Monograph: |
Paraamino salicylate
The properties are similar to sod aminosalicylate , so see sod aminosalicylate record below
for the details.
Sodium Aminosalicylate
White to cream-coloured practically odourless crystalline
powder. Sodium aminosalicylate 1.38g is approximately
equivalent to I g of aminosalicylic acid. Soluble I in 2 of wa-
ter; sparingly soluble in alcohol; very slightly soluble in chlo-
roform and in ether. A 2% solution in water has a pH of 6.5 to
8.5.
Aqueous solutions are unstable and should be freshly pre-
pared. The USP directs that solutions should be prepared
within 24 hours of administration and that a solution must not
be used if it is darker in colour than a freshly prepared solu-
tion. Store at a temperature not exceeding 40Β° in airtight con-
tainers. Protect from light.
Solutions of sodium aminosalicylate in sorbitol or syrup de-
graded more quickly to m-aminophenol than those in glycerol
or propylene glycol. Colour developed in all solutions but
was not found to be an accurate indicator of decomposition of
sodium aminosalicylate as it reflected only oxidation of m-
aminophenol.
Adverse Effects and Treatment
Aminosalicylic acid and its salts may cause the side-effects of
salicylates (see Aspirin).
Castro-intestinal side-effects are common and include nau-
sea. vomiting, and diarrhoea; they may be reduced by giving
doses with food or in association with an antacid but occa-
sionally may be severe enough that therapy has to be with-
drawn. Alteration of gastro-intestinal function may lead to
Malabsorption of vitamin B12, folate, and lipids. Salts of ami-
nosalicylic acid may be better tolerated than the acid. Toler-
ance in children is better than in adults.
Hypersensitivity reactions have been reported in 5 to 10% of
adults, usually during the first few weeks of treatment, and
include fever, skin rashes, less commonly, arthralgia, lym-
phadenopathy, hepatosplenomegaly, and rarely, a syndrome
resembling infectious mononucleosis. Other adverse effects
which have been attributed to a hypersensitivity reaction to
aminosalicylate include jaundice and encephalitis. Blood dis-
orders reported include haemolytic anaemia in patients with
glucose-6-phosphate dehydrogenase deficiency, agranulocy-
tosis, eosinophilia, leucopenia. and thrombocytopenia. Psy-
chosis may occasionally occur. Prolonged treatment may
induce goitre and hypothyroidism. Crystalluria may occur.
Effects on the liver. Drug-induced hepatitis occurred in
0.32% of 7492 patients receiving antituberculous drugs; ami-
nosalicylic acid was the most common cause.
Precautions
Aminosalicylic acid and its salts should be administered with
great care to patients with impaired renal or hepatic function
and in patients with gastric ulcer. They should be used with
caution in patients with glucose-6-dehydrogenase deficiency.
The sodium salt should be administered with caution to pa-
tients with heart failure.
Aminosalicylates interfere with tests for glycosuria using
copper reagents and for urobilinogen using Erhlich's reagent.
Pregnancy and breast feeding. The use of aminosalicylic
acid or its salts is not recommended in pregnant patients due
to gastro-intestinal intolerance. In addition, the literature
suggests that first-trimester exposure may be associated with
congenital defects.
Small amounts of aminosalicylic acid are present in breast
milk. A maximum concentration of 1.1 mcg per mL has been
reported in a lactating woman 3 hours after administration of
a 4 g dose of aminosalicylic acid.
Interactions
The adverse effects of aminosalicylates and salicylates may
be additive. Probenecid may also increase toxicity by delay-
ing renal excretion and enhancing plasma concentrations of
aminosalicylate. The activity of aminosalicylic acid may be
antagonised by ester-type local anaesthetics such as procaine.
Antimicrobial Action
Aminosalicylic acid is bacteriostatic and is active only against
mycobacteria. It has a relatively weak action compared with
other antituberculous drugs but most strains of Mycobacteri-
um tuberculosis have been reported to be inhibited by I ng per
mL. Resistance develops quickly if aminosalicylic acid is
used alone.
Pharmacokinetics
When given by mouth, aminosalicylic acid and its salts are
readily absorbed, and peak plasma concentrations occur after
about I lo 4 hours.
Aminosalicylate diffuses widely through body tissues and flu-
ids, although diffusion into the CSF occurs only if the menin-
ges are inflamed. Some aminosalicylate is bound to plasma
proteins.
Aminosalicylate is metabolised in the intestine and liver pri-
marily by acetylation. Urinary excretion is rapid, and 80% or
more of a dose is excreted within 24 hours: 50% or more of
the dose is excreted as the acetylated metabolite. The half-life
of aminosalicylic acid is approximately I hour.
Aminosalicylate is distributed into breast milk (sec under Pre-
cautions above, for more details).
Uses and Administration
Aminosalicylic acid and its salt, are given by mouth in the
Treatment of tuberculosis, when other more potent
drugs cannot be used. They should always be given with other
antituberculous drugs.
Aminosalicylic acid may be given, often as the sodium salt. in
a daily dose of 10 to 12g in 2 or 3 divided doses for adults
and 150 to 300 mg per kg body-weight in 3 or 4 divided doses
for children.
A wide range of dosage forms has been used in an attempt to
overcome the bulk and exceedingly unpleasant taste of the
aminosalicylates. The salts appear to be better tolerated than
the free acid and solutions in iced water prepared immediately
before use may be less unpleasant to take.
Administration In renal Impairment. Most clinicians
recommend that aminosalicylic acid should be avoided in pa-
tients with renal impairment. An increase in plasma clear-
ance of aminosalicylic acid (attributed to increased hepatic
metabolism) has been noted in patients with renal impair-
ment. so attempting to give aminosalicylate in reduced doses
to such patients may lead to subtherapeutic serum concentra-
tions.
Inflammatory bowel disease. Together with corticoster-
oids, derivatives of 5-aminosalicylic acid are one of the main-
stays of the treatment of inflammatory bowel disease.
However, aminosalicylic acid (4-aminosalicylic
acid) has also been investigated, and promising results have
been reported with enemas in ulcerative colitis.
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