams; 1 pound= 454 gms
BAC = [Alc] x 0.81
Adjusts for percent of blood that is water.

17. Metabolism Less than 5% of total dose is excreted unchanged
urine, breath, sweat, etc.
Liver is primary metabolic site
Alcohol dehydrogenase (ADH) + Aldehyde dehydrogenase (ALDH)
Genetic differences – Asians, Am. Indians
Calories kcal/g
(protein & carbohydrates = 4.1 kcal/g; fat=9.0 kcal/g)

18. Metabolism Catalase system & Cytochrome P450 system (esp. CYP2E1)
Methanol, isopropanol, or ethylene glycol, and diethylene glycol (antifreeze) poisonings
Increases Acetaminophen toxicity

19. Elimination Elimination driven by metabolism
Metabolism is usually saturated
Zero-order elimination
BAC decreases 0.015% per hour on average
Range is %/hr

20. Alcohol - Mechanism Many actions via GABA receptor.
Associates with receptor
Increases effectiveness of GABA
Results in more inhibition

21. Alcohol - Low Doses Apparent stimulation Reduced anxiety Euphoria
inhibition of inhibitory brain functions (or dis-inhibition)
Reduced anxiety
Euphoria
Impaired thought processes
Decreased mechanical efficiency

22. Alcohol - Moderate Doses
Altered heart rate,
Flushing of skin - sensation of warmth,
Lowered body temperature,
Increased secretion of saliva and gastric juices,
Increases urination,
Slowing of the electroencephalogram (EEG),
Slowed reactions and reflexes, and reduced muscular coordination.

23. Alcohol - Moderate Doses
Impairment of complex and recently learned tasks.
Reduced performance on tests that require
a high degree of attention
concentration
vigilance

24. Alcohol - High Doses Drunkenness, disorientation & confusion
Slurred speech & blurred vision
Poor muscular control
Nausea and vomiting
Respiratory depression
Unconsciousness (general anesthesia)
“Passed out”
Death due to respiratory & circulatory failure.

25. Alcohol - Intoxication
Mellanby effect
Greater impairment when BAC is increasing rather than decreasing.
Acute tolerance

26. Alcohol Impairment Four General Impairments
Loss of Judgment and Self Control
Impairment of Vision and Hearing
Clumsiness of Voluntary Muscles
Decreased Awareness of Surroundings

27. Blackouts Alcohol-induced antegrade amnesia.
The individual may appear normal and able to function
Associated with alcoholism

28. Hangover
Nausea, weakness, dizziness, poor coordination, multiple aches and pains.
Hypersensitivity to sensory stimulation
Acute withdrawal syndrome

29. BAC & Intoxication BAC % Effects 0.02-0.03
Mood elevation, Slight muscle relaxation.
Relaxation & warmth, slowed reactions, Decreased fine muscle coordination.
Impaired balance, speech, vision, hearing, gross muscle coordination.
Gross impairment of physical & mental control.
Severely intoxicated, Very little control of mind or body.
Unconscious, Deep coma, Death from respiratory depression

30. BAC – Time Course 200 lb male 125 lb female
One drink each hour beginning at 6 PM.
Male, one drink = BAC of
Female one drink = BAC of

31. Alcohol Forensics Retrograde Extrapolation (“backward estimation”)
Assumption is that no further alcohol consumption or absorption occurred.
Important in traffic & other types of transportation accidents.

32. BAC & Driving Relative Fatality Risk BAC
National Highway Traffic Safety Administration, DOT HS April 2000

33. Underage Drinkers
Underage Drinkers at Higher Risk of Brain Damage than Adults – American Medical Association Report,
Verbal and nonverbal information recall most affected, with a 10% performance decrease in alcohol users
Significant neuropsychological deficits in early to middle adolescents (ages 15 and 16) with histories of extensive alcohol use

34. Brain Imaging Studies

35. New Developments Alcohol administration by inhalation
“Alcohol-without-liquid” AWOL
Involves vaporization of alcohol and the inhalation of the vapor.
Rapidly absorbed in the lungs.
False Claims:
No hangover?
Low carbohydrates?

36. Summary General nature of depressant drugs.
Origins and effects of ethyl alcohol.
Alcohol content of different beverages.
Discuss the ADME of alcohol.
Discuss alcohol pharmacology.
BAC, relationship to effects, and how to calculate.
Nature of alcohol impairment, acute and chronic.
Time course of BAC and how to estimate the time for total alcohol elimination.
Discussed the impact of alcohol use on society