Opioids Flashcards
(118 cards)
1
Q
Tranduction
A
stimulus > AP
2
Q
Transmission
A
signal from peripheral to central viaa 3 neuron system
3
Q
describe the 3 order neuron system that makes up transmission
A
1st order: periphery to dorsal root ganglion in dorsal horn
2nd Order: dorsal horn to thalamus
3rd order: Thalamus to cerebral cortex
4
Q
Modulation
A
signal modified as it advances up to cerebral cortex
5
Q
where does perception occur?
A
occurs in cerebral cortex and limbic system
6
Q
what is the most important site of pain signal modulation?
A
substania gelationosa in dorsal horn (rexed lamina 2&3)
7
Q
outline the descending inhibitory pathway. What part of pain process is this?
A
part of modulation
periaquaductal gray > substania gelatinosa
rostroventral medulla > substania gelatinosa
8
Q
when is pain inhibited? what step of pain process would this fall under?
A
modulation
- spinal neurons release GABA and or Glycine
- descending pain pathway releases NE, serotonin, and endorphins
9
Q
pain is augmented by what?
A
central sensitization
wind up
10
Q
what drugs target tranduction?
A
NSAIDs
LAs
steroids
antihistamines
opioids
11
Q
what drugs target transmission?
A
LAs
12
Q
what drugs target modulation
A
neuraxial opioids
NMDA antagonists
alpha 2 agonists
AchE Inhibitors
SSRIs
SNRIs
13
Q
what drugs target perception?
A
general anesthetics
opioids
alpha 2 agonists
14
Q
describe opioids mechanism of action
A
- opioid binds receptor
- G protein activated
- adenylate cyclase inhibited
- decreased cAMP production
- decreased Ca++ condcutance into cell > decreased neurotransmitter release from pre-synaptic cell
6.^ K+ conductance out of cell > hyper polarizes post synaptic membrane.
15
Q
name the opioids receptors
A
Mu
delta
kappa
ORL-1
16
Q
Where are opioid receptors located?
A
Brain
spinal cord
peripheral
17
Q
Where are opioid receptors located in the brain specifically?
A
periaquductal gray, locus coeruleus, rostral ventral medulla
18
Q
Where are opioid receptors located in the spinal cord specifically?
A
primary afferant neurons in dorsal horn and interneurons
19
Q
Where are opioid receptors located in the periphery specifically?
A
sensory neurons and immune cells
20
Q
Mu opiod receptor effects
A
bradycardia
miosis
urinary retention
N/V
prurits
sedation
euphoria
21
Q
what are the effects of delta opiod receptor
A
urinary retention
prurits
22
Q
what are the affects of kappa opiod receptor
A
diuresis
anti-shivering
miosis
sedation/dysphoria
hallucinations/delerium
23
Q
what effects to all opiod receptors have in common?
A
supraspinal and spinal analgesia
resp depression
24
Q
specific effects of Mu1 receptor
A
analgesia spinal and supraspinal
bradycardia
25
specific effects of Mu2 receptor
spinal analgesia
bradycardia
resp depression
constipation
physical dependence
26
specific effects of Mu3 receptor
immune supression
27
how are opioids metabolised? what is the exception?
hepatic biotransformation
exception is Remi through non-specific esterases
28
which opioids have active metabolites?
morphine
meperedine
hydromorphone (some texts say yes some say no)
29
morphine active metabolites and which are active vs inactive?
morphine-3-glucuronide - inactive
morphine-6-glucuronide - active
30
tell me about M-6-G
water soluble so tends not to cross BBB at normal concentrations.
risk of accumlation in renal failure though and then some can cross BBB
there is also risk of this if you give healthy person lots of morphine I beleive
31
meperidine active metabolite
normeperidine
32
tell me about normeperidien
1/2 as potent as meperidine
decreases seizure threshold and increases CNS excitability
avoid in dialysis patient and caution in the elderly
33
hydromorphone active metabolite and how is it excteted?
hydromorphone-6-glucuronide
excreted by the kidneys
34
what happens when opioids stimualte the edinger westphal nucleus?
increased PNS stimulation of ciliary ganglion and Cranial nerve 3 > pupil constriction
35
does tolerance to pupil constriction from opiods occur?
no
36
how do opioids affect SSEP?
minimally, thus okay to use remi in spines
37
cv effects of opioids
brady cardia with minimal effects on BP in healthy patients
38
do opioids cause myocardial depression?
No, only when they are combined with nitrous oxide
39
billiary effects of opioids. Which opiod does it the least?
contraction of sphincter of oddi > increased biliary pressure.
meperidine does this the least
40
are there gendener differences in opiods effects?
yes
in women:
greater analgesic potency
slower onset
^ DOA
lower post-op opioid consumption
41
name the naturally occurring opioids and from where they are derived
phenanthrene derivatives
morphine
codeine
42
name the semi-synthetic opioids and from where they are derived
morphine derivatives:
hydromorphone
heroin
naloxone
naltrexone
thebaine derivatives:
oxycodone
43
name the systhetic opioids and their respective class
piperdines: meperidine
phenylpiperdines:
fentanyl
sufentanil
remifentanil
alfentanil
diphenylpropylamines: methadone
44
decribe the opoids and their relative potency
meperidine 100mg
morphine 10mg
dialudid 1.4mg
alfentanil 1000mcg
remi 100mcg
fentanyl 100mcg
sufentanil 10mcg
45
the potency of methadone depends on what?
patients daily opioid therapy and the duration of therapy
46
define dependence
will go through withdrawal if they stop drug
47
define addiction
can't stop using it despite negative consequences
48
tolerance and physical dependence are most likely due to what?
receptor desensitization and increased sythesis of cAMP
49
two what two physical affects of opiods does tolerance not develop?
miosis and constipation
50
early s/s of opioid withrawal?
diaphoresis, insomnia, restlesness
51
late s/s of opioid withdrawl?
abdominal cramping and N/V
52
which opiodis release histamine?
meperidine
morphine
codeine
53
meperidine mech of action
stimulates Mu and kappa receptors
also weak SSRI
54
which opioid is structurally similar to atropine? what can this cause?
meperidine
anticholinergic side effects
55
what does normeperidine do?
can cause myoclonus
decrease seizure threshold and increase CNS excitability
56
when to avoid meperidine
in dialysis pt and elderly
57
when can meperidine cause serotonin syndrome?
if patient is taking MAOIs
58
s/s of serotonin syndrome
hyperthermia
mental satus changes
hypereflexia
seizures
death
59
name some MAOIs
phenelzine
isocarboxazid
tranylcypromine
60
which opioid has the lowest pKA? what is it?
alfentanil at 6.5
61
what is the significance of the low pKA of alfentanil?
90% ionized at physiolgic pH. Fast onset despite it's low pKa
62
what is alfentanil useful for?
blunt hemodynamic response to short very stimulating procedures like:
intubation and retrobulbar block
63
how is alfentanil metabolised?
CYP3A4 metabolism but with a low hepatic extraction rate
64
what is the significance of alfentanils low hepatic extraction rate?
can be prolonged by erythromycin
65
remifentanil mech of action
mu r agonist
66
remi's context sensitive half time?
4min
67
in what route can you not use remi? why?
neuraxial because it has glycine
68
remi dose
0.1-1.0mcg/kg/min
69
remi dose is based on what weight? why?
lean body weight beacause it does not distribute throughout body becaue it is metabolized so quickly
70
what drugs can prevent OIH from remifentanil?
ketamine and magnesium sulfate
71
which opiod is a racemic mixture?
methadone
72
good uses for methadone?
chronic tx or opioid abuse
chronic pain syndromes
cancer pain
73
methadone mech of action
mu agonist and NMDA antagonist
inhibits reuptake of monoamines in synaptic cleft
74
methadone oral bioavailability
80%
75
methadone DOA
3-6hrs
76
which opioid has risk of prolonging QT syndrome
methadone
77
oliceridine mech of action
mu agonist
78
when oliceridine indicated
chronic pain when other opioids fail
79
daily dose of oliceridine should not exceed
27mg
80
when to changes oliceridine dose
not for renal or mild-mod hepatic failure
do decrease dose when pt is on CYP3A4/CYP2D6 inhibitors
81
oliceridine contraindications
gi obstruction including paralytic ileus
82
oliceridine SE
mild QT prolongation
^ risk of seizures in pt with history of seizures
83
skeletal muscle ridigity is most common from which opioids?
lipphilic opioids
sufentanil, fentanyl, femifentanil, alfentanil
84
how is opioid induced s. muscle rigidity cuased?
from rapid IV administration
85
where is the greatest resitance to ventilation during opioid induce s. muscle rigidity?
larynx
86
tx for opioid induced skeletal m. rigidity
paralysis and intubation
87
pro/cons of partial opioid agnoists
analgesia with decreased risk of resp depression
low risk of dependence
ceiling effect
88
name some partial opioid agonists
buprenorphine
nalbuphine
butorphanol
89
buprenorphine mech of action
partial mu agonist
90
bupreorphine analgesia compared to morphine
greater
91
buprenorphine reversability with naloxone?
hard to reverse because it has such great affinity for Mu receptor
92
buprenorphine DOA
8hrs
93
other admin route available for buprenorphine
transdermal
94
nalbuphine mech of action
kappa agonist
mu antagonist
95
nalbuphine analgesia compared to morphine
about the same
96
nalbuphine reversability with naloxone
yes, reversible
97
nalbuphine effects on CV system?
no increase in BP, HR, PAP, RAP, so useful in pt with history of heart disease
98
butorphanol mech of action
kappa agonist
mu antagonist
99
butorphanol analgesia compared to morphine
greater
100
can butorphanol be reversed by naloxone?
yes
101
what is anothre use of butorphanol?
post-op shivering
102
name other partial opioid agonists
pentzocine
nalorphine
bremazocine
dezocine
meppazinol
103
name some opioid antagonist
naloxone
methylnaltrexone
nalmefene
naltrexone
104
naloxone mech of action
competitively antagonize mu, kappa, delta receptors but greatest affinty for mu r
105
naloxone dose
1-4mcg/kg but better to just give 20-40mcg at a time to prevent overshooting
106
naloxone doa
30-45min so may need re-dose
107
can you use naloxone in a gtt?
yes
108
biggest risk with naloxone?
in a patient with pain it can cause sympathetic stimulation > neurogenic pul edema, tachycardia, dysrhthmias and sudden death
109
does naloxone cross the placenta?
yes, so it can precipitate opioid withdrawal in neonate
110
beside resp depression, what else might you want to reverse with naloxone?
opioid induced pruritis
111
does methylnaltrexone cross the BBB?
no
112
tell me more about methylnaltrexone
can reverse opioid induce resp depression
useful to mitigate peripheral risks of opioids like opioid induce bowel dysfunction
113
tell me about nalmefene
like naloxone but doa is much longer
can be used to maintain recovering opioid abusers
114
tell me about naltrexone
does not undergo signficant 1st pass metaboilsm
only given orally
doa 24hrs
extended release can be used for etoh withdrawal and also to maintain recovering opioid abusers
115
what is the gold standard for post op opioid delivery?
PCA
116
was does PCA basal rate do and not do?
does increase risk of resp depression
does not provide sup pain releif or improve sleep
117
resp depression is RR < ?
10
118
what is the lockout time on PCA pump based on?
time for demand dose to reach an effective plasma concentration
