Drugs for TB Tuberculosis

A positive TB test suggests TB bacteria is present in the blood. Other additional TB Tests include chest xray and sputum cultures to detect active versus latent TB. Drugs for TB: What drugs treat tuberculosis TB? In this quick and easy lesson, we will explain the main drugs -rifamycin, isoniazid, pyrazinamide, ethambutol, and streptomycin – that treat Mycobacterium tuberculosis or TB and provide study aid mnemonics to aid in your USMLE learning.

Rifamycin and Rifampin in Treating TB

USMLE Antimicrobials on Rifamycin Drug: Rifamycin is a class of drugs that include rifampin and rifabutin. The mechanism of action of Rifamycins, including rifampin and rifabutin specifically, inhibits DNA-dependent RNA polymerases.

MOA: inhibit DNA-dependent RNA polymerase and thus inhibit mRNA synthesis

Clinical Use: Treat mycobacterium tuberculosis or TB

Rifamycins are also used in combination with dapsone to delay resistance to dapsone when used to treat leprosy. Rifamycins or rifampins are also commonly used for prophylaxis of Neisseria meningococcus or H. influenzae type b.

Adverse Effects of Rifamycin and Rifampin

What are the adverse effects of rifamycins, rifampins, and rifabutin?

Red/orange fluids (harmless)

Minor hepatoxicity and drug interactions because rifampin RAMPS up the P450 system. Note that only rifampin ramps up P450 not rifabutin.

How do bacteria produce resistance against Rifamycins, rifampins and rifabutin?

Mutations reduce drug binding to RNA polymerase. Usually should combine with another drug to reduce resistance.

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Isoniazid Treatment for TB

Isoniazid

Used for prophylaxis against m. tuberculosis

M. tuberculosis has lots of mycolic acids on its cell membrane, which is the perfect target for the drug Isoniazid. The mechanism of action of isoniazid: isoniazid decreases synthesis of mycolic acids. Isoniazid is also known as INH. Isoniazid must be activated by bacterial catalase-peroxidase, which is encoded by KatG.

Clinical Use of Isoniazid: Prophylaxis against TB. For latent TB, also used to treat TB.

Adverse Effects of Isoniazid: hepatoxic, affects P450, vitamin B6 deficiency, seizures. Vitamin B6 deficiency caused by isoniazid produces symptoms of peripheral neuropathy and sideroblastic anemia, so health practitioners should administer isoniazid with vitamin B6 pyridoxine.

Mechanism of Resistance: If KatG (catalase-peroxidase) in the bacteria is mutated, then INH cannot be activated.

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Pyrazinamide Treatment for TB

Pyrazinamide:

Pyrazinamide is also another drug that is used to treat M. Tuberculosis (RIPE mnemonic). Mechanism of action: The mechanism of pyrazinamide is not known very much, but in general the drug is activated into pyrazinoic acid in the intracellular part of bacteria. Pyrazinamide works best in acidic pH like phagolysosomes. Adverse side effects of pyrazinamide: hyperuricemia and hepatotoxicity.

Which TB drugs cause hepatotoxicity?

Which tuberculosis drugs cause hepatotoxicity?

A. rifampin

B. isoniazid

C. pyrazinamide

D. All of the above

Answer: Allof the above!

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Ethambutol Treatment for TB

Ethambutol:

Ethambutol is also a drug that treats M. tuberculosis or TB. Ethambutol works by inhibiting synthesis of arabinogalactin by blocking arabinosyltransferase. This inhibition reduces carbohydrate polymerization of mycobacterium cell wall’s arabinogalactan component.

Side effects of ethambutol are optic neuropathy (red-green color blindness), but this can be reversible. Mnemonic for Ethambutol’s side effects: EYEthambutol

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Streptomycin Treatment for TB

Streptomycin

Streptomycin is a 2nd line drug for mycobacterium tuberculosis or TB. Streptomycin interferes with 30s unit of ribosome. Adverse effects are tinnitus, vertigo, ataxia, and nephrotoxicity.

Which TB drug causes red-green blindness?

Which antimyobacterial drug causes red-green blindness?

Answer: Ethambutol!

Which antimyobacterial drug to treat TB causes a side effect of peripheral neuropathy?

Answer: Isoniazid (so give Vitamin B6 too!)

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