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Summer pharm 3 > Gout > Flashcards

Gout Flashcards

1
Q

What is gout

A

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

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2
Q

What are tophi

A

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

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3
Q

Define hyperuricemia

A

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

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4
Q

How is uric acid produced

A

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

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5
Q

What is the physiology in a “gouty” joint

A

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

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6
Q

Drugs used to treat gout target

A

inhibiting crystal phagocytosis and PMN/Macrophage release of inflammatory mediators

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7
Q

What causes overproduction of uric acid

A

not fully known.

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

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8
Q

What causes underexcretion of uric acid (more common)

A

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

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9
Q

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

A 
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
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10
Q

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

A 
anchovies 
brain
gravies
kidney
liver
sardines
sweetbreads
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11
Q

What drugs can induce hyperuricemia/gout

A 
diuretics 
nicotinic acid 
salicylates 
ethanol
pyrazinamide 
ethambutol
cytotoxic drugs 
cyclosporine
levodopa
*know drug class or name of speciic drugs*
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12
Q

What is acute gout

A

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

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13
Q

DDx for gout is

A 
infection 
FB
fracture 
AVN
atypical RA 
arthritis
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14
Q

What are the other tyoes of gout

A

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

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15
Q

What is definitive Dx for gout

A

joint tap and microscopic exam for uric acid crystals

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

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16
Q

What is the clinical triad of gout

A

inflammatory monoarthritis
elevated serum uric acid level
response to colchicine

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17
Q

Goals in treatment of gout are

A

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

18
Q

Drug therapy for gout includes

A

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

19
Q

What agent is used to reduce pain quickly

A

Indomethacin!

20
Q

What is the MOA of Colchicine

A

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

21
Q

How should colchicine be used

A

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

22
Q

ADE of colchicine include

A

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

23
Q

How can corticosteroids be administered for gout treatment

A

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

24
Q

ADE of corticosteroids are

A 
adrenal suppression 
growth inhibition 
muscle waisting 
osteoporosis 
salt retention 
glucose intolerance 
behavioral changes
25
Q

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

A

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

26
Q

Xathine oxidase inhibitors can be use for

A

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

27
Q

When should you initiate XOI (allopurinol or febuxostat)

A

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

28
Q

How do you dose XOI

A

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

29
Q

What does xanthine oxidase do

A

It converts Xanthine to Uric acid

So if you inhibit this enxyme, then you will get less production of uric acid

30
Q

What is the first like urate lowering therapy

A

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)

31
Q

ADE of Allopurinol are

A

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)

32
Q

Another first line urate lowering therapy is

A

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)

33
Q

NEVER use Febuxostat with

A

Azathioprine

34
Q

ADE of Febuxostat are

A 
high LFT 
nausea 
arthralgias 
rash 
Toxicities: LFT, renal function
35
Q

What is Probencid

A 
Uricosuric therapy (increase excretion) 
Need to drink TONS of water to help flush system 
do NOT use if rCl <50, or Hx of urolithiasis
36
Q

XOI + fenofibrate or losartan can be used to

A

augment uric acid excretion

Good in patients with other disorders

37
Q

What is Pegloticase

A

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

38
Q

What is Lesinurad

A

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

39
Q

Indications for using Lesinurad are

A

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

40
Q

ADE of Lesinurad are

A 
acute gout attack during initiation 
HA
GERD
adverse cardiovascular fxn 
Renal function toxicity
41
Q

What off label gout drugs target IL-1

A

Anakinra
Canakinumab
Rilonacept

42
Q

What is Canakinumab

A

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

Summer pharm 3 (13 decks)

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