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CNS Depressants. Concepts, principles, and examples. Terms and concepts. Depressant, sedative, tranquillizer, anxiolytic, hypnotic Levels of sedation: Conscious levels: Anxiolytic, behavioral disinhibition, sedation Unconscious levels: Hypnagogic state, sleep, anaesthesia, coma.

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cns depressants

CNS Depressants

Concepts, principles, and examples

terms and concepts
Terms and concepts
  • Depressant, sedative, tranquillizer, anxiolytic, hypnotic
  • Levels of sedation:
    • Conscious levels: Anxiolytic, behavioral disinhibition, sedation
    • Unconscious levels: Hypnagogic state, sleep, anaesthesia, coma.
julien s principles of cns depressants
Julien’s 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.
mechanisms of action
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.
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

The mental status exam
general cns depressants
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
the barbiturates
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
barbiturates continued
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
nonbarbiturate hypnotics
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
antianxiety agents
Antianxiety agents
  • Dicarbamate derivatives
    • Meprobamate (Equanil, Miltown)
    • Mebutamate (Capla), tybamate (Solacen)
    • Carisoprodol (Rela, Soma)
  • Benzodiazepines
general anaesthetics
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
slide12

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

Cl-

B

D

Z

Cl-

Cl-

Cl-

Cl-

Outside