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PMCOL 343 > pain 3 > Flashcards

pain 3 Flashcards

1
Q

what are endorphins

A

endogenous opioid ligands

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2
Q

what are 4 types of endogenous opioid ligands

A

met- or leu-enkephalin
beta-endorphins
dynorphins
endomorphins

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3
Q

what does met and leu enkephalin come from

A

preproenkephalin

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4
Q

what do beta-endorphins come from

A

POMC

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5
Q

what do dynorphins come from

A

preprodynorphin

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6
Q

what kind of molecules are the endogenous opioid ligands

A

peptide hormones

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7
Q

how are the endogenous opioid ligands peptide hormones made

A

cleaved from larger precursors

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8
Q

what sequence do endorphins and dynorphins contiain

A

the leu or met enkephalin sequence

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9
Q

if pain is good, then why do you want this mechanism

A

to turn it off in VERY extreme circumstances

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10
Q

what kind of G protein is linked to opioid receptors

A

Gi

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11
Q

what 2 things does Gi do

A

inhibit adenylyl cyclase and low cAMP levels

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12
Q

what does Gi do to K+ conductance

A

increase

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13
Q

what channels are activated by Gi

A

GIRK channels

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14
Q

what does Gi do to membrane

A

hyperpolarization

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15
Q

what channels are suppressed by Gi - what does this cause

A

N-type Ca++ current - less NT release

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16
Q

what does Gi do to NT release

how

A

decrease - suppressed Ca++ current

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17
Q

what kinase cascade does Gi activate

A

MAP kinase cascade

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18
Q

what does the MAP kinase cascade do

A

changes in gene expression - addicted and dependence

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19
Q

what are 4 sites of actions of opioids

A

periphery
higher centers
dorsal horn
periaqueductal gray and rostral ventral medulla

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20
Q

what do opioids do at the periphery

A

reduce neurogenic inflammation

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21
Q

what do opioids do at the higher centers - which one

A

cingulate cortex and thalamus, alter psychological response to pain (makes less suffering)

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22
Q

what do opioids do at the dorsal horn and how

big one

A

reduce NT release from terminals of afferent Adelta and C fibres

-act on Ca++ channels to reduce release of aa and substance P)

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23
Q

where do opioids act to stop release of NTs (in synapse)

A

presynaptically

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24
Q

what do opioids do at the periaqueductal gray (PAG) rostral ventral medulla (RVM)

A

inhibit the pathway through

activation of mu receptors on GABA releasing neurons which project onto the pain inhibitory neuron

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25
Q

what does PAG stand for

A

periaqueductal gray

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26
Q

what does RVM stand for

A

rostral ventral medulla

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27
Q

where are PAG and RVM and what do they do

A

part of the descending pathway that projects to the substantia gelatinosa to inhibit pain

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28
Q

what happens to GABA release when opioids activate mu receptors on GABA releasing neurons

A

less GABA release

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29
Q

how do opioids allow pain inhibitory neurons to work

A

they activate mu receptors on GABA releasing neurons that project onto pain inhibitory neurons

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30
Q

where are the GABA interneurons located in the pain inhibitory pathway

A

PAG RVM

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31
Q

what causes the differences in properties of different opioids (2)

A

differences in

  • pharmockinetics
  • affinity for different opioid receptor subtypes
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32
Q

what are the opioid receptors

A

mu
delta
kappa

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33
Q

what are all opioids to the my delta or kappa receptors

A

full agonists or partial agonists

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34
Q

does morphine have analgesia properties

A

analgesia

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35
Q

how does morphine do analgesia (which receptors)

A

mu kappa

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36
Q

what does morphine do to your brain physiologically

A

sedation and mental clouding

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37
Q

what does morphine do to brain psychologically

A

euphoria and tranquility

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38
Q

how does morphine cause euphoria (which receptor)

A

delta and mu and central DA pathways

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39
Q

what does morphine do to respiratory center

how

A

depression by direct effect on brainstem resp center (prebotzinger complex)

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40
Q

what does morphine do to cough

how

A

depress, by depressing its reflex by acting in the cough centre in the medulla

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41
Q

what does morphine do to nausea

how

A

increase it, by stimulation of chemoreceptor trigger zone in medulla

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42
Q

what does morphine do to eye

how

A

miosis (pin point pupil)

excitatory action of parasympathetic nerves innervating the pupil

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43
Q

which receptors cause morphines act on the pupil

A

mu and kappa

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44
Q

which receptor is involved in morphine tolerance and dependence

A

mu

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45
Q

which receptor is involved in morphine constipation

A

mu and delta

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46
Q

what does morphine do to intestines

A

constipation by increasing colonic tone to point of spasm, increase tone of anal sphincter

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47
Q

what does morphine do to postural reflexes

how

A

postural hypotension

inhibition of baroreceptor reflex

48
Q

what does morphine do to cutaneous blood vessels

A

dilates them, causing warm skin

49
Q

why do you get sweating and itching with morphine

A

because cutaneous vessels are dilated which may involve the release of histamine and lead to swelling and itching

50
Q

what does morphine do to peeing

A

makes it feel urgent but inhibits urinary voiding reflex

51
Q

what does morphine do to bile duct

A

increase tone in sphincter of Oddi and bile duct, increase pain of gall stones (biliary colic and epigastric distress)

52
Q

what is biliary colic and epigastric distress

A

increase tone in sphincter of Oddi and bile duct, increase pain of gall stones

53
Q

what are 2 drugs used to control diarrhea

A

dipehnoxylate

loperamide

54
Q

what is dipehnoxylate

A

drug used to control diarrhea

55
Q

what is loperamide

A

drug used to control diarrhea

56
Q

what is 1 drug used to suppress cough

A

dextromethorphan

57
Q

what is dextromethorphan

A

drug used to suppress cough

58
Q

is dextromethorphan analgesic

A

no

59
Q

what are 4 examples of full opioid agonists

A

morphine
heroin
methadone
fentanyl

60
Q

does everyone vomit with morphine

A

no

61
Q

how is morphine administered which is bad

A

subcutaneously, IV, oral (not efficient)

62
Q

why is morphine not great when oral (2 things)

A

first pass metabolism in liver turns it into morphine-6-glucoronide, doesnt cross BBB as well as morphien

63
Q

what is the difference with heroin and morphine

A

heroin is more lipid soluble so it enters the brain very rapidly

64
Q

what is heroin metabolized into and where

A

morphine in the brain

65
Q

what happens to people with heroin use

A

tolerance and dependence

66
Q

what is duration of action of methadone

A

long

67
Q

is methadone an analgesic

A

yes

68
Q

what is the use of methadone

A

suppresses opioid withdrawal syndrome for heroin addicts

also in chronic and cancer pain

69
Q

how is methadone usually taken

A

orally

70
Q

why is methadone good for chronic and cancer pain

A

it is a long lasting analgesic

71
Q

what is the potency difference with fentanyl and morphine

A

fentanyl 80x more potent

72
Q

what is the duration of action of fentanyl

A

short

73
Q

where does fentanyl act

A

mu opioid receptor

74
Q

how is fentanyl often given medically (drug combos)

A

can be used alone for anaesthesia induction, or sometimes in combination with inhalent or IV or neuroleptic

75
Q

what are some conditions fentanyl is used for

A

chronic and cancer pain and painful procedures in children

76
Q

what are 3 opioid agonists of lesser potency

A

codein
buprenorphine
oxycodone

77
Q

what does codeine do

A

analgesia and resp depressant

78
Q

does codeine do analgesia

A

yes

79
Q

how is codeine often taken

A

orally

80
Q

does codein have high affinities for opioid receptors

A

no

81
Q

how is codeine activated

A

metabolized into morphine

82
Q

how is codeine often administered (which other drugs) why

A

acetaminophen or aspirin

-synergistic effects between NSAIDs and opioids

83
Q

what is the mechanism of action of buprenorphine

A

partial agonist at mu receptors

84
Q

what is the duration of action of buprenorphine

A

long

85
Q

what is the use of buprenorphine medically

A

alternate to methadone management of opioid withdrawal

86
Q

what is the onset of action of oxycodone

A

fast

87
Q

why does oxycodone have a high abuse potential

A

it has a fast onset and it is well absorbed

88
Q

how is oxycodone usually administered and why

A

orally because it is well absorbed in GI tract

89
Q

how is oxycodone often administered (which other drugs)

A

with acetaminophen or alone

90
Q

what is the mechanism of action of tramadol

A

low affinity for u receptors and blocks serotonin uptake

91
Q

what is the u receptor affinity of tramadol vs. that of morphine

A

1/16 affinity of morphine

92
Q

what kind of opioid is tramadol

A

atypical

93
Q

is tramadol an analgesic

A

yes

94
Q

does naloxone block the analgesic effects of tramadol

A

not completely

95
Q

why can tramadol be potentially used in opioid resistant neuropathic pain

A

because it blocks serotonin uptake

96
Q

what does tramadol do to descending serotonergic inhibitory processes

A

potentiates (IDK)

97
Q

what is the mechanism of action of tapentadol

A

mu agonist (weak), NA uptake inhibitor

98
Q

compare nausea made from morphine and tapentadol

A

worse nausea in morphine

99
Q

rate morphine tramadol and tapentadol in order of best to worst

A

morphine>tapentadol>tramadol

100
Q

what is naloxone

A

antagonist, most at mu than delta and kappa

101
Q

what does naloxone do to normal individuals and why

A

little effect unless you have your endogenous system working overdrive (ex: it will reduce acupuncture reduced analgesia)

102
Q

how is naloxone used

A

to treat opioid overdose

103
Q

what do you use to treat opioid dependence

A

buprenorphine + naloxone

104
Q

what happens when you orally ingest buprenorphine + naloxone

why

A

allows absorption of buprenorphine and no withdrawal (naloxone is minimally bioavailable by oral routes)

105
Q

what happens when you IV administer buprenorphine + naloxone

why

A

rapidly induces opioid withdrawal symptoms

because naloxone blocks mu receptors so it gives those bad symptoms

106
Q

is buprenorphine or naloxone activated when taken orally

A

only buprenorphine

107
Q

is buprenorphine or naloxone activated when taken IV

A

mostly naloxone will show its effects (antagonist)

108
Q

what does opioid withdrawal do to BP

A

hypertension

109
Q

what does opioid withdrawal do to pupils

A

dilate

110
Q

what does opioid withdrawal do to poop

A

diarrhea

111
Q

what does opioid withdrawal do to heart

A

tachycardia

112
Q

what does opioids do to pupils

A

pinpoint pupils

113
Q

what are 3 common things that both opioids and withdrawal cause

A

sweating
vomiting
hallucinations

114
Q

what are 2 ways to treat opioid withdrawal

A

methadone or clonidine

115
Q

what causes muscle fasciculation and what is it

A

withdrawal, muscle twitches under skin

116
Q

what is clonidine used for

A

opioid withdrawal

117
Q

what is the mechanism of action of clonidine

A

alpha2 agonist

PMCOL 343 (31 decks)

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