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Neuro 2 > Pharm: Insomnia and Migraine > Flashcards

Pharm: Insomnia and Migraine Flashcards

1
Q

GABA

  1. location
  2. function
A
  1. basal forebrain

2. negative regulator of ascending pathways and of neuronal activity in the cortex

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2
Q

orexin

  1. location
  2. function
  3. stimulates
  4. regulated by
A
  1. lateral hypothalamus
  2. rapid transition btwn see and wake state
  3. monoaminergic nuclei, dopaminergic centers, neuropeptide Y
  4. suprachiasmatic nucleus and limbic system (emotional arousal)
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3
Q

ascending pathways of arousal

A
  1. cholinergic: activate thalamus

2. activate cerebral cortex: histamine, dopamine, serotonin, NE, orexin, MCH, GABA (inhibition)

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4
Q

NT at each location for ascending pathway of arousal

  1. upper pons, pedunculopontine, laterodorsal tegmental nuclei
  2. tuberomammillary nucleus
  3. A10 cell group
  4. dorsal and median raphe nuclei
  5. locus coerulus
  6. lateral hypothalamus
  7. basal forebrain
A
  1. cholinergic
  2. histamine
  3. dopamine
  4. serotonin
  5. NE
  6. orexin or MCH
  7. GABA
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5
Q

monoamergic nuclei

A

promote wakefulness

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6
Q

dopaminergic centers

A

reward systems

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7
Q

neuropeptide Y

A

increase food intake

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8
Q

benzodiazepines

A

-zepam/-zolam
increase frequency of GABA channel opening: binds alpha subunit
acts on BZ-1, 2 and 3
CYP3A4
Tx: insomnia
safer than barbiturate
AE: PHYSICAL DEPENDENCE, rebound, sedation/ cognitive impairment
CI: PREGNANCY
caution: HEPATIC, COPD, DEPRESSION, DRIVING, CNS drug interactions, GLAUCOMA

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9
Q

antidepressants

A 
TCA
works thru: H1 antagonism 
CYP
Tx: insomnia (off label)
DI: alcohol, CNS depressants
BBW: SUICIDAL IDEATION
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10
Q

benzodiazepine receptor agonists

A 
oral: formulated with immediate and extended release 
ZZZ's
acts on BZ-1
CYP
can use in pregnant 
Tx: insomnia
AE: PHYSICAL DEPENDENCE
caution: HEPATIC, COPD, DEPRESSION, DRIVING, CNS drug interactions
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11
Q

1st generation antihistamines

A 
OTC
H1 antagonist 
Tx: insomnia (off label)
AE: anticholinergic: xerostomia, blurred vision, urinary retention, increased intraocular pressure
RAPID TOLERANCE to sedation
caution: narrow angle GLAUCOMA
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12
Q

ramelteon

A 
melatonin receptor agonist
suprachiasmatic nucleus inhibition
CYP
Tx: insomnia (off label)
AE: FEW; headache, somnolence, nausea, insomnia, URTI
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13
Q

suvorexant

A 
oral
dual orexin receptor antagonist
w/out food: delays action
CYP3A4
reduce dose: OBESE FEMALES
Tx: insomnia 
AE: SOMNOLENCE (driving), SUICIDAL IDEATION, narcoleptic (SLEEP PARALYSIS, hallucinations)
CI: alcohol, CNS depressants, narcolepsy
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14
Q

estazolam

A

benzodiazepine
short T1/2
inactive metabolites

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15
Q

flurazepam

A

benzodiazepine

accumulation of metabolites

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16
Q

quazepam

A

benzodiazepine
accumulation of metabolites
CYPB6 > CYP3A4

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17
Q

temazepam

A

benzodiazepine

NO CYP

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18
Q

triazolam

A

benzodiazepine

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19
Q

doxepin

A

only FDA approved antidepressant for insomnia

also: NE, 5-HT reuptake blocker, anticholinergic

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20
Q

mirtazapine

A

antidepressant

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21
Q

trazodone

A

antidepressant

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22
Q

zolpidem

A 
oral
nasal, sublingual: fast onset 
benzodiazepine receptor agonist
short-acting: approved for middle of the nigh awakening (only indication for sublingual formulation)
WOMEN: reduce dose
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23
Q

zaleplon

A

benzodiazepine receptor agonist
Aldehyde DH
ethnic variability: ASIAN

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24
Q

eszopiclone

A

benzodiazepine receptor agonist

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25
Q

diphenhydramine

A

1st gen. antihistamine

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26
Q

doxylamine

A

1st gen. antihistamine

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27
Q

concerns with drugs to treat insomnia

A
  1. somnolence (driving)
  2. unconscious night activity
  3. suicide ideation
  4. narcolepsy-associated events (sleep paralysis, hallucination, mild cataplexy)
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28
Q

GABA-A receptor

A

Cl- channel

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29
Q

barbiturates

A

increase duration of GABA channel opening
Tx: insomnia
AE: profound CNS depression that is lethal at high doses

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30
Q

Why are benzodiazepines safer than barbiturates?

A

benzodiazepines have a CEILING EFFECT at high doses

only lethal when consumed with alcohol

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31
Q

Benzodiazepine signs of withdrawal

A
  1. anxiety, irritable, restless
  2. obstructing sleep apnea
  3. severe ventilatory impairment
  4. caution with tapering
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32
Q
  1. BZ-1
  2. BZ-2
  3. BZ-3
A
  1. sedation, amnesia
  2. anxiolysis
  3. myorelaxation, anticonvulsant
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33
Q

midazolam

A

benzodiazepine

short T1/2

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34
Q

diazepam

A

benzodiazepine

long T1/2

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35
Q

oxazepam

A

short T1/2

inactive metabolites

36
Q

lorazepam

A

short T1/2

inactive metabolites

37
Q

What is the benefit of benzodiazepines with a short half life or inactive metabolites?

A

long half lives and drugs with active metabolites are more likely to have cumulative effects with multiple doses like excessive drowsiness

38
Q

flumazenil

A

IV
short T1/2: may need to redose
benzodiazepine and benzodiazepine receptor agonist ANTAGONIST
use: reverse sedation or overdose (ABRUPT awakening)
AE: dysphoria, agitation, withdrawal, SEIZURES
does NOT reverse sedation of other drugs

39
Q

melatonin receptors

  1. MT1
  2. MT2
  3. MT3
A
  1. GPCR, attenuates SCN activity and induces sleep
  2. GPCR, maintains circadian rhythm
  3. NOT involved in sleep regulation
40
Q

Drug classes that cause insomnia

A
  1. antidepressants: MAOI, TCA, SSRI
  2. stimulants
  3. antibiotics
  4. asthma meds
  5. decongestants
  6. beta-blockers
    others: felbamate, levodopa, bupropion, venlafaxine
41
Q

NSAIDs

A

COX inhibitor
decreases MAPK and therefore CGRP and Sub. P
most effective if taken sooner
Tx: acute migraine
AE: gastric irritation, nephrotoxic, potentiate migraine nausea
DI: attenuate diuretics, ACE inhibitors, ARBs, B blocker, vasodilators, alpha 1/2 agonist
CI: avoid in LATE PREGNANCY (prolong labor; potency of ductus arteriosus)

42
Q

acetaminophen or aspirin

with: caffeine, butalbital

A

Tx: acute migraine
AE:
1. caffeine: potentiate CV interactions, cerebral vasoconstriction
2. acetaminophen: G6PD def. important at high doses
3. butalbital: drowsy, CYP, resp. depression, porphyria, EtOH

43
Q

5-HT (1B) and (1D) specific agonist

A

oral
-triptans
MOST EFFECTIVE
1. selective carotid/intracranial vasoconstriction
2. presynaptic inhibition of trigeminovascular inflammatory response
Tx: acute migraine
AE: drowsy, heaviness of chest, serotonin syndrome (if given with SSRI)
CI: HEART DISEASE, uncontrolled HTN, ISCHEMIC BOWEL
do NOT give less than 24hrs following ergot or triptan
caution: vascular risks (eg. DM)

44
Q

ergots

A

vasoconstrictor
agonist: central 5HT, alpha (decrease amine reuptake, vasoconstriction)
Tx: acute migraine, also can control hemorrhage or promote uterine contractions
AE: St. Anthony’s fire
CI: PVD, CAD, MI uncontrolled HTN, sepsis
TERATOGEN, NO BREASTFEEDING
DI: TRIPTAN 24 HR RULE, CYP3A4 (increase ergots), DA and B blocker (potentiate vasoconstriction)

45
Q

opioids

A

may be effective in ALLODYNIA (hypersensitive to benign stimuli that triptans are ineffective for)
Tx: acute migraine
AE: DEPENDENCE, RESPIRATORY DEPRESSION, QT

46
Q

amitriptyline

A

block NE and 5-HT reuptake and anticholinergic
use: migraine prophylaxis (not FDA approved)
AE: AGGRESSION, weight gain, dry mouth, sedation

47
Q

valproic acid

A 
Na channel blocker
increased GABA
use: migraine prophylaxis
AE: HEPATIC, weight gain, sedation
TERATOGEN
highly protein bound
48
Q

propranolol, timolol

A

decrease arterial dilation and NE induced lipolysis
use: migraine prophylaxis (only one for CHILDREN)
AE: AV block, fatigue, exercise intolerance
CI: asthma, DM

49
Q

topiramate

A 
block Na and glutamate
increase GABA
use: migraine prophylaxis
AE: PARETHESIA, fatigue
narrow therapeutic range
50
Q

BOTOX

A

local injection
decrease mediator release and muscle activation
use: migraine prophylaxis

51
Q

antiemetics

A

through either D2 blockade or anticholinergic blockade

52
Q

butalbital

A 
barbiturate
Tx: acute migraine 
AE: sedative, ANALGESIC OVERUSE, RESPIRATORY DEPRESSION
CYP inducer
CI: PORPHYRIA, EtOH, sedatives
53
Q

prochlorperazine

A

antiemetic: central D2 blockade
other: cholinergic and alpha adrenergic blockade
Tx: migraine N/V
AE: dyskinesia, hypotension, glaucoma, urinary retention, BPH

54
Q

metclopramide

A

antiemetic: central D2 blockade
other: pro kinetic, increased ACh
Tx: migraine N/V
AE: increased prolactin: GYNECOMASTIA

55
Q

promethazine

A

antiemetic: cholinergic blockade
other: H1 and weak D2 blockade
Tx: migraine N/V
AE: glaucoma, urinary retention, BPH, drowsy, Parkinson-like Sx

56
Q

chlorpromazine

A

antiemetic: central D2 blockade
other: cholinergic and alpha adrenergic blockade
Tx: migraine N/V
AE: dyskinesia, hypotension, glaucoma, urinary retention, BPH

57
Q

ketoprofen

A

NSAID

58
Q

fenoprofen

A

NSAID

59
Q

nabumetone

A

NSAID

LONGEST ACTING: decreases analgesic overuse

60
Q

ibuprofen

A

NSAID

61
Q

naproxen

A

NSAID

LONG ACTING: decreases analgesic overuse

62
Q

almotriptan

A

5-HT (1B) and (1D) specific agonist

63
Q

elitriptan

A

5-HT (1B) and (1D) specific agonist

increase propranolol and CYP3A inhibitor levels

64
Q

frovatriptan

A

5-HT (1B) and (1D) specific agonist

LONGEST action, slow onset

65
Q

naratriptan

A

5-HT (1B) and (1D) specific agonist

long action, slow onset

66
Q

rizatriptan

A

5-HT (1B) and (1D) specific agonist
prevent breakdown of MAOI
increase propranolol levels

67
Q

sumatriptan

A

5-HT (1B) and (1D) specific agonist
nasal: faster onset
SC: fastest onset, most prominent AE
prevent breakdown of MAOI

68
Q

zolmitriptan

A

5-HT (1B) and (1D) specific agonist
nasal: faster onset
prevent breakdown of MAOI
increase propranolol levels

69
Q

dihydroergotamine

A

ergot

70
Q

ergotamine

A

ergot

71
Q

hydrocodone

A

opiate

72
Q

oxycodone

A

opiate

73
Q

codeine

A

opiate

74
Q

Migraine Tx

  1. mild/ moderate or menstrual
  2. moderate-severe
  3. prophylaxis
A
  1. NSAIDs
  2. short acting triptan: oral or faster nasal spray
  3. topiramate, valproate, propranolol, timolol, metoprolol
75
Q

analgesic overuse

A

frequent use of anti migraine drugs leading to paradoxical worsening of migraine Sx

76
Q

Triptans that

  1. prevent breakdown of MAOI
  2. increase propranolol levels
  3. increase CYP3A inhibitor levels
A
  1. rizatriptan, sumatriptan, zolmitriptan
  2. elitriptan, rizatriptan, zolmitriptan
  3. elitriptan
77
Q

St. Anthony’s fire

A

aka: ergotism
excessive intake of ergots
disorientation, convulsions, muscle cramps, dry gangrene

78
Q
  1. What is first line for migraine in the 1st trimester of pregnancy?
  2. What can be added if condition persists into later trimesters?
A
  1. acetaminophen

2. opioids

79
Q

What drugs should be used for initial menstrual migraine therapy?

A

prophylactic NSAIDs

80
Q
  1. When is appropriate to Tx menstrual migraines with oral contraceptives?
  2. When is it not?
  3. Why?
A
  1. migraine without aura
  2. migraine with aura
  3. increased risk of stroke (increased even more by smoking, HTN, hyperlipidemia)
81
Q

ketorolac

A

IM
use to avoid opioid dependence
Tx: pain/migraine

82
Q

Which drugs are most likely to produce analgesic overuse syndrome?

A 
opioids
aspirin/acetaminophen/caffeine
butalbital combinations
moderate: triptans, short-acting NSAIDs
low: long acting NSAIDs, tramadol, ergot
83
Q

Mind-Body therapies for migraine

A
  1. biofeedback
  2. cognitive behavior therapy
  3. relaxation training
84
Q

riboflavin

A

alternative migraine therapy

CI: pregnancy

85
Q

coenzyme Q10

A

alternative migraine therapy

86
Q

feverfew

A

alternative migraine therapy: reduce freq.
CI: pregnancy
AE: mouth sores, GI

87
Q

butterbur

A

alternative migraine therapy: reduce freq.
CI: pregnancy, pyrrolizidine alkaloid toxicity
AE: GI

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