Osteoarthritis

Question 1

What is the pathophysiology of OA?

Answer 1

It is a disease of cartilage - NOT part of aging

Enhance degrading enzymes: matrix metalloproteinases

Inflammatory process involved (cytokines, prostaglandin) –> chondrocyte apoptosis and nitric oxide production –>degradation

Initial attempt at repair with chondrocyte proliferation

Reparative attempts fail with progressive cartilage degradation as the disease advances

Question 2

Osteoarthritis

Answer 2

• Usually, begins after age 40
• Biomechanical: leads to destruction of cartilage matrix
• Develops slowly over many years
• Usually affects weight-bearing joints such as knees, hips, lower spine; may be uni- or bilateral
• Pain begins with the use of joints; inflammatory signs are less common
• Morning stiffness usually <1 hour

-Does not generally cause any feelings of unwellness
Common in males and females

• Osteophytes may be present
• Absent inflammatory markers

Question 3

Acetaminophen:

MOA and Use

Answer 3

• MOA: Exerts action within CNS. Inhibits COX, which decreases prostaglandins synthesis, though this process it exerts analgesic and antipyretic effects.
• No anti-inflammatory effect

-believed to inhibit the synthesis of prostaglandins in the central nervous system and work peripherally to block pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center

• Indicated for mild-moderate OA pain

Question 4

Acetaminophen:

Adverse Reactions

Answer 4

Monitoring
• Adverse reactions
– Possible mild increase in LFTs (reversible)
– Dizziness,excitement,disorientation(large doses)
– Fatalindoses>15g
– Hemolytic anemia (rare)

Question 5

Acetaminophen:

Dosing

Answer 5

Dosing
– Typically max dose of 4gm/day (QID dosing)
– 325–500 mg QID; arthritis dosing available as 650 mg (2) tabs BID – <3gminelderly
– Minimize use/avoidifsignificantETOHuseorhepaticimpairment

Question 6

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Mechanism of Action

Answer 6

Inflammatory response: inflammatory process involved cytokines, prostaglandin, histamine, prostaglandins, leukotrienes
• Lipo-oxygenase and cyclo-oxygenase (COX) are enzymes required to release the inflammatory mediators
• Exact MOA unknown
• Inhibits COX and prostaglandin activity

Question 7

COX-1

Answer 7

COX-1 (nonselective): expressed systematically and synthesized continuously, present all the time in ALL the tissues and cells; has a role in homeostatic maintenance

Question 8

COX-2

Answer 8

COX-2 (selective): inducible enzyme synthesized mainly in response to pain and inflammation

Question 9

NONSPECIFIC NSAIDS inhibit which receptors

Answer 9

COX-1 and COX-2

Question 10

Celebrex inhibits which receptors?

Answer 10

Only three COX-2 have been developed

Question 11

Pharmacokinetics of NSAIDS

Answer 11

• With oral administration: rapidly and almost completely absorbed
• ~90% protein bound
• Metabolized by way of CYP enzymes in liver
• Excreted by kidney

Question 12

Pharmacodynamics of NSAIDS

Answer 12

• Mediated chiefly through inhibition of prostaglandin biosynthesis
• COX-1: reversibly impact PLT aggregation
• All reverse vasodilation of inflammation
• Have analgesic and antipyretic effects
• Do not alter the course of OA or other arthritic disorder

Question 13

Pharmacotherapeutics of NSAIDS

Answer 13

• Assess renal function prior to initiation of therapy and periodically during treatment
• Caution with history of GI disorders
• NSAIDs are Category C
• Most NSAIDs are excreted in the breast milk

Question 14

NSAIDS Side Effects

Answer 14

General SE for all NSAIDS
l CNS: a headache, tinnitus, dizziness
l CV: fluid retention, HTN, edema, rarely MI/CHF
l GI: abdominal pain, N/V, PUD, GI bleed, gastritis
l Heme: thrombocytopenia, neutropenia, bruising
l Hepatic: elevated LFTs, liver failure
l Pulmonary: asthma
l Skin: rashes
l Renal: IRF, renal failure, hyperkalemia, proteinuria
l Pysch: Indocin may exacerbate depression (choose different NSAID)
BLACK BOX WARNING
CONTRAINDICATED CABG POST-OP PAIN

Question 15

Drugs that interact with NSAIDs

Answer 15

• Antihypertensives
• Anticoagulants
• Drugs that may increase risk for GI bleeding or ulceration

Question 16

Patient education about NSAIDS

Answer 16

• Educate
    – Use of NSAIDs – Potential s/e
    – s/s GI bleeding
• Exercise
• Weight loss (if indicated)
• Nonpharmacologic management • Referral

Question 17

NSAIDS FOR OA

Answer 17

• Ibuprofen(Advil):800mgTID(max3200mg/day)
• Naproxen(Aleve):500mgBID(max1500 mg/day)
• Diclofenac(Zorvolex):35mgTID
• Sulindac(Clinoril):150–200mgBID(max400 mg/day)
• Meloxicam(Mobic):7.5–15mgQD(max15 mg/day)
• Piroxicam(Feldene):20mgQD(max20mg/day)
• Celecoxib(Celebrex):100–200mgBID(max400 mg/day

Question 18

Topical Agents

Answer 18

• NSAIDs available at topical agent
• Same potential s/e as oral preparations – Flector Patch (1.3% diclofenac)
– Voltaren Gel (1% diclofenac)
– Pennsaid (1.5% diclofenac)

Question 19

OA of the hand

Answer 19

1st: topical NSAIDs
2nd: APAP
3rd: NSAIDs
* Steroids for flares

Question 20

OA of Hip

Answer 20

1st: APAP
2nd: NSAID with GI protection
3rd: Opioid with GI protection

Question 21

OA of Knee

Answer 21

1st: APAP + topical NSAID
2ND: NSAID + GI PROTECTION
3RD: OPIOID +/- APAP
*STEROID FOR FLARES