Block 2 Lecture 3 -- Anxiolytic and Hypnotic Drugs Flashcards Preview

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Flashcards in Block 2 Lecture 3 -- Anxiolytic and Hypnotic Drugs Deck (87):
1

What is anxiety?

inappropriate worry in absence of a true threat that significantly impairs QoL.

2

Sxs of OCDs.

obsession
thoughts of murder + sex
hallucinations
fear to use public toilets

3

Sxs of social phobias.

fear of excessive humiliation
" public speaking
" public toilets

4

Sxs of mixed anxiety and depressive disorder.

-- anxiety
-- inner tension, depression
-- aggressiveness

5

Sxs of panic disorder.

-- fear of dying
-- fear of going
-- chest pain + SOB

6

How is GAD treated?

1st: CBT
2nd: anti-depressant
3rd: anti-depressant combos

7

What are the FDA-approved anti-depressants available for GAD treatment?

1st: SSRIs
-- es/citalopram, paroxetine, fluoxetine
-- +NET: duloxetine, venlafaxine
2nd: buspirone
also: hydroxyzine
also: combos, anti-convulsants
short-term: BZDs

8

What is hydroxyzine?

h1 antagonist

9

When is buspirone used in GAD?

2nd line as adjunct to SSRI or as monotherapy

10

Describe the onset of SSRIs

2-4 weeks

11

What happens if a GAD patient fails the 1st-line anti-depressant?

try another anti-depressant

12

What is agoraphobia?

avoidance of triggers evoking panic

13

How are agoraphobia and other anxiety disorders treated?

similar to GAD when chronic
-- anti-depressants (1+), buspar, combos
-- BZDs for exacerbations or agoraphobia
-- beta-blockers for acute panic

14

What drugs may cause secondary anxiety disorders?

1) NET/DAT-active anti-depressants
2) sympathomimetics
3) thyroid hormone
4) stimulants

15

What might anxiety disorders be secondary to?

1) medical conditions
2) drugs
3) drug withdrawal

16

For what conditions are barbs indicated?

1) induction of anesthesia
2) epilepsy
3) severe tension/migraine HA

17

MoA of barbs:

APLs of GABAa
-- increase duration of channel opening
-- synergistic with EtOH, BZDs, Z drugs, opioids

18

How does one become tolerant to barbs?

1) rapid PK (1a2, 2c9, 2c19, 3a4)
2) slow PD (decrease GABA # and change composition)

19

Why are barb withdrawals life-threatening?

convulsions

20

How are barbs categorized?

duration of action

21

ultra-short acting barbs:

methohexital
thiopental

22

What are ultra-short-acting barbs indicated for?

1) induction of anesthesia
2) terminal anesthesia

23

What are the intermediate-acting barbs?

1) pentobarbital
2) butalbital

24

What are the long-acting barbs?

phenobarbital

25

How is phenobarb used?

long-acting barb for anti-convulsant

26

How is butalbital used?

included with ASA/APAP and caffeine
-- w/ codeine for tension HA

27

What is the old lethal injection cocktail?

sodium thiopental, pancuronium br, KCl

28

What is the newer lethal injection cocktail?

hi-dose Na thiopental or pentobarbital

29

Where are alpha-1 containing GABAa receptors located?

most abundant, most widely distributed
-- also in VTA and HT
(hypnotic, anticonvulsant, amnestic, addiction)

30

Where are alpha-2 containing GABAa receptors located?

limbic, cortex, striatum (anxiolytic properties when agonized)

31

Where are alpha-3/5 containing GABAa receptors located?

spinal cord (muscle relaxant properties when agonized)

32

What is the MoA of BZDs?

non-selectively interact with a1/2/3/5 subunits of GABAa receptors
-- increase affinity for GABA
-- increase frequency of channel opening

33

Why don't BZDs cause fatal respiratory depression?

do not directly open Cl channel

34

How long should BZDs be used?

DNE 2-4 weeks or past acute exacerbation

35

What co-morbidites can be problematic with BZD use especially if used w/ EtOH or opiates?

liver disease
respiratory issues (sleep apnea included)
child

36

Describe metabolism of BZDs.

-- no enzyme induction
-- catabolized by 3a4 and c19
-- active metabolites may be GABAa APLs

37

What enzyme does grapefruit juice inhibit?

3a4

38

What factors of BZD selection should be selected for longer-acting effects?

active mets
lipid soluble

39

What are sxs of BZD withdrawal?

due to downregulation of GABA...
-- anxiety, muscle cramping/twitching, psychosis, panic, ANS sxs, convulsions

40

What are the longer-acting BZDs?

-- clonazepam (longer t1/2)
-- chlordiazepoxie (active mets but low potency)
-- diazepam (long t1/2 + active mets)

41

What are the ultra-rapid-acting BZDs?

midazolam
lorazepam

42

How is midazolam used?

anesthetic

43

How is clonazepam used?

anxiolytic, anti-convulsant

44

How is alprazolam used?

anxiolytic, agoraphobia

45

What BZDs are used for sleep?

1) flurazepam
2) temazepam
3) triazolam

46

What other drugs act on the BZD-binding site?

1) flumazenil
2) flunitrazepam

47

What is flumazenil?

BZD-binding site antagonist
-- IV admin for BZD overdose

48

What is flunitrazepam?

rapid-onset APL of GABAa via the BZD-binding site
-- date-rape

49

What are non-barb, non-BZD anxiolytic sedatives?

1) buspirone!

50

What is the MoA for buspar?

5ht1a partial agonist

51

Where is 5HT1a dense?

amygdala and limbic regions

52

What is the main use for buspar?

GAD
-- no efficacy for acute panic
-- not as efficacious as SSRIs for other anxiety-related disorders

53

Describe metabolism of buspar.

3a4
-- caution MAOI or SSRI

54

What are the advantages of buspar?

fewer ADRs and less sedation

55

Describe the ADRs of buspar.

n/v, dizziness, ha

56

What are the disadvantages of buspar?

-- 2-4 week onset

57

How is non-rem sleep regulated?

raphe (5-HT) and NTS (NE and autonomics)

58

How is REM sleep regulated?

cholinergic regions of forebrain and midbrain

59

What are the primary complaints of primary sleep disorder?

1) getting to sleep
2) staying asleep
3) waking up too early
4) sleeping at wrong time

60

What are dyssomnias?

primary insomnia, primary hypersomnia, narcolepsy, jet lag, shift-work disorder, sleep apnea, non-24

61

What are parasomnias?

nightmares, night terrors, sleepwalking, bruxism

62

What sedative drugs are used for primary sleep disorders?

1) trazodone
2) TCAs
3) clonidine
4) CNS-acting muscle relaxants

63

MoA of trazodone.

5ht1a partial agonist; 5ht2a antagonist; SSRI

64

What are the general categories of drugs used for sleep disorders?

1) sedatives
2) BZDs
3) Z-drugs
4) melatonin and MTr agonists
5) OXr antagonists

65

What effects do BZDs have on sleep?

1) quicker induction
2) quicker time to REM
3) decreased awakenings
4) more sleep (greatest increase in stage 2 non-rem)

5) decreased total REM

66

What are ADRs of BZDs used for sleep?

-- risk for hangover
-- rapid-onset = abuse
-- rebound insomnia
-- rebound REM sleep

67

What is the MoA of Z-drugs?

a1-selective-GABAa (HT sleep center); bind BZD site

68

What are Z-drugs used for?

effective for sleep induction and maintenance only

69

How do Z-drugs differ?

half-life

70

What is the shorter-acting Z drug?

zalepon (sonata) shorter --1hr-- than zolpidem (ambien)--2hr--

71

What are the MTr agonists?

ramelteon
tasimelteon

72

What is the MoA for ramelteon?

Mt1/Mt2 receptor agonist

73

Which MTr is thought to be more important for sleep?

MT2

74

Describe the MTr.

Gi coupled, dense in circadian regions of HT

75

What are the advantages of ramelteon?

1) non-scheduled
2) does not disturb REM
3) 30-min onset with 2 hr t1/2

76

Describe metabolism of ramelteon.

30 min onset
2 hour half-life
1a2 metabolism

77

What are ADRs of MTr agonists?

HA, sedation, fatigue, N/V

78

How does tasimelteon differ from ramelteon?

1) $$
2) more M2-selective
3) 1a2 and 3a4

79

What are OXr antagonists?

suvorexant

80

What are orexins?

wake-promoting peptides synthesized by orexin neurons

81

Describe OX1/OX2 receptors.

Gs GPCRs on wake-active neurons; localized to lateral and posterior HT

82

Why is suvorexant scheduled?

anorectic (abuse potential)

83

What concentration of EtOH is the legal limit?

17 mM

84

How does EtOH work at 1mM?

potentiation of delta-subunit GABAa receptors

85

How does EtOH work at 10 mM?

GlyR potentiation
inhibition of a7 nAChR, NMDAr, vgCA channels

86

How does EtOH work at 50 mM?

1) potentiation of GABAa, a4-nAChR, NMDAr, 5ht3
2) inhibition of AMPA and kainate

87

EtoH MoA:

1) indirect intx with target proteins
-- membrane fluidization
-- lateral membrane pressures
-- replaces H2O at lipid-protein surfaces
2) direct interaction with allosteric/orthosteric receptor sites
-- low affinity