PASER GRANULES

Indications

• Active tuberculosis due to susceptible strains of Mycobacterium tuberculosis
• Treatment of multi-drug resistant tuberculosis in combination with other anti-tuberculosis agents

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Aminosalicylic acid exhibits its bacteriostatic effects through two primary mechanisms. First, it inhibits the synthesis of folic acid by binding to pteridine synthetase with greater affinity than para-aminobenzoic acid, which is crucial for folate synthesis. This inhibition prevents the bacteria from utilizing external folic acid sources, thus slowing down cell growth and replication. Second, aminosalicylic acid may inhibit the synthesis of mycobactin, a cell wall component that reduces iron uptake by Mycobacterium tuberculosis. This highly specific antimicrobial action makes aminosalicylic acid less effective against other microorganisms.

Pharmacodynamics

Aminosalicylic acid is classified as bacteriostatic, meaning it prevents the multiplication of Mycobacterium tuberculosis without directly killing the organisms. It is typically used in combination with other anti-tuberculosis drugs, such as isoniazid, to enhance the overall effectiveness of treatment and reduce the likelihood of developing bacterial resistance. The drug produces a toxic inactive metabolite in acidic conditions and has a relatively short serum half-life of about one hour.

Pharmacokinetics

Aminosalicylic acid is rapidly absorbed, with a short half-life, leading to prompt metabolism and elimination from the body. The drug's pharmacokinetic properties necessitate careful management in dosing to maintain effective therapeutic levels while minimizing potential toxicity. It is important to monitor patient response and adjust doses accordingly.

Interactions

• aminosalicylicacid+topicalanaesthetics,local: Moderate (increases risk of methaemoglobinaemia)
• aminosalicylicacid+prilocaine: Moderate (increases risk of methaemoglobinaemia)
• aminosalicylicacid+topicalprilocaine: Moderate (increases risk of methaemoglobinaemia)
• aminosalicylicacid+dapsone: Unknown (increases risk of methaemoglobinaemia)

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Aminosalicylic acid should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Aminosalicylic acid is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a well-closed container, at room temperature, away from moisture and direct sunlight.

Formulations

• Aminosalicylic acid tablet

Mechanism of action

There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against <i>Mycobacterium tuberculosis</i>. 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 <i>M. tuberculosis</i>. The antimicrobial activity of aminosalicylic acid is highly specific, and microorganisms other than Mycobacterium tuberculosis are unaffected. Most nontuberculous mycobacteria are not inhibited by the drug. Aminosalicyclic acid is a structural analog of paraaminobenzoic acid, and its mechanism of action appears to be very similar to that of the sulfonamides. Since the sulfonamides are ineffective against Mycobacterium tuberculosis, and aminosalicyclic is inactive against sulfonamide susceptible bacteria, it is probable that the enzymes responsible for folate biosynthesis in various microorganisms may be quite exacting in their capacity to distinguish various analogs from the true metabolite.

Pharmacodynamics

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 <i>Mycobacterium tuberculosis</i> (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.