Aminosalicylic Acid

Synonyms :
2-HYDROXY-4-aminobenzoic acid, 4-aminosalicylate, 4-aminosalicylic acid, Aminosalicylic acid, p-aminosalicylic acid, para-amino salicylic acid, para-aminosalicylic acid, PAS, Paser

Status : approved

Category

Antitubercular Agents

Therapeutic Classification

DRUGS FOR TREATMENT OF TUBERCULOSIS

ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF TUBERCULOSIS

Description

An antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid. [PubChem]

Used

For the treatment of tuberculosis

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.

Dosage

Form Route Strength
Tablet oral 500 mg
Granule, delayed release oral 4 g

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

Toxic Effect

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

Metabolism

Hepatic.

Protein Binding

50-60%

Chemical Classification

This compound belongs to the class of organic compounds known as aminosalicylic acids. These are salicylic acids carrying an amino group on the benzene ring.

Aminosalicylic acids

Organic compounds

Benzenoids

Benzene and substituted derivatives

Benzoic acids and derivatives

Salt : Aminosalicylate Sodium

Chemical Name

2-HYDROXY-4-aminobenzoic acid

Brands

name Dosage form Country
Nemasol Sodium Tab 500mg tablet Canada
Paser granule, delayed release US

Drug Drug Interactions

  •  Abciximab  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Acenocoumarol  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Acetazolamide  : Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination.
  •  Acetylsalicylic acid  : May enhance the anticoagulant effect of other Salicylates.
  •  Alteplase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Ammonium chloride  : May increase the serum concentration of Salicylates.
  •  Anistreplase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Citric Acid  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Dalteparin  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Diclofenamide  : Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination.
  •  Dicoumarol  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Edetic Acid  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Enoxaparin  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Ethoxzolamide  : Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination.
  •  Ethyl biscoumacetate  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Fondaparinux sodium  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Ginkgo biloba  : May enhance the anticoagulant effect of Salicylates.
  •  Heparin  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Hyaluronidase  : Salicylates may diminish the therapeutic effect of Hyaluronidase.
  •  Methotrexate  : Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern.
  •  Phenindione  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Phenprocoumon  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Pralatrexate  : Salicylates may increase the serum concentration of Pralatrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern.
  •  Probenecid  : Salicylates may diminish the therapeutic effect of Probenecid.
  •  Reteplase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Ridogrel  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Salicylate-sodium  : May enhance the anticoagulant effect of other Salicylates.
  •  Streptokinase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Sulodexide  : Salicylates may enhance the anticoagulant effect of Anticoagulants.
  •  Tenecteplase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Treprostinil  : May enhance the adverse/toxic effect of Salicylates. Bleeding may occur.
  •  Urokinase  : Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur.
  •  Warfarin  : Salicylates may enhance the anticoagulant effect of Anticoagulants.

Food Interactions

  • Take without regard to meals.

Calculated Property

kind Value Source
logP 0.62 ALOGPS
logS -1.1 ALOGPS
Water Solubility 1.18e+01 g/l ALOGPS
logP 0.83 ChemAxon
IUPAC Name 4-amino-2-hydroxybenzoic acid ChemAxon
Traditional IUPAC Name aminosalicylic acid ChemAxon
Molecular Weight 153.1354 ChemAxon
Monoisotopic Weight 153.042593095 ChemAxon
SMILES NC1=CC(O)=C(C=C1)C(O)=O ChemAxon
Molecular Formula C7H7NO3 ChemAxon
InChI InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11) ChemAxon
InChIKey InChIKey=WUBBRNOQWQTFEX-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 83.55 ChemAxon
Refractivity 40 ChemAxon
Polarizability 14.29 ChemAxon
Rotatable Bond Count 1 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 3.68 ChemAxon
pKa (strongest basic) 2.19 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 1 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Mycobacteria

Target within organism

  • Prostaglandin G/H synthase 2 : in Human
  • Inhibitor of nuclear factor kappa-B kinase subunit alpha : in Human
  • Arachidonate 5-lipoxygenase : in Human
  • Group IIE secretory phospholipase A2 : in Human
  • 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase : in Mycobacterium tuberculosis