Pain Management: NSAIDs/APAP Flashcards
(111 cards)
1
Q
4 types of pain
A
nociceptive
inflammatory
neuropathic
functional
2
Q
nociceptive pain
A
occurs in response to noxious stimuli, in order to prevent further damage
3
Q
inflammatory pain
A
occurs in response to tissue damage or infection in order to promote healing
4
Q
neuropathic pain
A
occurs as the result of damage or pathological changes in either the PNS or the CNS
5
Q
functional pain
A
occurs due to an abnormality in processing by, or functioning of, the CNS in response to normal stimuli
6
Q
acute pain is typically from what types of pain?
A
nociceptive or inflammatory
7
Q
chronic pain is typically from which types of pain?
A
neuropathic, inflammatory, functional.
8
Q
mild/moderate acute pain
two tiers of treatment
A
1st tier: NSAIDs or APAP
2nd tier: opioids
9
Q
severe acute pain
two tiers of treatment
A
1st tier: opioids
2nd tier: opioids plus NSAIDS or APAP
10
Q
acute pain treatment modailities
A
NSAIDS, APAP, opioids
11
Q
chronic pain treatment modalities (8)
A
TCAs AEDs lidocaine SSRI/SNRI long acting opioids clonidine or bactrim pregabalin APAP/NSAIDs (inflammatory)
12
Q
nociceptor stimulation pathology:
what 6 substances does injured tissue cause the release of?
A
bradykinin serotonin potassium histamine prostaglandins substance P
13
Q
nociceptor stimulation pathology
A
injured tissue causes the release of bradykinin, serotonin, potassium, histamine, prostaglandin, and substance P. they further sensitize or activate nociceptors. This results in a lowering of the pain threshold.
14
Q
nociceptor activation
A
action potentials are produced and transmitted to the spinal cord along myelinated a-delta-fibers and unmyelinated c-fibers
15
Q
pain signals are transmitted via the spinal cord to
A
the thalamus
16
Q
after pain signals reach the thalamus,
A
they are transmitted to cortical regions where pain is actually perceived.
17
Q
a-delta-fibers transmit
A
sharp and fast pain
18
Q
c-fibers transmit
A
slower, dull, diffuse pain
19
Q
modulation of pain occurs through what 3 processes?
A
endogenous opioids
descending pathway
cognitive behavioral treatments
20
Q
pain modulation: endogenous opioids
A
endorphins act on opioid receptors in the CNS to inhibit pain impulses
21
Q
pain modulation: descending pathway
A
inhibition of pain transmission in the dorsal horn of the spinal cord
22
Q
pain modulation: cognitive behavioral treatments
A
reduce pain perception by altering pain processing in the cortex
23
Q
inflammatory pathway produces
A
prostaglandins
24
Q
arachidonic acid
A
liberated from CMs when cells are damaged. from there, it can convert to prostaglandins by cox enzymes
25
3 prostaglandins
thromboxane (TXA2)
prostaglandin e2 (PGE2)
prostacyclin (PGI2)
26
in response to tissue injury, nociceptors release which prostaglandins?
PGE2 & PGI2
27
PGE2 & PGI2 actions
Prostaglandins which facilitate inflammation and sensitize nociceptors to painful stimuli
28
COX inhibitor drug uses
anti inflammatory
analgesic
antipyretic
29
adverse effects of cox inhibitors
gastric ulceration
bleeding
renal impairment
30
cox inhibitor MoA
inhibit cox which is the enzyme that converts arachidonic acid into prostaglandins and related compounds.
31
inhibition of COX-1 also leads to
gastric ulceration
bleeding
renal impairment
32
which COX is good cox and which is bad cox?
COX-1 : goood
| COX-2: bad
33
what is the one benefit of inhibiting cox 1
decreased risk for MI on low dose daily ASA
34
When cells are damaged and release cox2, what will be produced?
PGE2 and PGI2, sensitizing nociceptors and facilitating inflammation
35
cox 2 inhibition Thera effects
anti inflammatory
analgesic
anti pyretic
potential for reducing tumorigenic growth
36
Cox inhibiting drugs with anti inflammatory properties
NSAIDS
37
cox inhibiting drug that does not have an anti inflammatory property
APAP (acetaminophen)
38
why isn't acetaminophen anti inflammatory?
Distributes almost exclusively in the CNS.
Binds to and inhibits cox in the CNS, leading to analgesia and antipyretic
Does not effect COX in peripheral tissues
39
NSAIDS are nonselective, meaning
they bind to and inhibit COX 1 and 2
40
only FDA approved sole cox-2 inhibitor
celecoxib
41
benefit of acetaminophen over nsaid
no renal impairment, gastric ulcers, or risk of bleeding.
42
aceta MoA
inhibits cox in the CNS
43
PO bioavailability of aceta
85-100%
44
peak plasma time of po aceta
within 1 hour
45
protein binding of aceta vs NSAIDs
aceta: low protein binding
NSAIDs: high protein binding
46
metabolism of aceta
| excretion
mainly in the liver
undergoes phase I via CYP2E1 and II, but vastly done in phase II.
in phase II, aceta is conjugated to glucoronic acid, sulfuric acid, and cysteine. then excreted.
small proportion of aceta goes through phase I. If not able to complete and this metabolite builds up, hepatotoxicity can occur.
47
elimination of aceta in adults time
2-3 hours
48
acetaminophen in the setting of inflammatory pain
may be used as an analgesic adjunct but is inadequate for this type of pain as a single agent.
49
acetaminophen in neuropathic or functional pain
lacks efficacy
50
current FDA recommended daily dose of aceta
4g
| can effect liver function
51
what dose of acetaminophen can be fatal and why?
15g
| severe hepatotoxicity and potentially renal failure via acute tubular necrosis
52
treatment for acetaminophen overdose
acetylcysteine
53
NAPQI
toxic metabolite of acetaminophen
54
NAPQI and glutathione
glutathione binds to NAPQI, renders it harmless, and it is excreted in the urine
55
NAPQI with insufficient glutathione
hepatotoxicity
56
N-acetylcysteine will
act as glutathione, bind to NAPQI for excretion.
57
single and daily doses of aceta are not to exceed...
single: 1g
daily: 4g
58
at what adult weight must daily and single aceta doses be adjusted?
<50kg
59
which CYP enzyme metabolizes aceta in phase I? (3)
CYP2e1
CYP1a2
CYP3a4
60
Alcohol does what to CYP450?
induces it
61
CYP450 does what in aceta metabolism?
converts aceta to NAPQI
62
glutathione is effected how by alcohol?
depleted
63
alcohol + aceta
| metabolism
CYP450 is induced by alcohol. More of the toxic metabolite, NAPQI, is produced. Alcohol reduces glutathione, which neutralizes NAPQI. this leads to too much NAPQI -> hepatotoxicity.
64
why are renal impaired patients susceptible to aceta toxicity?
kidney produces some degree of NAPQI because small amounts of phase I metabolism occur in the kidney. If you have impaired renal function, the NAPQI isn't able to clear out of the nephron. the kidney is then damaged by the NAPQI.
65
first generation NSAIDs inhibit
cox-1 and cox-2
66
first generation NSAID therapeutic indications: (5)
- inflammatory disorders ie: RA
- mild/moderate pain
- antipyretic
- dysmenorrhea/heavy menstrual bleeding
- promote closure of patent ductus arteriosus
67
first generation of NSAIDS suppress inflammation but
pose risk of serious harm
68
first generation NSAIDs in dysmenorrhea
uterus SM produces prostaglandins associated with cramping. blocking cox can alleviate.
cox 2 is associated with heavy bleeding. blocking can alleviate.
69
prototype of 1st gen NSAID
ASA
70
low dose ASA indication
antithrombotic
71
higher dose ASA indication
antipyretic
analgesic
anti inflammatory
72
absorption of ASA
within 1hr
73
protein binding of ASA
high
74
traditional NSAIDS (tNSAIDs) were developed to
be safer alternatives to asa
75
what is the primary difference between ASA and tNSAIDs?
the way they bind to cox.
asa: irreversible inhibition
tNSAIDs: reversible inhibition
76
ASA inhibition of COX1&2
irreversible, meaning that the ASA binds for life. as ASA concentrations fall, ASA is still bound to the cox.
77
ASA prior to surgery & rationale
ASA must be stopped a week prior to surgery. the life of a platelet is 8-10 days. ASA will bind to a PLT for its entire life. you need a week to give the body a chance to make PLTs that have not been bound to ASA
78
tNSAID inhibition type of COX
reversible.
as the concentration of tNSAIDs decrease below therapeutic, cox are able to produce prostaglandins again. Dosing needs to be repeated to keep this effect.
79
two most common OTC tNSAIDs
ibuprofen
| naproxen
80
ibuprofen vs naproxen
ibuprofen: better for dysmenorrhea
naproxen: better for joint pain but more GI effects
81
FDA warning for tNSAIDs
can cause MI or stroke in those treated chronically with tNSAIDs.
82
thromboxane prostacyclin imbalance hypothesis
We have a balance between prostaglandin signaling and plts/endothelial cells. Endothelial cells express COX 2, producing prostacyclin (required for normal vasodilation/inhibition of plt agg). that balances out thromboxane production by cox1 and plts. in plts, cox1 produces thromboxane a2, promoting vasoconstriction and plt agg. normally there is this balance between the two, promoting homeostasis.
-balance between prostaglandin signaling and plts/endo cells. endothelial cells express cox2. cox 2 produces prostacyclin which does vasodilation and prevents aggregation. so endo cells = open vessels and free flowing plts.
-thromboxane production by cox1 and plts = thromboxane 2 which = vast con and agg. so cox1-> thromboxane-> constricted vessels and sticky platelets.
when you inhibit cox2, you're tipping the scales more towards constricted vessels and platelet aggregation.
selective cox2 inhibitors are well known for propensity to cause mi/stroke because they inhibit cox2 in endothelial cells. decrease prostacyclin signaling = thromboxane production in platelets, vasoconstriction and plt agg. this leads to mi and stroke. tNSAIDs and ASA (non selective), promote inhibition of cox2 and prostacyclin. then youre tilted toward thromboxane - vasoconstriction, htn, plt agg, clot formation.
83
Cox 2 selective inhibitor suffix
coxibs
84
cox 2 selective inhibitors were created
to be safer alternatives to tNSAIDs in terms of GI bleed/ulcerations
85
some tNSAIDs are now known to be cox-2-selective. they are:
meloxicam
diclofenac
etodolac
86
cox-2-selective inhibitors are ____ inhibitors of cox-2
reversible
87
T or F: cox-2-inhibitors are just as effective as tNSAIDs in suppressing inflammation and pain
true.
88
adverse effects of cox-2-selective inhibitors
impaired renal function
htn
edema
inc risk for MI/stroke
89
Vioxx
former cox-2-selective inhibitor drug which was very effective/had low GI effects but was pulled from the market because of MI/strokes after studies showed a link. The results were suppressed initially until more organizations did their own studies and the link was stronger established.
90
celecoxib new research is showing
higher risk for cardiac calcification and aortic stenosis
91
acute, mild to moderate, nociceptive and inflammatory pain treatment modality
aspirin, tNSAIDs, coxibs
92
chronic mild to moderate pain
ASA*
tNSAIDs
*ASA is not really used anymore in a chronic way.
93
NSAIDs in neuropathic and functional pain
are not effective
94
precision trial: celecoxib
evaluating CV safety of celecoxib compared to naproxen or ibuprofen in pts with arthritis.
suggesting that the risk, in moderate doses, is equal among these meds.
95
why is GI mucosa damaged in NSAID use?
Arachidonic acid is converted to prostaglandins in the GI tract.
COX 1 is expressed in GI tract, which converts arachidonic acid to PGE2 and PGI. These things have gastric protective effects like mucous secretion, bicarb, and increased mucosal blood flow. When inhibited, peptic ulcers and GI bleeding may occur.
96
why are kidneys damaged in NSAID use?
cox 1 and 2 are expressed in the kidney. They produce PGE2&PGI which facilitate GFR and Na/water excretion.
when these enzymes are blocked, we get edema, HTN, and kidney injury.
97
why are there CV effects in NSAID use?
we have a natural balance between cox 1 and 2 in the CV system's endothelial cells and platelets. when the balance is disturbed, constriction effects become dominant, leading to MI/stroke.
98
GI effects of NSAIDs
```
pain
nausea
diarrhea (rare)
gastic ulcers
bleeding
```
99
platelet effects in NSAID use
inhibited activation, therefore a risk of hemorrhage.
100
renal effects in NSAID use
salt/water retention
edema
decrease FX of anti-HTN/diuretics
hyperkalemia
101
CV effects in NSAID use
MI
| stroke
102
hypersensitivity effects in NSAID use
rhinitis
edema
asthma
103
hypersensitivity in NSAID use: rationale
arachidonic acid can be converted into lipoxygenase as well. these are known to produce inflammation. if you inhibit cox, there will be more arachidonic acid available to be converted by things like lipoxygenase, which can convert arachidonic acid into leukotrienes which promote bronchospasm, mucous plugging, and further inflammation. aka leukotriene shunt.
104
combining asa with any other nsaid
contraindicated.
| synergistic effects on GI mucosa
105
risk of ulcer complications by ASA or tNSAIDs is increased by what other drugs? (3)
warfarin
glucocorticoids
SSRIs
106
NSAIDs and ACE inhibitors
1. ACEs will be less effective
| 2. additive effects against renal function
107
Which meds that bind to albumin may be displaced due to NSAIDs binding to albumin as well?
warfarin
mtx
sulfonylureas
108
ibuprofen blocks the interaction of ASA with _____
cox 1
109
what should you do if a patient on daily ASA needs inbuprofen or another NSAID? and why?
take ASA 1-2 hours before ibuprofen.
ASA binds irreversibly to cox1 and platelets. When you introduce ibuprofen, it will have no effect because the plts will be bound to asa.
110
Options for preventing GI bleeding on NSAIDs/ASA
- lowest effective dose possible
- substitute acetaminophen instead
- use a cox-2 selective instead
- administer NSAID/ASA with a PPI
- reduce NSAID/ASA dose and add opioid.
111
Advil dual action
new drug
| 250mg aceta/125mg ibuprofen
