Wusop Muscle/immune Ex 1

Front 1

S/Sx of OA

Back 1

Crepitus, Morning stiffness <30, tenderness to palp, gelling, minimal warmth/redness, NORMAL labs, joint space narrowing

Front 2

Pathohpys of OA

Back 2

Damage to cartilage:Trauma, injury, abnormal joint loading
Chondrocytes remodel cartilage in response
Imbalance of cartilage remodeling: inflammation, chondrocyte function Cartilage decreases, softens and becomes brittle

Front 3

Explain the nonpharmacologic treatments of OA & discuss their place in treatment

Back 3

Physical Therapy / Occupational therapy
Weight Reduction. Exercise:
Aerobic Strength training, Range of motion
Assistive Devices (canes)
Patellar taping, neoprene sleeve, heat wraps

Front 4

Pharmacologic treatments of OA

Back 4

APAP, NSAIDs, topical, Glucosamine/ Chondroitin, Tramadol, Opiods, Intrarticular Corticosteroids, Hyaluronic Acid

Front 5

Describe pharmacodynamic properties of acetaminophen used in OA

Back 5

1st line, high oral absorp, onset of 1 hr, hepatic metab, glucuronidation, CYP2e1
Dose: 2.6-4 g/day, or w liver impairment 2g/day
ADR Hepato/renaltoxic
DI: Isoniazid incr, bleeding risk

Front 6

Pharmacodynamic properties of NSAIDs in OA

Back 6

For pain not controlled by APAP, inhib COX (1&2) to prevent prostaglandin syn. High AUC, sulindac nabumetone= hepatic activation, all hep. metab.
Efficacy all =! May switch chemical classes

Front 7

Name NSAID Acetic Acids and doses for OA

Back 7

Etodolac
800-1200 mg/day in divided doses
Diclofenac
100-150 mg/day in divided doses, 200 max
Nabumetone
500-1000 mg 1-2 times daily

Front 8

Name NSAID Propionic Acids and doses

Back 8

Ibuprofen
1200-3200 mg/day in 3-4 divided doses
Naproxen
250-500 mg BID, 1500 max
Naproxen sodium
275-550 mg BID, 1375 max

Front 9

Name NSAID Fenamates and doses

Back 9

Piroxicam
10-20 mg daily
Meloxicam
7.5 mg daily, 15 max

Front 10

Topical options of OA

Back 10

Capsaicin – depletes substance P from afferent nerve fiberseffect not seen for up to 2 weeks
Dose 0.025%-0.075% applied between 2-4 times daily
Adverse events
Burning, stinging or redness at application site.
Diclofenac Gel 1% Dose
2g applied to elbow, wrist, or hand QID
4g applied to ankle, knee, or foot QID

Front 11

Intraarticular steroids

Back 11

Triamcinolone 10-20 mg or methylprednisolone 20-40 mg
3-4 injections maximum yearly per joint
More effective in patients with joint effusions
Initial relief w/in 24-72 hours
Peak effect in 7-10 days
Lasts 4-8 weeks
ADR Systemic
Hyperglycemia
Edema
Elevated blood pressure
Dyspepsia
HPA axis suppression
Local
Joint infection
Osteonecrosis
Tendon rupture
Skin atrophy

Front 12

Hyaluronic Acid

Back 12

Found in synovial fluid and may reduce inflammation
Injected once weekly for 3-5 weeks
Side effects: Joint swelling/effusions/stiffness, skin reactions,
Not effective for hip OA
Future: intraarticular suspensions, hydrogels, lipid based formulations, microparticles

Front 13

Surgery for OA

Back 13

Arthroscopic debridement
Total joint arthroplasty,
Indication for hip replacement – “radiographic evidence of joint damage & moderate to severe persistent pain or disability, or both, that is not substantially relieved by an extended course of nonsurgical management”.
Available for knee, hip, wrist, ankle, vertebral disks, hands, shoulders, elbows
Benefits: May restore patient’s previous activity level, quality of life
Risks: Thrombosis, anesthesia risks, infection of joint/bone, dislocation of joint
Considerations: Long, painful rehabilitation; anticoagulation; potential need to replace artificial joint after 10-20 years

Front 14

Describe the role of uric acid in the pathophysiology of gout and hyperuricemia

Back 14

Uric acid is the end product of purine degradation
ii. Humans lack the enzyme uricase which is needed for degradation of uric acid into a more water soluble product (allantoin) for renal excretion, therefore resulting in hyperuricemia
iii. In gout, uric acid accumulates either due to overproduction or underexcretion

Front 15

Describe the mechanism behind increased uric acid levels in overproducers

Back 15

Diet, Conversion of nucleic acid to purine nucleotides
De Novo synthesis of purine bases:
2. Two enzyme abnormalities
a. Increase in activity of the enzyme phosphoribosyl pyrophosphate (PRPP) synthetase
b. Decrease in hypoxanthine guanine phophoribosyl transferase (HGPRT)
3. Average uric acid production is 600-800 mg

Front 16

Describe the mechanism behind increased uric acid levels in underexcretors

Back 16

1. 80-90% of patients with gout
2. Elimination of uric acid
a. Renal excretion
i. Glomerular filtration in urine
ii. Tubular reabsorption out
iii. Tubular secretion in
iv. Postsecretory reabsorption out
b. Enzymatic breakdown in GI tract
3. Factors that decrease uric acid excretion
a. Dehydration
b. Insulin resistance

Front 17

Drugs that increase uric acid levels:

Back 17

i. Diuretics
ii. Nicotinic acid
iii. Salicylates (< 2 grams/day)
iv. Ethanol
v. Pyrazinamide
vi. Levodopa
vii. Ethambutol
viii. Cytotoxic drugs- damages cells releases DNA
ix. Cyclosporine

Front 18

Gout Risk factors

Back 18

i. Age
ii. high SCr and BUN
iii. Male
iv. Hyperuricemia
v. Obesity
vi. Blood Pressure
vii. Alcohol intake
viii. High meat or fish intake

Front 19

Factors that may precipitate an attack:

Back 19

1. Stress
2. Trauma
3. Alcohol intake
4. Infection
5. Surgery
6. **Rapid lowering of uric acid levels due to ingestion of a uric acid lowering drug
7. Ingestion of medications that increase uric acid levels

Front 20

Describe the clinical presentation of gout

Back 20

i. More than one attack of acute arthritis
ii. Max inflammation developed w/in 1 day
iii. Monoarthritis attack
iv. Redness over joints
v. First metatarsophalangeal joint involvement
vi. Unilateral first mettarsophalangeal joint attack
vii. Tophus
viii. Hyperuricemia
ix. Asymmetric swelling w/in joint on x-ray
x. Subcortical cysts w/o erosions on x-ray
xi. Urate monohydrate microcrystals in joint
xii. Joint fluid culture negative for organisms-

Front 21

Describe the lab findings in gout

Back 21

Uric acid levels >10 mg/dL= treat
Leukocytosis

Front 22

Describe the radiologic findings in gout

Back 22

c. Likely will not see changes in early disease

Front 23

Identify non-drug therapy for gout

Back 23

i. Weight loss and exercise
ii. Decrease alcohol intake
iii. Correct underlying causes
1. Hyperlipidemia?
2. Insulin resistance
iv. Reduce saturated fat and purine intake
v. Increase fluid intake
vi. Decrease salt consumption
vii. Joint rest and ice for acute attack

Front 24

When do you treat gout?

Back 24

i. Frequent flares (≥ 2/year)
ii. Severe gouty arthritis attack
iii. Complicated uric acid nephrolithiasis
iv. Substantially elevated uric acid level (>10 mg/dL)
v. 24 hr urinary excretion or uric acid >1000 mg
vi. Patient w/ tophi

Front 25

When do you use prophylatic therapy for gout?

Back 25

a. Severe attack of gouty arthritis
b. Complicated course of uric acid lithiasis
c. Substantially elevated serum uric acid levels (> 10 mg/dL)
d. 24 hour urinary excretion of uric acid > 1000 mg
e. Frequent recurrent attacks ( 2-3 attacks per year)
f. Patient with tophi
ii. Should be started 6-8 weeks after acute attack

Front 26

What drugs do you use for an acute gout attack?

Back 26

b. NSAIDs
c. Colchicine
d. Corticosteroids
e. W/o treatment, attack will resolve spontaneously in 3-14 days

Front 27

What drugs do you use for chronic management for gout?

Back 27

a. Colchicine
b. Xanthine oxidase inhibitors
c. Uricosurics

Front 28

Gout: Indomethacin

Back 28

i. Start max dose with symptom initiation
ii. Continue for 24 hours after complete resolution
iii. Taper over 2-3 days
iv. Example dosing with indomethacin
75 mg initially, followed by 50 mg every 6 hours for 2 days, then 50 mg every 8 hours for 1 – 2 days

Front 29

Gout: Prednisone

Back 29

Prednisone 30-60 mg for 3-5 days tapered by 5 mg over 10-14 days. multiple joint involvement

Front 30

Gout: Intraarticular Triamcinolone

Back 30

20-40 mg, Beneficial for attacks involving only 1-2 joints
iii. Ensure joint is not infected first

Front 31

Gout: corticosteroids precautions

Back 31

i. Patients with diabetes (increases BG)
ii. Hx of GI disorders
iii. Cardiovascular diseases
iv. Psychiatric disorders
v. Bleeding disorders

Front 32

Gout: colchicine

Back 32

MOA: Interferes with the inflammatory process but has no analgesia activity
ii. Inhibits phagocytosis of uric acid
iii. Blocks the release of chemotactic factors
Dose:1.2 mg X 1 dose, then 0.6 mg 1 hour later
ii. Renal adjustments rq'd
iii. Favorable response is seen if given within 24 – 48 hours of the onset of symptoms
d. ADRs:
i. Dose dependent nausea, vomiting, diarrhea
ii. Neutropenia
iii. Axonal neuromyopathy
e. DDIs: macrolides clathromycin= agranuocytosis, PGP CYP3a4
f. Contraindications
g. Blood dyscrasias
h. Severe cardiac or GI disease
i. Hepatic failure
j. Severe renal disease (CrCl <10 ml/min)

Front 33

Gout: ATCH, 6. Adrenocorticotropic Hormone

Back 33

Stimulates production of cortisol and corticostrone
b. Dose: 40-80 IU IM every 6-8 hours x 2-3 days
c. Similar efficacy to corticosteroids
d. Difficult to obtain in US
e. Used as alternative when contraindications are present to other medication

Front 34

Prophylactic gout: Allopurinol

Back 34

Xanthine Oxidase Inhibitor,
ii. MOA: Inhibits conversion of hypoxanthine to xanthine and xanthine to uric acid by xanthine oxidase
iii. Efficacy is dose dependent
iv. Dose
1. 100 mg daily for 1st 2 weeks
2. Increase by 100 mg up to 300 mg daily, over 300 break up dose
3. Tophaceous gout may require 400-600 mg BIDdaily, max is 800 mg/day
4. Renal adjustment needed- cant always get high enough to treat
a. > 90 mg/min – 300 mg daily
b. 60 – 89 ml/min – 200 mg daily
c. 30 – 59 ml/min – 100 mg daily
d. 10 – 29 ml/min – 50 – 100 mg daily
e. < 10 ml/min – USE CAUTIOUSLY
v. ADRs
1. Skin rash, TEN,
2. Leukopenia
3. GI disturbance
4. Headache
5. Urticaria
6. Hepatitis
7. Interstitial nephritis
8. Eosinophilia
9. **Allopurinol hypersensitivity syndrome**- renal failure
vi. Drug interactions
vii. Comments/Contraindications:
1. Not for an acute attack
2. Use cautiously in renal impairment
3. Do Not initiate until 4 – 6 weeks after an acute attack
4. Concurrent prophylaxis with colchicine may prevent flare ups during initial therapy
5. Titrate dose to UA level of < 6 mg/dL
6. Continue therapy during flare ups

Front 35

Prophylactic gout: Febuxostat

Back 35

ii. MOA: xanthine oxidase inhibitor
Dose: Initial: 40 mg daily, Usual 40-80 mg daily
iv. ADRs: GI disturbance, increase hepatic enzymes- liver
v. May be very useful in patients that are allergic to allopurinol
iii. No renal adjustment needed

Front 36

Prophylactic gout: Uricosuric Drugs Probenecid

Back 36

i. MOA: Increase renal secretion of uric acid by inhibiting postsecretory reabsorption.
ii. Dose: 250 mg BID X 1-2 weeks, then 500 mg BID X 2 weeks. Then increase by 500 mg increments every 1-2 weeks until control is achieved or 2g/day
ADR: 1. Uric acid stones
2. GI irritation
3. Rash and hypersensitivity
4. Precipitation of acute gouty arthritis
vi. Do not use in
1. Impaired renal function (<50 ml/min)
2. History of renal calculi
3. Overproducers not effective

Front 37

Probenicid DDI/ Contraindications:

Back 37

1. Penicillins
2. Cephalosporins
3. Sulfonamides
4. Indomethacin
v. Comments/Contraindications
1. Best agent for underexcretors
2. Maintain proper hydration or may need to alkalinize the urine
3. May precipitate a gout attack upon initiation
4. Not for an acute gout attack
5. CrCl < 50 ml/min – DO NOT USE
6. History of renal caliculi

Front 38

Sulfinpyrazone:

Back 38

Gout uricosuric: i. Dosing
1. Initial: 50 mg BID x 3-4 days then 100 mg BID
2. Increase by 100 mg each week
3. Max dose: 800 mg/day
ii. May act as antiplatelet
iii. Side effects more severe than Proben...

Front 39

f. Colchicine for Gout prophylaxis

Back 39

i. Dose: 0.5-0.6 mg BID
ii. Patients with
1. No visible tophi
2. Normal or slightly elevated uric acid levels
iii. May be used during the first 6-12 months of uric acid lowering therapy to prevent gout attack just for inflammation

Front 40

Gout Nephrolitiasis Tx:

Back 40

1. Hydration
2. Alkalinization of the urine
a. Maintain urine pH at 6-6.5
b. Potassium bicarbonate 60-80 mEq/day
c. Potassium citrate 60-80 mEq/day
d. Acetazolamide
i. Better choice in those patients who cannot tolerate the above agent
ii. Carbonic anhydrase inhibitor
1. Produces rapid and effective urinary alkalinization
2. Dose: 250 mg at bedtime
e. Low purine diet
f. Low protein diet
g. Reduction of urinary uric acid excretion
3. Recurrent nephrolithiasis
a. Xanthine oxidsase inhibitors