NSAIDs

Question 1

what does inflammation/pain occur due to?

Answer 1

Immune response to injury, infection, and disease processes

Question 2

What is pain and inflammation regulated by?

Answer 2

cytokines and eicosanoids

Question 3

what do prostaglandins regulate?

Answer 3

inflammation and pain response

Question 4

Role of Eicosanoids:

Answer 4

• Pain
• Inflammation
• Fever
• Thrombus
• Normal Gastric fx
• Normal Kidney fx
• Vascular/Respiratory Regulation

Question 5

Eicosanoid involvement in kidney disease

Answer 5

PGEs are beneficial & helps maintain fx

Question 6

Eicosanoid involvement in circulatory disease

Answer 6

TBXs involved in coagulation cascade

Question 7

Eicosanoid involvement in heart disease

Answer 7

PGEs believed to be involved in atherosclerosis

Question 8

Eicosanoids Involvement in Cancer

Answer 8

certain eicosanoids involved in the development of Colon and other GI tract cancers

Question 9

Eicosanoids Involvement in Alzheimer’s disease

Answer 9

some evidence that chronic inflammation mediated by eicosanoids may be involved in the pathogenesis of this disease

Question 10

Eicosanoids involvement in uterine disease

Answer 10

PGEs involved in dysmenorrhea and child
birth

Question 11

Eicosanoids Involvement in lung disease

Answer 11

Leukotrienes involved in airway constriction
in asthma (NSAIDS have no effect on Leukotrienes)

Question 12

How is peripheral pain and inflammation treated?

Answer 12

• By blocking prostaglandin PGE production
• Aspirin and all NSAIDs inhibit Cox enzyme

Question 13

Two COX isoforms

Answer 13

COX-1 (normal function) and COX -2
(emergency)

Question 14

COX 1

Answer 14

specific to the mucosa of gut (stomach) and kidney
 involved in protective layer in the stomach — protects against ulcers
 involved in glomerular filtration— kidney function

Question 15

COX 2

Answer 15

involved in pain, inflammation and fever

Question 16

COX 2 Specific Inhibitors

Answer 16

• Relatively new
   Celecoxib (Celebrex), Rofecoxib (Vioxx) & Valdecoxib (Bextra):
   Analgesic, anti-pyretic, anti-inflammatory effects, but fewer GI and kidney side effects
   Interferes with ACE-inhibitors, diuretics, warfarin, and lithium

Question 17

COX-2 inhibitors may….

Answer 17

increase clotting and increase HTN and cardiac issues

Question 18

Uses of NSAIDs

Answer 18

• Mild to moderate pain: ideal for pain from minor sx, musculoskeletal injury, menstruation or simple HA
• inflammation
• antipyretic (fever)
• vascular disorders and prophylaxis of blood clot: inhibition of thromboxanes reduces platelet activation
• prevention of cancer

Question 19

How is aspirin unique compared to other NSAIDs

Answer 19

• it irreversibly inhibits platelet aggregation (used in low doses after MI/CVA)

Question 20

Other benefits of aspirin

Answer 20

• anti inflammatory
• analgesic (mild to mod)
• anti pyretic
• not given to children due to Rye’s syndrome

Question 21

What is the #1 problem with conventional NSAIDs

Answer 21

• Gastric Discomfort
   “enteric coating” and co-medication with antacid only marginally successful in preventing dysfunction
   PGEs promote mucous production
   Ulcer (peptic or duodenal) may result (long term use not recommended)

Question 22

What is the #1 problem with conventional NSAIDs

Answer 22

• Gastric Discomfort
   “enteric coating” and co-medication with antacid only marginally successful in preventing dysfunction
   PGEs promote mucous production
   Ulcer (peptic or duodenal) may result (long term use not recommended)

Question 23

Other side effects of NSAIDs

Answer 23

 Acute nephritis (in patients with renal disease or who are dehydrated or in shock)
 Reye’s Syndrome: in children (including teens) w/ fever, may exacerbate fever (multiple NSAIDS)  CV shock in people w/ hypersensitivity (Aspirin)
 May prolong healing: inhibits connective tissue remodeling

Question 24

Pain killers taken off the market

Answer 24

• Vioxx
• Bextra
• Both COX-2 inhibitors
• Lead to drugs being required to state the adverse effects on the box cover and include a warning about the risks associated with the entire class of drugs

Question 25

Black Box Warning

Answer 25

 Since 2005 the FDA advised manufacturers of several common pain killers that their labeling would have to include a so-called "black-box warning"  This warning is to alert patients about the increased risks of heart attacks and ischemic strokes for patients taking these medications

Question 26

Drugs with black box warnings

Answer 26

 Ibuprofen,  Indomethacin  Ketoprofen  Fenoprofen  Naproxen  Diclofenac  Celebrex

Question 27

What is indomethacin useful in treating?

Answer 27

 RA and JRA  Anklosing Spondylitis  Gout  OA of hips  Heterotopic ossification

Question 28

Side effects of indomethacin

Answer 28

same as other NSAIDs but somewhat more frequent

Question 29

Analgesic AND antipyretic effects =

Answer 29

NSAIDs

Question 30

Does acetaminophen have anti-inflammatory effect?

Answer 30

NOPE also doesnt have anti-coagulant effects

Question 31

Acetaminophen is NOT associated with...

Answer 31

GI tract irritation or upset, Reye’s syndrome or kidney toxicity ** Now recommended by Rheumaology Associations for OA

Question 32

What can acetaminophen be toxic to?

Answer 32

the liver - can cause liver necrosis

Question 33

acetaminophen MOA

Answer 33

 Not clear – weakly inhibits COX enzyme blocking prostaglandin release, but appears to work more in CNS, not peripher

Question 34

What is RA

Answer 34

 A chronic, systemic, auto-immune disease  Involves multiple systems, but characterized by synovitis and destruction of articular tissue  Pain, stiffness, inflammation of synovial joints  Marked by exacerbation & remission  Progressive: leading to severe joint destruction and erosion

Question 35

Difference between RA and OA

Answer 35

RA is bilateral and typically effects hips and hands

Question 36

Immune System and RA

Answer 36

 Autoimmune response to unknown antigen (virus or susceptible genetic trait)  The antibodies are produced against antigens in connective tissue  Macrophages, T and B-lymphocytes involved

Question 37

Arthrogenic Mediators

Answer 37

 cytokines (growth factors, interleukins)  eicosanoids (prostaglandins, leukotrienes)  enzymes (protease and collagenase)

Question 38

Pathophysiology of RA

Answer 38

 Athrogenic mediators result in articular cartilage & bone destruction: cytokines, eicosanoids, collagenases and proteases

Question 39

pathophysiology of RA - cytokines

Answer 39

overgrowth of synovium

Question 40

pathophysiology of RA - Eicosanoids

Answer 40

pain, swelling, chemo- attraction, increase blood flow and vascular permeability

Question 41

Pathophysiology of RA - collagenases and proteases

Answer 41

destroy cartilage and bone

Question 42

Goals of Drug therapy

Answer 42

1. Decrease Pain - this is done by decreasing overall joint inflammation 2. Arrest the disease process - (arrest or prevent physical deformities) - this is accomplished only through the disease modifying anti- rheumatic drugs (DMARDs) *** however, few of the agents currently available halt the disease process

Question 43

How Drugs are Used for RA:

Answer 43

1. Staged control of pain and disease progression 2. NSAIDs are used exclusively for mild symptoms 3. Glucocorticoids are only used: to control acute exacerbation, local injection of a severe joint, severe/progressive form of RA 4. DMARDs are used independently or together 5. Most common is methotrexate in combination with a TNF inhibitor

Question 44

Upside down drug pyramid for RA

Answer 44

DMARDs, COX 2, NSAIDs anti-metabolites glucocorticoids

Question 45

Osteoarthritis

Answer 45

 Intrinsic defect in the cartilage or secondary to a trauma or overuse  Primary: no apparent cause  Secondary: trauma, infection, metabolic dx  Typically occurs in larger joints, but also in DIP of fingers  Genetic component and associated with obesity

Question 46

NSAIDs vs Acetaminophen in OA

Answer 46

Inflammation is not a primary concern in OA  NSAIDS may have a slight benefit for the small inflammatory component of OA, but this may be over-shadowed by GI problems  Acetaminophen is better tolerated and produces the same analgesic effect

Question 47

Viscosupplementation for OA

Answer 47

- Goal: change consistency of synovial fluid - Hyaluronan: increases synovial joint fluid consistency and limits progression of erosion