Sedatives/Hypnotics, Anti-anxiolytics, and insomnia

Why are barbiturates rarely used?

they have a narrow therapeutic index + dangerous, resulting in lots of side effects (respiratory depression, CV depression, coma, death)

Why are BZDs used instead of barbiturates?

they have a broader TI so they are safer and have less SE

What is the MOA of BZDs?

allosterically bind to GABA-A sensitizing it to GABA, increasing the Cl- ion channel opening frequency, resulting in hyperpolarization of the cell

How does the affect of BZD change as dose increases?

Starts as anti-anxiety

then sedative

then hypnotic/stupor

What are examples of long acting BZDs?

Diazepam (Valium)

Clonazepam (Klonopin)

What kind of drugs are Diazepam (Valium) and Clonazepam (Klonopin)?

long acting BZDs

What are examples of medium acting BZDs?

Lorazepam (Ativan)

Temazepam (Restoril)

What kind of drugs are Lorazepam (Ativan) and Temazepam (Restoril)?

medium acting BZDs

What is an example of short acting BZDs?

Alprazolam (Xanax)

What kind of drug is Alprazolam (Xanax)?

short acting BZD

What is the most common side effect of BZDs?

drowsiness

What are the side effects of BZDs?

drowsiness

physical dependence

sedation + psychomotor impairment

memory impairment

cognitive impairment

withdrawal symptoms

What kind of drug is Flumazenil?

Benzodiazepine antagonist

when is flumazenil used?

suspected BZD overdose

reversal of sedative effects of BZD given during general anesthesia

What is the side effect of Flumazenil?

can cause BZD withdrawal

What is Busiprone (Buspar) used for?

generalized anxiety disorder

What are the "other" atypical anxiolytics?

Busiprone (Buspar)

Sympathetic blockers (alpha2 agonists, beta blockers

What is the MOA of Busiprone (Buspar)?

partial agonist of 5HT1A receptors therefore decreasing serotonins effect

What is the effect of Busiprone (Buspar)?

anti-anxiety with no sedation or anticonvulsant properties

What is the disadvantage of Busiprone (Buspar)?

anxiolytic effects take 3-4 weeks to work

What is the side effect of Busiprone (Buspar)?

dizziness

drowsiness

Gi distress

How do alpha-2 agonist work as an anxiolytic?

decreases sympathetic outflow (decreases NE release)

How does a beta blocker work as an anxiolytic?

decrease the peripheral symptoms of anxiety

If someone has acute onset anxiety, what would be a good drug to tx them with?

short acting BZD (Xanax)

If someone has chronic anxiety, what are good drugs to treat them with?

Buspirone (Buspar)

SSRIS

If someone has panic attacks what is a good drug to treat them with?

SSRI

What is the main difference between Eszopiclone (Lunesta) and Zopidem (Ambien)?

Eszopiclone (Lunesta) has a longer half life and is used for long term treatment of insomnia

Zopidem (Ambien) has a short half life and is used at night for insomnia

what makes both Zopidem (Ambien) and Eszopiclone (Lunesta) have a rapid onset?

they are both very lipid soluble

What is the MOA of Eszopiclone (Lunesta) and Zopidem (Ambien)?

bind to BZD site of GABA-A receptor, hyperpolarizes the cell

What are the side effects of Zopidem (Ambien) and Eszopiclone (Lunesta)?

daytime sedation

GI upset

What is Ramelteon (Rozerem)?

analog of melatonin

What is Ramelteon (Rozerem) used for?

treat sleep onset difficulties of insomnia

What are the three main drugs used to treat insomnia?

Eszopiclone (Lunesta)

Zopidem (Ambien)

Ramelteon (Rozerem)

How does histamine control wakefulness?

it is used in wake-promoting neurotransmission

What drugs have anti-histamine affects?

BZD??

antipsychotics

TCAs

tetracyclines

What systems that promote wakefulness?

Orexin system

Histamine

Serotonin

NE

What are sleep promoting neurotransmitters?

GABA

melatonin

galanin