AntiInflammatory, Antipyretic and Analgesic Agents Flashcards
1
Q
what is inflammation?
A
A normal body response
2
Q
inflammation occurs in response to
A
- infection
- physical trauma
- noxious chemicals
3
Q
Goals of inflammation (3)
A
- prevent damage from invading organisms
- set stage for tissue repair
- remove toxins
4
Q
what released blood clotting proteins at wound sites
A
platelets
5
Q
what secretes factors that mediate vasodilation and vasoconstriction
A
mast cells
6
Q
what secretes factors that kill and degrade pathogens
A
neutrophils
7
Q
what removes pathogens by phagocytosis? (2)
A
neutrophils and macrophages
8
Q
what secretes hormones called cytokines that attract immune system cells to the site and activate cells
A
macrophages
9
Q
the inflammatory response continues until the foreign material is ____ and the wound is ______
A
eliminated, repaired
10
Q
the inflammatory response is ____
A
complex
11
Q
name 4 inflammatory agents
A
- prostaglandins
- bradykinin
- histamine
- chemotactic factors
12
Q
when healing is complete the inflammatory response usually _____
A
subsides
13
Q
what is produced from almost all cells in the body
A
prostaglandin
14
Q
what is derived from unsaturated fatty acids present in membranes
A
prostaglandins
15
Q
prostaglandins work as ____ hormones
A
local
16
Q
True or False: Prostaglandins produce locally and act locally
A
TRUE
17
Q
what makes prostaglandins different from endocrine hormones?
A
prostaglandins produce locally and act locally, endocrine glands produce locally but act distantly
18
Q
what acid are prostaglandins derived from?
A
arachidonic acid
19
Q
arachidonic acid is a component of the ____ ______ _____ and is also ______
A
cell membrane phospholipid, proinflammatory
20
Q
what separates arachidonic acid from plasma lipids in response to inflammatory stimuli
A
phospholipase A2
21
Q
what is the starting point for inflammation?
A
phospholipase A2
22
Q
phospholipase A2 is inhibited by _____ to reduce inflammation
A
steroids
23
Q
once arachidonic acid is freed from the cell membrane can follow 1 of 2 pathways, what are they?
A
- Lipoxygenase
- cycloxygenase
24
Q
lipoxygenase pathway includes
A
leukotrienes
25
cyclooxygenase pathway incldues (3)
prostaglandins, thromboxanes, prostacyclines
26
thromboxanes are
procoagulant
27
prostacyclines are
anticoagulant
28
how many isoforms of cyclooxygenase exist?
2
29
what are the 2 isoforms of cyclooxygenase?
COX 1 and COX 2
30
COX 1 has two main functions, name them
Gastric protection, platlet function
31
COX 2 has 3 main functions, name them
pain, bone formation, fever
32
Do COX 1/2 have the same or different binding sites?
different
33
why is it important that COX 1/2 have different binding sites?
to allow for selective targeting
34
5 total functions of COX1
GI protection, platlet function, vascular homeostasis, reproductive and kidney functions, pain/fever/inflammation
35
4 total functions of COX2
pain/fever/inflammation, bone formation
36
vascular homeostasis is a function of
COX1
37
vascular homeostasis requires the production of (2)
Prostaclycin (PG12) and Thromboxane A2 (TX A2)
38
Prostacyclin (PG12) in vascular homeostasis is responsible for
producing vascular endothelium and works as an anticoagulant
39
Thromboxane A2 (TX A2) in vascular homeostasis is responsible for
Platelet production and pro-coagulation
40
3 primary functions of prostacyclin in vascular homeostasis
1. keep platelets inactive
2. prevent platelet aggregation
3. promote vasodilation
41
3 primary functions of thromboxane A2 in vascular homeostasis
1. activate platelets
2. recruits platelets to site of injury
3. promotes vasoconstriction
42
prostacyclin (PG12) inhibits _____ _____ secretion
gastric acid
43
PG2 and PGF2a stimulate
production of protective mucus in small intestine and stomach
44
what prostaglandin production is Cox-2 responsible for?
Prostaglandin E2
45
Prostaglandin E2 is responsible for (5)
1. temp regulation
2. pain
3. inflammation
4. bone healing
5. vasodilation
46
COX-1 and COX-2 both impact (3)
1. pain
2. fever
3. inflammation
47
COX-1 ONLY impacts (3)
1. GI protection
2. platelet production
3. vascular homeostasis
48
what are NSAIDs?
non-steroidal anti-inflammatory drugs
49
what are NSAIDs NOT?
steroids
50
true or false: steroids have powerful anti-inflammatory actions
TRUE
51
are NSAIDs stronger or weaker than steroids?
weaker
52
what are 2 pros to NSAIDs rather than steroids?
1. long term therapy
2. less toxic side effects
53
what is a toxic side effect from steroids?
hyperglycemia
54
what is the mechanism of action for NSAIDs
Competitive Cyclooxygenase inhibitors
55
what medication is the one exception in NSAIDs that are not competitve COX inhibitors?
aspirin
56
how do competitive COX inhibitors work?
by blocking the hydrophobic channel by which the substrate arachidonic acid accesses the active enzyme site
57
3 primary therapuetic effects of a competitive COX inhibitor?
1. anti-inflammatory
2. Analgesia
3. Anti-pyrexia
58
What does COX inhibition do during its anti-inflammatory property?
COX inhibition decreases prostaglandin formation
59
do NSAIDs alone fix the underlying process or cause of the inflammation?
NO
60
if you wanted to treat chronic inflammation what should you do with your NSAID doseage?
increase it
61
NSAID dose increase =
more adverse side effects
62
what is thought to be responsible for analgesia?
COX2 inhibition
63
what are the most important prostaglandins involved in pain?
PGE2 and PG12
64
how does PGE2 work?
sensitizes nerve endings to actions of chemomediators released by inflammatory process
65
what is pain production by PGE2 and PG12 inhibited by
NSAIDs
66
True or False: NSAIDs have relatively equivalent efficacy
TRUE
67
NSAIDs are best for which pain?
muscular, bone, vascular
68
what type of pain are NSAIDs not good for?
visceral (abdomen/organs)
69
70
PGE2 synthesis leads to an elevated
set-point of anterior hypothalamus thermoregulatory center (cause of fever)
71
do NSAIDs inhibit or promote or inhibit PGE2 synthesis and release?
INHIBIT
72
do NSAIDs have an effect on normal body temperature?
no
73
how are NSAIDs absorbed
near complete GI absorption. absorbed rapidly
74
does food reduce the rate of absorption of NSAIDs
yes
75
does food reduce the extent of absorption
no
76
where are most NSAIDs metabolized?
liver
77
NSAIDs with a short halflife
Diclofenac, ketoprofen, ibuprofen, indomethacin
78
NSAIDs with a long halflife
Naproxen, sulindac, nabumetone, piroxicam
79
most NSAIDs peak in
1-2 hours
80
What are 7 adverse effects to NSAIDs
1. Nausea
2. Vomiting
3. GI distress
4. Peptic Ulceration
5. Bleeding
6. HA & Dizziness
7. Elevated LFT
81
what medication might prevent adverse NSAID effects?
concomitant use of H2 receptor blockers or PPIs
82
what is a way to decrease adverse NSAID effects
taking NSAIDs with food or milk
83
How could NSAIDs cause possible bleeding?
stops platelets from sticking together
84
the inhibition of vasodilation prostaglandins. Could decrease renal blood flow and GFR leading to tissue injury
Nephrotoxicity
85
Nephrotoxicity leads to retention of
sodium and water
86
what does sodium/water retention lead to
edema, HTN, increased creatinine, hyperkalemia
87
What is an adverse effect with NSAIDs specifically for asthmatics?
hypersensitive reactions (rash, bronchospasm)
88
How are COX-2 inhibitors unique?
in their selectivity
89
how are COX-2 inhibitors unique in their selectivity?
they inhibit COX2 while leaving COX1 unaffected
90
Pros of using a COX2 inhibitor
less GI bleeding, less dyspepsia, no effect on platelet function
91
what are adverse effects to COX2 inhibitors
increase risk of cardiovascular thrombotic events (MI & Stroke)
92
what medication is contraindicated in a patient with a sulfa allergy?
celecoxib
93
indications for COX2 inhibitors (3)
rheumatoid arthritis, osteoarthritis, acute pain
94
COX2 agents
Celecoxib, Meloxicam
95
what are two medications that were removed from market due to their double incidence of MI and CVA
Rofecoxib and valdecoxib
96
what is aspirin?
irreversible inhibitor of COX1 at low doses
97
reversible COX inhibitors include
NSAIDs
98
how does aspirin work?
by decreasing thromboxane A2
99
when is aspirin considered anti-inflammatory?
high doses
100
why is aspirin anti-inflammatory only at high doses?
it lacks significant COX-2 effect
101
is aspirin a better anti platelet or a better anti-inflammatory?
anti platelet
102
Aspirin has a higher relative specificity for COX-1 meaning that there is a higher risk
GI events
103
Adverse GI effects are common due to (especially in high doses)
decreased mucus secretions
104
More adverse effects to aspirin
Nausea, heartburn, dose-related GI bleeding, ulcer bleeding, gastric perforation
105
How do you decrease GI side effects with aspirin?
co-administering aspirin with a PPI ("-prazole") OR enteric coated ASA
106
cons of enteric coated ASA
may decrease antiplatelet function
107
how long do you hold aspirin prior to surgery?
1 week
108
is aspirin reversible or irreversible?
irreversible effect for life of plaetlet
109
why do we use caution when combining ASA and NSAIDs
NSAIDs have a greater affinity for COX-1, it could antagonize the protective effects (anti-platelet) of ASA
110
bronchospasms as a result of hypersensitivity from ASA are more common in patients with (3)
1. asthma
2. nasal polyps
3. recurrent rhinitis
111
in addition to bronchospasms in ASA hypersensitivity, what else could you see in a patient affected by this?
rash, rhinitis, edema, anaphylaxis & shock`
112
aspirin is contraindicated in
children
113
letting a child take aspirin could increase their risk of
Reye's Syndrome
114
Reye's syndrome is (rapid/slow) progressing
rapid
115
What are effects of Reye's Syndrome
Liver Failure, Cerebral Edema, Death
116
what is the mortality rate for Reye's Syndrome
35%
117
Is ASA given more a secondary or primary prevention?
Secondary
118
A Secondary Prevention medication is something that
reduces the risk of that illness recurring immediately after (ex. MI and ASA)
119
Primary prevention in medication
a preventative measure for people who meet the criteria to be at risk for the disease
120
Tertiary prevention is
long term
121
a constellation of symptoms associated to a mild form of toxicity (hint: ASA)
Salicyilism
122
When can Salicyilism occur?
pts with chronic use of large doses of ASA
123
earliest signs of Salicylism toxicity
N/V, diaphoresis, sensorineural hearing loss, tinnitus
124
later symptoms of Salicylism toxicity
vertigo, hyperventilation, tachycardia, hyperactivity
125
what type of kinetics do you want with ASA?
first order
126
first order kinetics
rate of elimination is proportional to dose
127
if you increase ASA doses, the metabolism becomes saturated and you begin following
zero order kinetics, causes increase of halflife
128
zero order kinetics
fixed amount of drug metabolized per unit of time
129
salicylic acid is a (weak/strong) acid
weak
130
Salicylic acid exists in a (charged/uncharged) form
both
131
uncharged molecules can move easily across
cellular barriers
132
Hallmarks of Acute Salicylate overdose
Hyperpnea, tachypnea, metabolic acidosis, tachycardia
133
severe salicylate intoxication can cause
AMS, coma, death, hyperthermia
134
what are the goals of treatment in acute salicylate poisoning
correct fluid and electrolyte balance and enhance excretion
135
what do you administer to increase the systemic pH in acute salicylate poisoning?
Sodium Bicarbonate
136
how does sodium bicarbonate work?
Alkalinization - it traps salicylate anions in the blood and within the renal tubule which limits diffusion to the CNA and facilitate excretion
137
Acetaminophen is considered a (strong/weak) inhibitor of prostaglandin synthesis
weak
138
what does Acetaminophen inhibit
prostaglandin synthesis in CNS
139
what are the main effects of acetaminphen?
1. analgesia (block pain impulse)
2. antipyresis (inhibit hypothalamic heat regulation)
140
what does acetaminophen not do?
anti-inflammatory and antiplatelet effect
141
functions of analgesia and antipyresis start how long after taking tylenol?
analgesia - 5-10 min
antipyresis - 30 min
142
how long does tylenol last
4-6 hours
143
IV acetaminophen is how much more expensive than oral
at least 10x
144
adverse effects of acetominophen
1. hepatotoxicity
2. rash
145
hepatoxicity can cause
hepatic necrosis and is high risk in pt with underlying disease
146
does acetominophen have an adverse effect on the GI system?
NO
147
where is acetaminophen primarily absorbed?
small intestine
148
what is the primary metabolism for acetaminophen?
hepatic metabolism
149
where is most of acetaminophen conjugated?
the liver to inactive glucronidated or sulfated metabolite
150
a small portion of acetaminopehn is hydroxylated to form
NAPQI
151
NAPQI is a
highly reactive metabolite - can react with sulfhydryl groups and lead to liver damage
152
maximum dose of tylenol
no more than 1 gram every 4 hours and no more than 4 grams every 24 hours
153
what is the leading cause of drug-induced liver failure in the US?
acetaminophen
154
Phase 1 (0-24 hours) of acetaminophen toxicity
N/V, general malaise, ASYMPTOMATIC
155
Phase 2 (24-72 hours) of acetaminophen toxicity
RUQ pain, elevated liver enzymes, pronlonged PT
156
Phase 3 (72-96 hours) of acetaminophen toxicity
hepatic necrosis, encephalopathy, coagulopathy, renal failure
157
Phase 4 (4 days-2wks) of acetaminophen toxicity
complete resolution of hepatic dysfunction
158
what graph is used for acetaminophen overdose?
Rumack-matthew nomogram
159
treatment for acetaminophen overdose
N-acetylcysteine (NAC)
160
how does NAC work?
maintains or restores glutathione levels and acts as a substrate for conjugation of NAPQI
161
NAC reduces the extent of ____ injury
liver
162
when is NAC most effective
when given early (within 8 hours)
163
is all inflammation temporary?
NO
164
are all causes of inflammation the same?
NO
165
a collection of disorders where the body is being damaged by its own immune system
autoimmune diseases
166
autoimmune disorders require a combination of _____ and _____
anti-inflammatory and immunosuppressive agents
167
a group of medicines used in combination with anti-inflammatory medications to treat autoimmune diseases
Disease-modifying anti-rheumatic drugs (DMARDs)
168
goals of DMARDs
1. slow disease progression
2. prevent further tissue damage
3. induce remission
169
traditional DMARDs (5)
1. Methotrexate
2. Hydroxychloroquine
3. Leflunomide
4. Sulfasalazine
5. glucocorticoids
170
Biologic DMARDs (7)
1. adalimumab
2. etanercept
3. rituximab
4. certolizumab
5. golimumab
6. infliximab
7. abatacept
171
methotrexate is a ____
folate acid antagonist
172
how does methotrexate work?
inhibits cytokine production and purine nucleotide biosynthesis
173
True or False: methotrexate is a immunosuppressive and anti-inflammatory
true
174
can methotrexate be combined with other agents
yes
175
side effects of methotrexate (4)
1. mucosal ulceration
2. nausea
3. cytopenia
4. liver function test elevation
176
methotrexate is contraindicated in
pregnancy
