Pharmacology - Inflammation

Question 1

The major cytokines involved in inflammation are:

Answer 1

IL-1 - endogenous pyrogen
IL-8 - chemotacttic agent
TNF - regulates the production of other cytokines and induces fibrosis and tissue catabolism

Question 2

What are the two cyclooxygenases involved in the inflammatory response?

Answer 2

COX-1 and COX-2
COX-1 - made constitutively throughout the body, makes TXA2
COX-2 induced during inflammation, makes prostaglandins
Both COXs are inhibited by NSAIDs

Question 3

Histamine is released from:

Answer 3

mast celle and basophils

functions to dilate capillaries, increase venule permeability and involved in sensitization

Question 4

Kinins are released from:

Answer 4

kinin system

same effects as histamine, but more chronic

Question 5

Cytokines are released from:

Answer 5

primarily lymphoid cells

functions in immunoregulation, inflammation, fever, chemotaxis, tissue catabolism, induction of COX-2 etc.

Question 6

Eicosanoids are released from:

Answer 6

lymphoid and non-lymphoid cells

functions same as histamine, plus contraction/relaxation

Question 7

MOA: acetylsalicylic acid

Answer 7

irreversibly blocks the synthesis of eicosanoids bby acetylating COX-1 and COX-2

Question 8

Class: acetylsalicylic acid

Answer 8

Salicylate

Question 9

What is the primary site of ASA transformation?

Answer 9

Liver

Question 10

Therapeutic uses: ASA

Answer 10

1. Anti-inflammatory
2. Analgesic effects
3. Antipyretic effects (blocks PGE2)
4. Platelet effects - increases bleeding time by inhibiting TXA2 synthesis (and thus, platelet aggregation)

Question 11

T/F: ASA is not effective at relieving visceral pain.

Answer 11

True

Question 12

Side effects: ASA

Answer 12

GI irritation and bleeding (loss of protective effect of PGE2 and PGI2);
Anemia;
Hepatotoxicity
Hypersensitivity rxns
Salicylate toxicity
Nephrotoxocity

Question 13

Class: Diflunisal

Answer 13

Salicylate

Question 14

MOA: Diflunisal

Answer 14

Competitive inhibitor of COX-1 and COX-2

Better half life than ASA

Question 15

Uses: Diflunisal

Answer 15

Best for sprains and strains;
Dental pain;
Postepisiotomy pain;
Osteoarthritis
Cancer pain with bone mets

Question 16

Side effects: Diflunisal

Answer 16

Fewer GI side effects and platelet effects than ASA

Question 17

Class: Acetominophen

Answer 17

Para-amino phenol

Question 18

MOA: Acetominophen

Answer 18

Reversibly inhibits COX-1 and COX-2

Question 19

Uses: Acetominophen

Answer 19

NOT anti-inflammatory

for pain and fever

Question 20

Side effects: Acetominophen

Answer 20

Fulminant liver failure possible w/ overdose;

renal tubular necrosis - rare and with chronic use

Question 21

What is the toxic intermediate formed by the metabolism of acetaminophen, that gets removed by glutathione in moderate and low doses?

Answer 21

N-acetyl-benzoquinoneimine

Question 22

What is given to reverse acetaminophen overdose?

Answer 22

Acetylcysteine (Mucomyst)

restores glutathione levels

Question 23

Class:
Indomethacin
Sulindac

Answer 23

Indole

Question 24

MOA:
Indomethacin
Sulindac

Answer 24

Reversible inhibits COX-1 and COX-2;

favors COX-1

Question 25

Uses:
Indomethacin
Sulindac

Answer 25

RA
Ankylosing spondylitis
Osteoarthritis
Gout

Question 26

What is the difference between indomethacin and sulindac?

Answer 26

Sulindac is half as potent as indomethacin

No renal toxicity

Question 27

What is the therapeutic difference between ASA and indomethacin?

Answer 27

Indomethacin is 10x more potent than ASA

Question 28

Side effects:
Indomethacin
Sulindac

Answer 28

Thrombocytopenia
Aplastic Anemia
Severe frontal headaches

Question 29

What is the ONLY indication for indomethacin in children?

Answer 29

closure of ductus arteriosis

Question 30

Class:
Ibuprofen
Flurbiprofen
Naproxen
Oxaprozin

Answer 30

Proprionic acid derivative

Question 31

MOA:
Ibuprofen
Flurbiprofen
Naproxen
Oxaprozin

Answer 31

Reversibly inhibits COX-1 and COX-2

favors COX-1

Question 32

Uses: 
Ibuprofen
Flurbiprofen
Naproxen
Oxaprozin

Answer 32

RA;
osteoarthritis;
Ankylosing spondylitis;
Acute gout attacks

Question 33

What prioprionic acid derivative has the longest half life?

Answer 33

Naproxen (13 hours) and Oxaprozin (50 hours)

Question 34

Class: Piroxicam

Answer 34

Enolic Acid

Question 35

Uses: Piroxicam

Answer 35

RA
Osteoarthritis
recommended bc of its long half life (45 hours)

Question 36

Side Effects: Piroxicam

Answer 36

Same as ASA

GI irritation and bleeding (loss of protective effect of PGE2 and PGI2);
Anemia;
Hepatotoxicity
Hypersensitivity rxns
Salicylate toxicity
Nephrotoxocity

Question 37

MOA: Piroxicam

Answer 37

Reversibly inhibits COX-1 and COX-2

favors COX-1

Question 38

Class:
Keterolac
Diclofenac

Answer 38

Heteroaryl acetic acids

Question 39

MOA:
Keterolac
Diclofenac

Answer 39

Reversibly inhibits COX-1 and COX-2

favors COX-1

Question 40

What NSAID is injectable (intramuscular)?

Answer 40

Keterolac

Potent analgesic - use for postoperative pain

Question 41

Side Effects: Keterolac

Answer 41

Same as ASA

GI irritation and bleeding (loss of protective effect of PGE2 and PGI2);
Anemia;
Hepatotoxicity
Hypersensitivity rxns
Salicylate toxicity
Nephrotoxocity

Question 42

Class:
Celecoxib
Etoricoxib

Answer 42

COX-2 inhibitor

Question 43

MOA:
Celecoxib
Etoricoxib

Answer 43

selectively inhibits COX-2

Question 44

Selective COX-2 inhibitors are contraindicated in what patient populations?

Answer 44

Pregnant patients

Patients with heart problems

Question 45

Do NSAIDS inhibit leukotriene synthesis?

Answer 45

No

They inhibit prostaglandin, prostacycline and thromboxane synthesis