Gout

Question 0

Causes

Answer 0

Uric acid buildup in the blood also called hyperuricemia

Question 1

Signs and Symptoms of Gout

Answer 1

Severe pain, burning, and swelling and typically occurs in one joint which is most often the metatarsophalangeal joint (big toe)

Question 2

Risk factors

Answer 2

1. Male
2. Obesity
3. Excessive alcohol consumption
4. Hypertension
5. Chronic kidney disease
6. Lead intoxication
7. Advanced age
8. Medications that increase uric acid levels

Question 3

Medications known for the highest risk of increasing uric acid

Answer 3

Diuretics ,especially thiazides and loops, niacin, aspirin at high doses, Purazinamide, cyclosporine, Tacrolimus

Question 4

Nonpharmacologic treatment

Answer 4

Avoid the following foods: organ meats, high fructose corn syrup and alcohol

Limit these foods high in purine content: fruit juice, table sugar, sweetened drinks and desserts, salt, beef, lamb, pork and seafood

Things that may reduce the risk of gout: low-fat dairy products, vegetables, hydration, weight loss and exercise

Question 5

Pathophysiology of uric acid production

Answer 5

1. Purines increase (diet and alcohol)
2. Causes production of xanthine
3. Xanthine oxidase converts xanthine to urate (allopurinol and fenuxostat inhibit this)
4. Urate oxidase converts urate to allantoin and uric acid crystals

Question 6

Pharmacologic therapy

Answer 6

Goal: treat acute attacks, prevent flareups, and reduced uric acid levels

Acute treatment: colchicine (colcrys), NSAIDs (indomethacin, naproxen, celecoxib, Sulindac), steroids (prednisone and methylprednisolone)
+ can supplement with topical ice therapy (PATIENT SHOULD NOT DISCONTINUE ANY PROPHYLACTIC THERAPY DURING THIS TIME)

Prevention: started in patients with >= 2 acute attacks per year or who have tophi; xanthine oxidase inhibitors (allopurinol and fubuxostat), probenecid can be used if xanthine oxidase inhibitors do not get the uric acid to a level of less than 5 to 6

Last line and used in severe, refractory disease: Pegloticase

Question 7

Colchicine (colcrys)

Answer 7

Dose: 1.2mg followed by 0.6 mg in one hour for a total of 1.8mg

Prophylactic regimen: 0.6mg BID starting 12 hr later and continue at least until the acute attack subsides

Contraindications: concomitant use of PGP or strong CYP3A4 inhibitors in the presence of renal hepatic impairment

Warning: clearance decreased and renal hepatic impairment

Side effects: nausea, vomiting, diarrhea and approximately 80% of patients and myelosuppression myopathy and neuropathy is dose related

Notes: recommended only when treatment is started within 36 hours of onset of symptoms (do not use if pt already on prophylactic colchicine and has received an acute regimen in the last 14 days)

Question 8

NSAIDs

Answer 8

Avoid in severe renal disease

Avoid in CV disease (especially celecoxib)

Indomethacin (indocin): first drug approved for gout and is traditionally the DOC but has psychiatric side effects: confusion, depression, psychosis

Question 9

Steroids: given IM, PO, IV, intra-articular

Answer 9

Prednisone: 0.5mg/kg/day for 5-10 days no taper OR 0.5mg/kg/day for 2 days, then taper over 7-10 days

Methylprednisolone (medrol, solu-medrol)

Side effects of both: hyperglycemia, hypertension, nervousness, insomnia, increased appetite, edema

Question 10

Colchicine drug interactions

Answer 10

Substrate of CYP3A4 and PGP. FATAL toxicity can occur if colchicine is combined with strong 3A4 inhibitors, such as clarithromycin or a strong inhibitor of P-gp, such as cyclosporine.

Caution when using with a statin or fibrate

Question 11

Colchicine Counseling

Answer 11

At first sign of attack take 2 tablets and take one more tablet within an hour.

Do not exceed this amount (can have serious side effects)

Do not take second dose if you experience nausea, vomiting, or diarrhea

Question 12

Allopurinol (Zyloprim)

Answer 12

Initial dose: 50-100mg daily, then slowly titrate up until UA target reached (<5-7)

Warning: hypersensitivity reactions can occur, including severe rash (SJS/TEN), can do genetic testing HLA-B (Asians Inparticular)

Caution in pts with liver impairment

Side effects: rash, acute gout attack, inc LFTs

Notes: max starting dose of 50mg daily in CKD pt

Question 13

Febuxostat (Uloric)

Answer 13

Contraindications: concomitant use with azathioprine or mecaptopurine

Warning: hepatotoxicity, d/c if LFTs >3x ULN

Side effects: inc. LFTs, rash

Notes: a lot more expensive than allopurinol, no dose adjustment needed in renal pts

Question 14

Probenecid

Answer 14

Contraindications: concomitant aspirin, Uric acid kidney stones, acute gout attack, blood dyscrasias

Warnings: inc risk of hemolytic anemia in pts with G6PD deficiency

Notes: requires adequate renal function

Question 15

Pegloticase (krystexxa)

Answer 15

Refractory cases only

Black box warning: anaphylactic rxn, premedication with antihistamines and corticosteroid can be done. D/c Rx if UA >6

Contra: G6PD def.

Warnings: acute gout flares can occur with initiation therefor pt should be on NSAID or colchicine prophylacticly

Side effects: antibody formation, gout flare, infusion rxn, nausea, bruising, urticaria, erythema, pruritis

Notes: very expensive, do not use in combination with allopurinol