Pathophysiology of anxiety and sleep disorders - Yang

What is the main target of neurotransmitters for biological regulators of sleep?

GABA

What do Benzodiazepines bind to? What does it cause?

Binds to GABAa a1-5, increases frequency of channel opening

What do Barbituates bind to? What does it cause?

Binds to GABAa a1-5, increases duration of channel openings, and has direct effects of GABA a channels at high doses

What is the source of metabolites for Benzodiazepines?

1 position alkylation

What happens due to the annealation of the 1-2 bond with an electron-rich ring like triazole or imidazole?

High affinity and decreased half life

Diazepam

1) Duration of Action

2) Treatment for

Long half life with slow elimination rate, treats seizures and accumulation of metabolites

Clonazepam

1) elimination rate

2) uses/treatment for?

Intermediate elimination rate, used as anticonvulsant

What is a rapid elimination rate BZD?

midazolamA

What type of drug between BZDs and Barbiturates have a high CNS effect risk?

Barbituates

Pharamcological Properties of BZDs. Use? SE?

Decreased REM, stage 3 and 4. Anticonvulsant with side effects that are dose dependent

What treats BZD overdose?

Flumazenil

List the Z-hypnotic examples and thier duration of treatment for insomnia

Zolpidem and Zaleplon are short term and eszopiclone are long term

What are things to warn about when using Z-hypnotics?

Sleep-driving, sleep-cooking, sleep-eating, sleep-sex

BBT are dangerous why?

Cause respiratory depression causing death

GABA B uses what specific G protein?

Gi

What is the concern with using Gamma-hydroxybutyric Acid (GHB). What GABA does it bind to?

No antagonist, GABA B

Ramelteon

1) MOA

2) Use

3) SE/Risks effects

Melatonin agonist, serves as master clock for regulating circardian rhythm, no abuse, withdrawal, or dependency

What drug is an orphan product that is a melatonin agonist?

Tasimelteon

Suvorexant:

1) MOA and where

2) Effects and where

Orexin receptor antagonist in the hypothalamus, reduces rewarding stimuli (DA release) between the VTA and nucleus accumbens

What antihistamines have an antihypnotic effect?

diphenhydramine, doxylamine, pyrilamine

What are herbal/natural products have sedative-hypnotic effects?

Melatonin and valerian

What is there to note about valerian?

Hepatotoxicity

Norepinephrine project to where?

amygdala (fear center)

How does GAD come about in the CNS?

Glutamate is converted to GABA by glutamic acid decarboxylase

Buspirone:

1) MOA

2) duration of action

3) risks/se

partial 5HT1a agonist, longer onset of action than BZD due to adaptive repsonse, low abuse potential

Propranolol

1) dosing

2) effects

Test dose initially and decreases peripheral symptoms of anxiety