Insomnia Tx

Question 1

Many of the drugs used to tx insomnia act on what receptor?

Answer 1

GABA

Question 2

How does GABA cause wakefulness?

Answer 2

Again note that two ascending pathways are involved in the ascending arousal system- the cholinergic (ACh) cell groups in the the upper pons, the pedunculopontine (PPT) aand the laterodorsal tegmental nuclei (LDT) activate the thalamus. A second pathway activates the cerebral cortex to faciliate processing of thalamic inputs and this arises from neurons in the monoaminergic cell groups, including the tuberomamillary nucleus (TMN) containing histamine, the A10 cell group containing dopamine the dorsal and median raphe nculei containing serotonin, and the locus coeruleus (LC) containing (NA). This pathway also receives contributions from peptidergic neurons in the lateral hypothalamus (LHA) containing orexin or melanin-concentrating hormones and from basal forebrain neurons that contain GABA or ACh

GABA functions as a negative regulatory of these ascending pathways and also functions as an inhibitor of neuronal activity in the cortex

Question 3

What mediates the very rapid transition between sleep and awake states?

Answer 3

Orexin containing axons. These neurons provide a link between the limbic system, energy homeostasis, the brain stem, and other systems

Question 4

How do orexin neurons promote waking?

Answer 4

through monoaminergic nucleus that are wake-active. Stimulation of dopaminergic neurons by orexins modulates reward systems (VTA)

Peripheral metabolic signals influence orexin neuronal activity to coordinate arousal and energy

Question 5

What does stimulation of Neuropeptide Y by orexin cause?

Answer 5

increased foos intake

Question 6

The suprachiasmatic nucleus (SCN), the central body clock, send input to proexin neurons via what?

Answer 6

the dorsomedial hypothalamus (DMH)

Question 7

Inout from the limbic system (amygdala and bed nucleus of the stria terminalis; BST) might be important to regulate what?

Answer 7

the activity of orexin neurons upon emotional stimuli to evoke emotional arousal or fear-related responses

Question 8

Question 9

What are the benzodiazepines used for insomnia tx?

Answer 9

Estazolam

flurazepam

quazepam

Temazepam

Triazolam

Question 10

What are the antidepressants used for insomnia tx?

Answer 10

doxepin

mirtazapaine

Trazodone

Question 11

What are the denzodiazepine receptor agonists used for insomnia tx?

Answer 11

zolpidem

zaleplon

eszopiclone

Question 12

What are the melatoni receptor agonist used for insomnia tx?

Answer 12

ramelteon

Question 13

What are the 1st gen antihistamines used for insomnia tx?

Answer 13

diphenhydramine

doxylamine

Question 14

What are the dual orexin receptor antagonist used for insomnia tx?

Answer 14

suvorexant

Question 15

Question 16

Key points about insomnia

Answer 16

-most drugs are used “off label” used at reduced doses for insomnia

Question 17

Question 18

Describe the GABA receptor

Answer 18

A multimeric transmembrane spanning protein complex that provides for gating of chloride entry into the cell.

Note that while barbiturates, benzodiazepines, benzodiazpine receptor agonists, and flumazenil all bind to the GABA receptor, but at different points

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