Anti-Anxiety Agents

Front 1

Drugs that end in -____ are benzos? Other benzos?

Back 1

-olam
-epam
Clorazepate

Front 2

Drugs that end in -____ are barbiturates? Others?

Back 2

-barbital
Thiopental
Meprobamate
Chloral hydrate

Front 3

Non-benzo/barbiturates anti-anxiety agents

Back 3

Buspirone
Zolpidem
Zaleplon
Zopiclone
Gaboxadol

Front 4

Which benzos have the shortest half life? Why?

Back 4

Lorazepam
Oxazepam

They start as hydroxylated compounds --> glucoronidate compounds (the form they are excreted in)
They have less drowsy effects
Onset is slower, though, b/c t is absorbed from gut

Front 5

Which benzo has the highest lipid solubility? What effect does this have?

Back 5

Diazepam
Quick onset

Front 6

Which classes of anxiolytics cross the placenta?

Back 6

Benzos and barbiturates

Front 7

How are barbiturates metabolized? Exceptions?

Back 7

All are metabolized in liver, except fro phenobarbital

Front 8

What role do norE and 5HT play in anxiety?

Back 8

Incresaed levels improve mood and can treat anxiety and depression

Front 9

Features of primary insomnia?

Back 9

Resembles normal sleep pattern, but increased sleep latency, multiple awakenings, or decreased total sleep time

Front 10

How long does it take for buspirone to relieve anxiety sx?

Back 10

A week or more, so not ideal for treating anxiety from a phobia or panic d/o

Front 11

What is used for emergency tx of seizures?

Back 11

barbiturates (also useful for pre-surgical sedation)

Front 12

What do BZ do to the sleep cycle?

Back 12

Decrease time spent in slow wavev sleep (deepest stage of sleep) and decresae the time in REM
# of REM episodes decreased
Sleep latency decreased
Onset to REM decreased

Front 13

What type of BZ should be used in ppl with sleep-onset insomnia and no daytime anxiety?
What abt for those with daytime anxiety?

Back 13

Compounds with short t1/2
BZ with longer t1/2

Front 14

What would happen to a pt with sleep apnea who took BZ?

Back 14

Decreases upper airway muscle tone and decreased arousal response to hypoxia
Would be BAD

Front 15

Do barbiturates or BZ have a better safety profile? Why?

Back 15

BZ are safer
Higher therapeutic:lethal ratio

Front 16

Which anxiolytics are useful for sedation?

Back 16

Alprozolam
Buspirone
Chlordiazepoxide
Diazepam
Halazepam
Lorazepam (low dose)
Oxazepam
Phenobarbital
Prazepam

Front 17

Which anxiolytics are useful for hypnosis?

Back 17

Chloral hydrate
Estazolam
Flurazepam
Lorazepam (high dose)
Quazepam
Secobarbital
Temazepam
Triazolam
Zaleptlon
Zolpidem

Front 18

All barbiturates are derived from _____?

Back 18

Barituric acid

Front 19

What confers the sedative-hypnotic effects of barbiturates?

Back 19

alkyl or aryl group at position 5

Front 20

What are thiobarbiturates? Example?

Back 20

Contain S group, more lipid soluble and have mroe rapid onset of effects
Thiopental

Front 21

What role does lipid solubility play in pharmacokinetics?

Back 21

Incresaed lipid solubility --> acts quicker and longer

Front 22

Where is the GABA binding site?

Back 22

btwn the alpha and beta subunits

Front 23

Where is the BZ binding pocket?

Back 23

btwn the alpha and gamma subunits

Front 24

What subunits do barbiturates require?

Back 24

alpha and beta subunits (gamma not needed)

Front 25

What do BZ do to GABAergic transmission?

Back 25

increases the frequency of channel opening and increases receptor affinity for GABA

Front 26

What is the alpha1 subunit associated with in BZ?

Back 26

sedative and amnestic effects

Front 27

What is the alpha2 subunit associated with in BZ?

Back 27

anxiolytic effects

Front 28

What is the alpha3 subunit associated with in BZ?

Back 28

noradrenergic, serotonergic, and cholinergic neurons

Front 29

What do barbiturates do to GABAergic transmission?

Back 29

increse the duration of channel opening

Front 30

What do barbiturates do to AMPA receptors?

Back 30

reduce the glutamate mediated neuronal excitation

Front 31

Which drugs are least likely to alter sleep patterns?

Back 31

Zolpidem
Zaleplon

Front 32

Phases of BZ/barbiturate biotransformation?

Back 32

Removal of substituent at position 1 or 2 of diazepam ring --> N-desalkylated compound
Hydroxylation --> oxazepam or nordazepam
Conjugation of 3-OH compound with glucaronic acid

Front 33

Which is the slowest part of the biotransformation process?

Back 33

forming 3-OH from desalkylated compounds

Front 34

How are BZ/barbs excreted?

Back 34

in urine

Front 35

What drug interacts with warfarin? Why?

Back 35

Chloral hydrate
Displaces warfarin from its plasma proteins

Front 36

Adverse side effects of BZ?

Back 36

Euphoria
Impaired judgement
Loss of self-control
Hostility and violence at high doses
Anterograde amnesia
Tolerance/dependence

Front 37

How does pharmacodynamic tolerance of BZ occur?

Back 37

Down-regulation of BZ receptors

Front 38

How is the t1/2 associated with w/d sxs?

Back 38

longer t1/2 less likely to produce w/d

Front 39

What can be used to alleviate w/d sx from short acting drugs?

Back 39

longer acting ones (diazepam)

Front 40

Contraindications for BZ?

Back 40

other CNS depressants
Anti-convulsants
TCAs
OTC histamines

Front 41

What can cross react with BZ?

Back 41

Barbiturates and EtOh

Front 42

How can BZ OD be treated?

Back 42

Flumazenil (BZ antagonist) and conservative tx (mechanical ventilation, maintenance of plasma volume, etc)

Front 43

What is flumzenil?

Back 43

BZ receptor antagonist
Blocks actions of BZ, zolpidem, zaleplon
NOT effective against barbiturates, opioids, EtOH, or anesthetics

Front 44

What aspect of BZ OD does flumezenil reverse?

Back 44

sedative effect
reversal of respiratory distress less predictable

Front 45

How is flumazenil administered?

Back 45

IV
Has short t/12 (1hr), so must be given repeatedly

Front 46

What is contraindication for flumazenil?

Back 46

Seizures that are controlled with BZ
BZ dependent ptts
Co-ingestion of drugs that are epileptogenic in OD
Pts with head trauma or increased intracranial P

Front 47

How does flumazenil work?

Back 47

Binds GABA receptor and competitively inhibits BZ binding

Front 48

Adverse side effects of barbiturates?

Back 48

HA
Retrograde amnesia
Delirium
Prolonged somnolence
Paradoxical excitement myocardial, resp, circ depression
N/V
Nightmares, hallucinations
Tolerance

Front 49

Minor w/d sx from barbiturates? Major w/d x?

Back 49

anxiety, muscle twitching, tremor, etc
Convulsions, delirium, death

Front 50

How do barbiturates and digitalis interact?

Back 50

Increases the rate of its metabolism, decreasing effectiveness

Front 51

What is the absolute contraindication of barbiturates in pts?

Back 51

Pts with porphyria (deficiency in heme pathway, depositing porphyrin in the tissue)
Barbiturates increase porphyrin synthesis

Front 52

Barbiturate OD features?

Back 52

NOT reversed by flumazenil
Most common cause of death is from resp failure

Front 53

What is buspirone used to treat?

Back 53

GAD
NOT for acute anxiety or panic attacks

Front 54

What are the cross tolerances of buspirone?

Back 54

NONE!

Front 55

MOA of buspirone?

Back 55

interacts w DA and 5HT receptors

Front 56

Contraindications for buspirone?

Back 56

MAOIs

Front 57

Features of zolpindem and zaleplon?

Back 57

Have hypnotic but not anxiolytic actions

Front 58

What antagonizes zolpidem and zaleplon?

Back 58

Flumazenil

Front 59

Adverse effects of zolpidem and zaleplon?

Back 59

Zolpidem --> day after mental and motor depression and daytime sedation
Zaleplon has no more side effects than placebo

Front 60

Contraindications for Zolpidem and Zaleplon?

Back 60

Cimetidine
Elderly
Hepatic impairment
Compromised respiratory status

Front 61

Zopiclone?

Back 61

GABAA agonist
Longer lasting than Zolpidem and zaleplon
Reduces sleep latency, nighttime awakenings and increases total sleep time

Front 62

What effect does Zopiclone have on sleep architecture at low doses?

Back 62

None

Front 63

What effect does Zopiclone have on sleep architecture at hiihg doses?

Back 63

suppresses REM

Front 64

Which of the Z drugs can be used long term?

Back 64

Zopiclone

Front 65

Contraindication for zopiclone?

Back 65

Ingestion with large doses of other CNS depressents (ex: EtOH) = LETHAL!

Front 66

Gaboxadol?

Back 66

has lower affinity for gamma subunits, but also binds alpha, beta, delta receptors which are extrasynaptic

Front 67

Benefits of gaboxadol?

Back 67

Does not interact with BZ or EtOH (affects different receptors)

Front 68

What role does gaboxadol play in sleep?

Back 68

Decreases sleep latency and duration

Front 69

Adverse side effects of gaboxadol?

Back 69

NONE!

Front 70

Which BZ are long acting?

Back 70

Diazepam
Chlorazepate
Halazepam
Flurazepam

Front 71

Which BZ are short or intermediate acting?

Back 71

Triazolam
Midazolam
Alprazolam

Front 72

What is the difference between how long and medium acting BZ are metabolized?

Back 72

Long acting have 2 intermediate compounds before they get glucoronidated, short/medium acting have only 1 intermediate before they get glucoronidated