pain 3 Flashcards
(117 cards)
1
Q
what are endorphins
A
endogenous opioid ligands
2
Q
what are 4 types of endogenous opioid ligands
A
met- or leu-enkephalin
beta-endorphins
dynorphins
endomorphins
3
Q
what does met and leu enkephalin come from
A
preproenkephalin
4
Q
what do beta-endorphins come from
A
POMC
5
Q
what do dynorphins come from
A
preprodynorphin
6
Q
what kind of molecules are the endogenous opioid ligands
A
peptide hormones
7
Q
how are the endogenous opioid ligands peptide hormones made
A
cleaved from larger precursors
8
Q
what sequence do endorphins and dynorphins contiain
A
the leu or met enkephalin sequence
9
Q
if pain is good, then why do you want this mechanism
A
to turn it off in VERY extreme circumstances
10
Q
what kind of G protein is linked to opioid receptors
A
Gi
11
Q
what 2 things does Gi do
A
inhibit adenylyl cyclase and low cAMP levels
12
Q
what does Gi do to K+ conductance
A
increase
13
Q
what channels are activated by Gi
A
GIRK channels
14
Q
what does Gi do to membrane
A
hyperpolarization
15
Q
what channels are suppressed by Gi - what does this cause
A
N-type Ca++ current - less NT release
16
Q
what does Gi do to NT release
how
A
decrease - suppressed Ca++ current
17
Q
what kinase cascade does Gi activate
A
MAP kinase cascade
18
Q
what does the MAP kinase cascade do
A
changes in gene expression - addicted and dependence
19
Q
what are 4 sites of actions of opioids
A
periphery
higher centers
dorsal horn
periaqueductal gray and rostral ventral medulla
20
Q
what do opioids do at the periphery
A
reduce neurogenic inflammation
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)
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)
23
Q
where do opioids act to stop release of NTs (in synapse)
A
presynaptically
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
25
what does PAG stand for
periaqueductal gray
26
what does RVM stand for
rostral ventral medulla
27
where are PAG and RVM and what do they do
part of the descending pathway that projects to the substantia gelatinosa to inhibit pain
28
what happens to GABA release when opioids activate mu receptors on GABA releasing neurons
less GABA release
29
how do opioids allow pain inhibitory neurons to work
they activate mu receptors on GABA releasing neurons that project onto pain inhibitory neurons
30
where are the GABA interneurons located in the pain inhibitory pathway
PAG RVM
31
what causes the differences in properties of different opioids (2)
differences in
- pharmockinetics
- affinity for different opioid receptor subtypes
32
what are the opioid receptors
mu
delta
kappa
33
what are all opioids to the my delta or kappa receptors
full agonists or partial agonists
34
does morphine have analgesia properties
analgesia
35
how does morphine do analgesia (which receptors)
mu kappa
36
what does morphine do to your brain physiologically
sedation and mental clouding
37
what does morphine do to brain psychologically
euphoria and tranquility
38
how does morphine cause euphoria (which receptor)
delta and mu and central DA pathways
39
what does morphine do to respiratory center
| how
depression by direct effect on brainstem resp center (prebotzinger complex)
40
what does morphine do to cough
| how
depress, by depressing its reflex by acting in the cough centre in the medulla
41
what does morphine do to nausea
| how
increase it, by stimulation of chemoreceptor trigger zone in medulla
42
what does morphine do to eye
| how
miosis (pin point pupil)
| excitatory action of parasympathetic nerves innervating the pupil
43
which receptors cause morphines act on the pupil
mu and kappa
44
which receptor is involved in morphine tolerance and dependence
mu
45
which receptor is involved in morphine constipation
mu and delta
46
what does morphine do to intestines
constipation by increasing colonic tone to point of spasm, increase tone of anal sphincter
47
what does morphine do to postural reflexes
| how
postural hypotension
| inhibition of baroreceptor reflex
48
what does morphine do to cutaneous blood vessels
dilates them, causing warm skin
49
why do you get sweating and itching with morphine
because cutaneous vessels are dilated which may involve the release of histamine and lead to swelling and itching
50
what does morphine do to peeing
makes it feel urgent but inhibits urinary voiding reflex
51
what does morphine do to bile duct
increase tone in sphincter of Oddi and bile duct, increase pain of gall stones (biliary colic and epigastric distress)
52
what is biliary colic and epigastric distress
increase tone in sphincter of Oddi and bile duct, increase pain of gall stones
53
what are 2 drugs used to control diarrhea
dipehnoxylate
| loperamide
54
what is dipehnoxylate
drug used to control diarrhea
55
what is loperamide
drug used to control diarrhea
56
what is 1 drug used to suppress cough
dextromethorphan
57
what is dextromethorphan
drug used to suppress cough
58
is dextromethorphan analgesic
no
59
what are 4 examples of full opioid agonists
morphine
heroin
methadone
fentanyl
60
does everyone vomit with morphine
no
61
how is morphine administered which is bad
subcutaneously, IV, oral (not efficient)
62
why is morphine not great when oral (2 things)
first pass metabolism in liver turns it into morphine-6-glucoronide, doesnt cross BBB as well as morphien
63
what is the difference with heroin and morphine
heroin is more lipid soluble so it enters the brain very rapidly
64
what is heroin metabolized into and where
morphine in the brain
65
what happens to people with heroin use
tolerance and dependence
66
what is duration of action of methadone
long
67
is methadone an analgesic
yes
68
what is the use of methadone
suppresses opioid withdrawal syndrome for heroin addicts
| also in chronic and cancer pain
69
how is methadone usually taken
orally
70
why is methadone good for chronic and cancer pain
it is a long lasting analgesic
71
what is the potency difference with fentanyl and morphine
fentanyl 80x more potent
72
what is the duration of action of fentanyl
short
73
where does fentanyl act
mu opioid receptor
74
how is fentanyl often given medically (drug combos)
can be used alone for anaesthesia induction, or sometimes in combination with inhalent or IV or neuroleptic
75
what are some conditions fentanyl is used for
chronic and cancer pain and painful procedures in children
76
what are 3 opioid agonists of lesser potency
codein
buprenorphine
oxycodone
77
what does codeine do
analgesia and resp depressant
78
does codeine do analgesia
yes
79
how is codeine often taken
orally
80
does codein have high affinities for opioid receptors
no
81
how is codeine activated
metabolized into morphine
82
how is codeine often administered (which other drugs) why
acetaminophen or aspirin
| -synergistic effects between NSAIDs and opioids
83
what is the mechanism of action of buprenorphine
partial agonist at mu receptors
84
what is the duration of action of buprenorphine
long
85
what is the use of buprenorphine medically
alternate to methadone management of opioid withdrawal
86
what is the onset of action of oxycodone
fast
87
why does oxycodone have a high abuse potential
it has a fast onset and it is well absorbed
88
how is oxycodone usually administered and why
orally because it is well absorbed in GI tract
89
how is oxycodone often administered (which other drugs)
with acetaminophen or alone
90
what is the mechanism of action of tramadol
low affinity for u receptors and blocks serotonin uptake
91
what is the u receptor affinity of tramadol vs. that of morphine
1/16 affinity of morphine
92
what kind of opioid is tramadol
atypical
93
is tramadol an analgesic
yes
94
does naloxone block the analgesic effects of tramadol
not completely
95
why can tramadol be potentially used in opioid resistant neuropathic pain
because it blocks serotonin uptake
96
what does tramadol do to descending serotonergic inhibitory processes
potentiates (IDK)
97
what is the mechanism of action of tapentadol
mu agonist (weak), NA uptake inhibitor
98
compare nausea made from morphine and tapentadol
worse nausea in morphine
99
rate morphine tramadol and tapentadol in order of best to worst
morphine>tapentadol>tramadol
100
what is naloxone
antagonist, most at mu than delta and kappa
101
what does naloxone do to normal individuals and why
little effect unless you have your endogenous system working overdrive (ex: it will reduce acupuncture reduced analgesia)
102
how is naloxone used
to treat opioid overdose
103
what do you use to treat opioid dependence
buprenorphine + naloxone
104
what happens when you orally ingest buprenorphine + naloxone
| why
allows absorption of buprenorphine and no withdrawal (naloxone is minimally bioavailable by oral routes)
105
what happens when you IV administer buprenorphine + naloxone
| why
rapidly induces opioid withdrawal symptoms
| because naloxone blocks mu receptors so it gives those bad symptoms
106
is buprenorphine or naloxone activated when taken orally
only buprenorphine
107
is buprenorphine or naloxone activated when taken IV
mostly naloxone will show its effects (antagonist)
108
what does opioid withdrawal do to BP
hypertension
109
what does opioid withdrawal do to pupils
dilate
110
what does opioid withdrawal do to poop
diarrhea
111
what does opioid withdrawal do to heart
tachycardia
112
what does opioids do to pupils
pinpoint pupils
113
what are 3 common things that both opioids and withdrawal cause
sweating
vomiting
hallucinations
114
what are 2 ways to treat opioid withdrawal
methadone or clonidine
115
what causes muscle fasciculation and what is it
withdrawal, muscle twitches under skin
116
what is clonidine used for
opioid withdrawal
117
what is the mechanism of action of clonidine
alpha2 agonist
