Chloroquine & Hydroxychloroquine

CHLOROQUINE & HYDROXYCHLOROQUINE

Mechanism of Action

Chloroquine and hydroxychloroquine are nonbiologic drugs mainly used for malaria  and in the rheumatic diseases. The mechanism of the anti-inflammatory action of these drugs in rheumatic diseases is unclear. The following mechanisms have been proposed: suppression of T-lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lyso-somal enzymes, inhibition of DNA and RNA synthesis, and the trapping of free radicals.

Pharmacokinetics

Antimalarials are rapidly absorbed and 50% protein-bound in the plasma. They are very extensively tissue-bound, particularly in mela-nin-containing tissues such as the eyes. The drugs are deaminated in the liver and have blood elimination half-lives of up to 45 days.

Indications

Antimalarials are approved for rheumatoid arthritis, but they are not considered very effective DMARDs. Dose-response and serum concentration-response relationships have been documented for hydroxychloroquine and dose-loading may increase rate of response. Although antimalarials improve symptoms, there is no evidence that these compounds alter bony damage in rheumatoid arthritis at their usual dosages (up to 6.4 mg/kg/d for hydroxychloroquine or 200 mg/d for chloroquine). It usually takes 3–6 months to obtain a response. Antimalarials are often used in the treatment of the skin manifestations, serositis, and joint pains of systemic lupus erythe-matosus, and they have been used in Sjögren’s syndrome.

Adverse Effects

Although ocular toxicity  may occur at dosages greater than 250 mg/d for chloroquine and greater than 6.4 mg/kg/d for hydroxychloroquine, it rarely occurs at lower doses. Nevertheless, ophthalmologic monitoring every 12 months is advised. Other toxicities include dyspepsia, nausea, vomiting, abdominal pain,rashes, and nightmares. These drugs appear to be relatively safe in pregnancy.