60. Gout Flashcards
Gout is a type of arthritis caused by a buildup of____ primarily in the joints
uric acid (UA) crystals
Uric acid is produced as an end-product of ____ metabolism
Purine
Gout typically occurs in 1 joint, most often the ___ joint
Metatarsophalangeal joint (MTP, the big toe)
In addition to a uric acid level, ___ can be evaluated to identify if UA crystals are present
sample of synovial (joint) fluid
Risk factors for gout
Male sex
Obesity
Excessive alcohol consumption (particularly beer)
Others: HTN, CKD, lead intoxication, advanced age, and using meds that increase UA levels
Drugs that increase uric acid
Aspirin, lower doses
Calcineurin inhibitors (tacrolimus, cyclosporine)
Diuretics (loop and thiazides)
Niacin
Pyrazinamide
Select chemotherapy (with tumor lysis syndrome)
Select pancreatic enzyme products
Foods to avoid to lower risk of gout
Organ meats
High-fructose corn syrup
Alcohol
T/F: treat hyperuricemia with drugs even if asymptomatic
False - asymptomatic hyperuricemia is not to be treated with drugs
Ppx gout drugs are used to lower UA levels, with a goal UA level of < ___
6mg/dL
What meds can be used to treat gout acute pain
Colchicine
Steroids (often intra-articular injections)
NSAIDs (often high starting dose)
What meds can be used as gout ppx?
Xanthine oxidase inhibitor (XOI): allopurinol (preferred) or febuxostat
An acute gout flare can occur when an XOI is started so give initially with ___ or ___
colchicine or an NSAID
If XOI didn’t work well enough and UA remains > 6 mg/dL, what can you add on?
Add on probenecid or lesinurad to daily XOI
Replace XOI with IV pegloticase (Krystexxa)
Colchicine (Colcrys) treatment dosing
Two 0.6mg tablets followed by 0.6mg in 1 hr (do NOT exceed total of 1.8mg in 1 hr)
When using colchicine, do NOT exceed total of ___mg in 1 hr
1.8mg in 1 hr
Contraindications for colchicine
Do NOT use in combo with P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment
Warnings for colchicine
Myelosuppression
Do not use with cyclosporin, diltiazem, verapamil, gemfibrozil, or statins – increase myopathy risk
Side effects for colchicine
Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decrease vit B12
Use colchicine within ___hrs of symptom onset (for treatment)
Wait ___ hrs after treatment dose before resuming prophylaxis dosing
36 hrs
12 hrs
Which NSAIDs are used in gout?
Indomethacin (Indocin)
Naproxen (Aleve)
Celecoxib (Celebrex)
Which steroids are used in gout?
Prednisone, prednisolone
Methylprednisolone (Medrol, Solu-Medrol)
Methylprednisolone (Medrol, Solu-Medrol) can be used intra-articular if ___large joints are involved
1-2
Acute side effects of steroids
Increased BG, BP, insomnia, appetite
Fatal toxicity can occur if colchicine is combined with strong CYP ___ inhibitors or strong P-gp inhibitor
3A4
Colchicine is major substrate of 3A4 and p-gp
When starting chronic uric acid lowering treatment, ____ should be used as prophylaxis to reduce risk of attacks
colchicine, steroids, or NSAIDs
Pharmacogenomic consideration with allopurinol use
HLA-B*5801 allele screening should be done for pts at high risk of severe hypersensivity reaction (including certain Asian groups)
____ is a uricosuric and a second-line treatment that can be used if XOIs are contraindicated or not tolerated or added when UA level is not at goal
Probenecid
Alternative lesinurad (taken WITH XOI)
Probenecid MOA
inhibits reabsorption of UA in the proximal tubule of the nephron (increase UA excretion)
Requires adequate renal function to be effective
____ a recombinant uricase enzyme, is reserved for severe, refractory disease
Pegloticase
Xanthine oxidase inhibitors MOA
decrease uric acid production
Warnings for allopurinol (Zyloprim, Aloprim)
Hypersensitivity reactions, including severe rash (SJS/TEN, DRESS)
HLA-B*5801 testing prior to use if high risk (esp for Asian pts), do not use drug if + )
Hepatotoxicity, bone marrow suppression
Side effects of allopurinol (Zyloprim, Aloprim)
Rash, acute gout attacks, nausea, diarrhea, increased LFTs
D/t high rate of gout attacks when beginning allopurinol or febuxostate, use with colchicine (0.6mg once or twice daily) or an NSAID for the first ____
3-6 months
Febuxostat (Uloric) Boxed warning
Increased risk of CV death compared to allopurinol in pts with established CV disease
Use should be limited to those who cannot tolerate allopurinol or if not effective
Uricosurics MOA
inhibit reabsorption of uric acid in the kidneys, increase UA excretion
Probenecid can be used to (increased/decrease) beta-lactam levels
Increase levels by decreasing beta-lactam renal excretion
Recombinant uricase MOA
Converts uric acid to allantoin (excreted)
Pegloticase (Krystexxa) dosing frequency
IV every 2 weeks
Boxed warning for pegloticase (Krystexxa)
Anaphylactic reactions - premedicate with antihistamines and steroids (higher risk with UA > 6)
Life-threatening hemolytic reactions and methemoglobinemia may occur with G6PD deficiency
Contraindications for pegloticase (Krystexxa)
G6PD deficiency
Do NOT use pegloticase (Krystexxa) in combo with ____ (increased risk of anaphylaxis)
allopurinol, febuxostat, or probenecid
Do not use ___ or ___ with febuxostat and use caution combining these with allopurinol
Mercaptopurine (active metabolite of azathioprine) or azathioprine
Allopurinol and febuxostat increase conc of mercaptopurine
___ is a urate-oxidase enzyme used in the treatment of tumor lysis syndrome (TLS). Contraindicated with ___ deficiency.
Rasburicase (Elitek)
G6PD
