T3 Komiskey - Sedative-Hypnotics

Front 1

Name the classifications of drugs that are commonly used as sedatives.

Back 1

Anti-depressants, barbituates, benzodiazepines, typical antipsychotics, atypical antipsychotics; non-benzodiazepine sedatives (newest)

Front 2

what is the main control center of the circadian rhythms of sleep and temperature?

Back 2

the SUPRACHIASMATIC NUCLEUS (SCN) - part of the hypothalamus (located above the optic chiasm) - controls synchronized sleep according to patterns of light and dark

Front 3

what endocrine gland does the suprachiasmatic nucleus regulate and what does it secrete?

Back 3

SCN regulates the pineal gland (posterior to thalamus): PG secretes melatonin (hormones increases sleepiness)

Front 4

what receptors does melatonin act on?

Back 4

MT1, MT2, and MT3 receptors

Front 5

What are the stages of normal sleep?

Back 5

stage 1 (drowsiness), Stage 2 (light sleep), Stage 3&4 (deep, "slow-wake" sleep), REM (rapid eye movement "dream sleep", almost awake, occurs mostly in morning)

Front 6

explain the order of the sleep patern stages.

Back 6

go 1-2-3-4-3-2-REM-2-3-4-3-2-REM (each cycle lasts ~90minutes)

Front 7

explain when stages 3 and 4 occur and what about the stages length?

Back 7

stage 3 and 4 occur early in the night and the length will decrease as the night progresses

Front 8

what part of the CNS is responsible for arousal?

Back 8

reticular formation in midbrain (extends from the medulla to the forebrain)

Front 9

name the area and neurons that are important for promoting sleep.

Back 9

ventrolateral preoptic area (VLPA) contains ventrolateral preoptic nucleus that inhibits other neurons that are responsible for wakefulness. it sends inhibitory GABA projections to places that keep you awake: locus coeruleus (NE), raphe (5-HT), and the tuberomammillary nucleus (histamine)

Front 10

if you were to lesion the VLPA (ventrolateral preoptic area) what would happen?

Back 10

lesions produce total insomnia, leading to death

Front 11

what waves will predict the onset of REM? where is this activity first detected?

Back 11

PGO (pontogeniculooccipital) waves- high amplitude electrical potentials; pons --> lateral geniculate of hypothalamuc --> occipital cortex

Front 12

what neurotransmitter and what part of the pons is responsible for modulating REM?

Back 12

ACh neurons in the peribrachial pons modulate REM sleep; increase ACh, increase REM; these peribrachial neurons fire at a high rate during REM

Front 13

explain the production of rapid eye movement.

Back 13

pontine ACh neurons project to the thalamus (control cortical arousal), to the forebrain (arousal and desynchrony), and to the TECTUM (RAPID EYE MOVEMENT)

Front 14

name the area that is anterior and dorsal to the hypothalamus that contains cells that extend throughout the thalamus and cerebral cortex; it release inhibitory GABA (essential for sleep) as well ACh for arousal.

Back 14

basal forebrain

Front 15

name and describe two sleep disorders.

Back 15

INSOMNIA: difficulty getting to or remaining asleep and NARCOLEPSY: falling asleep at odd times; narcopleptics have a reduced CSF levels or altered activity of the neuropeptide OREXIN(neuropeptide transmitter responsible for the ability to stay awake)

Front 16

What is orexin and what does it stimulate?

Back 16

orexin is a peptide neurotransmitter released in a pathway from the hypothalamus that is highly responsible for the ability to stay awake; it stimulates ACh-releasing cells in the forebrain and brainstem

Front 17

what does adenosine do in regard to sleep and arousal?

Back 17

accumulation of adenosine in the brain will inhibit the basal forebrain cells responsible for arousal and CAUSE SLEEP. (caffeine blocks adenosine receptors)

Front 18

in order to go to sleep, you must have decreased arousal. how does this occur?

Back 18

to go to sleep: 1. the brain and body decrease its temperature, 2. decrease stimulation by finding a quiet environment, 3. the brain accumulates adenosine - inhibits the basal forebrain cells from releasing ACh

Front 19

Describe the different types of insomnia.

Back 19

TRANSIENT: <3days and caused by brief environmental or situational stress; SHORT-TERM: 3days - 3weeks caused by stressors such as illness, grief, or job problems; LONG-TERM INSOMNIA: lasting for more than 3 weeks (causes: major pychiatric illnesses and drugs, medical condition, or conditioned or learned behavior, sleep apnea)

Front 20

If a depressed patient is on an SSRI and she can't sleep, what maybe should you try?

Back 20

switch her to trazodone; anti-depressent that is good at inhibiting serotonin reuptake (structure similar to a BZD)

Front 21

when should you not use a sedative-hypnotic?

Back 21

sleep apnea

Front 22

Name some sedative-hypnotics that don't really help the quality of sleep.

Back 22

Barbituates decrease REM; Benzodiazepines reduce slow-wake non-REM sleep and produce cognitive changes (next day confusion, falling, rebound next-day anxiety, worsen sleep apnea)

Front 23

when a person is on a long-term treatment with a Benzodiazepine, what do you have to be careful of when taking them off?

Back 23

taper it down, may cause seizures, rebound insomia, and altered sleep patterns

Front 24

in deciding what sedative is best, which 3 are preferred over barbituates?

Back 24

benzodiazepines, and non-BZD: zolpidem and zaleplon

Front 25

what sedative-hypnotics are preferred in elderly?

Back 25

Benzodiazepines

Front 26

What drugs should be avoided in treating insomnia?

Back 26

avoid barbs, glutethimide and meprobamate (all have high abuse potential and easy to overdose)

Front 27

name 2 short active barbituate sedative hypnotics.

Back 27

pentobarbital sodium and secobarbitoal sodium (good for s/term tx of insomnia or preoperatively)

Front 28

what is the MOA of most sedative hypnotics?

Back 28

most sedative hypnotics bind to the GABA receptor and cause Cl- channels to open, thus hyperpolarizing and inhibiting the effect of neuronal excitability

Front 29

what is the MOA of barbituates?

Back 29

multiple MOA: 1. increase GABA effect (increase Cl channel opening duration), 2. directly activate GABAa channels at high concentrations; 3. block glutamate NT effects; 4. Block Na channels; barbs DO NOT relieve pain and may lead to tolerance and dependence and death by overdoes: NOT GENERALLY USED TODAY FOR SLEEP-AIDs

Front 30

in order for a benzodiazepine to bind to the GABA receptor, what must be present?

Back 30

BZDs need GABA to be present on the GABA receptor in order to work; it will cause an even greater influx of Cl and hyperpolarize with greater affinity

Front 31

name some non-benzo sedatives; how long are they recommended for use?

Back 31

zolpidem and zaleplon (recommended for 7-10 days only); and chloral hydrate (older, cheap, converted to trichlorothanol, slow clearance)

Front 32

name barbituates toxicities/side-effects that may occur.

Back 32

alcohol and barbs - respiratory and CV depression; ADDITIVE: CNS depression; anterograde amnesia with Benzos (date rape);;;;Barbs use cyt P450 enzymes

Front 33

Name a drug that has been approved for narcolepsy, excessive somnolence and obstructive sleep apnea. explain its MOA.

Back 33

modafinil; MOA: activates orexin producing neurons (alpha agonist, facilitates Glu, reduces GABA)

Front 34

what is the drug ramelteon (Rozerem)'s MOA and what are its indications?

Back 34

used to tx adults with difficulty of sleep onset; not a controlled substance; MOA: melatonin receptor (MT1, MT2) agonist (not to be used in renal impairment)

Front 35

name the BNZ antagonist that can halt the effects of benzodiazepines.

Back 35

flumazenil

Front 36

name a common side-effect of high dose Benzodiazepines.

Back 36

anterograde amnesia

Front 37

Name drugs that are used to treat insomnia.

Back 37

BNZs(daytime sedation, REM reduced; rebound with bizzare dreams); NON-BZDs(less daytime sedation and no effects on REM): ZOLPIDEM (can eat, cook, and drive while asleep) and ZALEPLON

Front 38

what alpha receptors will BZDs use? which ones are good for sedation, anxiety, and which will produce anterograde amnesia?

Back 38

BZDs are sensitive to alpha 1,2,3,5; 1 is good for sedation; 2&3 are good for anti-anxiety; 1&5 will produce amnesia

Front 39

what are common long-term effects of BZD abuse?

Back 39

lethargy, irritability, nausea, loss of sexual interest, increased appetite, and increased weight