Aminosalicylic acid
Encyclopedia
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 disease
s (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.
. PAS formed part of the standard treatment for tuberculosis
prior to the introduction of rifampicin
and pyrazinamide
.
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). PAS was once available in a combination formula with isoniazid called Pasinah or Pycamisan 33
PAS has also been used in the treatment of inflammatory bowel disease
, but has been superseded by other drugs such as sulfasalazine and mesalazine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).
, 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
.
(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 hormone
s. Drug interactions include elevated phenytoin
levels. When taken with rifampicin
, the levels of rifampicin
in the blood fall by about half.
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.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
used to treat tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. This organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
has been use since the 1940s for the treatment of inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
s (IBDs), where it has shown greater potency in ulcerative colitis and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
. 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
Mesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
, 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 streptomycinStreptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...
. PAS formed part of the standard treatment for tuberculosis
Tuberculosis treatment
Tuberculosis treatment refers to the medical treatment of the infectious disease tuberculosis .The standard "short" course treatment for TB is isoniazid, rifampicin , pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months...
prior to the introduction of rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
and pyrazinamide
Pyrazinamide
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...
.
Its potency is less than that of the current five first-line drugs (isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...
, rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, ethambutol
Ethambutol
Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
, pyrazinamide
Pyrazinamide
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...
, and streptomycin
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...
) 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). PAS was once available in a combination formula with isoniazid called Pasinah or Pycamisan 33
PAS has also been used in the treatment of inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, but has been superseded by other drugs such as sulfasalazine and mesalazine
Mesalazine
Mesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
.
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 heatHeat
In physics and thermodynamics, heat is energy transferred from one body, region, or thermodynamic system to another due to thermal contact or thermal radiation when the systems are at different temperatures. It is often described as one of the fundamental processes of energy transfer between...
, aminosalicylic acid is decarboxylated
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
to produce CO2
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
and 3-aminophenol
3-Aminophenol
3-Aminophenol is a compound with formula C6H4. It is an aromatic amine and aromatic alcohol. It is an isomer of 2-aminophenol and 4-aminophenol....
.
The U.S. FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
assigned PAS to pregnancy category
Pregnancy category
The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites that are present in breast...
C, indicating that it is not known whether it will harm an unborn baby
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
.
Side effects
Gastrointestinal side-effectsAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
(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
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
. Patients with glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
should avoid taking aminosalicylic acid as it causes haemolysis. Thyroid goitre
Goitre
A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
is also a side-effect because aminosalicylic acid inhibits the synthesis of thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s. Drug interactions include elevated phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
levels. When taken with rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, the levels of rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
in the blood fall by about half.
History
PAS was discovered by the Swedish chemist Jörgen LehmannJörgen Lehmann
Jörgen Erik Lehmann was a Danish-born Swedish physician and chemist best-known for his discovery in the 1940s that para-amino salicylic acid would make an excellent orally-available tuberculosis therapy...
upon the report that the tuberculosis bacterium avidly metabolized salicylic acid
Salicylic acid
Salicylic acid is a monohydroxybenzoic acid, a type of phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin...
. 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
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...
, which had nerve toxicity and to which TB could easily develop resistance. Late in the 1940s, researchers at Britain's Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
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.