Sedative Hypnotics and Anxiolytics Flashcards
Anxiety brain circuitry is found where?
Amygdala
Difference between Sedation, Hypnosis, Anesthesia, and Coma
Sedation – Reduced Responsiveness
Hypnosis – Drug Induced Sleep
Anesthesia – Amnesia, analgesia, lost muscle tone
Coma – Unconsciousness for 6+ hours,no sleep cycles
GABA is produced from ______
Glutamate
What types of Channels does GABA act on
A - Ligand Gated Cl- Channel
B, C – GPCR
Diseases associated with GABA
Epilepsy, Muscle Spacticity, Addition/Alcoholism
Details of the GABA A receptor
Pentamer
Different subunit combinations possible (usually 2 alpha1, 2 beta2, and 1 gamma2)
Benzos prefer to bind…..
Z compounds prefer to bind…
Benzo – alpha 2, 3 5
Z – alpha 1 receptors
(This is why sedative/hypnotic drugs can work differently)
Effect of Cl- GABA channels on neuronal potential
Moves close to Cl- equilibrium potential (-70) decrasing likelihood of cell firing.
How does GABA A work normally?
Two GABA molecules bind the GABA A receptor, causing Cl- influx that hyperpolarizes the cell membrane
How do benzodiazepines interact with GABA A? How is this different from Z compounds?
They allosterically bind to a site distant from the GABA binding site, enhancing the activity of GABA at that site. Z compounds bind to the BZD site directly
Difference in the function of Benzos and Barbs
benzos increse frequency of openings
barbs increase the duration of opening
At high doses Barbiturates become…
GABA-mimetics
May act at AMPA glutamate receptors
What do molecules with inverse agonist action do? Exampe?
bind the BZD site and make it harder for GABA to open the channel
Example of a BZS site antagonist
Flumenazil
Important details about Midazolam
Rapid onset, fast recovery
Acute seizure control, pre-surgery anxiolysis, amnesia, sedation
Important details about Alprazolam
Mainly for panic, GAD
Rapid Acting, Moderate Duration
Important details about flurazepam
Long duration
For insomnia
Next day sedation is possible, intermediate should maybe be an intermediate
Benzos are broken down by…
CYP 3A4, 2C19. Grapefruit juice can interfere
Benzo adverse effects
Amnesia (in short acting) Daytime sedation (in longer acting) Resp/CV Depression Withdrawl Dependence Potentiated by P450 inhibitors
How to treat a Benzo overdose
Maintain airway, renal fxn
Positive inotropic drugs
Flumazenil
Effects of Benzo withdrawl
Since receptors are downregulated, removal of Benzos will cause an increase in excitability, increasing lieklihood of patient seizures
Benzo or Barb – who is easier to OD on
barb – stronger action at GABA-A, ability t open GABA channels
How are Barbiturates commonly used? Rarely used?
Severely brain injured patients to induce coma to bring down intracranial pressure
Rarely – Seizures, Anesthesia
The death penalty drug
Pentobarbital
Important details about Buspirone
5HT1A partial agonist
Less sedation, withdrawl, abuse. Slow Onset
Used for GAD (NOT for panic)
BZDs used as hypnosedatives
Triazolam (short)
Temazepam (medium)
Flurazepam (long)
Z compounds used to treat insomnia
Zolpidem
Zeleplon
esZopiclone
Z compounds are selective for ____ containing receptors
alpha1
Important details about Ramelteon
MT1, MT2 agonist
acts on SCN to promote sleep
Which sleep stage has K complexes + sleep spindles
Stage 2
Effect of BZD/Barbs on sleep stages
Longer 2
Shorter 3/4/REM
Effect of Z compounds on sleep stages
Longer (Or Same) 2
Shorter (or same) REM
