CNS Depressants

1
CNS Depressants

• Concepts, principles, and examples

2
Terms and concepts

• Depressant, sedative, tranquillizer, anxiolytic,
  hypnotic
• Levels of sedation
• Conscious levels Anxiolytic, behavioral
  disinhibition, sedation
• Unconscious levels Hypnagogic state, sleep,
  anaesthesia, coma.

3
Juliens principles of CNS depressants

• CNS depressants are additive with each other and
  with the behavioral state of the user.
  Supradditive synergistic.
• CNS depressants are antagonists of the behavioral
  stimulants, but in a non-specific fashion.
• Rebound or withdrawal is unlikely after a single
  dose of a CNS depressant.
• Dependence, psychological dependence, and
  tolerance do occur to CNS depressants.

4
Mechanisms of action

• Reversible depression of excitable tissue
  barbiturates and non-barbiturates, ethyl alcohol,
  and general anaesthetics.
• Greater depression of polysynaptic pathways, such
  as the reticular activating system (RAS).
• Potentiating the GABAA receptor complex
  barbiturates prolong Cl- access 4 to 5 times.

5
The mental status exam

• 1. General appearance
• 2. Sensorium
• a. Orientation
• b. Clarity/cloudiness
• 3. Behavior/manner
• 4. Stream of talk
• 5. Cooperativeness
• 6. Mood (Feeling)

• 7. Affect (expression)
• 8. Perception
• a. Illusions
• b. Hallucinations
• 9. Logical thought?
• 10. Knowledge
• 11. Intellect function
• 12. Insight/judgment

6
General CNS depressants

• Barbiturates A family of over 2500 derivatives
  of barbituric acid, of which about 50 have been
  marketed. First used in 1912 (phenobarbital).
• Nonbarbiturate hypnotics Early 1950s
• Tranquillizers
• General anaesthetics
• Abused inhalants

7
The barbiturates

• Pharmacological phenomena
• Pharmacokinetics
• Ultra-short acting Short (re)distribution
  half-lives
• Short- to long-acting Long elimination
  half-lives
• Low selectivity and low TI
• Sleep abnormalities
• REM suppression
• REM rebound and rescidivism

8
Barbiturates, continued

• Psychopharmacological phenomena
• Repeated use leads to tolerance and dependence
• Individual reactions may be be different from
  sedation depression, agitation, and aggressive
  behavior may occur, influenced by
• mental set
• social setting
• pain
• Affects movement and judgment like alcohol

9
Nonbarbiturate hypnotics

• Glutethimide (Doriden), ethchlorvynol (Placidyl),
  and methyprylon (Noludar) in early 1950s
• The methaqualone (Quaalude) episode
• 1951 Malaria treatment
• 1965 Tranquillizer and panacea
• 1972-73 Abuse epidemic
• 1973 Placed on Schedule II
• 1984 Withdrawn from market by manufacturer

10
Antianxiety agents

• Dicarbamate derivatives
• Meprobamate (Equanil, Miltown)
• Mebutamate (Capla), tybamate (Solacen)
• Carisoprodol (Rela, Soma)
• Benzodiazepines

11
General anaesthetics

• Membrane fluidization and ion channel
  perturbation
• Gas Nitrous oxide
• Volatile liquids
• Ether
• Halothane
• -fluranes ( iso-, des-, en-, and sevo-)
• Injectable GABA agonists
• Barbiturates, propofol (Diprovan), etomidate

12
The GABAA Receptor Complex
Cl-
Cl-
Cl-
Cl-
Cl-
Inside
Cl- ion channel
B A R B
B A R B
G A B A
G A B A
Cl-
E t O H
B D Z
Cl-
Cl-
Cl-
Cl-
Cl-
Outside