Antimycobacterial drugs Tuberculosis

Treatment of mycobacterial infections is complicated due:

• Limited information regarding antimycobacterial drug actions

• development of resistance

• The intracellular location of mycobacteria

• Chronic nature of the infection

• Patient compliance

Tuberculosis

• Supervised & unsupervised treatment

• Initial phase & continuation phase

Initial phase

• 2 months

• Isoniazid • Rifampicin • Pyrazinamide• Ethambutol• Streptomycin

Continuation phase

• 4 months

• Isoniazid

• rifampicin

• Pregnancy and breastfeeding

• Children

Prevention of tuberculosis

• Reactivation of previously latent disease

• prophylaxis for close contacts

Monitoring

• Hepatic function

• Renal function (streptomycin & ethambutol)

Isoniazid • INH

• cheap and highly effective

• Cornerstone in any treatment protocol

Mechanism of action

• Mycolic acid

• cell wall synthesis

Pharmacokinetics

• Oral administration

• Genetic control of acetylation

Side effects

• Neurotoxicity (pyridoxine)

• Hepatotoxicity

• Hemolysis

Rifampin (rifampicin)

• Essential drug for tuberculosis

• Antibacterial spectrum

• DNA-dependant RNA polymerase

Pharmacokinetics

• Oral administration

• Red orange excretions

Side effects

• Heptotoxicity

• Drug interactions – Contraceptive

Rifabutin

• AIDS

• M. avium complex

Ethambutol

• Arbinosyl transferase

• arabinogalactan

• oral administration

• Renal excretion

Side effects

• Dose-dependant visual disturbance

• Snellen chart

• Reversible

Pyrazinamide

• Bacteriocidal active against growing intracellular dividing forms of M. tuberculosis

• Pyrazinoic acid

• First 2-3 months

• Tuberculosis meningitis

Side effects

• Nongouty polyarthralgia

• Hepatotoxicity

Streptomycin

• Ototoxicity

• Nephrotoxicity

Alternative drugs

• Less effective

• More serious side effects

Alternative drugs

• Amikacin

• Ciprofloxacin and ofloxacin

• Ethionamide (GIT and neurological)

• P-aminosalicylic acid

Leprosy (M. leprae)

• Triple therapy • Dapsone• Clofazimine • Rifampin

• 6-24 months

Dapsone

• Structurally related to sulfonamide

• M. leprae

• Pneumocyctis jiroveci

• Folate biosynthesis

• S.E: hemolysis

Clofazimine

• DNA replication

• Red brown discoloration of the skin

• Anti-inflammatory effects