Barker Flashcards
1
Q
chronic pain is defined as _____
A
lasting greater than 3 months
2
Q
types of chronic pain
A
nociceptive
neuropathic
visceral
mixed
3
Q
what is nociceptive pain?
A
tissue
- arthritis
(inflammatory)
4
Q
types of neuropathic pain
A
central
peripheral
5
Q
central neuropathic pain examples
A
stroke
MS
spinal cord injury
migraine
6
Q
peripheral neuropathic pain examples
A
infection (post herpes)
diabetic neuropathy
7
Q
what is visceral pain?
A
internal organs
-pancreatitis
-IBS
(inflammatory)
8
Q
mixed pain examples
A
low back
cancer
9
Q
2 functions of pain
A
warning system
aiding in repair
10
Q
inflammatory pain description
A
throbbing, pulsating
11
Q
neuropathic pain description
A
tingling, burning, shooting, stabbing
12
Q
visceral pain description
A
squeezing
13
Q
peripheral receptors and channels in pain
A
temperature sensitive
acid sensitive
chemical irritant sensitive
14
Q
types of temperature sensitive channels/receptors
A
TRP
TRPV - heat
TRPM - cold
15
Q
acid sensitive channels are activated how and conduct what
A
ASIC
activated by H+ protons
conduct Na+
16
Q
chemical irritant sensitive channels release what
A
histamine
bradykinin
17
Q
what is the reflex arc
A
bypasses CNS and goes from periphery to spinal cord to muscle (ex. touching something hot)
18
Q
which channel very important for action potential traveling to spinal cord?
A
Na 1.8
19
Q
receptors at spinal cord
A
NMDA
AMPA
mGluR
20
Q
three pain fibers
A
alpha beta
alpha delta
C fibers
21
Q
alpha beta pain fibers pain signal transduced and speed
A
non-noxious (touch, pressure)
innervate
faster
22
Q
alpha delta pain fibers pain signal transduced, speed, myelination
A
pain, cold
myelinated
fast
“first pain”
23
Q
c fibers pain signal, speed, myelination
A
pain, temp, touch, pressure, itch
unmyelinated
slow
PROLONGED pain
“second pain” dull / aching
24
Q
what is peripheral sensitization?
A
repeated stimuli reduces firing threshold
increased expression of pain receptors (more sensitive to the touch)
25
what does substance P do?
vasodilation
degranulation mast cells
histamine release
inflammation and prostaglandins
26
which neuropeptide is released when there is injury?
substance P
27
what happens in neuropathic pain sensitization when we have more afferent activity
overexpression Na channels
- enhanced excitability
- generation action potentials
28
what happens with post-synaptic receptors more activated and AMPA / NMDA
increased AMPA and NMDA expression and sensitivity
29
how do we get more AMPA and NMDA expression?
increased PLC and PKC
30
where is there high expression of opiod receptors in brain?
descending pathway of brain stem
31
cortex does what with pain
identifies location of pain
32
amygdyla does what with pain
processing of the feeling, anxiety, emotion
33
prefrontal cortex does what with pain
plans action and decisions
determines what we will do as a result of pain
34
nucleus accumbens does what with pain
release dopamine and serotonin
35
what is an opiate
naturally occuring, plant derived
36
phenanthrenes SAR
three rings
37
3 position ester/ether does what
decreased potency (codeine)
38
6 position does what
increases activity (hydrocodone from codeine)
39
nitrogen substitution does what
gives antagonist / partial agonist activity
(buprenorphine or naloxone)
40
how are endogenous peptides activated
large proteins cleaved into opioid subtype selective peptides
41
POMC protein cleaved to what peptide that codes what receptor
beta endorphin > mu opiod
42
preproenkephalin cleaved to what peptides that code what receptor
leu- enkephalin > delta
met - enkephalin > mu and delta
43
preprodynorphin cleaved to what peptides and code what receptos
dynoprhin > kappa
44
opiod receptors are _____ and do what
GPCR
Gi - inhibit cAMP
45
opiod receptors do what to channels
open GIRK K+ channels
close Ca+ channels
(decrease firing)
46
endogenous opiod of Mu
endorphin
47
endogenous opiod of Kappa
dynorphin
48
endogenous opiod of delta
enkephalin
49
endogenous opiod of nociceptin
nociceptin
50
sigma receptors are what
not an an opioid receptor
51
what do opiod receptors do presynaptically?
inhibit calcium channel, decrease in neurotransmitter release
52
what do opiod receptors do postsynaptically?
open GIRK channel
efflux of K+ making more negative and hyperpolarization
53
what is a component of runners high in mu opioid receptors?
beta- endorphins
54
use of mu opiod therapeutically
analgesia (not chronic)
sedation
anti tussive
55
opiod induced side effects are ____ target
on target
56
on target side effects of mu opiod receptors
respiratory depression
constipation
pruritus (itch)
urinary retention
N/V
miosis
57
activation of kappa opiod receptor does what
dysphoric and aversive, negative effects
reduce dopamine release
58
which opiod receptor can counteract the effects of mu
kappa
59
delta opiod receptors have a role in what
protection
stroke/ischemia/hypoxia
reduce anxiety, depression
60
delta receptors as drugs ?
NO FDA approved ones
61
opiod reward centers
ventral tegmental
nucleus accumbens
62
how do depressants cause dopamine release with opioid binding
opiod binds mu
Gi - decrease neurotransmitter release
less GABA to activate GABA A
less dopamine inhibition
more dopamine release
more dopamine receptor activation
63
what is morphines bioavailability
25%
64
morphine cyps
2D6
3A4
65
which opiods are prodrugs
heroin
codeine
tramadol
66
which do not have active metabolites
fentanyl
methadone
67
codeines active metabolites
hydrocodone
morphine
68
heroin active metabolite
morphine
69
tramadol active metabolite
o- desmethyltramadol
70
what does CYP3A4 do to opioids
converts to nor, inactive
71
what does CYP2D6 do to opioids
activates
72
extensive metabolizers have ___ concentrations of morphine
50% higher, more side effects
73
poor metabolizers effects from codeine
none
74
what drugs are broken down by plasma esterases?
sufentanil
remifentanil
alfentanil
(esterase linkages)
75
which opioid has SNRI properties
tramadol
76
which opioid renal excreted
meperidine
not recomended
77
meperidine toxic metabolite
normeperidine
CYP3A4
78
which opiod blocks NMDA receptors
methadone
79
which opioid QTC?
methadone
80
pentazocine receptors
kappa agonist
partial agonist/antagonist at mu
81
butorphanol receptors
kappa agonist
partial agonist/antagonist at mu
82
nalbuphine receptors
full agonist kappa
antagonist at mu
83
buprenorphine receptors
partial mu agonist
weak kappa agonist
weak delta antagonist
84
senna causes what
colonic contraction
85
methadone: speed, PK
slow acting
accumulation
full agonist
86
buprenorphine is a ____
partial agonist
87
subutex has ____
abuse potential
88
naltrexone is a _____
antagonist
89
naltrexone bioavailability
decent oral
best if pt has been drug free for 1 month or more
causes withdrawal
90
naloxone bioavailability
limited oral bioavailability
short half life
91
non-pharm treatment of neonatal abstinence syndrome
swaddling
hypercaloric formula
feedings frequently
redhydration
92
best pharm treatment for withdrawal baby
buprenorphine and morphine
could do methadone or clonidine too
93
examples of eicosanoids
arachidonic acid metabolites
prostaglandins (red, heat, pain)
thromboxanes
leukotrienes (swelling)
cytokines (pain)
94
COX-1 protects what
GI expression
95
which drug irreversibly inhibits COX enzymes
aspirin
96
which drugs inhibit leukotrine synthesis
indomethacin
diclofenac
97
can aspirin have tolerance to analgesia
no
98
risk in aspirin for children
Reyes Syndrome
99
absorption of aspirin and salicylates
rapid
100
aspirin and salicylate half life
ASA 15 min
salicylate 6-20 hours
101
increased excretion of ASA / salicylate with what
increased urinary pH
(from like bicarb)
102
effects of aspirin poisioning
vertigo
tinnitus
respiratory alkalosis (hyperventilation)
metabolic acidosis (low blood pH)
103
treatment of aspirin / salicylate poisioning
reduce salicylate load
increase urinary excretion
dextrose and sodium bicarb
104
ibuprofen is a _____ COX inhibitor
reversible
105
half life ibuprofen
2 hr
106
half life naproxen
14 hr
107
diclofenac risk
peptic ulcer and renal dysfunction
108
what is misoprostal
PGE1 analog, used with diclofenac
109
indomethacin is a ______ inhibitor of PG biosynthesis
potent reversible inhib
110
indomethacin risk
lots of severe side effects long term
111
what is the less toxic derivative of indomethacin
sulindac
112
meloxicam COX selectivity
at low doses COX 2 selective
113
meloxicam halflife
20 hours
114
piroxicam half life
57 hours
115
adverse effects of NSAIDS
renal issues with peripheral edema!
risk of bleeding
inhibition of uterine motility
GI ulceration
116
acetaminophen is effective as what
analgesic
antipyretic
117
advantage of tylenol over NSAIDs
no GI toxicity
118
disadvantage of tylenol over NSAIDs
hepatic necrosis
greater risk renal toxicity
119
risk with alcohol and Tylenol
hepatic necrosis
increase in toxic acetaminophen metabolites (NAPQI)
120
how does hepatic necrosis happen
increase in NAPQI with depleted GSH to break it down
121
COX 2 selective agents benefit and harm
benefit - reduced GI bleed / ulcer
risk - blood clot, CV issues`
122
which NSAIDs are COX 2 selective
celecoxib
diclofenac
meloxicam
123
NSAID contraindications
CKD
peptic ulcer disease
hx / GI bleed
124
NSAIDs risks
cardiovascular risk
interfere with bone healing
asthma exacerbations
125
local anesthetics are ____ blockers
sodium channel
-caine
126
which sodium channel blocker has high allergy risk
benzocaine
esters
127
which drugs are sodium channel blockers?
local anesthetics
anticonvulsants: lamotrigine, carbemazepine, ozcarba
tricyclic antidepressants: amitriptyline
128
which anticonvulsant off label peripheral neuropathy
lamotrigine
129
how can SNRIs provide analgesia
alpha 2 receptors in spinal cord
130
duloxetine pain uses
diabetic pain
fybromyalgia
peripheral neuropathy
131
velafaxine off label use pain
diabeteic neuropathic pain
132
SNRI without sodium channel functionality?
milnacipran for fibromyalgia
133
calcium channel blockers as analgesics
gabapentin
pregabalin
134
gabapentin and pregabalin selectivity
alpha 2 delta
Cav 1, 2 selective
135
half life of pregabalin and gabapentin
4-8 hours
136
metabolism and interactions of gabapentin and pregabalin
no drug drug interactions
not metabolized
137
stimulant drugs
coacaine
amphetamines
meth
bath salt
ecstasy
nicotine
138
depressant drugs
alcohol
GHB
cannabis
opioids
inhalants
139
psychedlic drugs
LSD
psilocybin
PCP
mescaline
ketamine
140
what does schedule 1 mean
no medical use
141
schedule 1 drugs
marijuana
THC
LSD
heroin
142
schedule II drugs
cocaine
PCP
morphine
hydrocodone/oxycodone
143
what does schedule II mean?
high abuse potential
144
what does schedule III mean?
moderate abuse
145
schedule III drugs
ketmaine
buprenorphine
marinol (THC in capsule)
146
what does schedule IV mean
low abuse potential
147
schedule IV drug example
benzos
148
which drugs act indirectly on GPCRs
cocaine
amphetamine
MDMA
ecstacy
alcohol
149
how does cocaine and amphetamiens work
dopamine transporter
release neurotransmitters
150
which drugs work on ion channels
nicotine
PCP
ketamine
benzos
barbs
151
how does nicotine work
achetylcholine receptor agonist
152
how does PCP and ketamine work
antagonist at NMDA receptors
153
how do benzos and barbiturates work
positive allosteric modulators at GABA A receptors
154
which drugs work directly on GPCRs
opiods
LSD
caffeine
155
nucleus accumbens does what
pleasure / valuation
156
VTA does what in brain
source of dopamine
157
dopamine hypothesis of addiction
dopamine assigns value to reward
value gives incentive salience
158
dopamine doesn't encode liking but does what
makes reward predictions
159
rewarding substances do what to glutamate AMPA receptors
increase them
160
mild
moderate
severe
substance abuse rating
mild - 2-3
moderate - 4-5
severe - 6+
161
physical dependence is what
tolerance
body needs drug
162
physical withdrawal symptoms
goose bumps - cold turkey
muscle spasms - kicking habit
sweating
tremors
N/V
163
dangerous withdrawal symptoms
grand mal seizures
delirium tremens (DTs)
164
psychological dependence is what
addition
compulsive need /craving
165
positive reinforcement
user feels pleasure
166
negative reinforcement
user escapes negative or painful event
167
