Para-Amino Salicylic Acid

Para-Amino Salicylic Acid is an Antitubercular agent belonging to 4-Aminosalicylic Acid Derivatives

Para-Amino Salicylic Acid is used in the Treatment of Tuberculosis.

Para-Amino Salicylic Acid is Readily absorbed (>90%); peak plasma concentration after oral dosing: 1-4 hr and get diffuses into most body tissues and fluids (including breast milk) except CSF (unless meninges inflamed). Plasma protein binding: sodium salt: 15%; acid: 50-70% and get metabolised Intestinally and hepatically (>50%) mainly by acetylation and get excreted Via urine: ≥80% dose within 24 hr (50% as acetylated metabolite).

The Duration of action of Para-Amino Salicylic Acid was within 1.5 to 2 h

The Tmax of Para-Amino Salicylic Acid was achieved within 6 hr.

Para-Amino Salicylic Acid shows common side effects likethyroid goitre, hypoglycaemia; pericarditis, vasculitis, nausea, vomiting, etc.

Para-Amino Salicylic Acid is available in the form of granules.

Para-Amino Salicylic Acid is available in India, Germany, China, Italy, USA

Para-aminosalicylic acid (also known as aminosalicyclic acid) is bacteriostatic and active against M. tuberculosis. Other mycobacteria are usually resistant. It prevents plate biosynthesis in sensitive organisms. It has a relatively weak action compared with other anti-TB drugs and resistance may develop quickly if it is used alone, however it is still sometimes used in multi-drug resistant tuberculosis in combination with other anti-TB drugs.

Para-Amino Salicylic Acid is used in the Treatment of Tuberculosis.

Para-Amino Salicylic Acid is approved for use in the following clinical indications

Tuberculosis: Treatment of tuberculosis, as part of an appropriate combination regimen, in the setting of multidrug resistance or intolerance to other agents

Para-Amino Salicylic Acid is available in various strengths as 4g/packet

Para-Amino Salicylic Acid is available in the form of Granules..

• Dosage Adjustment in Kidney Patient

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Contraindicated in patients with severe impairment in the manufacturer’s labeling; however, some experts suggest a dose of 4 g twice daily.

Patients on hemodialysis: Contraindicated in patients with end-stage renal disease in the manufacturer’s labeling; however, some experts suggest a dose of 4 g twice daily, administered after hemodialysis on dialysis days

• Dosage Adjustment in Hepatic impairment Patient

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution

● Dosage Adjustment for Pediatric Patients

Tuberculosis (second-line agent):

Children ≤40 kg and Adolescents <15 years: Oral: 200 to 300 mg/kg/day (usually 100 mg/kg/dose 2 to 3 times daily). Note: Use in combination with other antituberculous agents.

Children >40 kg and Adolescents ≥15 years: Refer to adult dosing.

Para-Amino Salicylic Acid is contraindicated in patients with known allergy to the drug.

• Para-Amino Salicylic Acid is also contraindicated in pregnant and lactating women and in patients who have severe renal disease and porphyria.

Concerns related to adverse effects:

• Salicylate sensitivity: Patients with nasal polyps and asthma may have an increased risk of salicylate sensitivity.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; contraindicated in patients with severe or end-stage renal disease.

Para-Amino Salicylic Acid may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

• Aminosalicylic acid is present in breast milk.
• Following the administration of oral aminosalicylic acid 4 g to a lactating woman (postpartum age not presented), peak maternal serum concentrations were 70.1 mcg/mL at 1 hour, peak breast milk concentrations were 1.1 mcg/mL at 3 hours, and the half-life of aminosalicylic acid in the breast milk was calculated to be 2.5 hours . Using the peak breast milk concentration from this single case report, the relative infant dose (RID) of aminosalicylic acid was calculated to be <1% compared to an infant therapeutic dose of 200 to 300 mg/day. In general, breastfeeding is considered acceptable when the RID of a medication is <10% . Because information is limited, infants exposed to aminosalicylic acid via breast milk should be monitored for adverse events such as anorexia, diarrhea, nausea, vomiting, or hypersensitivity reactions

Pregnancy Category C:

Aminosalicylic acid has been reported to produce occipital malformations in rats when given at doses within the human dose range. Although there probably is a dose response, the frequency of abnormalities was comparable to controls at the highest level tested (two times the human dosage). When administered to rabbits at 5 mg/kg, throughout all three trimesters, no teratologic embryocidal effects were seen. Literature reports on aminosalicylic acid in pregnant women always report coadministration of other medications. Because there are no adequate and well controlled studies of aminosalicylic acid in humans, (aminosalicylic acid) granules should be given to a pregnant woman only if clearly needed.

Tuberculosis

Limit intake of refined carbs such as maida and sugar-laden foods as they offer only empty calories devoid of nutrients.

Deep-fried foods and junk foods packed with saturated fats and trans-fat would worsen symptoms associated with TB such as diarrhoea, abdominal cramps, and fatigue.

Totally steer clear of alcohol during the entire period of treatment, as it can interfere with treatment and may result in side effects.

Avoid taking excessive caffeine and carbonated beverages.

• Common Adverse effects

Nausea, vomiting, diarrhoea, abdominal pain

• Less Common Adverse effects:

Thyroid goitre, hypoglycaemia; pericarditis, vasculitis

• Rare Adverse effects

Encephalopathy, fever, skin eruptions, agranulocytosis, haemolytic anaemia, leucopenia, thrombocytopenia, hepatitis, jaundice, optic neuritis, eosinophilic pneumonia.

May decrease absorption of digoxin and vitamin B12; additive adverse effects of amino salicylates and salicylates; probenecid may increase toxicity by delaying renal excretion and enhancing plasma concentrations of amino salicylate; activity of amino salicylic acid may be antagonized by ester-type local anesthetics such as procaine; may enhance effect of oral anticoagulants (may need to adjust dose); ammonium chloride may increase risk of Crystalluria (do not use concurrently).

The common side effects of Para-Amino Salicylic Acid include the following gastrointestinal intolerance manifested by nausea, vomiting, diarrhea, and abdominal pain.

• Acute symptoms: Crystalluria, renal failure, nausea and vomiting.
• Treatment: Sodium bicarbonate (alkalinise urine) and forced diuresis to prevent crystalluria and nephrotoxicity.

Pharmacodynamic

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.

Pharmacokinetics

• Absorption: Readily absorbed (>90%); peak plasma concentration after oral dosing: 1-4 hr. Time to peak, serum: 6 hr.
• Distribution: Diffuses into most body tissues and fluids (including breast milk) except CSF (unless meninges inflamed). Plasma protein binding: sodium salt: 15%; acid: 50-70%.
• Metabolism: Intestinally and hepatically (>50%) mainly by acetylation.
• Excretion: Via urine: ≥80% dose within 24 hr (50% as acetylated metabolite). Half-life: approx 1 hr (reduced in renal impairment).

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Para-Amino Salicylic Acid -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Para-Amino Salicylic Acid
• https://europepmc.org/article/med/6988203