Tuberculosis Drugs

Tuberculosis is a difficult to treat infection that requires a multi-drug therapy approach. Active tuberculosis requires a four-drug regimen for the first 2 months, followed by 2 drug therapy for four months. Latent TB is treated with prolonged course of isoniazid.  

Ethambutol is a bacteriostatic drug that inhibits arabinosyl transferase, which assists in synthesis of the mycobacterial cell wall. Adverse effects include optic neuritis with loss of red-green discrimination.  

Isoniazid disrupts the cell wall by decreasing mycolic acid synthesis by inhibiting acyl carrier protein reductase and β-ketoacyl-ACP synthase. Resistance is in the form of mutation of the targeted enzyme and over-expression of the targeted enzymes.  Hepatitis, peripheral neuropathy, and seizures refractory to typical therapy that requires vitamin B6 for rescue.   

Pyrazinamide works by an unclear mechanism but is activated by pyrazinamidase to pyrazinoic acid. Resistance arises from a lack of pyrazinamidase enzyme. Hepatitis is a possible adverse effect.

Rifabutin, rifampin, and rifapentine work by inhibition of mycobacterial DNA-dependent RNA polymerase, which blocks RNA transcription. Resistance arises from mutations in the DNA-dependent RNA polymerase gene, which decreases affinity.  Notably, these medications turn urine, sweat, tears, and other secretions red/orange and can also cause hepatitis.

Class Drugs

• Ethambutol

• Isoniazid

• Pyrazinamide

• Rifabutin

• Rifampin

• Rifapentine

Class Mechanism of Action

See individual drugs

Class Applications

Mycobacterium tuberculosis causes tuberculosis (TB)

• Latent TB

Non-active infection with no signs or symptoms

• Treatment is 9 months of isoniazid (INH)

• Alternative therapy:

Weekly INH + rifapentine

• Active TB

First 2 months, 4 drug therapy:

Isoniazid

• Rifampin

• Ethambutol

• Pyrazinamide

• Next 4 months, 2 drug therapy:

Isoniazid

• Rifampin

Class Adverse Effects

Resistance

• Naturally occurring

Due to duration of treatment and poor compliance, selection for resistant TB strains can occur

• Multi-drug therapy is used to combat this resistance

See individual drugs for adverse effects

Drug Table

Drug Name	Application	Comments	Image
Ethambutol		Mechanism; -Inhibits arabinosyl transferase, which assists in synthesis of cell wall; -Bacteriostatic; Adverse Effects; -Optic neuritis, loss of red-green discrimination	"Ethan" "Ambulance"
Isoniazid		Mechanism; Disrupts cell wall by decreasing mycolic acid synthesis by inhibiting:; 1. Acyl carrier protein reductase; 2. β-ketoacyl-ACP synthase; Adverse Effects; Resistance; -Mutation or alteration of targeted enzymes; -Over-expression of targeted enzymes; Hepatitis; Peripheral neuropathy; -Limited by supplementation of Vitamin B6 (pyridoxine); Seizures; -Treated with Vitamin B6; -Generally refractory to anti-convulsants	"Ice" "Zit"
Pyrazinamide		Mechanism; Activated by pyrazinamidase to pyrazinoic acid; Mechanism unclear; Adverse Effects; Resistance; -Lack of pyrazinamidase; Hepatitis; -May precipitate gout attacks (hyperuricemia)	"Pyramid" "Zima"
Rifabutin		Mechanism; Inhibits mycobacterial DNA-dependent RNA polymerase, blocking RNA transcription; Adverse Effects; Resistance; Mutations in the DNA-dependent RNA polymerase gene, which decreases affinity; Hepatitis; Preferred in patients with HIV who take protease inhibitors or NNRTIs (non-nucleoside reverse transcriptase inhibitors) due to fewer drug interactions; Turns urine, sweat, tears, and other secretions red/orange	"Rifle" "Butt"
Rifampin	Tuberculosis; Leprosy	Mechanism; Inhibits mycobacterial DNA-dependent RNA polymerase, blocking RNA transcription; Adverse Effects; Resistance; Mutations in the DNA-dependent RNA polymerase gene, which decreases affinity; Hepatitis; Induces CYP450 enzymes leading to drug interactions; Turns urine, sweat, tears, and other secretions red/orange	"Rifle" "Amp"
Rifapentine		Mechanism; Inhibits mycobacterial DNA-dependent RNA polymerase, blocking RNA transcription; Pharmacokinetics; Longer half-life leads to once weekly dosing in latent TB; Adverse Effects; Resistance; Mutations in the DNA-dependent RNA polymerase gene, which decreases affinity; Turns urine, sweat, tears, and other secretions red/orange	"Rifle" "Pen"