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PHRM 845 > Barker > Flashcards

Barker Flashcards

1
Q

chronic pain is defined as _____

A

lasting greater than 3 months

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2
Q

types of chronic pain

A

nociceptive
neuropathic
visceral
mixed

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3
Q

what is nociceptive pain?

A

tissue
- arthritis
(inflammatory)

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4
Q

types of neuropathic pain

A

central
peripheral

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5
Q

central neuropathic pain examples

A

stroke
MS
spinal cord injury
migraine

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6
Q

peripheral neuropathic pain examples

A

infection (post herpes)
diabetic neuropathy

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7
Q

what is visceral pain?

A

internal organs
-pancreatitis
-IBS
(inflammatory)

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8
Q

mixed pain examples

A

low back
cancer

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9
Q

2 functions of pain

A

warning system
aiding in repair

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10
Q

inflammatory pain description

A

throbbing, pulsating

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11
Q

neuropathic pain description

A

tingling, burning, shooting, stabbing

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12
Q

visceral pain description

A

squeezing

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13
Q

peripheral receptors and channels in pain

A

temperature sensitive
acid sensitive
chemical irritant sensitive

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14
Q

types of temperature sensitive channels/receptors

A

TRP
TRPV - heat
TRPM - cold

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15
Q

acid sensitive channels are activated how and conduct what

A

ASIC
activated by H+ protons
conduct Na+

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16
Q

chemical irritant sensitive channels release what

A

histamine
bradykinin

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17
Q

what is the reflex arc

A

bypasses CNS and goes from periphery to spinal cord to muscle (ex. touching something hot)

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18
Q

which channel very important for action potential traveling to spinal cord?

A

Na 1.8

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19
Q

receptors at spinal cord

A

NMDA
AMPA
mGluR

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20
Q

three pain fibers

A

alpha beta
alpha delta
C fibers

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21
Q

alpha beta pain fibers pain signal transduced and speed

A

non-noxious (touch, pressure)
innervate
faster

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22
Q

alpha delta pain fibers pain signal transduced, speed, myelination

A

pain, cold
myelinated
fast
“first pain”

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23
Q

c fibers pain signal, speed, myelination

A

pain, temp, touch, pressure, itch
unmyelinated
slow
PROLONGED pain
“second pain” dull / aching

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24
Q

what is peripheral sensitization?

A

repeated stimuli reduces firing threshold
increased expression of pain receptors (more sensitive to the touch)

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25
Q

what does substance P do?

A

vasodilation
degranulation mast cells
histamine release
inflammation and prostaglandins

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26
Q

which neuropeptide is released when there is injury?

A

substance P

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27
Q

what happens in neuropathic pain sensitization when we have more afferent activity

A

overexpression Na channels
- enhanced excitability
- generation action potentials

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28
Q

what happens with post-synaptic receptors more activated and AMPA / NMDA

A

increased AMPA and NMDA expression and sensitivity

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29
Q

how do we get more AMPA and NMDA expression?

A

increased PLC and PKC

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30
Q

where is there high expression of opiod receptors in brain?

A

descending pathway of brain stem

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31
Q

cortex does what with pain

A

identifies location of pain

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32
Q

amygdyla does what with pain

A

processing of the feeling, anxiety, emotion

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33
Q

prefrontal cortex does what with pain

A

plans action and decisions
determines what we will do as a result of pain

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34
Q

nucleus accumbens does what with pain

A

release dopamine and serotonin

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35
Q

what is an opiate

A

naturally occuring, plant derived

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36
Q

phenanthrenes SAR

A

three rings

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37
Q

3 position ester/ether does what

A

decreased potency (codeine)

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38
Q

6 position does what

A

increases activity (hydrocodone from codeine)

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39
Q

nitrogen substitution does what

A

gives antagonist / partial agonist activity
(buprenorphine or naloxone)

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40
Q

how are endogenous peptides activated

A

large proteins cleaved into opioid subtype selective peptides

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41
Q

POMC protein cleaved to what peptide that codes what receptor

A

beta endorphin > mu opiod

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42
Q

preproenkephalin cleaved to what peptides that code what receptor

A

leu- enkephalin > delta
met - enkephalin > mu and delta

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43
Q

preprodynorphin cleaved to what peptides and code what receptos

A

dynoprhin > kappa

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44
Q

opiod receptors are _____ and do what

A

GPCR
Gi - inhibit cAMP

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45
Q

opiod receptors do what to channels

A

open GIRK K+ channels
close Ca+ channels
(decrease firing)

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46
Q

endogenous opiod of Mu

A

endorphin

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47
Q

endogenous opiod of Kappa

A

dynorphin

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48
Q

endogenous opiod of delta

A

enkephalin

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49
Q

endogenous opiod of nociceptin

A

nociceptin

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50
Q

sigma receptors are what

A

not an an opioid receptor

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51
Q

what do opiod receptors do presynaptically?

A

inhibit calcium channel, decrease in neurotransmitter release

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52
Q

what do opiod receptors do postsynaptically?

A

open GIRK channel
efflux of K+ making more negative and hyperpolarization

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53
Q

what is a component of runners high in mu opioid receptors?

A

beta- endorphins

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54
Q

use of mu opiod therapeutically

A

analgesia (not chronic)
sedation
anti tussive

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55
Q

opiod induced side effects are ____ target

A

on target

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56
Q

on target side effects of mu opiod receptors

A

respiratory depression
constipation
pruritus (itch)
urinary retention
N/V
miosis

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57
Q

activation of kappa opiod receptor does what

A

dysphoric and aversive, negative effects
reduce dopamine release

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58
Q

which opiod receptor can counteract the effects of mu

A

kappa

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59
Q

delta opiod receptors have a role in what

A

protection
stroke/ischemia/hypoxia
reduce anxiety, depression

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60
Q

delta receptors as drugs ?

A

NO FDA approved ones

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61
Q

opiod reward centers

A

ventral tegmental
nucleus accumbens

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62
Q

how do depressants cause dopamine release with opioid binding

A

opiod binds mu
Gi - decrease neurotransmitter release
less GABA to activate GABA A
less dopamine inhibition
more dopamine release
more dopamine receptor activation

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63
Q

what is morphines bioavailability

A

25%

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64
Q

morphine cyps

A

2D6
3A4

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65
Q

which opiods are prodrugs

A

heroin
codeine
tramadol

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66
Q

which do not have active metabolites

A

fentanyl
methadone

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67
Q

codeines active metabolites

A

hydrocodone
morphine

68
Q

heroin active metabolite

69
Q

tramadol active metabolite

A

o- desmethyltramadol

70
Q

what does CYP3A4 do to opioids

A

converts to nor, inactive

71
Q

what does CYP2D6 do to opioids

72
Q

extensive metabolizers have ___ concentrations of morphine

A

50% higher, more side effects

73
Q

poor metabolizers effects from codeine

74
Q

what drugs are broken down by plasma esterases?

A

sufentanil
remifentanil
alfentanil
(esterase linkages)

75
Q

which opioid has SNRI properties

76
Q

which opioid renal excreted

A

meperidine
not recomended

77
Q

meperidine toxic metabolite

A

normeperidine
CYP3A4

78
Q

which opiod blocks NMDA receptors

79
Q

which opioid QTC?

80
Q

pentazocine receptors

A

kappa agonist
partial agonist/antagonist at mu

81
Q

butorphanol receptors

A

kappa agonist
partial agonist/antagonist at mu

82
Q

nalbuphine receptors

A

full agonist kappa
antagonist at mu

83
Q

buprenorphine receptors

A

partial mu agonist
weak kappa agonist
weak delta antagonist

84
Q

senna causes what

A

colonic contraction

85
Q

methadone: speed, PK

A

slow acting
accumulation
full agonist

86
Q

buprenorphine is a ____

A

partial agonist

87
Q

subutex has ____

A

abuse potential

88
Q

naltrexone is a _____

A

antagonist

89
Q

naltrexone bioavailability

A

decent oral
best if pt has been drug free for 1 month or more
causes withdrawal

90
Q

naloxone bioavailability

A

limited oral bioavailability
short half life

91
Q

non-pharm treatment of neonatal abstinence syndrome

A

swaddling
hypercaloric formula
feedings frequently
redhydration

92
Q

best pharm treatment for withdrawal baby

A

buprenorphine and morphine
could do methadone or clonidine too

93
Q

examples of eicosanoids

A

arachidonic acid metabolites
prostaglandins (red, heat, pain)
thromboxanes
leukotrienes (swelling)
cytokines (pain)

94
Q

COX-1 protects what

A

GI expression

95
Q

which drug irreversibly inhibits COX enzymes

96
Q

which drugs inhibit leukotrine synthesis

A

indomethacin
diclofenac

97
Q

can aspirin have tolerance to analgesia

98
Q

risk in aspirin for children

A

Reyes Syndrome

99
Q

absorption of aspirin and salicylates

100
Q

aspirin and salicylate half life

A

ASA 15 min
salicylate 6-20 hours

101
Q

increased excretion of ASA / salicylate with what

A

increased urinary pH
(from like bicarb)

102
Q

effects of aspirin poisioning

A

vertigo
tinnitus
respiratory alkalosis (hyperventilation)
metabolic acidosis (low blood pH)

103
Q

treatment of aspirin / salicylate poisioning

A

reduce salicylate load
increase urinary excretion
dextrose and sodium bicarb

104
Q

ibuprofen is a _____ COX inhibitor

A

reversible

105
Q

half life ibuprofen

106
Q

half life naproxen

107
Q

diclofenac risk

A

peptic ulcer and renal dysfunction

108
Q

what is misoprostal

A

PGE1 analog, used with diclofenac

109
Q

indomethacin is a ______ inhibitor of PG biosynthesis

A

potent reversible inhib

110
Q

indomethacin risk

A

lots of severe side effects long term

111
Q

what is the less toxic derivative of indomethacin

112
Q

meloxicam COX selectivity

A

at low doses COX 2 selective

113
Q

meloxicam halflife

114
Q

piroxicam half life

115
Q

adverse effects of NSAIDS

A

renal issues with peripheral edema!
risk of bleeding
inhibition of uterine motility
GI ulceration

116
Q

acetaminophen is effective as what

A

analgesic
antipyretic

117
Q

advantage of tylenol over NSAIDs

A

no GI toxicity

118
Q

disadvantage of tylenol over NSAIDs

A

hepatic necrosis
greater risk renal toxicity

119
Q

risk with alcohol and Tylenol

A

hepatic necrosis
increase in toxic acetaminophen metabolites (NAPQI)

120
Q

how does hepatic necrosis happen

A

increase in NAPQI with depleted GSH to break it down

121
Q

COX 2 selective agents benefit and harm

A

benefit - reduced GI bleed / ulcer
risk - blood clot, CV issues`

122
Q

which NSAIDs are COX 2 selective

A

celecoxib
diclofenac
meloxicam

123
Q

NSAID contraindications

A

CKD
peptic ulcer disease
hx / GI bleed

124
Q

NSAIDs risks

A

cardiovascular risk
interfere with bone healing
asthma exacerbations

125
Q

local anesthetics are ____ blockers

A

sodium channel
-caine

126
Q

which sodium channel blocker has high allergy risk

A

benzocaine
esters

127
Q

which drugs are sodium channel blockers?

A

local anesthetics
anticonvulsants: lamotrigine, carbemazepine, ozcarba
tricyclic antidepressants: amitriptyline

128
Q

which anticonvulsant off label peripheral neuropathy

A

lamotrigine

129
Q

how can SNRIs provide analgesia

A

alpha 2 receptors in spinal cord

130
Q

duloxetine pain uses

A

diabetic pain
fybromyalgia
peripheral neuropathy

131
Q

velafaxine off label use pain

A

diabeteic neuropathic pain

132
Q

SNRI without sodium channel functionality?

A

milnacipran for fibromyalgia

133
Q

calcium channel blockers as analgesics

A

gabapentin
pregabalin

134
Q

gabapentin and pregabalin selectivity

A

alpha 2 delta
Cav 1, 2 selective

135
Q

half life of pregabalin and gabapentin

136
Q

metabolism and interactions of gabapentin and pregabalin

A

no drug drug interactions
not metabolized

137
Q

stimulant drugs

A

coacaine
amphetamines
meth
bath salt
ecstasy
nicotine

138
Q

depressant drugs

A

alcohol
GHB
cannabis
opioids
inhalants

139
Q

psychedlic drugs

A

LSD
psilocybin
PCP
mescaline
ketamine

140
Q

what does schedule 1 mean

A

no medical use

141
Q

schedule 1 drugs

A

marijuana
THC
LSD
heroin

142
Q

schedule II drugs

A

cocaine
PCP
morphine
hydrocodone/oxycodone

143
Q

what does schedule II mean?

A

high abuse potential

144
Q

what does schedule III mean?

A

moderate abuse

145
Q

schedule III drugs

A

ketmaine
buprenorphine
marinol (THC in capsule)

146
Q

what does schedule IV mean

A

low abuse potential

147
Q

schedule IV drug example

148
Q

which drugs act indirectly on GPCRs

A

cocaine
amphetamine
MDMA
ecstacy
alcohol

149
Q

how does cocaine and amphetamiens work

A

dopamine transporter
release neurotransmitters

150
Q

which drugs work on ion channels

A

nicotine
PCP
ketamine
benzos
barbs

151
Q

how does nicotine work

A

achetylcholine receptor agonist

152
Q

how does PCP and ketamine work

A

antagonist at NMDA receptors

153
Q

how do benzos and barbiturates work

A

positive allosteric modulators at GABA A receptors

154
Q

which drugs work directly on GPCRs

A

opiods
LSD
caffeine

155
Q

nucleus accumbens does what

A

pleasure / valuation

156
Q

VTA does what in brain

A

source of dopamine

157
Q

dopamine hypothesis of addiction

A

dopamine assigns value to reward
value gives incentive salience

158
Q

dopamine doesn’t encode liking but does what

A

makes reward predictions

159
Q

rewarding substances do what to glutamate AMPA receptors

A

increase them

160
Q

mild
moderate
severe
substance abuse rating

A

mild - 2-3
moderate - 4-5
severe - 6+

161
Q

physical dependence is what

A

tolerance
body needs drug

162
Q

physical withdrawal symptoms

A

goose bumps - cold turkey
muscle spasms - kicking habit
sweating
tremors
N/V

163
Q

dangerous withdrawal symptoms

A

grand mal seizures
delirium tremens (DTs)

164
Q

psychological dependence is what

A

addition
compulsive need /craving

165
Q

positive reinforcement

A

user feels pleasure

166
Q

negative reinforcement

A

user escapes negative or painful event

PHRM 845 (38 decks)

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