Exam #01c (NSAIDs)

Question 1

What is the main biochemical mediator of sensitization of nociceptors?

Answer 1

prostaglandins

Question 2

Explain the MOA of NSAIDs

Answer 2

Pain is felt when damaged tissue releases biochemical mediators which stimulate nerve endings.

NSAIDs inhibit the formation of these biochemical mediators by inhibiting cyclooxygenase

Question 3

What are the (4) main indications for NSAIDs?

Answer 3

1. pain
2. fever
3. antiplatelet
4. inflammation (not APAP)

Question 4

What (4) advantages does APAP have over ASA in terms of AEs?

Answer 4

1. less GI upset
2. no antiplatelet effect
3. does not effect uric acid levels
4. OK in children with viral infections

Question 5

What is the major AE associated with APAP? Is it reversible? How is it treated?

Answer 5

Causes severe hepatotoxicity via toxic metabolic intermediates

Irreversible

Can be treated with Mucomyst (Acetylcysteine)

Question 6

True or False - APAP is an appropriate NSAID to treat a child with a viral infection, fever, and general inflammation?

Answer 6

False! - APAP is appropriate to treat everything EXCEPT inflammation

Question 7

Based on your current knowledge of blood thinners and APAP, APAP would not cause any interference with drugs like Warfarin?

Answer 7

True - APAP has no antiplatelet effect seen with other NSAIDs

Question 8

Under normal dosing, how is APAP metabolized?

How does APAP metabolism change if given high doses and what potential adverse effects can this cause?

Answer 8

APAP metabolized via phase II conjugation

With high doses, APAP is metabolized by CYP450 enzymes producing a toxic metabolite that can become covalently attached to the liver cells causing IRREVERSIBLE liver damage

Question 9

Where do NSAIDs and other COX-inhibitors interfere in the prostaglandin biosynthesis pathway?

Answer 9

NSAIDs and COX inhibitors reversibly inhibit cyclooxygenase from converting Arachidonic acid to PGG2 (prostaglandin precursor for many other mediators)

Question 10

Which prostaglandin agonist drug is given to patients that chronically take NSAIDs. What is its MOA?

Answer 10

Misoprostol

MOA: Misoprostol is a prostaglandin E2 agonist that, after binding, activates the Gi protein, inhibiting adenylate cyclase activity, which decreases [cAMP], and reduces gastric acid secretion

Question 11

What is the main difference between ASA and other NSAIDs with regards to COX inhibition?

Answer 11

ASA COX inhibition is IRREVERSIBLE b/c it acetylates the COX enzyme

Question 12

What are the main AEs associated with NSAIDs? What AE is worse with ASA compared with all other NSAIDs?

Answer 12

1. GI bleeding - from antiplatelet effects
2. Renal problems - esp taking chronically - prostaglandins affect renal perfusion)
3. CV effects - higher incidence of stroke, MI

GI bleeding, ulcer occurs more often with ASA than any other NSAID

Question 13

Although acetylsalicylic acid (ASA, Aspirin) can be used for pain, inflammation, and fever, what is it primarily used for today?

Answer 13

Use primarily in low doses for inhibition of platelet aggregation

Question 14

What is the concern with giving ASA to children with a viral infection?

Answer 14

Child could develop Reyes syndrome - vomiting and encephalopathy

Question 15

Tinnitus, vertigo, decreased hearing, hyperventilation (hyperpnea) are symptoms of salicylism caused by what NSAID?

Answer 15

ASA

Question 16

True or False - ASA is a highly protein bound drug and therefore can displace other highly protein bound drugs, increasing their effects?

Answer 16

True

Question 17

Which arylalkanoic acid NSAID comes as a suppository and injection (and PO)?

Answer 17

Indomethacin

Question 18

Which arylalkanoic acid NSAID comes as optical, topical gel, and in combo with Misoprostol (and PO)?

Answer 18

Diclofenac

Question 19

Which arylalkanoic acid NSAID comes as optical and injection (and PO)?

Answer 19

Ketorolac

Question 20

What is the Blob-blob theory?

Answer 20

There are 3 sites on COX important for binding and inhibition. They are:

1. Acid center (usually 1-2 C’s from a flat surface binds to a cationic site on the COX enzyme)
2. Flat hydrophobic area (usually an aromatic ring)
3. A second hydrophobic portion (binds to trough area on COX)

Question 21

True or False - the conformation which NSAIDs assume is important for activity with respect to COX binding?

Answer 21

True

Question 22

Which enantiomer is usually the active form of propionic acid derivative NSAIDs?

Answer 22

(S)-(+) enantiomer

Question 23

True or False - when a racemic mixture of propionic acid derivative NSAIDs are administered, a portion of the R is converted to S? Which 2 enzymes are responsible for this action?

Answer 23

True

fatty acyl-CoA synthetase AND epimerase

Question 24

Name (3) non-biologic DMARDs?

Answer 24

1. Methotrexate
2. Hydroxychloroquin
3. Leflunomide

Question 25

What are the (4) MOA of biological DMARDs?

Answer 25

1. TNF inhibitors
2. T-cell activation inhibitors
3. IL receptor antagonists
4. monoclonal antibodies that destroy B-cells (Rituximab)

Question 26

What (2) drugs are indicated for an acute gout attack?

Answer 26

1. Colchicine

2. Indomethacin

Question 27

What (4) drugs are used as gout prophylaxis?

Answer 27

1. probenicid
2. sulfinpyrazole
3. allopurinol
4. febuxostat

Question 28

What is MOA of allopurinol and febuxostat?

Answer 28

inhibits xanthine oxidase