DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 34–3
Disease-Modifying Anti-Rheumatic Drugs
REFERENCE
(CHAPTER
DRUG CLASS OR ACTION NUMBER)
Small molecules
Methotrexate Anti-folate 61
Leflunomide Pyrimidine synthase inhibitor 61
Hydroxychloroquine Anti-malarial 49
Minocycline 5-lipoxygenase inhibitor, tetracycline antibiotic 33, 55
Sulfasalazine Salicylate 34, 47
Azathioprine Purine synthase inhibitor 61
Cyclosporine Calcineurin inhibitor 35
Cyclophosphamide Alkylating agent 61
Biologicals
Adalimumab Ab, TNF-α antagonist 35
Golimumab Ab, TNF-α antagonist 35
Infliximab IgG-TNF receptor fusion protein (anti-TNF) 35
Certolizumab Fab fragment toward TNF-α 35
Abatacept T-cell co-stimulation inhibitor (binds B7 protein on 35
antigen-presenting cell)
Rituximab Ab toward CD20 (cytotoxic toward B cells) 62
Anakinra IL-1-receptor antagonist 35, 62
IL, interleukin; TNF, tumor necrosis factor.
with persistent moderate or high disease activity and indicators of
poor prognosis such as functional impairment, radiographic bony
erosions, extra-articular disease, and rheumatoid factor positivity.
Therapy is tailored to the individual patient, and the use of these
agents must be weighed against their potentially serious adverse
effects. The combination of NSAIDs with these agents is common.
Short-term glucocorticoids often are used to bring the level
of inflammation quickly under control. Glucocorticoids are not suitable
for long-term use because of adrenal suppression. The older
agents (gold, penicillamine) have unclear mechanisms of action
and tend to have slight efficacy and significant side effects. Their
pharmacology is described in more detail in previous editions of
this book.
PHARMACOTHERAPY OF GOUT
Gout results from the precipitation of urate crystals in
the tissues and the subsequent inflammatory response
(Terkeltaub et al., 2006). Acute gout usually causes an
exquisitely painful distal monoarthritis, but it also can
cause joint destruction, subcutaneous deposits (tophi),
and renal calculi and damage. Gout affects ~0.5-1% of
the population of Western countries. Once considered a
disease of kings and the rich, gout is no respecter of
class and is found at all socioeconomic strata. Indeed,
gout is the most common form of inflammatory arthritis
in the elderly.
The pathophysiology of gout is understood
incompletely. Hyperuricemia, while a prerequisite,
does not inevitably lead to gout. Uric acid, the end
product of purine metabolism, is relatively insoluble
compared to its hypoxanthine and xanthine precursors,
and normal serum urate levels (~5 mg/dL, or 0.3 mM)
approach the limit of solubility. In most patients with
gout, hyperuricemia arises from underexcretion rather
than overproduction of urate. Mutations of one of the
renal urate transporters, URAT-1, are associated with
hypouricemia (Enomoto et al., 2002); the uricosuric
effect of benzbromarone and probenecid can be
explained by inhibition of this transporter. Urate
tends to crystallize as monosodium urate in colder or
more acidic conditions. Monosodium urate crystals
activate monocytes/macrophages via the Toll-like
receptor pathway mounting an innate immune
response. This results in the secretion of cytokines,
including IL-1β and TNF-α; endothelial activation;
and attraction of neutrophils to the site of inflammation
(Terkeltaub et al., 2006). Neutrophils secrete