4-Aminosalicylic acid

4-Aminosalicylic acid

Systematic (IUPAC) name
4-amino-2-hydroxy-benzoic acid
Clinical data
Pregnancy cat.	C
Legal status	POM (UK)
Routes	Oral
Pharmacokinetic data
Protein binding	50–60%
Metabolism	Hepatic
Excretion	Renal
Identifiers
CAS number	65-49-6 Y
ATC code	J04AA01
PubChem	CID 4649
DrugBank	APRD00749
ChemSpider	4488 Y
UNII	5B2658E0N2 Y
KEGG	D00162 Y
ChEBI	CHEBI:27565 Y
ChEMBL	CHEMBL1169 Y
Chemical data
Formula	C7H7NO3
Mol. mass	153.135 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11) Y Key:WUBBRNOQWQTFEX-UHFFFAOYSA-N Y
Physical data
Melt. point	150.5 °C (303 °F)
N(what is this?)  acid (verify)

4-aminosalicylic acid, commonly known as PAS, is an antibiotic used to treat tuberculosis. This organic compound has been use since the 1940s for the treatment of inflammatory bowel diseases (IBDs), where it has shown greater potency in ulcerative colitis and Crohn's disease. It is thought to act via NF-κB (nuclear factor-kappa B) inhibition and free radical scavenging. 5-Aminosalicylic acid, sold under the name mesalazine, is a closely related compound that also has medical uses.

Medical uses

Aminosalicylic acid was introduced to clinical use in 1948. It was the second antibiotic found to be effective in the treatment of tuberculosis, after streptomycin. PAS formed part of the standard treatment for tuberculosis prior to the introduction of rifampicin and pyrazinamide.^[1]

Its potency is less than that of the current five first-line drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin) for treating tuberculosis, but it is still useful in the treatment of multidrug-resistant tuberculosis. PAS is always used in combination with other anti-TB drugs.

The dose when treating tuberculosis is 150 mg/kg/day divided into two to four daily doses; the usual adult dose is therefore approximately 2 to 4 grams four times a day. It is sold in the US as "Paser", which comes in the form of 4 g packets of delayed-release granules. The drug should be taken with acid food or drink (orange, apple or tomato juice).^[2] PAS was once available in a combination formula with isoniazid called Pasinah^[3] or Pycamisan 33^[4]

PAS has also been used in the treatment of inflammatory bowel disease,^[5] but has been superseded by other drugs such as sulfasalazine and mesalazine.

PAS has also been used for manganese chelation therapy, and seems to be superior to other chelation protocols (ex.: EDTA) in this regard (http://www.ncbi.nlm.nih.gov/pubmed/16766929 -> Effective treatment of manganese-induced occupational Parkinsonism with p-aminosalicylic acid: a case of 17-year follow-up study).

Pharmacology

With heat, aminosalicylic acid is decarboxylated to produce CO₂ and 3-aminophenol.

The U.S. FDA assigned PAS to pregnancy category C, indicating that it is not known whether it will harm an unborn baby.

Side effects

Gastrointestinal side-effects (nausea, vomiting, diarrhoea) are common; the delayed-release formulation is meant to help overcome this problem. It is also a cause of drug-induced hepatitis. Patients with glucose-6-phosphate dehydrogenase deficiency should avoid taking aminosalicylic acid as it causes haemolysis. Thyroid goitre is also a side-effect because aminosalicylic acid inhibits the synthesis of thyroid hormones. Drug interactions include elevated phenytoin levels. When taken with rifampicin, the levels of rifampicin in the blood fall by about half.^[6]

History

PAS was discovered by the Swedish chemist Jörgen Lehmann upon the report that the tuberculosis bacterium avidly metabolized salicylic acid. Lehmann first tried PAS as an oral TB therapy late in 1944. The first patient made a dramatic recovery. The drug proved better than streptomycin, which had nerve toxicity and to which TB could easily develop resistance. Late in the 1940s, researchers at Britain's Medical Research Council demonstrated that combined treatment with streptomycin and PAS was superior to either drug alone. Aminosalicylic acid is sold in the U.S. by Jacobus Pharmaceutical as Paser.

Synthesis

PAS is manufactured by the carboxylation of 3-aminophenol.^[7]

Other names

Like many commercially significant compounds, PAS has many names including para-aminosalicylic acid, p-aminosalicylic acid, 4-ASA, and simply P.

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External links

• Drugs.com
• RxList

References

1. ^ Mitchison DA (2000). "Role of individual drugs in the chemotherapy of tuberculosis Role of individual drugs in the chemotherapy of tuberculosis". Int J Tuberc Lung Dis 4 (9): 796–806. PMID 10985648. 
2. ^ "Paser". RxList. http://www.rxlist.com/cgi/generic/paser.htm. Retrieved 2008-10-10. 
3. ^ Smith NP, Ryan TJ, Sanderson KV, Sarkany I (1976). "Lichen scrofulosorum: A report of four cases". Br J Dermatol 94 (3): 319–325. doi:10.1111/j.1365-2133.1976.tb04391.x. PMID 1252363. 
4. ^ Black JM (1961). "Two incidents of tuberculous infection by milk from attested herds". Br Med J: 1732–1735. 
5. ^ Daniel F, Seksik P, Cacheux W, Jian R, Marteau P (2004). "Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced acute pancreatitis". Inflamm Bowel Dis 10 (3): 258–260. doi:10.1097/00054725-200405000-00013. PMID 15290921. 
6. ^ Boman G (1974). "Serum concentration and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid". European journal of clinical pharmacology 7 (3): 217–25. doi:10.1007/BF00560384. PMID 4854257. 
7. ^ Mitchell, S.C. & Waring, R.H. “Aminophenols.” In Ullmann’s Encyclopedia of Industrial Chemistry; 2002 Wiley-VCH, doi:10.1002/14356007.a02_099