1. Arousal spectrum: as it spans around an awake, alert, creative and problem solving person
from deficient arousal to excessive arousal
2. Sleep wake
... [Show More] switch: set of circuits in the hypothalamus that regulate sleep and wake discontinuously
3. Tubermamillary nucleus (TMN): Wake promoter (on)
4. Ventrolateral preoptic nucleus (VLPO): Sleep promoter (off)
5. Lateral hypothalamus (LAT): orexin containing neurons these are lost in narcolepsy
especially narcolepsy with cataplexy
6. Suprachiasmic nucleus (SCN): melatonin sensitive neurons brains internal clock
pacemaker
regulates circadian input to the sleep wake switch
7. Histamine: key neurotransmitter regulating wakefulness ultimate target of many drugs
produced from histidine
H1 and H3 receptors in brain
also acts on NMDA, but unclear how
all histamine neurons arise from a single small are of hypothalamus, the TMN
8. Homeostatic: sleep drive
9. Circadian: wake drive
10. Sleep regulation: small number of interconnecting systems or centers that are located chiefly in the brainstem and that mutually activate and inhibit one another.
11. Norepinepherine: controlling sleep patterns locus ceruleus
drugs and manipulations focused here reduce REM sleep
12. Acetylcholine: particularly in the production of REM sleep
disturbances in central cholinergic activity are associated with sleep changes in depression
13. Alzheimers dementia: reduced REM and slow wave sleep from loss of cholin- ergic neurons in basal forebrain
14. Melatonin: secretion from pineal gland inhibited by bright lig lowest serum concentrations during day
15. Suprachiasmatic nucleus: hypothalamus
anatomical site of a circadian pacemaker that regulates melatonin s the entrainment of the brain to a 24 hour sleep wake cycle
16. Dopamine: has an alerting affect
18. circadian rhythm:
19. Histamine synthesis: Histidine taken into histamine nerve terminals via a his- tidine transporter and converted into histamine by enzyme histidine decarboxylase (HDc) and packed into vesicles
20. Histamine metabolism: Termination: broken down intracellularly by histamine n-mehtly-transferase (histamine NMT) which converts histamine into n-mehtly-his- tamine, which then is converted by MAO-B into the inactive substance n-methly-in- doleacetic acid.
21. Histamine receptor H1: H1 - really involved in sleep G-protein linked receptor
Variety of intermediate steps to promoting sleep
22. Histamine receptor H2: -does not appear to be directly related to wakefulness
-G protein linked
23. Histamine receptor H3: autoreceptor presynaptic
24. MOA of caffeine: -Antagonist of endogenous neurotransmitters (Purines)
-caffeine antagonizes purine receptor and prevents adenosine from binding result- ing in increased dopamine action
25. pharmacokinetics: -how the body acts upon drugs
-mediated through hepatic and drug metabolism
26. Pharmacodynamics: -What is the action of the drug on the body? Accounts for therapeutic action and side effects of drug.
27. Half-life serum: -takes about 5 half-life cycles for drug to be eliminated
-concentrations may be higher in brain
28. steady state: -Balance between addition of drug and action of CYP metabo- lization.
-Takes about 5 half-life cy [Show Less]