Lecture 2: Anxiolytics and Hypnotics Flashcards
What drug is used for surgical anaesthetic?
GABA (inhibitory) agonist
GABAa receptor
ionotropic receptor
ligand-gated ion channel
influx of Cl-
hyperpolarization and less likely to fire
GABAb receptor
metabotropic receptor
binds to GPCR
promotes regulatory inhibition
What disease will the blocking of GABAa receptor lead to?
Seizures
5 increasing function of GABAergic transmission
- Anxiolytics
- Sedation
- Hypnosis
- Coma
- Death
Why are depressants addictive?
Depressant at low dose will DISINHIBIT dopamine neurons
leads to burst firing dopamine = dopamine surge
Barbiturates
increase opening duration of channel
USED FOR RAPID SEDATION and ANAESTHESIA
increase efficacy of GABA
chronic use lead to tolerance, dependence and addiction
crosses placenta, do not use when pregnant
additive effects with alcohol
superadditive effects with benzodiazepines
Phenobarbital, Pentobarbital, thiopental
increase opening duration of channel
more Cl- influx
increase efficacy of GABA
3 effects from binding to Benzodiazepines modulatory site
- agonism
- inverse agonism (produce anxiety, seizures, counteracts ethanol intoxication)
- antagonism
Benzodiazepines as agonist (diazepam)
anxiolytic and sedative hypnotic agents
increase GABA binding site affinity for GABA
increase potency of GABA
less GABA is required to open the Cl- channel
Zolpidem
positive allosteric modulator of GABAa receptors
binds to different site than benzodiazepines
only binds to alpha1 containing GABAa receptors
strong hypnotic, weak muscle relaxant
lower dose for women, metabolize slower than men
rapid onset (15 min)
adverse effect: parasomnias, appear awake, can perform complex task but no memory (anterograde amnesia)
4 adverse effects of BZDs
somnolence (sleepiness)
impairment of memory and cognition
impair motor function
disinhibition of behaviours (impulsivity)
Alcohol at GABA, Glutamate and Dopamine
GABA: increase GABAa receptor function, enhanced inhibition
Glutamate: inhibit glutamate receptors, decrease excitatory effects
Dopamine: Stimulate dopamine action, increase firing rate of dopamine neurons
NMDA glutamate receptor
sodium and calcium ion channel
alcohol acts as antagonist
less Na+ influx, less neuron excitation
Alcohol as CNS depressant
euphoria, disinhibition, impaired reaction time, balance, speech, vision, motor coordination
increase vasodilation
increase gastric secretion (ulceration)
higher dose: vomiting, unconsciousness, coma, death from respiratory depression
