Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm Block 2 > NSAIDS > Flashcards

NSAIDS Flashcards

1
Q

Properties of NSAIDs?

A

Anti-inflammatory
Anti-pyretic
Analgesic

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

Which NSAID does not have anti-inflammatory properties?

A

Acetaminophen

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

Mechanism of ALL NSAIDs?

A

Inhibition of cyclooxygenase

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

What are unique effects of aspirin/salicylic acid compared to other NSAIDs?

A

Uric acid secretion
- low doses decrease urate excretion, high doses increase urate excretion (by competing for uric acid/anion exchanger in renal tubules)

CNS effects with high doses
- can cross BBB, cause tinnitus, confusion, dilirium, dizziness, psychosis, high-tone deafness, coma, nausea and vomiting …stimulation followed by depression

Respiration
- direct stimulation of respiratory centers -> respiratory alkalosis

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

What are the major limitations for long-term NSAID use, especially aspirin?

A

GI side effects!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do NSAIDs cause GI effects?

A

Normally, cytoprotective prostaglandins protect the stomach via PGE2 and PGI2 made from COX-1 (inhibiting acid secretion, increasing mucosal blood flow, mucous and bicarb secretion)

NSAIDs block COX-1 so you inhibit those cytoprotective PGs, leading to irritation and ulcers. *blood loss, chronic use; 3x greater risk

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

How do NSAIDs affect platelets?

A

TXA2 promote platelet aggregation
PGI2 inhibits platelet aggregation (remember PGI2 synthase is ABSENT in platelets, only present in EC)

NSAIDs inhibit synthesis of TXA2 (since they block COX-1) so NSAIDs inhibit platelet aggregation

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

Explain the dose effect of aspirin on platelets

A

Remember NSAID mechanism (blocks COX-1 in platelets, less TXA2, so it inhibits platelet aggregation.

With aspirin, a single 80mg dose can increase bleeding time for one week. Acetylsalicylic acid IRREVERSIBLY inhibits COX and platelets lack nucleus so you have to wait until theres platelet turnover.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Reye’s syndrome?

A

SPECIFIC TO ASPIRIN

  • illness related to viral illness (often follows viral illnesses like varicella or influenza B)
  • Children 6-11 years old
  • Acute encephalopathy, liver degeneration
  • *That’s why you dont give children aspirin to children
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Side effects associated with all non-selective NSAIDs?

A

GI irritation
Inhibition of platelet aggregation/increase risk of bleeding
Decrease RBF in patients dependent of vasodilatory PGs
Hypersensitivity

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

What are the NSAIDs that are proprianic derivatives? How are they administered and what is their mechanism?

A

Ibuprofen
Naproxen
- Both oral
- Inhibits both COX-1 and COX-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Difference between Ibuprofen and Naproxen?

A

Half life:
Ibuprofen - 2 hours (take 3 or 4/day)
Naproxen - 14 hours (take 1/day)

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

What NSAID is used to treat gout? What is this drug also used to treat?

A

Indomethacin (indole derived NSAID)
Also used to close PDA through IV
Also preterm labor investigational use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the mechanism for indomethacin? Why is it not used regularly for pain or fever?

A

Reversible inhibition of COX-1 and COX-2

- Increased incidence of adverse side effects in 30-50% of patients, severe frontal headaches

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

What NSAID is derived for pyrrole? Mechanism and administration?

A

Ketorolac
Reversible inhibiter of COX-1 and COX-2
Oral, IV, IM - rapid onset, short duration

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

What is the main use of ketorolac? Is it more effective for pain or inflammation?

A

Alternative for opioid analgesics in the treatment of post-op pain

  • oral or injection, short term use <5 days
  • more effective for PAIN than inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Piroxicam is administered via ____ route ____ times per day since the half life is ____ hours.

A

oral, 1x per day, half life = 50 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the therapeutic use of piroxicam?

A

Symptomatic treatment of acute and chronic RA and osteoarthritis

19
Q

Piroxicam is metabolized via:

A

CYP2C9

20
Q

What is the therapeutic use of nabumetone? How is it administered and how often?

A

Management of RA and osteoarthritis

Oral, once a day (long half life)

21
Q

What is unique about Nabumetone compared to the other NSAIDs?

A

It’s a prodrug and maybe more COX-2 specific

22
Q

How does sulfasalazine act? Pharmacokinetics?

A

Oral drug that is used for local GI inflammation INDEPENDENT of COX inhibition.

  • inhibits cytokine production
  • inhibits lipoxygenase
  • free radical scavenger
  • Drug linked by azo NN triple bond which prevents its absorption in upper GI, cleaved later by colonic bacteria
23
Q

Therapeutic uses for sulfasalazine? Adverse effects?

A

Ulcerative colitis, RA

- Adverse effects in high % of patients due to sulfa moiety

24
Q

What is the theory behind creating COX-2 selective inhibitors?

A

COX-2 is the major isoform in inflammation BUT the major limitation of NSAID use was GI side effects.

COX-1 is responsible for the synthesis of cytoprotective PGs so if you can selectively block COX-2 you can fight inflammation while keeping your GI safe.

25
Q

What is a selective COX-2 inhibitor?

A

Celecoxib (celebrex!)

26
Q

Who cannot take celecoxib?

A

People with allergies to sulfa drugs because celecoxib has a sulfonamide side chain

27
Q

How does celecoxib work (molecular) so that it is selective for COX-2?

A

It binds to a COX-2 side hydrophilic binding site near the active site. (remember bigger binding site in COX-2)

This site is NOT present in COX-1.

28
Q

How is celecoxib administered? When does it’s concentration peak? Bound to proteins or not? How is it metabolized?

A

Oral
Peak concentration at 3 hours
Highly bound
Metabolized by CYP2C9 to INACTIVE metabolites

29
Q

What are some contraindications of celecoxib use?

A

Use with caution if they have a history of GI bleeding
Defiency of CYP2C9
Sulfonamide toxicity
Following coronary bypass graft surgery

30
Q

What are some side effects of celecoxib?

A

Increase risk of GI irritation, bleeding. ulceration
Increased risk of adverse CV thrombotic events like MI and stroke
Anemia - rare

31
Q

How does celecoxib increase risk of adverse CV thrombotic events like MI or stroke?

A

Selective COX-2 Inhibitor, less PGI2 (which normally inhibits platelet aggregation), more platelet aggregation

32
Q

Did the theory behind making COX-2 inhibitors work?

A

Theory was that you can avoid inhibiting COX-1 induced GI protective PGs BUT complicated ulcer rates between celecoxib and ibuprofen weren’t much different.

From graph

33
Q

How does CV risk compare between celecoxib and non-selective NSAIDs?

A

CV risk is higher in celecoxib

34
Q

Therapeutic uses of celecoxib?

A

Signs, symptoms of RA and osteoarthritis
Primary dysmenorrhea
Acute pain
Colorectal polyps

35
Q

Acetaminophen is a _____-derived NSAID

A

para-aminophenyl

36
Q

Mechanism of acetaminophen?

A

Not really understood
NO AFFINITY for active site of COX-1 or COX-2
- May have increased selectivity for COX in brain
- May prevent reduction of COX to peroxidase form (which you need to make PGs)

37
Q

Acetaminophen would be more effective when there are low concentrations of ______

A

Peroxides; at high levels, peroxides can out-compete with acetaminophen and NOT as effective

38
Q

Admin/Pharmocokinetics of acetaminophen?

A

Oral
Half life = 2 hours
Metabolized by liver microsomal system (CYP 2E1, 1A2, 3A4)
- Mostly undergoes glucuronidation (mostly) and sulfation = 95%
- Excreted by kidney

39
Q

Adverse effects of acetaminophen?

A

LITTLE TO NO GI ISSUES

Well tolerated at normal doses but most serious concern is hepatic toxicity

40
Q

How soon after acetaminophen toxicity will you see evidence of liver damage?

A

24/36 hours; elevated liver enzymes (aminotransferase)

41
Q

What effect does acetaminophen have on glutathione?

A

High doses will deplete glutathione stores and NAPQI intermediate reacts with sulfhydryl groups in liver proteins -> hepatic necrosis

42
Q

How do you manage hepatic toxicity induced by acetaminophen?

A

N-acetylcysteine (replenishes glutathion stores)

Earlier the better, less than 36 hours!

43
Q

How does alcohol effect acetaminophen toxicity?

A

Alcohol induces 2E1, a CYP involved in it’s toxic metabolite

Alcohol depletes glutathione?

44
Q

Therapeutic uses of acetaminophen?

A

Acute pain and fever

NO ANTI-INFLAMMATORY EFFECTS

Pharm Block 2 (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions