Arachidonic Acid

Question 1

PGE2 effects

Answer 1

Pain, fever, vasodilation, uterine contraction (inflammation)

Increased capillary permeability

Question 2

Leukotrienes role

Answer 2

–participants in allergic responses such as asthma

–Appreciate role of leukotrienes in some side-effects of nonsteroidal anti-inflammatory agents

Question 3

Some Cyclooxygenase Inhibitors

Answer 3

• Acetylsalicylic acid (Aspirin)
• Celecoxib (Celebrex) (only Cox2 inhibitors)
• Diclofenac (Votaren)
• Fenoprofen (Nalfon)
• Ibuprofen (Motrin etc)***
• Indomethacin (Indocin)
• Ketoprofen (Orudis)
• Ketorolac (Toradol)
• Meclofenemate (Meclomen)
• Naproxen (Votaren)***
• Oxaprozin (Daypro)
• Piroxicam (Feldene) - more long acting
• Sulindac (Clinoril)
• Tolmetin (Tolectin)

Question 4

Why aspirin specifically for preventing heart attacks?

Answer 4

Permanent (not reversible)

Question 5

Celecooxib (mechanism, advantage, disadvantage)

Answer 5

Doesn’t block COX1 (particularly in stomach) → Less gastric ulceration

COX2 inhibition in endothelium of coronary and cerebral circulation → suppressed prostacyclin synthesis - too much clotting → MIs

**Many COX2 have been withdrawn from market (increased risk of cardiovascular thrombosis**

Question 6

Acetaminophen (Tylenol)

Answer 6

Blocks cyclooxygenase in CNS but not in periphery

* NOT anti-inflammatory

*Both anti-pyretic and analgesic

Question 7

Aspirin (Acetylsalicylic Acid)

Answer 7

Irreversible COX inhibitor

Eliminate thromboxane A2 for platelet’s entire life (14d) (platelet doesnt have nucleus, can’t generate more cyclooxygenase)

Used to eliminate thrombosis (MI)

Gastric ulceration and blood thinning (in accidents, hemorrhagic strokes)

Question 8

Prostaglandins and inflammatory effects of rheumatoid arthritis

Answer 8

Ibuprofen and other NSAIDs used to tx sxs, but don’t halt or reverse disease progression

Question 9

Arachidonic acid –> ____ –> _________

Answer 9

PGE2

Inflammation

Question 10

Treat arthritis sxs by blocking Cyclooxygenase w/ agents such as:

Answer 10

Ibuprofen, Naproxen, Celebrex

Question 11

Glucocorticoids are _________ regulators

Answer 11

transcriptional

***Takes a little bit of time

Question 12

Corticosteroids reduce numbers of _________ but increase numbers of ___________

Answer 12

Reduce lymphocytes, eosinophils, monocytes, and basophils

Increase polymorphonuclear leukocytes

Question 13

Corticosteroids reduce release of _______ and ___________ (immuno)

Answer 13

Arachidonic acid and cytokines (interleukin 1 & 6 and TNF)

Question 14

Examples of Corticosteroids

Answer 14

• Dexamethasone (Decadron)
• Hydrocortisone
• Methylprednisolone (Medrol)
• Prednisone (Deltasone)

Question 15

Steroids are incredibly effective _____________

Answer 15

anti-inflammatories

Question 16

Toxicites of steroids

Answer 16

–Osteoporosis

–Immune suppression

–Peptic ulcers

–Myopathy (less prevalent)

–Cataracts

–Fluid accumulation and hyperglycemia

Question 17

Steroids are/are not considered disease modifying agents (DMARD) in RA

Answer 17

NOT (those are more biological modifiers and nonbio)

Question 18

Corticosteroids suppress immune responses (specifics)

Answer 18

–Suppress leukocyte numbers

–Suppress arachidonic acid release

——Synthesize proteins inhibiting phospholipase A2

–Suppress release of inflammatory cytokines such as interleukins and TNF

Question 19

Eicosapentaenoic Acid

Answer 19

Fish Oil

Question 20

Fish oil results in

Answer 20

PGE3, Thromboxane A3 or PGI3

–Produce thromboxane but Thromobxane A3 is not effective – Major outcome is a bleeding tendency and a virtual resistance to Cardiovascular disease

•Example is maritime diet characteristic of Inuits

Question 21

Fish oil is promoted as a treatment for ____________

Answer 21

Rheumatoid Arthritis

–Not mainstream at the moment

–Mechanism suggests that PGE3 is not inflammatory

Question 22

Prostaglandin E2 causes symptoms of ________________:

Answer 22

Inflammation:

–Edema

–Pain

–Redness

–Warmth

Question 23

Inhibitors of prostaglandin synthesis are useful in treating ___________ rheumatoid arthritis

Answer 23

inflammatory symptoms of

Question 24

Both Cyclooxygenase inhibitors and corticosteroids inhibit _____________ synthesis

Answer 24

prostaglandin

Question 25

Major effects of Corticosteroids

Answer 25

–Reduction in white blood cells

–Reduced arachidonic acid liberation, resulting in suppression of both prostaglandin and leukotriene synthesis