Sedative Hypnotics

Front 1

Sedatives, formerly known as __________, produce calmness and relaxation and are therefore AKA ___________.

Back 1

1. minor tranquilizers
2. anxiolytic (antianxiety agents)

Front 2

sedatives are not intended for ___________, as this use contributes to the abuse potential

Back 2

stress and tension of everyday living

Front 3

a sedative produces _______, while a hypnotic produces ___________, and all hypnotics are __________

Back 3

1. calmness and relaxation
2. sleep
3. sedatives

Front 4

Describe the stages of sleep:
1. Stage 0
2. Stage 1
3. Stage 2
4. REM sleep

Back 4

1. awake
2. onset of sleep
3. light, restful sleep that makes up 50% of total sleeptime
4. 25% of total sleep time

Front 5

with each sleep cycle, the ________ increases

Back 5

amount of REM sleep

Front 6

Do sedative-hypnotics tend to cause both physical and psychological dependence?

Back 6

Yes (It can occur within 1-3 months)

Front 7

Describe the dose-related effects of CNS depressants:
1. low doses
2. higher doses
3. highest doses

Back 7

1. sedative
2. hypnotic
3. anesthetic

Front 8

Are CNS depressants used to treat anxiety and/or insomnia?

Back 8

No

Front 9

CNS agents have a _______therapeutic index and exhibit ____________ activity

Back 9

1. narrow
2. anticonvulsant

Front 10

Barbituates are __________, which causes numerous drug interactions

Back 10

inducers of the P450 system

Front 11

ADR of barbituate sedative-hypnotics:
1. large doses lead to_______
2. chronic use leads to _______
3. barbituate abstinence syndrome?

Back 11

1. prolonged CNS depression
2. tolerance, dependence, and withdrawal
3. life threatening condition involving convulsions and delirium

Front 12

what are two components of barbituate tolerance?

Back 12

-enzyme induction and CNS changes

Front 13

how does overdose of barbituates lead to fatality?

Back 13

depression of medullaryrespiratory and CV control centers leads to respiratory failure

Front 14

barbituates have additive/synergistic CNS depression when used with __________

Back 14

other depressants such as alcohol

Front 15

indications for benzodiazepines?

Back 15

insomnia (characterized by difficulty falling asleep, frequent nocturnal waking or early morning waking)

Front 16

name three benzodiazepines used for insomnia?

Back 16

Estrazolam, Triazolam, Flurazepam

Front 17

benzodiazepines potentiate neuronal transmission involving pathways using _______ as an inhibitory neurotransmitter

Back 17

GABA

Front 18

There are two subtypes of the GABA-A receptor. Stimulation of which receptor results in sleep onset and cycle regulation?

Back 18

-BZ1

Front 19

which GABA-A receptor types are activated by benzodiazepines?

Back 19

-all are activated nonspecifically, which accounts for the wide range of actions of benzodiazepines

Front 20

1. which three agents can only activate one BZ binding site?
2. what does this binding account for?

Back 20

1. Zolpidem, Zalepon, and Eszopiclone
2. relatively selective hypnotic action and lack of anticonvulsant and muscle relaxant effects

Front 21

Both barbituates and benzodiazepines have additive/synergistic effects with other CNS depressants, which has more CNS depressant activity?

Back 21

barbituates

Front 22

Give three reasons why barbituates are more likely to be CNS depressants

Back 22

1. they bind to specific receptors that are different from BZ receptors
2. Direct GABAmimetic activity at higher concentrations
3. Inhibition of excitatory CNS neurotransmitters

Front 23

How do BZs affect sleep patterns?

Back 23

-decrease stages 0 and 1 and the # of wakenings
-increase stage 2 and REM sleep
-onset of REM is delayed and dreaming is diminished

Front 24

how soon does tolerance develop to benzos?

Back 24

several weeks

Front 25

which type of benzos are best at achieving rapid onset, duration through the night, and no residual hangover?

Back 25

short-acting and medium-acting

Front 26

__________is a short-acting benzo that is associated with rebound insomnia and early morning awakening

Back 26

Triazolam

Front 27

name two intermediate acting benzos?

Back 27

estazolam and temazepam

Front 28

_____________is a long-acting benzo agent with an active metabolite that has a long half-life

Back 28

Flurazepam

Front 29

which benzo agent has increased daytime anxiety after ten days of continuous use due to tolerance and "interdose withdrawal"?

Back 29

triazolam

Front 30

name an ADR of triazolam that is considered to be a class effect of benzos

Back 30

anterograde amnesia

Front 31

describe the withdrawal symptoms related to physical dependence on benzos and the method of discontinuance

Back 31

-muscle cramps, tremors, convulsion
-gradual withdrawal with a tapering schedule lasting > 2wks

Front 32

which nonbarbiturate, nonbenzo sedative-hypnotic agents are approved for short-term tx of insomnia? (2)

Back 32

-zolpidem and zaleplon

Front 33

which nonbarbiturate, nonbenzo sedative-hypnotic agents are approved for tx of insomnia? (3)

Back 33

-zolpidem ER, eszopiclone, and ramelteon

Front 34

chloral hydrate is rapidly absorbed and metabolized to its active metabolite, ___________

Back 34

trichloroethanol

Front 35

trichloroethanol,active metabolite of chloral hydrate, has what effects of sudden withdrawal/detoxification?

Back 35

seizures, hallucinations, and delirium

Front 36

describe the interaction between chloral hydrate with alcohol and CNS depressants

Back 36

-additive/synergistic effects because they competitively inhibit each other's metabolism

Front 37

zolpidem is a _______receptor agonist that preferentially interacts with __________receptor subtypes

Back 37

1. benzodiazepine
2. BZ1

Front 38

does the dose at which zolpidem exerts hypnotic effects cause anxiolytic, anticonvulsant, and muscle relaxant effects?

Back 38

nope

Front 39

how does zolpidem affect the sleep cycle?

Back 39

-decreases sleep latency (stage 1)
-increases total sleep time and duration

Front 40

therapy with zolpidem should be limited to what time period?

Back 40

7-10 days

Front 41

which ADR appear to be minimal with Zolpidem?

Back 41

tolerance, dependence, withdrawal, and rebound insomnia

Front 42

__________is the first and only ER sleep med that promotes falling asleep and maintaining sleep with no significant decrease in next-day performance.

Back 42

Zolpidem tartrate ER

Front 43

indication for zolpidem tartrate ER

Back 43

-tx of insomnia characterized by difficulties with sleep onset and/or sleep maintenance
-not limited to short-term tx

Front 44

MOA of Zaleplon

Back 44

-BZ1 receptor agonist
-shortens time to sleep onset
-DOES NOT increase sleep duration or reduce # of awakenings

Front 45

administration/dosing of zaleplon

Back 45

-admin immediately at bedtime or up to 4 hr prior to anticipated wake time for difficulty falling asleep
-does not cause residual sedation and next-morning memory impairment when dosed in middle of the night

Front 46

what kind of agent is eszopliclone?

Back 46

active S-isomer of the hypnotic zopiclone (a BZ1 receptor agonist)

Front 47

characteristics of eszopiclone:
1. effects on insomnia
2. ADR
3. limited to short term use?

Back 47

1.improves all components of insomnia
2. less likely to cause ADR such as dependence, abuse potential, residual daytime psychomotor and memory impairment
3. no

Front 48

___________is a selective melatonin receptor agonist that stimulates type 1 (MT1).

Back 48

ramelteon

Front 49

indication for ramelteon

Back 49

-adult insomnia characterized by difficulty with sleep onset
-not limited to short term use

Front 50

is ramelteon a controlled substance? Why or why not?

Back 50

-no-it has no evidence of abuse potential ordependence

Front 51

what are the pharmacological actions that benzodiazepine anxiolytics share?

Back 51

-hypnotic, anxiolytic,anticonvulsant, muscle relaxant, amnesiac

Front 52

what are the advantages of benzodiazepine anxiolytics?

Back 52

-rapid onset, high therapeutic index, and relatively few ADR

Front 53

what are the disadvantages of benzodiazepine anxiolytics

Back 53

-tolerance, impaired psychomotor skills, dependence (so D/c gradually)

Front 54

GAD::
1. 1st lline drugs
2. 2nd line drugs
3. when would you use benzos?

Back 54

1. antidepressants
2. buspirone
3. for acute relief or if symptoms warrant

Front 55

DOC of relieving stress-related anxiety related to major life stressful events

Back 55

-benzos
-especially effective for insomnia and restlessness

Front 56

Panic D/O::
1. 1st line drug and time to improved symptoms?
2. 2nd line drug and which one is effective within days?

Back 56

1. SSRIs-2-3 wks
2, BZs-alprazolam

Front 57

PTSD DOC

Back 57

SSRIs

Front 58

Alcohol Withdrawal Syndrome::
1. symptoms within 1st 2 days?
2. within 1st 3 days?

Back 58

1. tonic-clonic seizures
2, delirium tremens-hyperthermia, tachycardia, delirium, and hallucinations

Front 59

AWS::
1. DOC
2. agents with fewer rebound effects and withdrawal seizures
3. agents that do not undergo hepatic metabolism, metabolized to inactive compounds, and short duration of action?
4. what dose for elderly or pts with hepatic dz?

Back 59

1. BZs
2. Chlordiazepoxide and Diazepam (longer-acting)
3. Lorazepam and Oxazepam(short-acting)
4. 50% pf dose used in younger pts

Front 60

indications for diazepam

Back 60

-muscle relaxant, anticonvulsant, and preoperative medication

Front 61

indications for lorazepam?

Back 61

-preanestheic med to produce sedation and amnesia, status epilepticus

Front 62

indications for alprazolam?

Back 62

-panic D/O w/wo agoraphobia

Front 63

indications for chlordiazepoxide?

Back 63

acute alcohol withdrawal

Front 64

MOA of BZs

Back 64

-GABA-A rec is liandgated ion channel that when activated opens and allows chloride ion influx
-accumulation of chloride anions causes hyperpolarization of cell
-decreases/interrupts synaptic and neuronal transmission

Front 65

GABA-A rec contains _________binding sites for BZs, therefore BZs act as ___________of GABA activity

Back 65

1. three
2. allosteric modulators (frequency of Cl channel opening is increased adn GABA activity is enhanced but in absence of GABA they have no action)

Front 66

pharmacological actions of BZs produced by activation of GABA-A rec? (3)

Back 66

-hypnotic, anticonvulsant, and muscle relaxant

Front 67

what are the effects that occur at BZ doses beyond those needed for anxiolytic and amnesic effects?

Back 67

ataxia and sedation

Front 68

Therapeutic index of BZs

Back 68

-wide (high)

Front 69

IM admin of diazepam and clordiazepoxide is poorly absorbed due to ___________and peak levels are __________and ___________compared to oral dosing

Back 69

1. poorly absorbed due to precipitation in muscle causing slow erratic absorption
2. lower
3. take longer to reach

Front 70

___________is a common active metabolite for several BZs, including diazepam and accumulation of this can occur with chronic dosing and cause___________

Back 70

1. desmethyldiazepam
2. oversedation and ataxia

Front 71

withdrawal symptoms for BZs

Back 71

-muscle cramps, tremor, tonic-clonic seizures

Front 72

ADR for BZs

Back 72

CNS depression (drowsiness, sedation, lethargy, impaired psychomotor performance)

Front 73

results of overdose of BZs

Back 73

-only mild respiratory suppresion, unless taken with alcohol which can be fatal

Front 74

additive/synergistic effects of BZs and other CNS depressants can lead to ________

Back 74

severe ataxia

Front 75

only approved indication for buspirone?

Back 75

-mgmt of anxiety d/o or short-term relief of anxiety

Front 76

MOA of buspirone

Back 76

-reduces serotonergic activity in states of serotonin excess
-partial agonist for serotonin postsynaptic receptors
-antagonist in presence of 5HT
-full agonist at 5HT1A presynaptic receptors(inhibits 5HT release)

Front 77

what is the significance of buspirone not binding to BZ receptors or affecting GABAergic transmission?

Back 77

- no anticonvulsant or muscle relaxant effects
- lacks prominent sedative effects of other anxiolytics
-does not exhibit cross-tolerance with BZs and other sedative/hypnotics

Front 78

optimal result with buspirone require tx for how long?

Back 78

3-4wks

Front 79

what can happen as a result for buspirone's affinity for DA receptors?

Back 79

-potential to cause symptoms of dopamine blockade

Front 80

DI of buspirone?

Back 80

-MAOIs contraindicated
-P450 can cause buspirone to elevate up to 13x, causing drowsiness and dizziness

Front 81

effects of abrupt discontinuation of buspirone?

Back 81

none

Front 82

MOA of Flumazenil

Back 82

-BZ receptor competitive antagonist
-does NOT reverse effects of ethanol, barbituates, opioids,or general anesthetics

Front 83

indications for flumazenil

Back 83

-complete or partial reversal of sedative effects of BZs where::
-general anesthesia induced or maintained with BZs
-sedation prod by BZs for diagnostic and therapeutic procedures
-mgmt of BZs overdose is necessary (as adjunct to supportive measures)

Front 84

primary ADR of flumazenil

Back 84

-risk of seizures due to reversal of BZ effects in high risk populations:
-concurrent sedative-hypnotic w/d
-concurrent tricyclic antidepressant poisoning
-physical dependence on BZs