Sweatman Analgesia Flashcards
(125 cards)
1
Q
cause of death with opiate overdose
A
respiratory depression
2
Q
opiate agonists
A
codeine fentanyl hydromorphone methadone morphine oxycodone oxymorphone remifentanil tramadol
3
Q
opiate partial agonist/partial antagonist
A
butorphanol buprenorphine hydrocodone pentazocine nalbutine
4
Q
opiate antagonists
A
naloxone
nalmefene
naltrexone
5
Q
NMDA receptor antagonists
A
ketamine
dextreomethorphan
6
Q
TCA’s
A
amitriptyline
nortriptyline
imipramine
desipramine
7
Q
anticonvulsants
A
gabapentin
pregabalin
lomotrigene
carbamazepine
8
Q
endogenous opiod peptides in human body
A
from POMC, proenkephalin, preprodynorphan
enkephalins, endorphins, dynorphins
POMC=beta endorphin
9
Q
POMC gives rise to
A
beta endorphins
10
Q
anatomical distribution of POMC producing cells in the CNS
A
limited-arcuate hypothal, NTS, =project widely to limbic areas
mainly in pituitary
11
Q
circulating beta endorphin is derived predominantly from the
A
pituitary
12
Q
Proenkephalin peptides present in areas of CNS that involve…
A
processing of pain information
areas of motor control
neuroendocrine control
autonomic control
areas of behavior
13
Q
areas with high proenkephalin produciton
A
Processing pain=Spinal trigeminal nucleus
& periaqueductal gray area
motor control= striatum
autonomic control= medulla
neuroendocrine function= median eminence
Behavior= hippocampus, amygdala, frontal cerebral cortex
14
Q
endogenous opiate peptides in general regulate
A
pain, thermoregulation, appetite, reward
15
Q
proenkephalin cleaved into
A
methionine ekephalin (longer) and leucine enkephalin (shorter)
16
Q
circulating proenkephalins are derived from the adrenal
A
medulla and exocrine glands of the stomach
17
Q
modulatory abeta fibers can regulate pain signals at the level of the
A
dorsal horn
-lamina 1 and 2 where this shit synapses
18
Q
NSAIDS modulate
A
TRANSDUCTION: transduction of pain signal
19
Q
Na channel blockers (local anesthetics) block
A
CONDUCTION: signal conduction in nocioceptive fibers
20
Q
opioids, antidep, nsaids, anticonv, and alpha2 agonists all modulate transmission of pain in the spinal cord by
A
Transmission:
decreasing the intensity of graded potentials and thus the frequency of AP’s relayed from the peripheral to central pain pathways
21
Q
sensitizing agents act via
A
PKC and PKA
22
Q
what do sensitizing agents do?
A
modulate extent of original ion influx, modulate sensitivity of the VGsodium channels to increase liklihood of prop and cond of pain
23
Q
peripheral receptors transudcing chemical signals
A
B1, B2 (kinin)
ACIS-acid sensitive
P2X, P2Y-atp
24
Q
thermal receptor types
A
TRPV1-HOT
TRPV2-COLD?
25
ENKEPHALIN-MU, GABA-B, NE-A2 ALL INHIBIT SIGNAL TRANSMISSION VIA
inibit calcium entry into PRESYNAPTIC bouton-> vessicles do not fuse and are thus not rleased--> inhibit propagation of signal
26
postsynapticall
ENK, GABA, NE, ENDORPHIN all
activate K channels-hyperpolarization, less signal transduction
27
do opiates work presyn/postsyn/or both
both
28
activation of mu receptors by opiates causes
picture this as occuring via endogenous opioids in the dorsal spinal cord-inhibitory interneurons are doing this inhibition
dec calcium entry and less presynaptic NT release
hyperpolarization of postsynaptic membrane
29
sustained/intense
| activation of central pain trasmission pathways causes
central sensitization-through glutamine-NMDA
increases NA and CA influx
affects short term and long term (through protein expression)
excitability of synapse
30
drugs possibly used to prevent surgery induced sensitization
ketamine and dextromethorphan
31
NMDA inibitors
ketamine and dextromethorphan
32
side effects of ketamine
1. CV pressor, increae ICP
2. amnesia
3. hallucinations
33
allodynia definition
normally innocuous stimuli not painful
34
hyperalgesia
high intensity stimuli perceived as more painful
35
extraneuronal inflammatory components
bradykinin, H, PGE2, nerve growth factor,
GPCR effects, reduced activation threshold
increased current conducted
36
intraneuronal mechanisms of hypersensitivty
Substance p
| CGRP from termini of primary afferents
37
substance p and CGRP cause
inflammatory cells to rrelease TFN and histmine, as well as recruiting PMN's to generate inflammation
38
neuropathic pain mechanism
"continued perception of injury"
loss of neurotrophic supports alter gene epxtression in injured nevere fiber, altered sensitivity, and activity of nioceptive comonents,
39
rewiring of peripheral and central pain pathways following nerve damage involves
changes in sodium channel expression
*this is why you use carbamazepine for trigeminal neuralgia
40
sodium channel expression changes in neuronpathic pain
increase NAv expression-enhanced excitability
dereased NAv 1.8 and 1.9
loss of C fibers, =replaced by Abeta fibers
(slow replaced with fast)
41
gabapentinoids MOA
po deliver
inhibition of Ca channels
42
decrease dose for renal insufficiency
gabapentinoids
43
Mu receptor aka
OP3
44
delta receptor aka
OP1
45
kappa receptor aka
OP2
46
specificity for OP3/Mu
endorphins,
| *but other 2 as well
47
specificity for OP1/delta receptors
enkephalins,
| *but other 2 as well
48
specificty for Kappa/OP2 receto
dynorphins
49
function of Mu receptor
supraspinal and spinal analgesia, sedation, dec respiration, dec GI transit, modulate hormone and NT release
50
function of delta reeptors
suprapsinal and spinal analgesis, modulate hormone and NT release
51
opioid receptors in GI
kappa and mu
52
opiate receptors in respiraotry system
mu
53
function of kappa receptors
supraspinal and spinal analgesia, psychomimetic effects, decreased GI transit
54
prinicpal effects of all (except minimally with morphine) is on which receptor
ACTIVATION of mu OP3 receptors
accounts for benefit and side effects
morphine has little acitvity on Kappa
55
most potent opioid
fentanyl
then oxycodone, and oxymorphone
56
titrated opiate that is IV only
remifentanil
57
high oral potency
methadone
| *rest are low
58
medium oral potency and highest approx equivalent dose
meperidine
| *rest are low
59
drugs with high-ish agonism of kappa
in order
butorphanol
nalbuphine
pentazocine
60
kappa antgaonist
buprenorphine
61
partial ag on mu, antag on kappa and delta
buprenorphine
62
partial mu agonist
codeine, hydrocodone, pentazocine, buprenoprhine, butoprhanol
63
antagonist og muc and agonist of kappa
nelbuphine
64
opiate with high first pass metabolism, thus making interpatient variability tough to dose
morphine
oral dose much higher than IV
also, hyromorphone, oxymorphone, fentanyl
65
opiates with low first pass metab-oral dosing is adequate
codiene, oxycodone
66
opiates and plasma protein binding
weak
67
reservoir for opiates
skeletal muscles due to relative bulk
since not protein bound
68
accumulation of opiates in adipose
minimal
except fentenyl can accumulate if continuously infused
69
desensitization
Receptor phosphoryla/on by the protein GRK increases receptor affinity for beta-‐arres/n; this enhances interac/on between the two proteins and leads to internaliza/on.
70
side effects not likely to develop tolerance
miosis
constipation
convulsions
71
management of somnolence (2 ways
worse in early dementia or other centrally acting drugs
opiate rotation-alternate with one that has diff side effects
stimulants like methylphenidate, dexroampehtamine
72
reserved for symptomatic respiratory depression or for progressive obtundation siggestive of imminent decline
naloxone
reversal agent
73
classical triad opiate overdose
coma
pinpoint pupils
respiratory depression
74
explain coma from opiate overdose
decreased cortical stimulation via thalamus and hypothalamus
75
explain pinpoint pupils from opiate overdose
edinger westphall nucleus, CN III nucleus in the midbrain
76
explain respiratory depression from opiate overdose
decreased CO2 sensitivity
| dec RR and tidal volume
77
OP3 antagonist for opiate intoxication
naloxone
shortest half life
30-80 mins
78
OP3 antagonist for addiction
naltrexone
longer halflife in days
79
naltrexone and alcoholism
decreases atoh craving by decreasing baseline beta endorphin rlease
80
drugs that CAN be converted to morphine
hydrocodone and oxycodone cannot
heroin (HCE 1 and 2
codein (cyp 2d6)
*thus part of their effects are shared with those of morphine
81
hyperpyrexic coma contraindicates opiates from being used with
MAOi
82
will cause a greater codeine-->morphine
cyp2d6 converts 15% of it to morphine (more potent)
..allows it to build up
RENAL FAILURE
these are renally excreted
83
drugs that inhibit hydrocodone metabolism thus allowing it to build up to fatal levels
clarithromycin (CYP3a4 i)
interpatient cyp2d6 metabolism
valproic acid (inhibit glucoronidation)
84
meperidine metabolized to_____ which has. 1/2 analgesic potency and 3 x the CNS toxicity
normeperidine
first pass metabolism high!
85
opiate withdrawl
methadone
-->long ass half life
86
drug with 20% the efficacy of morphine but no Pulm depression side effects
ultram
87
opiate that can cause hypoglycemia
trmadol
88
renal impairment causes which drugs to accumulate
meperidine-normperidine
morphine glucuronides
codeine
tramadol
89
drugs that lack active metabolites and could be used in renal failure
hydromorphone
fentanyl
90
clinical pciture of drug withdrawl
agitation, diaphoresis, increased lacrimation, polierection, dilated pupils
91
siezures, hyperthermia, HTN or tahcycardia
etoh and sedative-hypnotic withdrawl
92
pulse and BO wnl
| slight tachycardia
opiate withdrawl
93
mydriasis, agitiation, tachycardia, htn --much more sever than opioid withdrawl
sympathomimetic intoxication
94
diarrhea and vomitting
different than opioid withdrawl syndrome by salivation bradycardia and altered level of concious
cholingeric agent intoxication
95
short term tx of opiate withdrawl
inpatients-> methadone
(long acting opiate)
outpatient--.clonidine=alpha2 agonist
treats the craving, sweating, piloerectio, anxiety
96
addiction is associated with
surged of dopamine in the nucleus assumbens
97
clas one addicitve drugs act on
GPCR's-disinhibition
98
class II addictive drugs act on
channels-ionotropic receptors-excitation
99
class III addictive drugs act on
transporters-inhibit reuptake
100
for physical dependence to be present...there must
appearance of withdral syndrome
101
for psycological dependence to be present-addiction-...
compulsive, relapsing, drugs use, despite negative conesequences
102
often triggered by cravings in response to contextual clues
addiction-psychological dependence
103
invariable occurs with chronic exposure
dependence
104
treatment of opiate withdrawl
opiate antagonist -naltrexone
or buprenorphine coformulated with naloxone
105
buprenorphine plue naloxone administration
if taken as indicated-analgesic benefit acheived
if crushed and injected-> naloxione will take away any euphoric effects
106
<180 days=
detoxification
107
>180 days is
maintenance
108
treatment of choice for opiate dependent pregnant women
methadone
109
side effects of methadone
prolonged QT and arrhythmia
reduced testosteron/libido
constipation, sweating, const.
110
ceiling effect of buprenorphine means
very low potential for overodose
111
giving an opiate dependent person buprenorphine will cause
withdrawl symptoms
very tight binding to opioid receptors
112
which opiates dont show up on EIA
heroine and codeine, morphine an d hydrocodone DO
fentanyl, meperidine, methadone
113
gabapentin MOA
binds to alpha2 delta subunit with no affinity of modulation of GABAa or GABAb
114
anticonvulsant with BBW for rash-steven johnsone syndrome
lamotrigene-carbamazepine
115
trigeminal neuralgia-blockade of synaptice transmission in trigem nucleus
carbamazepine
116
anticonvulsants carry what risk
suicidal ideation
117
MOA for carbamazepine and lamotrigene
inhibit Na channels
118
drug class that acts on serotinin and NE in ascending corticospinal monoamine pathways-blocking reuptake
TCA
119
tca have which cyp interaction
cyp2d6
120
opiates for cough
codeine-doesnt work
dextromethorphan-minialy effecting
work in NTS to reduce cough reflex
121
opiates for antidiarrheal meds
loperamide-no analgesic acitvity
deiphenoxylate
122
naltrexone for etoh addiction
opiate antagonist
blocks elevation of dopamine levels arising from signals in the Ventral Tegmental area, in the arcuate nucleus
123
acetaminophine plus hydrocodone
vicodin
124
acetaminophin plus oxycodone
percocet
125
acetaminophin plus codeine
tylenol with codeine
