HSER 341 - Benzodiazepines and Second Generation Anxiolytics
What is an Anxiolytic?
Medications used to reduce anxiety, agitation or tension
What are the most commonly used anxiolytic after their introduction in the 1960's?
What are more effective anxiolytics for chronic disorders and long-term use?
What are the five most commonly prescribed benzos?
librium; valium; xanax; dalmane; halcion
Benzodiazepines are ________ ________.
What is the mechanism of action of a benzodiazepine?
Facilitates the binding of GABA
GABA facilitates the influx of ________ ____, depressing the excitiability of the post-synaptic neuron.
What are the overall sites of action?
limbic system centers (old brain, emotion), cerebral cortex and brainstem
Fear, anxiety and panic are mediated by what areas of the brain?
amygdala; orbitofrontal cortex; and insula
What does the blocking of GABA-a function do?
Can increase activity of amygdala and elicit anxiety.
How are most benzo's taken?
Orally; some are available in injectable forms
When are peak plasma levels reached?
In about 1 hour
What are short-acting agents?
Benzos that are converted by the liver into inactive metabolites
What are long-acting agents?
Benzos that are converted by the liver in active metabolites that must be converted again into inactive compounds before they can be excreted.
What population have reduced ability to metabolize long-acting benzos?
What is the half-life of diazepam (Valium)?
60 hours; in elderly can take 7 - 10 days
What are exaggerated symptoms?
Cognitive dysfunction (dementia); impaired psychomotor skills
What area of the brain do low doses moderate anxiety, agitations and fear at ?
amygdala, orbitocortex, insula
What area of the brain - mental confusion and amnesia?
cerebral cortex and hippocampus
What area of the brain - mild muscle relaxant?
spinal cord, cerebellum, brain stem
What area of the brain - antiepiliptic actions?
cerebellum and hippocampus
What area of the brain - behavioral rewards, abuse potential/dependency?
VTA and nucleus accumbens
What is short term pharmacological treatment for?
stress-related anxiety - a few days to 3-4 weeks
What are common side effects?
sedation, drowsiness, ataxia, lethargy, mental confustion, motor impairment, cognitive impairment, disorientation, slurred speech, amnesia, hypnosis
Can dependence develop?
yes, when taken for long periods of time
What are normal withdrawal symptoms?
anxiety, insomnia, restlessness, agitation, irritability, unpleasant dreams
What are severe withdrawal symptoms?
hallucinations, psychoses, seizures
How long do W/D symptoms last?
1 - 4 weeks
For substance to be addictive?
Drug must be psychoactive & have effect on Reward system
What are examples of short-acting agents?
Halcion & Xanax
What are examples of long-acting agents?
Librium, Valium, Dalmane
What is the T1/2 short-acting dose for elderly reduced by 50%?
3 to 5 days
What is Rebound effect?
Insomnia & anxiety increases, when no longer taking drug(benzo's)
Anti-Depressant effects what activity?
Decreases neuronal activity
What causes seizures?
Benzodiazepines & Anxiolytics cause opposite effects on what?
Glutamate & GABA
Do Benzos effect a pregnancy?
Yes. ie: birth abnormalities, "floppy-infant syndrome"
Benzos & metabolites cross placental barrier.
True, able to go into fetus freely.
What can be excreted through breast milk?
Benzos, very lipid soluable
GABA decreases activity
Increases behavioral activity (giddy, bold talkative)
In Benzos addiction Relapse is common.
What is Benzodiazepine Antagonist?
Flumazenil, used for benzo overdose
Three(3) Nonbenzodiazepine's BRZAs
Zolpidem(Ambien), Zaleplon(Sonata), Eszopiclone(Lunesta), all very short acting and GABA subtypes
What is new and unique Anxiolytics?
Buspirone (BuSpar) Binds at 5HT (Serotonin) receptors.