Chapter 11: Antianxiety Drugs

What's the difference between sedation & hypnosis?

sedation: decreases activity, makes u less excited, and calms u down

hypnosis: makes u sleepy, helps to make u fall asleep and sleep naturally

T/F: With higher doses of a drug, it can facilitate hypnosis-like states, but not true hypnosis.

TRUE

Sedative-hypnotic agents create = ______

CNS depression = relaxation

What is the ideal balance between excitatory & inhibitory neuronal signaling?

We stop excitatory neurotransmitters (glutamate) via NDMA and AMPA

We activate inhibitory neurotransmitters (GABA) via GABA-R

What would happen if you blocked NMDA receptors?

Inhibits glutamate excitatory signaling

• excessive blocking can lead to dissociative states or psychosis

What are the top 3 most prescribed anti-anxiety drugs in America?

1. Alprazolam (Xanax)

2. Clonazepam (Klonopin)

3. Lorazepam (Ativan)

What class of drugs does "-zepam" belong to?

Benzodiazepines

What is the receptor for benzodiazepines?

GABA-A receptor

What is the GABA-A receptor?

a chloride channel

• doesn't mimic GABA

Do benzodiazepines enhance or inhibit the GABA-A receptor? What else does it do (2)

enhances GABA activity

↑ Inhibitory neuronal signaling

• Reduces the symptoms of anxiety

How do benzodiazepines change the membrane potential of neurons?

they increase chloride influx, which causes membrane hyperpolarization of the neuron

• Makes it less likely for the neuron to fire an action potential

What are the 5 types of adverse effects of benzodiazepines?

CARVT

1. CNS depression: fatigue, drowsiness, muscle weakness, etc.

2. Anterograde amnesia: pts don't remember what happened during tx/sedation

3. Respiratory effects: apnea after IV diazepam

4. Visual and dental effects: xerostomia, bitter/metal taste, narrow-angle glaucoma

5. Thrombophlebitis: blood clot in veins

T/F: Barbiturates are safer than benzodiazepines.

FALSE

• benzos are safer

How are benzodiazepines safer than barbiturates?

• Benzos have a wider therapeutic range (range of safe dose)

• Less likely to cause respiratory depression + Less potential for dependence and abuse when used as prescribed

T/F: You can get addicted to benzodiazepines and develop tolerance to them.

TRUE

• if long-term use & high doses

What is benzodiazepine antagonist? When is it used

Flumazenil (Romazicon)

• reverses sedating effects in the case of a benzo overdose

What would be the effects of Rifampin on the metabolism of benzodiazepines?

Rifampin increases CYP3A4 enzymes → which breaks down benzo drugs faster → and decreases benzo levels in blood → which decreases therapeutic effects of benzos

What would be the effects of grapefruit juice on the metabolism of benzodiazepines?

Grapefruit inhibits CYP3A4 → which decreases metabolism of benzos → and increases bioavailability of benzos and therapeutic effects → but higher risk of toxicity

What makes barbiturates more unsafe than benzodiazepines?

• high rate of abuse & withdrawal symptoms are worse

• complete CV and respiratory depression with overdose

How did Marilyn Monroe die?

*potential bonus question

Acute barbiturate poisoning

• ingestion of overdose

What is respiratory depression?

buildup of CO2 in blood; breathing becomes slow, shallow, or stopped altogether due to CNS depression

What is the difference between benzos and barbiturates regarding mechanisms of action?

• Benzos: Increase the frequency of chloride channels opening.

• Barbiturates: Increase the time in which chloride channels stay open.

• Both slow down brain activity

What are "Z" compounds? List 3 examples

Non-benzodiazepine, benzodiazepine receptor agonists

• Zolpidem (Ambien)

• Zaleplon (Sonata)

• Eszopiclone (Lunesta)

What receptor do Z compounds act on?

GABA-A receptor

What are Z compounds mainly prescribed for?

largely replaced benzodiazepines in the treatment of insomnia

Why can't you mix benzos or z compounds with alcohol? (3)

Can cause CNS depression

• enhances respiratory depression + sedation

• Increases risk of fatal overdose