Antimalarial

Antimalarial drugs have the obvious connotation of therapeutic utility against malaria, but certain drugs with activity against malaria also are immunomodulators used in rheumatology. Somewhat confusingly, some antibiotics, which are highly active against malaria are not explicitly called antimalarials.

In general usage, the term applies specifically to synthetic analogs of quinine, rather than antibiotics or other drugs with activity against malarial parasites and other protozoa. The major drugs of this type are:

• 4-aminoquinolone derivatives
  • Hydroxychloroquine
  • Chloroquine
• 9-aminoacridine derivatives
  • Quinacrine

Treatment of malaria

For malaria, chloroquine is the most important drug; quinacrine is no longer in commercial tablet production but, as a third-line agent, is available from compounding pharmacies. Chloroquine remains the drug of choice for chemoprophylaxis when resistance has not been reported.

Note that some antibiotics, such as tetracycline, doxycycline and clindamycin are important treatments for malaria, but are not quinine analogs.

Rheumatology

These are examples of disease-modifying anti-rheumatic drugs (DMARD), which directly affect the disease process rather than simply providing pain control.

Indications

Their most important use was in systemic lupus erythematosus, although monoclonal antibodies are now the first-line drugs. They also have applicability to rheumatoid arthritis, palindromic arthritis and psoriatic arthritis. When DMARDs are indicated, other DMARDs are often preferred, such as methotrexate in rheumatoid arthritis.

In a 1998 study comparing chloroquine and hydrochloroquine, hydroxychloroquine was less toxic but less effective than chloroquine, but there were no firm recommendations of one over the other. Hydroxychloroquine is considerably more expensive.

Their immunologic mode of action was not understood before their therapeutic use, but current thinking is that they decrease antigen production by macrophages and lymphoid dendritic cells. They do this by increasing their intracytoplasmic pH, leading to changes in the molecular assembly of class II major histocompatibility complex molecules.

With the decreased antigen production, T4-lymphocytes produce less cytokines, specifically including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 and tumor necrosis factor-alpha.

Side effects

Damage to the eyes are the greatest concerns. These drugs may deposit in the melanin of the pigmented epithelial layer of the retina. Since early damage is often reversible, thorough opthalmologic examination is advised every 6 to 12 months.

These drugs can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.