STEPTRACKERPHARMACOLOGY + RHEUMATOLOGY | INFLAMMATION & MSK | HIGH-YIELD REVIEW

Gout & Rheumatology Drugs

Gout drugs either calm the acute attack or lower urate long term; rheumatology drugs (DMARDs) slow joint destruction — each with monitoring rules you must know.

FOCUS ON
Acute gout: NSAIDs (indomethacin, naproxen), colchicine (binds tubulin → ↓ neutrophil migration; diarrhea, myopathy, neuropathy, marrow toxicity; CYP3A4/P-gp interactions), glucocorticoids (intra-articular/oral), IL-1 blockers. Do not start or stop urate-lowering drugs during an attack. Chronic urate lowering (target < 6 mg/dL; give colchicine/NSAID prophylaxis when starting): allopurinol (xanthine oxidase; HLA-B*58:01 → SJS/DRESS; ↑ azathioprine/6-MP toxicity), febuxostat (↑ CV death), probenecid (uricosuric; ↓ PCT urate reabsorption; avoid with stones; ↑ penicillin levels), pegloticase (uricase; G6PD → hemolysis, methemoglobinemia), rasburicase (tumor lysis). DMARDs: methotrexate (anchor drug; DHFR; folate supplementation; hepatotoxicity, pneumonitis, stomatitis, marrow, teratogen), hydroxychloroquine (retinopathy), sulfasalazine, leflunomide (DHODH; teratogen), JAK inhibitors (tofacitinib — VTE, zoster), biologics (TNF, IL-6, CD20, CTLA-4-Ig) — screen TB, HBV.
DRUG
MECHANISM
USE
ADVERSE · MONITOR
Colchicine
Binds tubulin → ↓ microtubules, neutrophil chemotaxis, inflammasome
Acute gout, gout prophylaxis, FMF, pericarditis, Behçet
Diarrhea, myopathy, neuropathy, marrow suppression; toxic with clarithromycin, statins
Allopurinol
Xanthine oxidase inhibitor (oxypurinol active)
Chronic gout, tumor lysis prevention, uric acid stones
SJS/DRESS (HLA-B*58:01), ↑ azathioprine/6-MP levels
Febuxostat
Nonpurine xanthine oxidase inhibitor
Gout when allopurinol not tolerated
↑ CV mortality, ↑ LFTs
Probenecid
Inhibits URAT1 urate reabsorption (PCT)
Underexcreters with normal renal function
Uric acid stones; ↑ levels of penicillin, methotrexate, cephalosporins
Pegloticase · rasburicase
Recombinant uricase → urate to allantoin
Refractory tophaceous gout · tumor lysis syndrome
Hemolysis and methemoglobinemia in G6PD deficiency; infusion reactions
Methotrexate
DHFR inhibition; ↑ adenosine (anti-inflammatory)
RA (first-line), psoriasis, psoriatic arthritis, vasculitis, ectopic pregnancy, cancer
Hepatotoxicity, pneumonitis, mucositis, cytopenias, teratogen; give folic acid; avoid alcohol
Hydroxychloroquine
↑ Lysosomal pH, ↓ TLR signaling, antigen presentation
SLE (all patients), mild RA, Sjögren
Retinopathy (annual eye exam), QT, hemolysis (G6PD)
Sulfasalazine
5-ASA + sulfapyridine
RA, UC, ankylosing spondylitis (peripheral)
Oligospermia, rash, hemolysis, agranulocytosis
Leflunomide
Dihydroorotate dehydrogenase inhibitor → ↓ pyrimidines
RA
Teratogen (cholestyramine washout), hepatotoxicity, diarrhea
Tofacitinib · baricitinib · upadacitinib
JAK inhibitors
RA, psoriatic arthritis, UC, alopecia
Herpes zoster, VTE, MACE, malignancy
TNF-α inhibitors
Infliximab, adalimumab, etanercept (decoy receptor), certolizumab, golimumab
RA, AS, psoriasis, IBD
TB/HBV reactivation, infections, drug-induced lupus, HF, demyelination
Abatacept · tocilizumab · rituximab
CTLA-4-Ig (blocks CD80/86) · anti-IL-6R · anti-CD20
RA refractory to TNF; tocilizumab giant cell arteritis
Infection; tocilizumab GI perforation, ↑ lipids; rituximab HBV, PML
Anakinra · canakinumab
IL-1 receptor antagonist · anti-IL-1β
Gout flares, Still disease, periodic fever syndromes
Infections, injection reactions

Mechanism — purine breakdown targets

Hypoxanthine → xanthine → uric acidXanthine oxidase (allopurinol, febuxostat block)
→
Kidney reabsorbs urateURAT1 (probenecid blocks)
→
Uricase converts to allantoinAbsent in humans — pegloticase, rasburicase supply it

Acute vs chronic gout

PHASE
DRUGS
AVOID
Acute flare
NSAID, colchicine, steroid
Starting allopurinol
Prevention
Allopurinol, febuxostat, probenecid
Low-dose aspirin, thiazides, loops
Renal impairment
Steroids (flare), dose-adjusted allopurinol
NSAIDs, probenecid

How it's tested

COMMON CONFUSIONAllopurinol inhibits the enzyme that inactivates azathioprine and 6-MP — reduce their dose by ~75% or risk marrow failure.
THE TRAPStarting urate-lowering therapy without prophylaxis can trigger flares as crystals mobilize — co-prescribe colchicine or an NSAID for months.
YOUR APPROACHGout: phase (acute vs chronic) → renal function → drug. RA: methotrexate first → add biologic/JAK → screen TB and HBV before biologics.

If you see… think…

Severe diarrhea and myopathy on gout drug + clarithromycin → colchicine toxicity
Rash, fever, eosinophilia after starting gout prevention → allopurinol DRESS (HLA-B*58:01)
Pancytopenia after allopurinol added to azathioprine → xanthine oxidase inhibition
Hemolysis after uricase infusion → G6PD deficiency
Tumor lysis treatment that breaks down urate → rasburicase
Annual eye exams on lupus drug → hydroxychloroquine
Mouth ulcers and pneumonitis on RA anchor drug → methotrexate
Positive interferon-γ release assay before biologic → treat latent TB first
Shingles on oral RA drug → JAK inhibitor
Decoy TNF receptor fusion protein → etanercept