different manifestations of colchicine toxicity and identify patients most at risk Risk factors for toxicity include: old age, renal impairment, hepatic impairment, chronic use, and concomitant interacting medications. Most adverse effects are related to dose and duration. • Common: gastrointestinal (GI) effects (nausea, vomiting, & especially diarrhea) can occur even at recommended doses. • Acute toxicity: renal failure, …
When should colchicine be avoided? • Concurrent use of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibitors in the setting of renal or hepatic impairment. Colchicine dose adjustments Dose Adjustment for Acute Gout Flare Dose Adjustment for Gout Prophylaxis Strong CYP3A4 inhibitors a 0.6 mg × 1 dose, 0.3 mg 1 hour laterDo not repeat in <3 …
How should colchicine be dosed in the treatment of gout? • Acute gout flare: 1.2 mg followed by 0.6 mg in 1 hour. Most effective if started in first few hours of gout attack. Similar efficacy to prior “high-dose” regimens used in the past. • Gout prophylaxis: 0.6 mg once or twice daily. Colchicine has no effect on serum …
Uses of colchicine clinical scenarios where colchicine may be used Treatment of acute gout attacks Sweet’s syndrome Prophylaxis against recurrent gout flares Other neutrophilic dermatoses FMF Pericarditis, initial and recurrent episodes Behćet syndrome Post-procedurally for atrial fibrillation ablations Cutaneous vasculitis Recurrent aphthous stomatitis
Mechanism of action and pharmacokinetics of colchicine • Irreversibly binds free tubulin dimers → disrupts microtubule polymerization → inhibition of neutrophil chemotaxis, phagocytosis, and cytokine secretion. • Inhibits phospholipase A2, which leads to lower levels of inflammatory prostaglandins and leukotrienes (LTB4). • May modulate pyrin expression. • Colchicine is not bound to plasma proteins and is highly lipid-soluble, readily …
Goals in the treatment of gout The goal in treatment of acute gouty arthritis is to quickly alleviate pain and restore joint function. The long-term treatment goals and purpose of ULT are to prevent recurrent attacks and the development of destructive arthropathy, tophi formation, or renal complications.
What T cell targeted therapies are available and how are they used? Abatacept (Orencia): a fully human fusion protein comprising the extracellular portion of CTLA4 and the Fc fragment of IgG1 (CTLA4Ig). Abatacept binds to CD80/CD86 on antigen-presenting cells (APCs) preventing these molecules from binding to their ligand, CD28, on T cells. This interferes with optimal …