WEEK 6: CHAPTER 24: DRUGS
USED IN TREATING
INFECTIOUS DISEASE
ANTIMYCOBACTERIALS
➢ Mycobacteria- among the most difficult to cure (e.g.
tuberculosis [TB])
o They grow slowly and are relatively resistant to drugs that
are largely dependent on how rapidly cells are dividing
o Have a lipid-rich cell wall relatively impermeable to
many drugs
o Are usually intracellular and inaccessible to drugs that
does not have good intracellular penetration
o Have the ability to go into a dormant state
o Easily develop resistance to any single drugs
o Pregnancy categories:
▪ Isoniazid: Pregnancy category A
▪ Streptomycin: Pregnancy category D
▪ The rest: Pregnancy category C
▪ Fetal death- d/t TB: isoniazid + rifampin +
ethambutol for TB tx if pregnant and if drug
resistance is a
possibility.
• Spectrum of coverage for various organisms/Pharmacodynamics
o Isoniazid - most active drug for tx of TB
▪ Bactericidal- against susceptible
mycobacteria (intracellular and extracellular
organisms)
▪ Interferes with lipid and nucleic acid biosynthesis
in growing organisms.
, ▪ Isoniazid and ethambutol- inhibits synthesis of mycolic
acid (important constituents for mycobacteria cell
walls
and are not found in mammalian cells).
o Rifamycins – rifampicin, rifabutin, rifapentine
, ▪ Bactericidal- against susceptible mycobacteria
▪ Bind to the beta subunit of mycobacteria DNA-
dependent RNA polymerase and inhibit RNA
synthesis
-> destruction of both multiplying and inactive bacilli.
▪ Readily penetrate most tissues and can kill
bacteria that are poorly accessible to many drugs.
▪ Rifampin and rifabutin: N. gonorrhoeae,
staphylococci, streptococci, Mycobacterium leprae,
MAC, and H.
influenzae type B.
▪ Rifampin-resistance develop rapidly when used as
monotherapy- should be combined with another active
abx for tx of established infections.
o Ethambutol
▪ Bacteriostatic- against susceptible mycobacteria
(M. tuberculosis, M. avium, M. kansasii)
▪ Inhibits synthesis of arabinogalactan (an essential
component of mycobacteria cells walls).
▪ Arrests cell multiplication -> cell death
▪ Enhances the activity of lipophilic drugs (rifampin
and ofloxacin) that cross the mycobacteria cell wall
primarily in lipid portions of this cell wall.
o Pyrazinamide- an analogue of nicotinamide
▪ Bactericidal – against M. tuberculosis in an
acidic environment (pH <5.6).
▪ Useful in tx of TB
▪ Exhibits good activity within macrophages and plays
a key role in killing intracellular organisms.
▪ Shortening therapy and preventing relapses
▪ Exact action is UNKNOWN.
, o Streptomycin – aminoglycoside, used now almost
exclusively to treat M. tuberculosis infections.
▪ Bactericidal in alkaline extracellular environment
▪ Added as the 4th drug to the regimen for TB
USED IN TREATING
INFECTIOUS DISEASE
ANTIMYCOBACTERIALS
➢ Mycobacteria- among the most difficult to cure (e.g.
tuberculosis [TB])
o They grow slowly and are relatively resistant to drugs that
are largely dependent on how rapidly cells are dividing
o Have a lipid-rich cell wall relatively impermeable to
many drugs
o Are usually intracellular and inaccessible to drugs that
does not have good intracellular penetration
o Have the ability to go into a dormant state
o Easily develop resistance to any single drugs
o Pregnancy categories:
▪ Isoniazid: Pregnancy category A
▪ Streptomycin: Pregnancy category D
▪ The rest: Pregnancy category C
▪ Fetal death- d/t TB: isoniazid + rifampin +
ethambutol for TB tx if pregnant and if drug
resistance is a
possibility.
• Spectrum of coverage for various organisms/Pharmacodynamics
o Isoniazid - most active drug for tx of TB
▪ Bactericidal- against susceptible
mycobacteria (intracellular and extracellular
organisms)
▪ Interferes with lipid and nucleic acid biosynthesis
in growing organisms.
, ▪ Isoniazid and ethambutol- inhibits synthesis of mycolic
acid (important constituents for mycobacteria cell
walls
and are not found in mammalian cells).
o Rifamycins – rifampicin, rifabutin, rifapentine
, ▪ Bactericidal- against susceptible mycobacteria
▪ Bind to the beta subunit of mycobacteria DNA-
dependent RNA polymerase and inhibit RNA
synthesis
-> destruction of both multiplying and inactive bacilli.
▪ Readily penetrate most tissues and can kill
bacteria that are poorly accessible to many drugs.
▪ Rifampin and rifabutin: N. gonorrhoeae,
staphylococci, streptococci, Mycobacterium leprae,
MAC, and H.
influenzae type B.
▪ Rifampin-resistance develop rapidly when used as
monotherapy- should be combined with another active
abx for tx of established infections.
o Ethambutol
▪ Bacteriostatic- against susceptible mycobacteria
(M. tuberculosis, M. avium, M. kansasii)
▪ Inhibits synthesis of arabinogalactan (an essential
component of mycobacteria cells walls).
▪ Arrests cell multiplication -> cell death
▪ Enhances the activity of lipophilic drugs (rifampin
and ofloxacin) that cross the mycobacteria cell wall
primarily in lipid portions of this cell wall.
o Pyrazinamide- an analogue of nicotinamide
▪ Bactericidal – against M. tuberculosis in an
acidic environment (pH <5.6).
▪ Useful in tx of TB
▪ Exhibits good activity within macrophages and plays
a key role in killing intracellular organisms.
▪ Shortening therapy and preventing relapses
▪ Exact action is UNKNOWN.
, o Streptomycin – aminoglycoside, used now almost
exclusively to treat M. tuberculosis infections.
▪ Bactericidal in alkaline extracellular environment
▪ Added as the 4th drug to the regimen for TB
