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PAS – Para-Aminosalicylic Acid for Tuberculosis

PAS (para-aminosalicylic acid) is an antibacterial drug used to treat tuberculosis, especially drug-resistant forms. It is classified as a second-line or reserve medication.

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Things worth knowing about "PAS"

PAS (para-aminosalicylic acid) is an antibacterial drug used to treat tuberculosis, especially drug-resistant forms. It is classified as a second-line or reserve medication.

What is PAS (Para-Aminosalicylic Acid)?

PAS, short for para-aminosalicylic acid (also known as 4-aminosalicylic acid), is a bacteriostatic antibiotic belonging to the salicylate class. First developed in the 1940s, it is one of the oldest drugs used in the treatment of tuberculosis (TB). Today, it is primarily used as a second-line or reserve agent, particularly in cases of tuberculosis caused by strains that are resistant to standard first-line drugs.

Indications

PAS is indicated for:

Multidrug-resistant tuberculosis (MDR-TB): When Mycobacterium tuberculosis is resistant to the primary drugs isoniazid and rifampicin.
Extensively drug-resistant tuberculosis (XDR-TB): When resistance extends to additional drug classes.
Use as a combination partner in long-term tuberculosis therapy to prevent the development of further resistance.

Mechanism of Action

PAS acts in a bacteriostatic manner, meaning it inhibits the growth and reproduction of mycobacteria rather than killing them directly. Its mechanism of action is multifaceted:

PAS inhibits folic acid synthesis in Mycobacterium tuberculosis by acting as a competitive antagonist of para-aminobenzoic acid (PABA), thereby disrupting bacterial metabolism.
It also interferes with the iron uptake of the bacterium, further restricting its growth.
More recent research suggests that PAS may also affect the thymidine biosynthesis pathway of the pathogen.

Dosage and Administration

PAS is available as enteric-coated granules or tablets and is taken orally. The typical adult daily dose is 8 to 12 grams, divided into two or three doses per day. The exact dosage is determined individually by the treating physician, taking into account body weight, kidney function, and tolerability.

PAS must always be administered in combination with other antituberculosis agents to prevent the emergence of resistance. Monotherapy is not permitted.

Side Effects

PAS can cause a range of side effects that may affect patient adherence to therapy:

Gastrointestinal complaints: Nausea, vomiting, diarrhea, and abdominal pain are common and may be reduced by taking the medication with meals.
Hepatotoxicity: PAS can cause liver damage; regular monitoring of liver function tests is required.
Thyroid dysfunction: Long-term use may contribute to hypothyroidism (underactive thyroid), especially when taken together with ethionamide.
Allergic reactions: Skin rash, fever, and in rare cases, severe hypersensitivity reactions.
Malabsorption: Impaired absorption of vitamin B12 and folic acid has been reported.

Drug Interactions

PAS can affect the plasma levels of other medications. Key interactions include:

Rifampicin: Concurrent administration may reduce the absorption of rifampicin; a time interval of several hours between doses is recommended.
Vitamin B12 and folic acid: PAS may reduce the absorption of these nutrients.
Anticoagulants: PAS may enhance the effects of blood-thinning medications.

Contraindications

PAS should not be used in patients with:

Severe renal impairment
Known hypersensitivity to salicylates
Severe hepatic disease

Clinical Relevance

Despite its side effect profile, PAS remains an important option in the management of drug-resistant tuberculosis. The World Health Organization (WHO) includes PAS on its List of Essential Medicines for the treatment of MDR-TB. With the global rise in resistant tuberculosis strains, PAS is regaining importance as a reserve medication in modern TB treatment regimens.

References

World Health Organization (WHO): WHO consolidated guidelines on tuberculosis, Module 4: Treatment. Geneva, 2022. Available at: https://www.who.int/publications/i/item/9789240048126
Nachega JB, Chaisson RE: Tuberculosis drug resistance: a global threat. Clinical Infectious Diseases, 2003; 36(Suppl 1):S24-S30.
Brunton LL, Hilal-Dandan R, Knollmann BC (eds.): Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th edition. McGraw-Hill, 2018.

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