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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 ________ ________.

GABA agonists

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.

chloride ions

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?

The elderly

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?

Glutamate unchecked.

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

Behavioral- Inhibition

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.

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