Chapter 18: NSAIDs and Acetaminophen Flashcards
1
Q
What is pain?
A
basic bodily sensation introduced by noxious stimulus
2
Q
t/f pain is a protective response to keep us from hurting ourselves
A
t
3
Q
thermal stimuli are sensed by ___ receptors
A
TRP heat sensitive cation channels
4
Q
mechanical stimuli are sensed by ___ receptors
A
mechanosensitive ion channel
5
Q
after the initial pain stimulus, how is pain taken to be processed?
A
AP travels back through the spinal cord and brain stem to the cortex to be processed
6
Q
the greater the pain stimuli, the AP is ____
A
more frequent
7
Q
what is adaptive pain?
A
painful stimulus that has a physiological purpose
8
Q
in adaptive pain, as soon as the noxious stimulus is removed, what happens to the pain stimulus?
A
goes away
9
Q
nociceptive/mechanical pain experienced when you’ve touched something hot and move your hand is an example of ____ pain
A
adaptive
10
Q
inflammatory pain when you’ve injured yourself and the immune system is helping to repair the damage and prevent infection is an example of ____ pain
A
adaptive
11
Q
what is maladaptive pain?
A
painful stimulus that has no physiological purpose
12
Q
maladaptive pain occurs when theres been ___ or ___ normal pain transduction
A
damage or disruption
13
Q
persistant pain that remains after an injury is healed is called ___ and is an example of ___type pain
A
chronic pain; maladaptive
14
Q
nerve pain may cause ___ pain where pain signals are initiated w/o a noxious cause
A
neuropathic
15
Q
neuropathic pain is a form of ___ type pain
A
neuropathic
16
Q
when can inflammatory pain be maladaptive?
A
if in an autoimmune disease that cause over production of cytokines and pro inflammatory mediators
17
Q
cytokines and pro inflammatory mediators stimulate ___ causing pain
A
nociceptive nerve fibers
18
Q
autoimmune diseases can cause ___ damage
A
tissue
19
Q
t/f pain is very subjective
A
true
20
Q
what are the 3 categories of pain perception?
A
mild, moderate, severe
21
Q
t/f pain intensity scales are useful for knowing if an analgesic is needed and what type
A
t
22
Q
for acute mild pain (1-3 on scale) what is the appropriate Rx treatment?
A
NSAIDs and acetaminophen
23
Q
for acute moderate pain (4-6 on scale) such as after minor surgery, the appropriate treatment is __
A
weak opioid such as codeine w/ or w/o a NSAID or acetaminophen
24
Q
for acute severe pain (7-10 on scale) such as after major trauma or surgery, the appropriate treatment is ___
A
opioids
25
t/f to best treat pain, you need to go to the root of the pain
t
26
arthritis pain is managed with what type of analgesic?
anti-inflammatory (steroids and NSAIDs)
27
disease modifying anti rheumatic drugs (DMARDs) and immunomodulators are a mainstay of therapy to reduce ___ caused by chronic inflammation
tissue damage
28
neuropathic pain can be modulated with drugs that affect ___
neurotransmission
29
decreasing the ___ of damaged nerves will reduce pain transmission
excitability
30
t/f antidepressants and anti seizure drugs have analgesic effects bc they decrease excitability of damaged nerves
t
31
if the underlying cause of pain is unknown, or treatment with other analgesics is not sufficient, what treatment option may be needed>
opioids
32
t/f once you get to the top of the analgesic ladder, you're stuck there and cant get anymore help
false
33
t/f non-pharm is important to chronic pain management
true
34
what are some non-pharm options that may be used for chronic pain?
physiotherapy, acupuncture, lifestyle modification
35
what are the steps of the analgesic ladder?
1. non-opioids +/- adjuvants
2. mild opioids + non-opioids +/- adjuvants
3. severe opioids +/- non-opioids +/- adjuvants
4. invasive treatment
36
ASA, ibuprofen, naproxen, indomethacin, diclofenac, and celecoxib are all ___ analgesics
NSAIDs
37
NSAIDs reduce inflammation by decreasing the production of ___ which reduces the stimulation of ___ receptors on nerve fibers and also reduces ___ that often accompanies inflammation
pro inflammatory mediators; chemical; swelling
38
does acetaminophen have significant anti-inflammatory effects
no
39
what is the normal protective function of inflammation?
avoid infection and repair tissue damage
40
in some cases, pain of inflammation persists due to sensitization of ___fibers
nociceptive
41
peripheral sensitization occurs when the nociceptive nerve fibre is stimulated by inflammatory mediators like __, and other signalling molecules like ___, __ and __
prostaglandins; bradykinins, adenosine, and neuropeptides
42
peripheral sensitization causes nociceptive nerve fibers to become more sensitive to pain so when pain is felt, it is perceived as being more __
intense
43
t/f sensitization of nociceptive fibers can become so intense that even stimulus that shouldn't cause pain will be perceived as painful
t
44
when a non-painful stimulus causes pain, it is called ___
allodynia
45
prostaglandins, leukotrienes, prostacyclin and thromboxane are all mediators of the ___ pathway
arachidonic acid
46
in the arachidonic acid pathway, ___ are used to make inflammatory mediators
phospholipids
47
what are the 2 cyclooxyrgenase isoforms?
1. COX1
| 2. COX2
48
COX___ is expressed in many tissues and helps maintain cellular functions such as mucous secretion, regulation platelet aggregation, and smooth muscle contraction
1
49
COX__ is expressed in many tissues, including kidneys and endothelium.
2
50
COX___ is responsible for increased inflammation
2
51
prostaglandins are pro-___ and have ___ activity
inflammatory; cytoprotective
52
thromboxane and prostacyclin regulate platelet ___
aggregation
53
COX 2 promotes the production of pro-inflammatory prostaglandins, particularly ___
PGE2
54
PGE2 drives the ___ response
immune
55
increased prostaglandins causes ___ in the periphery and ___ in the CNS
inflammation pain/swelling; fever
56
COX__ is the target of anti-inflammatory drugs
2
57
until the late __(year) it was not possible to selectively inhibit COX2
1990s
58
___ is currently the only clinically available, selective COX-2 inhibitor for human use in Canada
celecoxib
59
t/f Celebrex (celecoxib) requires a RX in Canada
t
60
all COX inhibitors are ____antagonists
competitive
61
indomethacin is typically only used in the clinical treatment of ___
gout
62
what is gout?
acute inflammation of the joints due to uric acid bulid0up and crystallization
63
in reversible inhibition of COX by something like ibuprofen, during periods when drug is not bound to the COX, it can function, but overall there is a decrease in ___ production
prostaglandin
64
when ibuprofen is used, higher concentration of ___ are needed to out-compete the drug to produce prostaglandins
arachidonic acid
65
what is the deference in stimulating an enzyme vs stimulating a receptor?
enzyme stimulation results in direct influence on cellular product production
receptor stimulation results in altered signalling pathway
66
in the presence of a competitive antagonist, the concentration needed to produce a product causes that curve to shift to the ___
right
67
as a reversible inhibitor of an enzyme is cleared from the body, the functionality of the enzyme is ___
restored to normal
68
even with repeated and continued dosing of COX inhibitors, if the cell received ____, a greater amount of arachidonic acid would be produced and could block out the drug
large inflammatory signal
69
what is an example of an irreversible COX inhibitor?
ASA
70
ASA binds to COX in what way?
covalently
71
when ASA binds to COX, it adds a ___ group to the enzyme active site
acetyl
72
___ is the byproduct of ASA interacting with COX
salicylate
73
what is the effect of ASA adding acetyl to COX?
prevents it from making prostaglandins
74
ASA acts as a ___antagonsit at the COX enzymes
non-competitive
75
when ASA is used, can enough arachidonic acid be made to reach peak prostaglandin production?
no, not until more COX are made
76
why are the irreversible effects of ASA not notable in most cell types?
most cells make new COX continually
77
t/f ASA is a poor anti-inflammatory compared to other NSAIDs
t
78
ASA is commonly used as a ___ agent
anti platelet
79
platelets express COX1 to produce ___ which is involved in platelet activation and aggregation
thromboxane A2
80
platelet aggregation is one of the first steps in ___
blood clotting
81
reducing the production of thromboxane A2 in platelets reduces the risk of ___ and __
heart attack and stroke
82
why is taking low-dose ASA as effective as taking an antiplatelet therapy?
bc ASA binds irreversibly to COX-1 and bc platelets are anuclear, they cannot make more platelets so the effect is maintained for the lifetime of the platelet
83
platelets express COX__
1
84
what is the lifetime of platelet?
8-9 days
85
if we inhibit every COX1 in every platelet at once, what would happen to the patient?
bleed out
86
why is ASA a better anti-platelet than anti-inflammatory / analgesic?
higher affinity for COX1 than COX 2
87
naproxen has a slight preference for COX___
2
88
why are diclofenac and indomethacin not used systemically or in particular cases only?
high affinity for COX and bc that includes COX1, there will be the ADR of blocking COX1
89
Celecoxib and Naproxen have much ___ half-lives compared to the other NSAIDs
longer
90
what is the dose of ASA required for anti-platelet function?
81 mg / day
91
what is the dose of ASA required for analgesic or anti inflammatory function?
650 mg Q4hr
92
the primary ADR related to NSAID use are related to the inhibition of ___, ___ and ___ synthesis that are used in normal processes
prostaglandin, thromboxane, prostacyclin
93
reduction in prostaglandin synthesis ny NSAIDs in the GI tract reduces ___, which makes the stomach and intestine more susceptible to peptic ulcers
secretions
94
t/f there is conflicting evidence if celecoxib has risk of peptic ulcers
t
95
if long-term NSAID use is needed, a ___ such as misoprostol or a ___ like omeprazole may be added to reduce risk of developing a peptic ulcer
cytoprotective agent; proton pump inhibitor
96
bc celecoxib does not block COX1, it has a lower risk of __ compared to other NSAIDs
GI bleeding
97
are NSAIDs contraindicated in patients with renal impairment? why/ why not?
yes; risk of nephrotoxicity
98
nephrotoxicity of NSAIDs is caused by ___ in the kidneys, which reduces renal function
inhibition of COX1/2
99
are NSAIDS contraindicated in patients with CVD / risk factors? Why/why not?
yes; reduction of COX2 production of prostacyclin in the endothelium which is important to blood clotting
100
t/f there are conflicting studies as to if celecoxib increases risk for MI and stroke
t
101
NSAIDs are contraindicated in the ___ trimester of pregnancy. why?
third; importance of COX in normal physiological processes
102
t/f short term use in trimesters 1-2 has no significant risk to the fetus
t
103
small amounts of NSAIDs can be excreted in the breast milk, so what type of NSAID should be chosen?
short-half life like ibuprofen
104
wherever possible ___ application of analgesic for local pain is preferred over systemic
topical
105
t/f topical application can still accumulate to have some systemic effects
t
106
post-surgery use of NSAIDs can have negative impact on ___ and ___
wound healing and bone remodelling after orthopaedic surgery
107
t/f even though NSAIDs are available OTC, they can still have serious ADR and interactions/contraindications
true
108
t/f the MOA of acetaminophen is not completely clear
true
109
the best evidence suggests that acetaminophen works by
being metabolized in the CNS into a compound that affects the endocannabinoid system that increases 5-HT in the spinal cord, giving analgesia
110
what are 3 benefits of using acetaminophen for analgesia?
1. low risk of GI ulcers
2. no anti-platelet effects
3. safe in pregnancy
111
acetaminophen has risk of toxicity in what organ?
liver
112
what is the max dose of acetaminophen daily?
4 g
113
acetaminophen use is contraindicated in patients with ___ and/or ___ impairment
renal; hepatic
114
hepatotoxicity of acetaminophen is worsened in the presence of ___
alcohol
115
the major metabolic pathways of acetaminophen are phase __ metabolism to ___ or ___ metabolites which are excreted by the kidneys
2; glucuronide; sulfate
116
a minor pathway exists where acetaminophen is oxidized by CYP enzyme into a toxic metabolite called___
NAPQI
117
what normally happens to the toxic NAPQI metabolite of acetaminophen?
further metabolized (phase 2) to make a glutathione conjugate which is excreted
118
what happens if there is not enough glutathione to convert the toxic NAPQI?
will accumulate and cause hepatotoxicity
119
why does alcohol worsen hepatotoxicity of acetaminophen?
induces the CYP enzymes that create the NAPQI metabolite
120
in acute acetaminophen overdose ___ can be administered to promote the glutathione rxn that eliminates the toxic metabolite
N-acetylcysteine
121
t/f treatment for hepatoxicity must be prompt
t
122
t/f in chronic alcohol users, even a normal dose of acetaminophen can cause liver toxicity
t
123
t/f the liver is resilient, but severe damage can be fatal
t
