37. Drug Action as Modulators on GABAaR Receptors Flashcards
Explain the modulation of GABAaR receptors by benzodiazepines.
Benzodiazepines increase frequency of Cl- ion channel opening (which is produced by GABA)
* increases potency of GABA
The acting duration of benzodiazepines is classified by what?
Determined by their ability to cross the blood-brain barrier.
* lipophilic agents –> shorter acting duration
* water-soluble agents –> longer acting duration bc of rapid disribution from the CNS to peripheral sites.
Explain the different possible classifications of benzodiazepines.
- long-acting –> 1-3 days
- intermediate-acting –> 10-20 hours
- short-acting –> 3-8 hours
Describe the pharmalogical actions of benzodiazepines.
- reduction of anxiety
- sedative/hypnotic
- amnesia
- anticonvulsant
- muscle relaxant
Describe the medical uses of benzodiazepines.
- anxiety disorders
- sleep disorders
- seizures
- muscular disorders
Describe benzodiazepine withdrawal syndrome.
High-dosage withdrawal –> more serious developments like seizures and psychotic reactions
Normal dosage withdrawal –> symptomatic patterns (short-lived “rebound” anxiety and insomnia)
Zolpidem
drug target:
drug class
drug action:
treatment for diseases:
drug target: GABAaR benzodiazepine
drug class non-benzodiazepine
drug action: GABAaR receptor agonist –> increass GABA effects in the CNS by binding to GABAaR at the same location as benzodiazepines.
treatment for diseases: short-term treatment of insomnia
Flumazenil
drug target:
drug action:
treatment for diseases:
drug target: GABAaR benzodiazepine
drug action: competitively inhibits the activity of benzodiazepines on the site of GABAaR receptors.
treatment for diseases: reverse the effects of benzodiazepine overdose or zolpidem
Explain the modulation of GABAaR receptors by barbiturates.
- at higher dose, barbiturates act as agonists of GABAaR receptors
- there is a distinct binding site on GABAaR receptors for barbiturates
- Barbiturates increase the duration of chloride ion channel opening at the GABAaR receptor –> increases efficacy of GABA
- the direct opening of the Cl- ion channel is why it has increased toxicity compared to benzodiazepines.
- relatively non-selective and bind to superfamily of ligand-gated ion channels
Phenobarbital
drug target:
drug action:
treatment for diseases:
drug target: barbiturate site on GABAaR receptor
drug action: GABAaR agonist –> increases the activity of GABA
treatment for diseases: sedative/hypnotic drug that can help with sleep during periods of anxiety
Describe the medical uses of GABAaR agonist, phenobarbital.
- first-line choice for treatment of neonatal seizure
- first-like drug for epilepticus
- anesthesia in intensive care
- insomnia
- physician assisted suicide
Explain the possible drug-drug interactions of phenbarbital.
- phenobarbital is a CYP450 enzyme inducer
- binds transcription factor receptors that activate P450 transcription –> increases amount of P450 enzymes
- increased P450 enzymes = decreased effectiveness of drugs that are metabolized by P450 enzymes.
Explain the modulation of GABAaR by alcohol.
Describe the modulation of GABAaR by alcohol.
- agonist of GABA receptors
- binds to certain GABA receptors in the brain, where it replicates the activity of the GABA neurotransmitter.
- has a depressive effect on the CNS
- too much alcohol –> overstimulate GABA pathways –> sedation/toxicity/overdose
- continued exposure –> makes people feel more stressed and make them want to drink more often
a. analgesic
c. all benzodiazepines have some sedative effects
b. Flumazenil
d. barbituates increase the potency of GABA
e. control blood pressure
