Brainscape's Knowledge GenomeTM

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


See full index

Pharm Block 2 > 3 - NSAIDs > Flashcards

3 - NSAIDs Flashcards

1
Q

What are three general properties of NSAIDs?

A

Anti-inflammatory
Anti-pyretic (fever)
Analgesic

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

In general, when you think about PGs and inflammation, think ______.

A

COX-2

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

What is the mechanism of action of ALL NSAIDs?

A

Inhibition of cyclooxygenases (however, not all inhibit COX-1 and COX-2)

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

COX-2 genes can be inhibited by _____?

A

Steroids.

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

What chemical compound is aspirin? What is its mechanism of action?

A

Acetyl salicylic acid.

It IRREVERSIBLY inhibits COX1 and COX2 through acetylation of a serine moiety in the active site.

This mechanism is aspirin-specific.

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

What are the therapeutic implications of irreversible inhibition of COX 1 and 2? What is this the basis for?

A

Only way to have active enzyme is through protein synthesis of new enzyme.

Platelets have no nucleus and can’t do protein synthesis so new platelets need to be made to overcome irreversible inhibition.

Basis for use of low-doze aspirin in CV disease (antiplatelet).

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

What are the pharmacokinetics of aspirin (acetylsalicylic acid)?

A

Oral absorption, limited by dissolution rate (chewing can increase absorption)

Crosses BBB and placental barrier.

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

How is aspirin metabolized?

A

Deacetylated (phase 1) to salicylic acid (13% excreted in urine-renal elim) then:

  1. Glucoronidation (phase II) - 34%
  2. Oxidation (phase 1) - 4%
  3. Glycination (phase II) - 49%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is plasma half-life of aspirin dependent on? What happens with high doses?

A

The dose.

With high doses of aspirin, the metabolism gets saturated and salicylic acid builds up.

As a result, the half life becomes dose-dependent and follows zero-order kinetics.

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

What are side effects that are unique to aspirin/salicylates that are unrelated to COX inhibition?

A

Uric acid excretion, CNS effects, Respiration.

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

What can cause uricosuric effects?

A

Any agent that increases the rate of excretion of uric acid.

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

What effect do PGs have on uric acid excretion? What effect does aspirin/salicylic acid have on uric acid excretion?

A

PGs: NO EFFECT.

Aspirin: decrease uric acid excretion at low doses, and increases uric acid excretion at high doses.

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

What are the CNS effects of salicylates? At what doses does this occur?

A

Tinnitus, high-tone deafness, confusion, dizziness, delirium, psychosis, and coma.

This occurs especially at high doses, overdoses, and with poisening.

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

What side effects are major limitations to long term therapy with NSAIDs, especially aspirin?

A

GI side effects.

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

What effect do PGs have on the GI system? How are they made?

A

PGE2 and PGI2 are the major PGs that are formed from COX1 and act on EP3 receptors.

Promote secretion of cytoprotective mucus in the intestine and inhibit acid secretion by the stomach.

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

What GI effects do NSAIDs have? What puts people at a greater risk for these side effects?

A

They block the production of cytoprotective PGs causing GI ulceration and irritation.

Chronic NSAID use puts people at a 3x greater risk.

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

What effects do PGI2 and TXA2 have on platelet aggregation? What type of COX is found in platelets?

A

PGI2 inhibits platelet aggregation.

TXA2 stimulates platelet aggregation.

COX-1 is in platelets.

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

How do NSAIDs increase bleeding time? What effect does a single dose of aspirin have?

A

By inhibiting platelet TXA2.

Since dose of aspirin inhibits bleeding time for one week; this is because platelets lack a nucleus and new COX can only be make with new platelets since aspirin irreversibly inhibits COX.

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

What is hypersensitivty to aspirin and other NSAIDs? What is the mechanism by which this occurs?

A

Intolerance that is NOT IgE mediated.

Occurs when the cyclooxygenase pathway is blocked, resulting in an increase in arachidonic acid and shunting to into the leukotriene pathway.

This can cause respiratory effects.

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

What effect do PGE2 and PGI2 have on the kidneys?

A

They increase renal blood flow and increase salt and water retention.

COX-1 in kidney, COX-2 also present and upregulated in diseased states.

21
Q

What are the renal side effects of NSAIDs? Who is at risk for these effects?

A

Decrease renal blood flow and promote salt and water retention.

Effects are more predominant in those dependent on the vasodilatory effects of PGs such as the elderly.

22
Q

How can NSAIDs cause acute renal failure?

A

In those with diseased state that rely on the vasodilatory effect of PGs in the kidneys to maintain adequate blood flow, giving NSAIDs prevents those effects and therefore ANGII’s vascocontrictive properties are not counteracted.

Results in too much vasoconstriction and inadequate RBF – renal failure.

23
Q

What effects do PGs have on the uterus/fetus?

A

PGF2alpha contraction
PGE2 contraction
PGI2 dilation (early pregnancy)

24
Q

What effects do NSAIDs have on pregnancy?

A

Prolonged gestation, prolonged labor, increased risk of postpartum hemorrhage, and intrauterine close of patent ductus arteriosus.

25
Q

What is salicylism?

A

aspirin poisoning.

26
Q

How does the metabolism of aspirin change with aspirin poisoning?

A

The enzymes from metabolism can be saturated, causing salicylic acid to build up.

This increases the half-life from 2-3 hours to 15-30 hours.

27
Q

What is Reye’s syndrome and who does it occur in? What did this teach us about who to give aspirin to?

A

Rare but severe and often fatal disease specific to aspirin use.

  • acute encephalopathy
  • liver degeneration

Occurs most often in children (6-11 yrs) and usually follows a viral illness.

Do not give children under 19 aspirin.

28
Q

What are the low dose, intermediate dose, and high dose therapeutic uses of aspirin?

A

Low: CV disease (anti-platelet)

Intermediate: low intensity pain/fever

High: chronic inflammatory disease/RA

29
Q

What are side effects of ALL non-selective COX-1 and COX-2 NSAIDs?

A

GI irritation

Inhibition of platelet aggregation and increased risk of bleeding

Decrease in RBF in pts dependent on vasodilatory PGs

Hypersensitivity (shunting through leukotriene pathway)

30
Q

What are propionic derivatives and what is their mechanism of action? How do their half-lives differ?

A

Ibuprofen: 3-4x/day (shorter half life)
Naproxen: one/day (longer half life)

Reversible inhibition of COX1 and COX2.

Orally given, less GI side effects than aspirin.

31
Q

What drug is an reversible inhibitor of COX1 and COX2, can be given orally and through IV, and is not routinely used to treat pain or fever? What is it used to treat?

A

Indomethacin

Prescription only - used for gout, preterm labor, and to close a patent ductus arteriosus.

32
Q

What drug is a reversible COX 1 and COX2 inhibitor that’s used as an alternative to opioid analgesics in the treatment of post-operative pain?

A

Ketorolac

Much more effective for pain than inflammation!

33
Q

What drug is a reversible inhibitor of COX1 and COX2 and has an extremely long half-life? What is it metabolized by?

A

Piroxicam

Metabolized by CYP2C9

34
Q

What drug is a selective inhibitor of COX2? What does this drug contain?

A

Celecoxib (celebrex)

Contains a sulfomide side chain (some patients may have allergic reactions to sulfa drugs).

35
Q

What is the theory behind the development of COX2 inhibitors?

A

COX2 is a major isoform associated with inflammation, and COX1 is responsible for the synthesis of cytoprotective PGs.

The theory is that if you selctively block COX-2, you can treat inflammation without any GI effects.

36
Q

What is the mechanism of action of Celecoxib (celebrex)?

A

Binds tightly to a distinct hydrophilic side pocket region of COX2.

COX2 specific because the binding site is not present in COX-1.

37
Q

How is celecoxib metabolized? How is it given?

A

Metabolized by CYP2C9 to inactive metabolites.

Orally administered.

38
Q

What adverse side effects of celecoxib? Who is it contraindicated in?

A

Increased risk of adverse thrombotic events, like MI/stroke.

Increased risk of GI irritation, ulceration, and bleeding.

Contraindicated in people with CV risk factors or disease.

39
Q

What does the FDA recommend for all NSAIDs (except aspirin)?

A

Must include a warning about the potential increased risk of of CV events and the increased risk of serious and potentially life-threatening GI bleeding.

40
Q

What are the therapeutic uses of Celecoxib?

A

Primary dysmenorrhea (cramping)

Acute pain

Colorectal polyps.

41
Q

What is the mechanism of action of APAP? What cells/tissues are resistant to the action of APAP?

A

May have increased selectivity for brain COX.

Inhibition by APAP might be more effective under reducing conditions of low peroxide concentration.

Cells or tissues with high levels of peroxide, like inflammatory sites are resistant to the action of APAP.

42
Q

How is APAP metabolized?

A

Partially by liver microsomal system (phase I)

CYP2E1, CYP1A2, and CYP3A4
-contributes to toxicity/adverse reactions

Mainly undergoes (phase II) glucoronidation and sulfation (95% of total)

43
Q

What are the adverse effects of APAP?

A

Well tolerated at normal doses; little to no GI issues

Most serious is hepatic toxicity.

44
Q

How would hepatic toxicity from APAP be managed clinically?

A

N-acetylcysteine - replenishes glutathione stores.

The earlier this is given the better, usually less than 36 hours.

45
Q

What are the therapeutic uses of acetaminophen?

A

Acute pain and fever.

NO anti-inflammatory effects.

46
Q

What selectively inhibits the gene transcription of COX-2 but not COX-1?

A

Steroids.

47
Q

Why does aspirin increase bleeding time?

A

TXA2 production in platelets decreases and therefore platelet aggregation is decreased.

48
Q

Explain why there are GI complaints associated with aspirin use?

A

Decreased productions of PGs that promote mucus secretion.

Pharm Block 2 (12 decks)

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