Gout

Question 1

What is gout

Answer 1

a clinical spectrum of diseases with:
elevated serum urate concentration (hyperuricemia)
recurrent attacks of acute arthritis w/ monosodium urate crystals in the synovial fluid
deposits of tophi in tissues around joints
interstitial renal disease
uric acid neprhosis

Question 2

What are tophi

Answer 2

monosodium urate crystals that get deposited in tissues in and around joints

Question 3

Define hyperuricemia

Answer 3

Men: 7+ mg
Women: 6+ mg
(hyperuricemia is an asymptomatic condition, but is necessary to diagnose gout)

Question 4

How is uric acid produced

Answer 4

it is the last step in degradation of pruines
higher in humans than animals
We do not have uricase enzyme (converts uric acid into a more soluble allantoin

Question 5

What is the physiology in a “gouty” joint

Answer 5

Synoviocytes phagocytize urate crystals and secrete inflammatory mediators
Mediators activate PMN and macrophages

Question 6

Drugs used to treat gout target

Answer 6

inhibiting crystal phagocytosis and PMN/Macrophage release of inflammatory mediators

Question 7

What causes overproduction of uric acid

Answer 7

not fully known.

suspected: enzyme P that is genetically determined, or, malignancy or myelo/lymphoproliferative disorder

Question 8

What causes underexcretion of uric acid (more common)

Answer 8

Decrease in renal excretion of uric acid for unknown reason**
Overabundance tried to be eliminated through GI tract but it can’t all be

Question 9

These are pruine rich foods, and should be avoided (5-100mg/3.5 oz serving)

Answer 9

asparagus 
bacon
beef
buillon
calf tongue 
cauliflower 
chicken 
duck 
goose
ham
lamb
kidney beans, lentils, lima beans, navy beans 
mushrooms 
oatmeal 
pork 
cod, crab, halibut, lobster, oyster, salmon, shrimp, snpper, trout, tuna
spinach
turkey

Question 10

These foods have VERY high levels of pruines, definitely avoid! (1000mg/3.5 oz serving)

Answer 10

anchovies 
brain
gravies
kidney
liver
sardines
sweetbreads

Question 11

What drugs can induce hyperuricemia/gout

Answer 11

diuretics 
nicotinic acid 
salicylates 
ethanol
pyrazinamide 
ethambutol
cytotoxic drugs 
cyclosporine
levodopa
*know drug class or name of speciic drugs*

Question 12

What is acute gout

Answer 12

attacks of joint inflammation, 3-10 days
80% of initial gout attacks are in 1 LE joint
MC affects first MTP (podagra- foot pain)
can mimic or co-exist w/ infection

Question 13

DDx for gout is

Answer 13

infection 
FB
fracture 
AVN
atypical RA 
arthritis

Question 14

What are the other tyoes of gout

Answer 14

Chronic: rheumatoid-like
Tophaceous: monosodium urate in soft tissues and joints

Question 15

What is definitive Dx for gout

Answer 15

joint tap and microscopic exam for uric acid crystals

serum uric acid levels drop during an attack! that’s why you tap the joint

Question 16

What is the clinical triad of gout

Answer 16

inflammatory monoarthritis
elevated serum uric acid level
response to colchicine

Question 17

Goals in treatment of gout are

Answer 17

terminate acute atatck
prevent recurrent attacks
prevent complications w/ chronic depositions of urate crystals in tissues
anti-inflammatory prophylaxis of acute gout during initiation of urate lowering therapy

Question 18

Drug therapy for gout includes

Answer 18

APAP
NSAIDS, ASA, cox-2 inhibitors, DMARDS
Acute gout: NSAIDs, Corticosteroids
Chronic: Colchicine, Probenecid, Allopurinol, Febuxostat

Question 19

What agent is used to reduce pain quickly

Answer 19

Indomethacin!

Question 20

What is the MOA of Colchicine

Answer 20

inhibition of microtubule assembly decreases macrophage migration and phagocytosis
Inhibits LT-B4= decreased inflammation

Question 21

How should colchicine be used

Answer 21

acute: gout pain resolution IF started w/in 36 hours of attack
-acute attack, dose at 1.2 mg, then 0.6 mg in 1 hr
helps avoid gout attacks when used prophylactiaclly

Question 22

ADE of colchicine include

Answer 22

dose dependent GI effects (diarrhea, nausea, vomiting)
reversible neuromyopathy
Toxicity: exacerbation of acute gout, hypersensitivity rxn
*Adjust dose when using CYP3A4 and P-glycoprotein inhibitors
Inhibits renal tubular secretion of methotrexate

Question 23

How can corticosteroids be administered for gout treatment

Answer 23

Oral: methylprednisone dose pack
IM: give tramcinolone, but follow with oral prednisone or prednisolone
Intraarticular: only if 1-2 joints involved, combine with NSAIDs, colchicine, or oral corticosteroids

Question 24

ADE of corticosteroids are

Answer 24

adrenal suppression 
growth inhibition 
muscle waisting 
osteoporosis 
salt retention 
glucose intolerance 
behavioral changes

Question 25

What anti-inflammatory regimens can be used during initiation of urate lwoering therapy

Answer 25

Colchicine .6mg 1-2x day Low dose NSAIDs w/ PPI Prednisone -whichever you choose, continue at least 6 months, or 3-6 months after you get to target serum uric acid

Question 26

Xathine oxidase inhibitors can be use for

Answer 26

prophylaxis of recurrent gout attacks in both underexcreters and overproducers of uric acid Allopurinol, Febuxostat

Question 27

When should you initiate XOI (allopurinol or febuxostat)

Answer 27

2+ gout attacks per year 1+ tophi CKD stage 2+ Hx of urolithiasis

Question 28

How do you dose XOI

Answer 28

titrate to a goal seum urate lelel <6mg or <5mg if S/Sx persist at 6mg

Question 29

What does xanthine oxidase do

Answer 29

It converts Xanthine to Uric acid | So if you inhibit this enxyme, then you will get less production of uric acid

Question 30

What is the first like urate lowering therapy

Answer 30

Allopurinol (XOI) Irreversibly* inhibits xanthine oxidase and lowers production of uric acid Used in chronic gout* starting at 100mg/day (50mg/d if w/ CKD) You can titrate up every 2-5 weeks (max dose 800)

Question 31

ADE of Allopurinol are

Answer 31

pruritis, rash, elevated LFT Acute hypersensitivity syndrome: highest risk in first few months (consider genetic testing in high risk koreans w/ CKD, Han chinese, or Thai)

Question 32

Another first line urate lowering therapy is

Answer 32

Febuxostat (XOI) Reversibly* inhibits xanthine oxidase and can be used in overproducers and underexcretors Start at 40mg daily, monitor in 2 weeks; if uric acid isn't <6mg, increase to 80mg do NOT need to dose adjust in renal disease or hepatic impairment! (but unsure in pts w/ CrCl <30)

Question 33

NEVER use Febuxostat with

Answer 33

Azathioprine

Question 34

ADE of Febuxostat are

Answer 34

``` high LFT nausea arthralgias rash Toxicities: LFT, renal function ```

Question 35

What is Probencid

Answer 35

``` Uricosuric therapy (increase excretion) Need to drink TONS of water to help flush system do NOT use if rCl <50, or Hx of urolithiasis ```

Question 36

XOI + fenofibrate or losartan can be used to

Answer 36

augment uric acid excretion | Good in patients with other disorders

Question 37

What is Pegloticase

Answer 37

A biologic for patients with refractory gout not responding to other Tx; it is essentially recombinant porcine-like uricase that metabolizes uric acid to allantoin Can be use din overproducers and under-excretors Heavy disease burden with chronic tophaceous disease Lowers uric acid levels and reduces deposits of uric acid crystals in joints and soft tissue

Question 38

What is Lesinurad

Answer 38

Inhibits function of transporter proteins involved in renal uric acid reabsorption and anion transfer= lowers serum uric acid levels and increases renal excretion of uric acid

Question 39

Indications for using Lesinurad are

Answer 39

patients w/ hyperuricemia associated with gout who do not achieve target serum uric acid levels with conventional therapies can be used in overproducers and underexcretors Must use W/ XOI 2/2 risk of renal failure if used alone

Question 40

ADE of Lesinurad are

Answer 40

``` acute gout attack during initiation HA GERD adverse cardiovascular fxn Renal function toxicity ```

Question 41

What off label gout drugs target IL-1

Answer 41

Anakinra Canakinumab Rilonacept

Question 42

What is Canakinumab

Answer 42

fully human anti-IL-1b MAB rapid and sustained pain relief at 150mg subQ safe to use in acute gout and gout prophylaxis