First-line tuberculosis drugs

The four first-line drugs hit Mycobacterium tuberculosis in different ways: isoniazid and ethambutol stop it building its cell wall (mycolic acids and arabinogalactan), rifampicin blocks its RNA polymerase, and pyrazinamide acts on slowly dividing bacilli at acidic pH. Resistance arises fast to any one drug alone, so they are given together: all four for 2 months, then isoniazid and rifampicin for 4.

• IsoniazidNever used alone for active TB, as resistance develops quickly; on its own it is a classic preventive treatment for latent infection.
• RifampicinRifampicin is the INN; rifampin is the US name. Its color stains urine, sweat, sputum, tears and soft contact lenses.
• PyrazinamideIts activity in acid conditions reaches bacilli that survive the other drugs; primary resistance to it is uncommon.
• EthambutolOften the fourth drug in the first 2 months, guarding against isoniazid resistance; the need for it is reviewed once susceptibility results are known.

• Active tuberculosis, as a four-drug start
• Latent TB infection (isoniazid, rifampicin)

• Hepatitis (isoniazid, rifampicin, pyrazinamide)Known forSerious
• Orange-red urine, sweat and tears (rifampicin)Known for
• Optic neuritis and vision loss (ethambutol)Known forSerious
• Peripheral neuropathy (isoniazid)Serious
• High uric acid and gout (pyrazinamide)
• Joint and muscle aches
• Nausea, vomiting and loss of appetite
• Rash and severe skin reactionsSerious
• Flu-like illness (rifampicin)

What the class has in common. Each drug's card has its own, and Known for marks what an exam expects you to know.

• Check liver tests at the start and watch for hepatitis; risk rises with age, alcohol and liver disease, and with drugs combined.
• Rifampicin speeds the breakdown of many drugs, including warfarin, hormonal contraceptives and several HIV drugs.
• Pyridoxine (vitamin B6) is given with isoniazid to people prone to neuropathy, such as those with diabetes or malnutrition.
• Test eyesight and color vision before and during ethambutol, and avoid it in people who cannot report vision changes.

Written for biofideX in plain words, after checking these references:

• WHO consolidated guidelines on tuberculosis: module 4: treatment and care, 2nd edition (WHO)
• Treatment for Drug-Susceptible Tuberculosis Disease (CDC)
• Treatment for Latent Tuberculosis Infection (CDC)
• Rifampin for injection: label (DailyMed)
• Antitubercular Agent (NCI Thesaurus)

For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.