Pharmacotherapy of Inflammation (Welsh)

Question 1

Eicosanoids (3)

Answer 1

Prostoglandins, leukotrienes, thromboxanes

Question 2

Prostanoids

Answer 2

Prostoglandins + Thromboxanes

Question 3

Prostaglandin I2 (PGI2)

Answer 3

Inhibits platelet aggregation, causes vasodilation

-opposite of TXA2

Question 4

Thromboxane A2 (TXA2)

Answer 4

Promotes platelet aggregation, causes vasoconstriction

Question 5

PGE2

Answer 5

• Promotes gastric mucous secretion, inhibit acid secretion

- In inflammation: increases vasodilation, vascular permeability, pain, fever

Question 6

Cox-1

Answer 6

• Constitutively active throughout body
• produces prostaglandins in “housekeeping” roles
• Differs from COX-2

Question 7

COX-2

Answer 7

• Induced by inflammation

- Produces more prostaglandins (arachidonic acid–>PGE2)

Question 8

NSAIDS (mechanism, effects, examples)

Answer 8

• Decrease PGE2 synthesis by inhibiting COX-2
• analgesic, antipyretic (fever), anti-inflammatory, antiplatelet (hence aspirin good for heart)
• aspirin, ibuprofen (advil), indomethacin, naproxen (aleve), diclofenac
• non-steroidal, unlike steroidal (hydrocortisone)

Question 9

NSAID side effects

Answer 9

Can downregulate COX-1 as well, thus decreasing gastric mucous secretion and causing GI discomfort
-not recommended for patients with existing ulcers or other GI conditions

Question 10

NSAID Induced Asthma

Answer 10

Blocking COX-2 pathway causes arachidonic acid buildup, shunted into 5-lipoxygenase pathway, overproduce leukotrienes–>cause inflammatory allergic responses like asthma, anaphylaxis. So carefully dose NSAIDS!

Question 11

Aspirin

Answer 11

• Long lasting NSAID (binds COX1/2 covalently)

- Old, brought back as anti-platelet (inhibits thromboxane)

Question 12

Inflammation Components (4)

Answer 12

Heat
Swelling
Redness
Pain

Question 13

Acetaminophen

Answer 13

Tylonel

• anti-pyretic and anti-analgesic, but NOT NSAID
• hepatotoxicity at 3x dose from metabolite NAPQI
• Overdose treated with NAC (N-acetylcysteine)

Question 14

Steroidal Anti-inflammatory Drugs (SAIDs)

Answer 14

• Steroids have anti-inflammatory effect by downregulating COX2–>inflammatory prostaglandins
• Immunosuppressive- reduce mast cell/macrophage activity, downregulating histamine and inflammation
• biologic is cortisol, synthetic variants are hydrocortisone, prednisolone, methylprednisolone, dexamethasone
• Side affects (ton) can be cushingsoid face (“moon face”)