anxiolytic and hypnotic drugs

Question 1

Describe different types of anxiety observed in humans

Answer 1

• panic disorder
  
  • overwhelming fear with marked somatic symptoms
  • social anxiety disorder
  • phobias
  • PTSD
  • OCD
  • generalised anxiety

Question 2

the animal models used to evaluate anti-anxiety drugs

Answer 2

• elevated maze/cross test
  
  • afraid to go on open side of cross
  • with drug walks on both sides
• light/dark box
  
  • hide in dark part of box
  • drug = no preference

Question 3

Describe the protein targets of commonly used anxiolytic drugs

Answer 3

• GABAa receptors are targets for anxiolytics, hypnotics
  
  • mediate fast inhibitory transmission in CNS
    
    • activation = hyperpolarisation and reduction in excitability
    • chloride selective = potential becomes negative
• propranolol - beta blocker
  
  • blocks physical sympathetic symptoms
• buspirone
  
  • general
  • partial agonist for serotonin
• anti-depressants
  
  • SSRI → receptors

Question 4

Discuss our current understanding of the mechanism of action of benzodiazepines at the molecular, cellular and whole animal level

Answer 4

physiological effects
- sedation
- hypnosis
- anterograde amnesia
- anti-convulsant
molecular interaction
- positive allosteric regulators of GABAa receptors
- increasing activity of GABAa
- increases Cl current across membrane

Question 5

Explain the concept of “Allosteric Modulation” and two state model of drug/receptor interactions

Answer 5

allosteric modulation
-> alters affinity of receptor by stabilising receptor in positive or negative way

two state model of GABA interaction
- positive allosteric modulators stabilise receptor causing increased affinity for GABA = increased binding
- negative allosteric modulators destabilise receptor causing reduced affinity for GABA remaining closed e.g beta carbolenes

Question 6

Describe the pharmacological effects, uses and unwanted side effects of this class of anxiolytic drugs

Answer 6

• sleepiness, impaired psychomotor function, amnesia
• tolerance
• misuse
• dependence

Question 7

Describe drugs used to treat insomnia (Hypnotic drugs)

Answer 7

• benzodiazepines
• melatonin receptor agonists
• orexin receptor antagonists
• over the counter sleep aids - H1 receptor antagonists
  
  • crosses BBB