NR 565 Week 6 Readings: Chapter 24
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
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
