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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
diphenhydramine
1st gen. antihistamine
26
doxylamine
1st gen. antihistamine
27
concerns with drugs to treat insomnia
1. somnolence (driving) 2. unconscious night activity 3. suicide ideation 4. narcolepsy-associated events (sleep paralysis, hallucination, mild cataplexy)
28
GABA-A receptor
Cl- channel
29
barbiturates
increase duration of GABA channel opening Tx: insomnia AE: profound CNS depression that is lethal at high doses
30
Why are benzodiazepines safer than barbiturates?
benzodiazepines have a CEILING EFFECT at high doses | only lethal when consumed with alcohol
31
Benzodiazepine signs of withdrawal
1. anxiety, irritable, restless 2. obstructing sleep apnea 3. severe ventilatory impairment 4. caution with tapering
32
1. BZ-1 2. BZ-2 3. BZ-3
1. sedation, amnesia 2. anxiolysis 3. myorelaxation, anticonvulsant
33
midazolam
benzodiazepine | short T1/2
34
diazepam
benzodiazepine | long T1/2
35
oxazepam
short T1/2 | inactive metabolites
36
lorazepam
short T1/2 | inactive metabolites
37
What is the benefit of benzodiazepines with a short half life or inactive metabolites?
long half lives and drugs with active metabolites are more likely to have cumulative effects with multiple doses like excessive drowsiness
38
flumazenil
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
melatonin receptors 1. MT1 2. MT2 3. MT3
1. GPCR, attenuates SCN activity and induces sleep 2. GPCR, maintains circadian rhythm 3. NOT involved in sleep regulation
40
Drug classes that cause insomnia
1. antidepressants: MAOI, TCA, SSRI 2. stimulants 3. antibiotics 4. asthma meds 5. decongestants 6. beta-blockers others: felbamate, levodopa, bupropion, venlafaxine
41
NSAIDs
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
acetaminophen or aspirin | with: caffeine, butalbital
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
5-HT (1B) and (1D) specific agonist
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
ergots
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
opioids
may be effective in ALLODYNIA (hypersensitive to benign stimuli that triptans are ineffective for) Tx: acute migraine AE: DEPENDENCE, RESPIRATORY DEPRESSION, QT
46
amitriptyline
block NE and 5-HT reuptake and anticholinergic use: migraine prophylaxis (not FDA approved) AE: AGGRESSION, weight gain, dry mouth, sedation
47
valproic acid
``` Na channel blocker increased GABA use: migraine prophylaxis AE: HEPATIC, weight gain, sedation TERATOGEN highly protein bound ```
48
propranolol, timolol
decrease arterial dilation and NE induced lipolysis use: migraine prophylaxis (only one for CHILDREN) AE: AV block, fatigue, exercise intolerance CI: asthma, DM
49
topiramate
``` block Na and glutamate increase GABA use: migraine prophylaxis AE: PARETHESIA, fatigue narrow therapeutic range ```
50
BOTOX
local injection decrease mediator release and muscle activation use: migraine prophylaxis
51
antiemetics
through either D2 blockade or anticholinergic blockade
52
butalbital
``` barbiturate Tx: acute migraine AE: sedative, ANALGESIC OVERUSE, RESPIRATORY DEPRESSION CYP inducer CI: PORPHYRIA, EtOH, sedatives ```
53
prochlorperazine
antiemetic: central D2 blockade other: cholinergic and alpha adrenergic blockade Tx: migraine N/V AE: dyskinesia, hypotension, glaucoma, urinary retention, BPH
54
metclopramide
antiemetic: central D2 blockade other: pro kinetic, increased ACh Tx: migraine N/V AE: increased prolactin: GYNECOMASTIA
55
promethazine
antiemetic: cholinergic blockade other: H1 and weak D2 blockade Tx: migraine N/V AE: glaucoma, urinary retention, BPH, drowsy, Parkinson-like Sx
56
chlorpromazine
antiemetic: central D2 blockade other: cholinergic and alpha adrenergic blockade Tx: migraine N/V AE: dyskinesia, hypotension, glaucoma, urinary retention, BPH
57
ketoprofen
NSAID
58
fenoprofen
NSAID
59
nabumetone
NSAID | LONGEST ACTING: decreases analgesic overuse
60
ibuprofen
NSAID
61
naproxen
NSAID | LONG ACTING: decreases analgesic overuse
62
almotriptan
5-HT (1B) and (1D) specific agonist
63
elitriptan
5-HT (1B) and (1D) specific agonist | increase propranolol and CYP3A inhibitor levels
64
frovatriptan
5-HT (1B) and (1D) specific agonist | LONGEST action, slow onset
65
naratriptan
5-HT (1B) and (1D) specific agonist | long action, slow onset
66
rizatriptan
5-HT (1B) and (1D) specific agonist prevent breakdown of MAOI increase propranolol levels
67
sumatriptan
5-HT (1B) and (1D) specific agonist nasal: faster onset SC: fastest onset, most prominent AE prevent breakdown of MAOI
68
zolmitriptan
5-HT (1B) and (1D) specific agonist nasal: faster onset prevent breakdown of MAOI increase propranolol levels
69
dihydroergotamine
ergot
70
ergotamine
ergot
71
hydrocodone
opiate
72
oxycodone
opiate
73
codeine
opiate
74
Migraine Tx 1. mild/ moderate or menstrual 2. moderate-severe 3. prophylaxis
1. NSAIDs 2. short acting triptan: oral or faster nasal spray 3. topiramate, valproate, propranolol, timolol, metoprolol
75
analgesic overuse
frequent use of anti migraine drugs leading to paradoxical worsening of migraine Sx
76
Triptans that 1. prevent breakdown of MAOI 2. increase propranolol levels 3. increase CYP3A inhibitor levels
1. rizatriptan, sumatriptan, zolmitriptan 2. elitriptan, rizatriptan, zolmitriptan 3. elitriptan
77
St. Anthony's fire
aka: ergotism excessive intake of ergots disorientation, convulsions, muscle cramps, dry gangrene
78
1. What is first line for migraine in the 1st trimester of pregnancy? 2. What can be added if condition persists into later trimesters?
1. acetaminophen | 2. opioids
79
What drugs should be used for initial menstrual migraine therapy?
prophylactic NSAIDs
80
1. When is appropriate to Tx menstrual migraines with oral contraceptives? 2. When is it not? 3. Why?
1. migraine without aura 2. migraine with aura 3. increased risk of stroke (increased even more by smoking, HTN, hyperlipidemia)
81
ketorolac
IM use to avoid opioid dependence Tx: pain/migraine
82
Which drugs are most likely to produce analgesic overuse syndrome?
``` opioids aspirin/acetaminophen/caffeine butalbital combinations moderate: triptans, short-acting NSAIDs low: long acting NSAIDs, tramadol, ergot ```
83
Mind-Body therapies for migraine
1. biofeedback 2. cognitive behavior therapy 3. relaxation training
84
riboflavin
alternative migraine therapy | CI: pregnancy
85
coenzyme Q10
alternative migraine therapy
86
feverfew
alternative migraine therapy: reduce freq. CI: pregnancy AE: mouth sores, GI
87
butterbur
alternative migraine therapy: reduce freq. CI: pregnancy, pyrrolizidine alkaloid toxicity AE: GI

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