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Chapter 8

PHAR 100 Chapter Notes - Chapter 8: Chloral Hydrate, Alcohol Withdrawal Syndrome, Depressant


Department
Pharmacology and Toxicology
Course Code
PHAR 100
Professor
Bill Racz
Chapter
8

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Lesson B.3 Sedative-Hypnotics and Anxiolytics
Objectives:
- State the mechanisms of action of benzodiazepines and barbiturates
- List the therapeutic uses and the rationale for the clinical use of benzodiazepines and barbiturates
- Describe the response to barbiturates and benzodiazepines at various doses and duration of use
- Describe the dependence liability for benzodiazepines and barbiturates
- Describe the withdrawal syndrome associated with barbiturate dependence
- Sedative-hypnotic agents are central nervous system depressants Dose dependent ranging from
antianxiety effects, sedation, hypnosis (sleep), general anesthesia and death
History of use
- Bromides, were the first agents clinically introduced (mid 19th century)
o Bromides are eliminated slowly from the body and can cause a drug accumulated condition
referred to as bromism (mental and neurological aberrations, skin rash and gastrointestinal
disturbances)
- Chloral hydrate and paraldehyde were recently thereafter introduced, slightly safer
- 1912 Age of the barbiturates
- 1950’s – meprobamate and glutethimide were overly used
- 1961 Era of the benzodiazepines, initiated by chlordiazepoxide; these drugs are still widely
used today
Therapeutic Uses (and drug of choice):
- Antianxiety relief (benzodiazepines)
- Sedative reduce sensory-motor function, reduce tension (benzodiazepines)
- Hypnotic sleep (short-acting benzodiazepines)
- Anticonvulsant agent for certain types of epilepsy control of generalized tonic-clonic and partial
seizures (phenobarbital) and to ensure the absence of seizures and epilepticus state
(benzodiazepines)
- Treatment of skeletal muscle spasms reduce elevated skeletal muscle tone and neuromuscular
disorders ie. cerebral palsy (benzodiazepines)
- Treatment of alcohol withdrawal syndrome cross-dependence of agents found in diazepam
Classification:
Benzodiazepines (diazepine, flurazepam)
Barbiturates (phenobarbital)
Other (chloral hydrate)
Benzodiazepines
- 1977 receptors for benzodiazepines were discovered; highest in density in the cerebral cortex,
cerebellum and limbic system
- These drugs:
o Increase synaptic inhibition and thus dampen neuronal response
o Activating the benzodiazepine receptors, they enhance the action of gamma-aminobutyric
acid (GABA), the major inhibitory neurotransmitter in the CNS
o They act on the same structure as GABA but not on the same receptors
o Locations are found in the cerebellum, cerebral cortex, limbic system, reticular activating
system and spinal cord
- Pharmacological Properties:
o Very high therapeutic index
o Relief from anxiety, decreased aggression
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