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