Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

DEN 7203 Pharmacological Concepts > NSAIDs > Flashcards

NSAIDs Flashcards

Lecture 6

1
Q

Describe the arachidonic acid pathway

A
  1. Phospholipids broken down into Arachidonic acid pathway by Phospholipase A2
  2. Arachidonic acid broken down into Prostaglandins (cyclooxygenase) and Leukotrienes (Lipoxygenase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Prostaglandins lead to ____
Leukotrienes lead to ____

A

Pain; airway reactivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are prostaglandins?

A

Ubiquitous, lipid soluble molecules derived from arachidonic acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is arachidonic acid?

A

Fatty acid liberated from cell membrane phospholipids through the cyclooxygenase pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do prostaglandins contribute to?

A
  • Vasodilation
  • Capillary permeability
  • Phagocytic activity of leukocytes
  • Pain and fever that accompanies inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Another product of the cyclooxygenase pathway, ____, promotes platelet aggregation and vasoconstriction

A

Thromboxane A2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Prostaglandins have a protective effect on:

A

GI system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do prostaglandins protect the GI system?

A
  • Inhibits the activation of neutrophils
  • Inhibits leukocyte-endothelial interaction
  • Inhibits acid secretion and increases mucus production
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

COX-1 is a ____ enzyme

A

Cyclooxygenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is COX-1 responsible for?

A

Physiologic production of prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

COX-1 is a house-keeping enzyme that regulates normal cellular processes (via production of PGs) such as:

A
  • Gastric cytoprotection
  • Vascular homeostasis
  • Platelet aggregation
  • Kidney function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where is COX-2 constitutively expressed?

A

Brain, kidney, bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

COX-2 expression is inducible at other sites by:

A
  • Oxidative stress
  • Injury
  • Ischemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is COX-2 responsible for?

A

Elevated production of prostaglandins in inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Classical NSAIDS inhibit ____ and are associated with ____

A

COX-1 and COX-2; Adverse effects of peptic ulceration and dyspepsia (indigestion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Newer NSAIDs selectively inhibit ____, fewer gastric side effects but reported increased risk for ____

A

COX-2; heart attack, stroke, thrombosis due to relative increase in thromboxanes in platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 3 main pharmacologic effects of NSAIDs?

A
  • Anti-pyretic
  • Analgesic effect
  • Anti-inflammatory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

NSAIDS inhibit:

A

Prostaglandin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does set point temperature increase in the hypothalamus?

A

During inflammation, IL-1 increases –> inc. COX-2 –> inc. PG –> inc. set point temp in hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

NSAIDs inhibit PG production in the hypothalamus and as a result ____

A

Resets temperature (anti-pyretic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do NSAIDs provide analgesic effect?

A

Decrease the PGs that sensitize pain receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

NSAIDs can work in combination with ____ and ____

A

Opioids; lessen the required opioid dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do NSAIDs provide headache pain relief?

A

NSAIDs decrease PGs which result in less vasodilation of cerebral vasculature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How do NSAIDs work as anti-inflammatory?

A
  • NSAIDs decrease PG synthesis by COX-2 in inflammatory cells
  • Decrease vasodilation, cell adhesion, migration, stabilizes lysosomes
  • Decreased vascular permeability and therefore less edema
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
NSAIDs are weak organic ____ that are ____ absorbed
Acids; well
26
NSAIDs are metabolized by:
CYP3A and CYP2C family of cytochrome P450 enzymes in the liver
27
NSAIDS undergo final ____ excretion but also ____ excretion and reabsorption. They are excreted ____ or ____ soluble metabolites
Renal; Biliary; unchanged; H2O
28
NSAIDs are ___ bound, usually to ____
Protein; albumin
29
Non-selective COX inhibitors are ____ potent or at least ____ inhibitors of COX-1 (vs COX-2) which can lead to adverse effects
More; equipotent
30
NSAIDs like Ibuprofen, Naproxen, and aspirin are more selective for which COX?
COX 1
31
____ is 100x more selective inhibitor of COX1 than COX2
Aspirin (still inhibits both)
32
True or false: Aspirin has a much greater affinity for COX1 compared to Naproxen or Ibuprofen
True (refer to bar graph)
33
____ is one of the most consumed drugs in the world
Aspirin
34
Aspirin inhibits:
COX1 and COX2 (nonselective and irreversible)
35
____ causes irreversible acetylation of a serine on COX-1 and COX-2
Aspirin
36
True or false: All NSAIDS are irreversible competitive inhibitors of COX1 and COX2
False - only aspirin does this
37
Aspirin is a weak organic ____, so favors absorption in the ____
Acid; stomach
38
True or false: aspirin is rapidly and completely absorbed
True
39
Aspirin is rapidly hydrolyzed into ____ by ____
Acetic acid and salicylate; gastric and plasma esterases
40
____ is the active metabolite of aspirin
Salicylate
41
Aspirin has a ____ half-life Salicylate has a ____ half-life at low doses and ____ at high doses
15 min; 2-3 hour; 12 hour
42
Aspirin acetylates COX in _______ while salicylate is a ____ of COX in platelets
Platelet irreversibly; Reversible inhibitor
43
Platelet life span
8 days
44
Low dose of aspirin is effective in:
- Prevention of transient ischemic attacks - unstable angina - coronary artery thrombosis with MI - Thrombosis after coronary artery bypass grafting (due to block of COX1 in platelets)
45
____ is associated with use of aspirin during a viral infection, often ____ or ____
Reye's syndrome; influenza; varicella
46
What is Reye's syndrome?
Acute childhood illness that produces acute encephalopathy and liver disease
47
Symptoms of acute encephalopathy
- Lethargy - Agitation - Delirium - Seizures
48
Without aggressive treatment, ____ of Reye's syndrome cases end in death
80-90%
49
With heroic treatment, mortality rate of Reye's syndrome can still exceed ____, and survivors are left with ____
30%; brain damage
50
What should you to to prevent Reye's syndrome?
NO ASPIRIN for children/teenagers with fever, including flu, chicken pox, and maybe also gastroenteritis, respiratory infection
51
Is acetaminophen associated with Reye's syndrome?
No
52
____ hyperreactivity can occur in asthmatic patients taking NSAIDs
Airway
53
Airway hyperreactivity - is it immune mediated?
No, but resembles drug allergy
54
Airway hyperreactivity is more common in patients with:
Asthma or nasal polyps
55
Possible cause of Airway hyperreactivity
- When COX enzymes are blocked, arachidonic acid pathway shifts, reducing bronchodilating PGs (PGE2) - Produces leukotrienes that constrict bronchioles, mimicking asthmatic attack - May include urticaria and angioedema
56
For patients with airway reactivity, use:
Acetaminophen
57
Adverse effects of NSAIDs
- Occult bleeding - Possible increases in intraoperative and postoperative hemorrhage in oral surgery - Renal issues
58
What is occult bleeding?
Hidden amounts of blood in stool
59
How does occult bleeding occur?
- Direct capillary and mucosal damage as aspirin disintegrates - COX1 inhibition interferes with cytoprotective mechanisms and platelet aggregation
60
NSAIDs are contraindicated in patients with ____, leads to dangerous _____
Ulcers; GI hemorrhage
61
In oral surgery, higher doses of aspirin may lead to:
Possible increases in intraoperative and postoperative hemorrhage
62
In oral surgery, with very high doses of NSAIDs, what is recommended to do?
Med consult and platelet function assay
63
Low dose therapy in oral surgery
Accepted practice is to not stop low-dose aspirin therapy for dental procedures but to consider local control measures if necessary (suturing, collagen in socket)
64
Normal renal function is dependent on:
PG synthesis
65
COX 1 and COX 2 produce the PGs that reduce ____ at the ascending loop of Henle and maintain proper dilation of renal vasculature
Water and Na+ reabsorption
66
Following inhibition of PGE2 synthesis in the kidneys, what happens?
Water and Na+ retention results in peripheral edema, elevation in blood pressure, and possible congestive heart failure
67
Acute renal failure is more likely with:
- Pre-existing renal insufficiency - Congestive heart failure - Dehydration (in these cases, renal arterioles are more dependent on PGs to maintain normal perfusion)
68
NSAIDs that inhibit COX 2 cause ____ GFR in the kidney
Reduced
69
Ibuprofen is a ____ COX inhibitor
Non-selective
70
Ibuprofen has ____ anti-inflammatory properties
Good
71
All propionic acids are:
Extensively and reversibly protein bound (99%)
72
Ibuprofen is a ____ derivative
Propionic acid
73
Ibuprofen can be administered in what forms for post surgical dental pain?
- Oral tablet - Liquid - IV - Topical creams for osteoarthritis - Liquid gels
74
____ has a lower incidence of side effects vs aspirin due to being less selective for COX 1 and less GI side effects
Ibuprofen
75
Ibuprofen interaction with anticoagulants is:
Uncommon (No irreversible inhibition of COX in platelets)
76
Chronic use of Ibuprofen
- Nausea - Dyspepsia - GI ulceration - Headache - Hypertension - Increase in liver enzymes
77
Naproxen (Aleve) is more or less irritating to the GI tract than ibuprofen>
More (likely due to greater selectivity for COX 1)
78
Naproxen half life
15 hours
79
COX2 selective inhibitors reduce ____ while minimizing ____
Inflammation and pain; undesirable GI adverse effects
80
Why are COX-2 inhibitors selective for COX-2?
Larger than non-selective COX inhibitors, so too bulky to access hydrophobic channel of COX-1, so less inhibition of COX1
81
Which COX-2 selective inhibitors have potential cardiovascular effects?
Vioxx and Bextra
82
COX-2 selective inhibitors are prescribed for:
Osteoarthritis, rheumatoid arthritis
83
____ is the only FDA-approved highly selective COX-2 inhibitor in the US
Celecoxib
84
Celecoxib is 10x more selective for ____ than ____
COX2 than COX1
85
Celecoxib effects
Decreases inflammation and pain with minimal GI problems and reduced effect on platelet aggregation
86
Celecoxib may cause allergic rxn due to:
Sulfonamide group
87
True or false: for dental pain, Celecoxib is superior to ibuprofen
False
88
start slidd 29

DEN 7203 Pharmacological Concepts (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions