Neuropharmacology (Pharmacology) Flashcards
What is the mechanism of action of barbiturates?
- Increased single-channel opening time of GABAA receptor on binding in absence of GABA
- Increases effects of GABA beyond physiological limits
Why are barbiturates toxic?
- Therapeutic index = 10
- Toxicity due to ability to cause mass CNS depression
How can barbiturate toxicity be increased?
Use with alcohol
What is the mechanism of action of benzodiazepines?
- Binds to GABAA receptor and increases it affinity for GABA
- Potentiates effects of GABA without increasing physiological maximum effect
What is the therapeutic index of benzodiazepines?
~100
How can GABAA receptor be insensitive to benzodiazepines?
- Presence of α4 & α6
- Absence of γ receptors and replacement by β or δ subunit
What effects of benzodiazepines are mediated by α1 subunit?
- Sedation
- Anticonvulsant
What effects of benzodiazepines are mediated by α2 subunit?
Anxiolytic effects
What are the clinical uses of benzodiazepines?
- Anxiolytic
- Sedation and sleep
- Reducing muscle tone
- Anticonvulsant
- Anterograde amnesia
What is the nature of benzodiazepine clearance?
Clearance is very slow (due to metabolites being active) so effects are very long lasting and may cause drowsiness
What is the possible mechanism behind benzodiazepine tolerance/dependence?
Altered expression of GABAA receptor subunits in different regions of the brain
What are the effects of sudden withdrawal of benzodiazepines?
- Anxiety
- Tremors
- Dizziness
- Tinnitus
- Weight loss
- Sleep disturbances
What are inverse agonists?
Molecules that bind to specific receptors to decrease its efficacy at rest or in the presence of ligand.
How does an inverse agonist differ from an antagonist?
- An antagonist inhibits activity of receptor by preventing agonist binding but does not affect the constitutive activity of the receptor.
- Inverse agonist inhibits activity of receptor by physically dampening down response of the receptor constitutively.
