Smith - Prostanoids And Anti-Inflammatory Drugs

Question 1

Acute inflammation is what?

Answer 1

Body’s normal protective response to an injury, irritation, or even surgery

Protective response

Eliminate initial cause of cell injury, clear out necrotic cells and damaged tissues

Question 2

What are 5 signs of acute inflammation?

LPHaRTS

Answer 2

Loss of function

Pain

Heat

Redness

Tenderness

Swelling

Question 3

What are some non-selective NSAIDS?

Answer 3

Aspirin
Ibuprofen
Acetominophen
Naproxen

Question 4

What are NSAIDS?

Answer 4

Nonsteroidal anti-inflammatory drugs

Question 5

What do NSAIDS do?

Answer 5

Inhibit cyclooxygenase enzymes

Question 6

What is an example of a selective NSAID?

Answer 6

COX2 - Celecoxib

Question 7

What are glucocorticoids?

Answer 7

Inhibit phospholipase A2

• Prednisone
• Cortisone

Question 8

What are DMARDs?

Answer 8

Disease modifying anti-rheumatic drugs

Question 9

What are the 2 types of DMARDs?

Answer 9

Traditional (non-biologic)

Biologic

Question 10

Where do a lot of our inflammatory mediators originate from?

Answer 10

Breakdown of arachidonic acid

Question 11

T/F - Glucocorticoids affect the pain process flow at a higher level than the NSAIDS target.

Answer 11

TRUE

Question 12

What are eicosanoids?

Answer 12

Oxygenation products of poly-unsaturated long-chain FAs

• G-coupled proteins
• Auto and paracrine fxs

Question 13

What are prostanoids?

Answer 13

Sub-class of eicosanoids

Question 14

What are 3 prostanoids?

Answer 14

Prostaglandins
-Mediate inflammatory and anaphylactic rxns

Thromboxanes
-Mediate vasoconstriction

Prostacyclins
-Active in resolution phase of inflammation

Question 15

Prostanoids have major effects on what?

Answer 15

Smooth muscle

Platelets and blood cells

Nerve terminals

Endocrine organs

Adipose tissue

Question 16

Aspirin and other NSAIDs provide non-specific ___________ of the cyclooxygenase (COX) enzymes.

Answer 16

Inhibition

Question 17

T/F - Non-selective COX inhibitors have both positive (anti-inflammatory) and adverse effects (upset stomach)

Answer 17

TRUE

Question 18

Tell me about COX-1.

Answer 18

Constitutive (platelets, kidney, GI)

Inhibition by classic NSAIDS increases risk for GI ulceration

Question 19

Tell me about COX-2.

Answer 19

Constitutive in kidney
-Inducible elsewhere by hormones, GFs, and inflammatory mediators

Inhibition by NSAIDs or by selective Coxibs

COX-2 selective inhibitors do NOT inhibit platelet aggregation or cause GI upset/ulceration

Question 20

Tell me about Aspirin.

Answer 20

Only NSAID that inhibits both COXs in an IRREVERSIBLE manner

Question 21

Tell me more about Aspirin.

Answer 21

Nonselective COX-1 and COX-2 inhibition

Anti-platelet aggregation effects

Rarely used for anti-inflammatory purposes (Dose for those effects is way too high)

Question 22

What are contraindications of Aspirin?

Answer 22

NSAID allergies

Avoid children with viral-induced illness (REYE SYNDROME)

Gout, hemophilia, blood thinners, ACE inhibitors, pregnancy near term

Question 23

Tell me about Ibuprofen.

Answer 23

Analgesic and antipyretic and antinflammatory

Interferes with the antiplatelet effect of low-dose aspirin

Question 24

Tell me about Naproxen.

Answer 24

Same as most other NSAIDs, but available in slow-release formulation (Aleve)

Question 25

When does a fever get to be too high?

Answer 25

103 degrees F

Question 26

What are some adverse effects common to all NSAIDs?

Answer 26

``` CNS - headache Cardiovascular - Edema *GI - Pain, dysplasia, nausea, vomiting, ulcers, bleeding Hematologic Hepatic Pulmonary - asthma Skin - rashes Renal insufficiency REYE SYNDROME ```

Question 27

Tell me about Celecoxib (Celebrex).

Answer 27

COX-2 selective inhibitor Analgesic, antipyretic, and anti-inflammatory, like Aspirin No effect on platelet aggregation 10-20x more selective for COX-2 than COX-1 - Lower GI adverse effects - No cardioprotective effects - Increased risk of edema, hypertension, MI, and stroke

Question 28

Tell me about acetaminophen (Tylenol).

Answer 28

NON-ASPIRIN pain reliever -Central-action effect on hypothalamus to cause vasodilation and sweating (reduces fever) —Analgesic mechanism thru elevation of the pain threshold

Question 29

Tell me more about acetaminophen.

Answer 29

Alternative to NSAIDs in pts with allergies, ulcers, bleeding problems, or taking blood thinners (warfarin) Adverse effects -Rash, chest pain, bone marrow suppression —Contraindicated for pts with liver disease and insufficiency due to alcoholism

Question 30

T/F - Acetaminophen is NOT an NSAID.

Answer 30

TRUE

Question 31

T/F - Acetominophen should NOT be taken as an anti-inflammatory drug.

Answer 31

TRUE

Question 32

Tell me about glucocorticoids.

Answer 32

Steroid hormones Prevents conversion of membrane phospholipids to arachidonic acid by inhibiting the phospholipase A2 enzyme -Decrease inflammation

Question 33

What are the short to medium-acting glucocorticoids? 3 of them

Answer 33

Hydrocortisone Cortisone Prednisone

Question 34

What is the long-acting glucocorticoid?

Answer 34

Dexamethasone

Question 35

What is a major side effect of overdosing on acetominophen?

Answer 35

Hepatotoxicity | -Days->weeks->liver failure->death

Question 36

Tell me about prednisone.

Answer 36

Blocks phospholipase A2, and thus shuts down immune responses Used for - Asthma - COPD - Crohn’s

Question 37

Tell me about non-biologic DMARDs

Answer 37

Suppress the progression of the disease by acting against the underlying immunological abnormalities

Question 38

What are 2 non-biologic DMARDs?

Answer 38

Methotrexate Azathioprine

Question 39

What are the main adverse effects of glucocortcoid use?

Answer 39

Bone weakening Skin thinning Heart risks Cataracts and glaucoma

Question 40

What is the 1st line DMARD for rheumatoid arthritis?

Answer 40

Methotrexate Inhibits transformylase and thymidylate synthetase enzymes Adverse: -Nausea, GI ulcers, stomatitis, hepatotoxicity —CONTRAINDICATED IN PREGNANCY —RISK OF LIFE-THREATENING EFFECTS IF TAKING NSAIDS SUCH AS ASPIRIN, NAPROXEN, OR OTHER SALICYLATES.

Question 41

Tell me about azathioprine.

Answer 41

PRODRUG that acts thru main metabolite, 6-thioguanine -Suppresses DNA synthesis and production of rapidly proliferating cells (B and T cell fxs) Used for: -rheumatoid arthritis Adverse: -Bone marrow suppression, GI upset, increased infection risk, increased lymphoma risk

Question 42

Tell me what the two biologic DMARDs are. (Larger molecules than non-biologics).

Answer 42

Proteins produced by recombinant DNA tech: -T-Cell modulators —Abatacept - TNFalpha-blocking agents - Adalimumab

Question 43

Tell me about abatacept.

Answer 43

Acts as fusion protein to prevent activation of T-cells Use: -Rheumatoid arthritis for those that are not responding well to anti-TNFalpha therapy Adverse: -Increased risk of lymphomas, infections, congestive heart failure, lupus-like syndrome MONTLY COST: $3500-$3800

Question 44

Tell me about adalimumab.

Answer 44

Prevents ligand from binding TNFalpha receptor Use: -Rheumatoid arthritis, psoriasis, refractory asthma Adverse: -Increased risk of lymphomas, infections, lupus-like syndrome 5 different TNFalpha inhibitors - Infliximab - Adalimumab - Certolizumab pegol - Golimumab - Etanercept (This one is a circulating receptor fusion protein)