Gout

Question 1

GOUT

Answer 1

Serum urate level > 8
Goal <6

Urate lowering agent: probenecid, allopurinol, febuxostat, lesiurad, pegloticase

For acute gouty attack : NSAIDS, colchicine, steroids

Question 2

NSAIDS

Answer 2

Start 12 to 48 hours of ACUTE ATTACK

Indomethacin: Oral or rectal 50 mg TID-
Naproxen 250 mg TID until attack subsides
Suldinac 200 mg BID x 7 days ( max 400 mg /d )

Avoid:
Renal insufficiency ( CrCl < 60 )
Peptic ulcers
HF or HTN
Hyperkalemia

Question 3

Indomethacin

Answer 3

50 mg q8 h for 3- 4 days then gradually taper off over 1 to 2 weeks’

Question 4

Colchicine

Answer 4

MOA: inhibits cell division ( tells you it’s affecting bone marrow suppression like a chemo agent )

DOSE: oral for ACCUTE ATTACK gouty arthritis ( gout flare )
- 2 tabs ( 0.6 mg ), THEN 1 tab 1 hour later ( total 3 tabs = max 1.8 mg / 24 hours ) Colcrys

Prophylaxis in beginning : added in beginning ( while adding antihyperurecmeic agents to avoid risk of acute flare )
0.6 qod, qd,. Max is 0.6 bid

NEVER Give IV: Death

Question 5

Colcrys is a 3a4 substrate

Answer 5

T Watching for DDI

INHIBITORS : will increase colchicine ( 169 deaths associated ) toxicity
Grapefruit juice
A : flu, keto , pos, voriconazole
P- Ritonavir , darunavir, atazanavir
C : clarithromycin, erythromycin ( CCB: diltiazem , verapamil )

Question 6

Colchicine SE’s

Answer 6

GI : severe diarrhea
BMS: agranulocytosis, aplastic anemia and thrombocytopenia
Loss of body and scalp hair
Renal : contraindicated with dz :
Hepatic
Malabsorption syndrome: decreases vitamin B12 level ( may need to supplement ) , fats

Question 7

Monitor during colchicine

Answer 7

CBC : if you get unusual bleeding, body aches, severe diarrhea, vomiting, contact MD
RENAL
HEPATIC

Question 8

Corticosteroids

Answer 8

First line: injection into site of inflammation, if cant, then give oral formulation

Methylprednisolone 5 mg / small joint
Triamcinolone : 2.5 - 5 / small joint
Betmethasone: 1.5-3 mg

Oral Prednisone: 30-50 mg per day until flare resolve and then taper over 7-10 days

Caution with HF: increase BP, edema,

Question 9

steroids SE’s
pneumonic PREDNISONE

Answer 9

PUD
Rash
Eye ( glaucoma )
Diabetes
Neurologic ( CNS ) : HA, mood, insomnia, seizure
Immunosuppression
Swelling ( Cushing )
Osteoporosis
Nausea ( we actually use dexamethasone to tx N/V for cisplatin. Start with 5HT then add steroid then emend )
Electrolyte ∆’s : ↑Na+, ↓K+ ( therefore increase BP )

Question 10

Management of chronic gout

Answer 10

Urate lowering meds should not be started during acute attack. Best to start 2 weeks after the attack.

Goal : reduce urate <6
Uricosuric drugs: Probenacid , Lesinuard

Xanthine oxidase inhibitors
Allopurinol uloric

PEGylated uric acid enzyme:

Kystexxa ( Pegloticase ) IV

Question 11

Probenacid

Answer 11

MOA: increase urinary excretion of urate.
Problem: doesn’t work well. Not first line.
Works on kidneys ( also used to increase plasma levels of PCN, cyclosporins, Nafcillins . Won’t allow you excrete these drugs so more in system. ) cydopavir can cause vancoli like renal tox so Probenacid protects the kidneys

Indication: HYPERURICEMIA with gout
Prolong PCN serum levels

With food.
Goes through kidney. Drink lots of water to keep urine alkaline. If CrCl < 50 ( clinically choose not to give ) package insert says 30

Question 12

Methotrexate and Probenacid DDI

Answer 12

Avoid Probenacid will increase [ MTX ]

Question 13

Lesinurad

Answer 13

Zurampic

MOA: uric acid transporter ( works on kidney ). It inhibits fxn of renal uric acid reabsorption.
Never given alone. Works in combination with allopurinol or febuxostat. If you stop these you stop add on lesinurad
With food and lots of water
Caution: avoid if CrCl < 30

Question 14

Xanthine oxidase inhibitors

Answer 14

First line for gout prevention
MOA: blocks Xanthine oxidase

Use if uric acid production > 800
Use if patient has kidney stones
Renal failure

Question 15

Allopurinol
MOA: xanithine oxidase inhibitor

Answer 15

Aloprim ; zyloprim
Food and lots of water
Reduce if CrCl drops. Dose adjust. CrCl 10-20 max 200 mg/ day , CrCl <10 100 mg /day

Used for Cancer therapy induced hyperuricemia: PO/IV

SE: RASH ( exfoliating dermatitis ) DC and tx with steroid
Hepatotoxicity and renal impairment
Bone marrow supression ( but minor compared to colchicine ), nausea

Monitor : CBC, uric acid levels, I & O , prothrombin time ( can enhance anticoagulant effect of warfarin )

HLAB*5801 : Han Chinese, Thai, Korean or anyone with CrCl <60

Question 16

Allopurinol DDI

Answer 16

Azathioprine ( imuran ) turns into 6MP. Both can decrease both need xanathine oxidase to metabolize these drugs.
- decrease allopurinol by 75%

Warfarin : monitor INR, enhances warfarin

Thiazides and ACE : increases risk of hypersensitivity ( additive. Rash risk )

Bone marrow supression: reallly worry if patient is receiving alkylating agents cyclophosphamide or i phosfamide.

Vitamin C : urinary acidification : increases risk of kidney stone formation

Question 17

Febuxostat

Answer 17

Uloric
MOA: non purine xanithine oxidase inhibitor ( but structurally different than allopurinol ). Clinically use this if you cant use allopurinol ( severe rash or HLAB5801 and cant use allopurinol , or if allopurinol not working well )

Metabolized in liver. Check LFTs uLoric
Renal metabolized too. Caution CrCL <30

Recommended to take with an NSAID or colchicine

SE: Different RASH : drug reaction rash with eosinophilia and systemic symtoms ( DRESS)
Nausea, arthralgia

Drug interactions
DDI like allopurinol

Question 18

Pegloticase injection

Answer 18

Krystexxa
IV q 2 weeks. Given over 2 hours
MOA: a PEGylated uric acid specific enzyme. Breaks down urate
Indication: tx of chronic goat in adult patients refractory to conventional therapy
Premedicate : antihistamine, apap, IV hydrocortisone ( #1 warning is anaphylaxis )

Contraindication : G6PD deficiency

SE: GOUTY Flares ( make sure on nsaid or colchicine on first 6 months of therapy ), CHF

Question 19

Thiazides, loops, levodopa, niacin( vitamin B3) , cyclosporine, tacrolimus , ethambutol, pyrazindamide, low dose asa can all increase uric acid

Alcohol ( beer with highest purine content)

High purine foods : red meat, liver kidney , shellfish and yeast can

Answer 19

Can call worsen or cause Gout

Question 20

Paradoxical affect of ASA on serum urate

Answer 20

Asa not used to tx acute gout because of the paradoxical effect of salicylates on serum urate, resulting from

Renal uric acid retention at low doses ( < 2 g /day )