indication

For the treatment of tuberculosis

pharmacology

Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.

mechanism of action

There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.

toxicity

LD₅₀=4 gm/kg (orally in mice); LD₅₀=3650 mg/kg (orally in rabbits)

biotransformation

Hepatic.

drug interactions

Azathioprine: Aminosalicylic acid may increase the toxicity of thiopurine, azathioprine.

Mercaptopurine: Aminosalicylic acid may increase the toxicity of thiopurine, mercaptopurine.

Sulindac: Risk of additive toxicity (e.g. bleed risk). Aminosalicylic acid may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.

Thioguanine: Aminosalicylic acid may increase the toxicity of thiopurine, thioguanine.

Tiaprofenic acid: Increased risk of gastrointestinal bleeding.

Tolmetin: Additive effects increase the risk of GI bleeding. Monitor for increased bleeding risk during concomitant therapy.

Trandolapril: The salicylate, Aminosalicylic acid, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Aminosalicylic acid is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the salicylate, Aminosalicylic acid. Monitor for increased bleeding during concomitant thearpy.

Warfarin: The antiplatelet effects of aminosalicylic acid may increase the bleed risk associated with warfarin.