NR565 Week 6 Study Guide
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
Sensitive to M. avium and M. kansasii; resistant to all mycobacterium
Irreversible inhibitor of protein synthesis.
Penetrates cells poorly
o Ethionamide- similar binding site and mechanism of action as isoniazid.
Ultimately blocks the synthesis of mycolic acids.
Bacteriostatic – M. tuberculosis
Can inhibit some other Mycobacterium species.
o Capreomycin – peptide abx
Bactericidal to susceptible mycobacteria.
Inhibits RNA synthesis -> decreasing replication of M. tuberculosis.
Resistance easily develops when given as monotherapy (should be given
as part of multidrug regimen)
o Bedaquiline – unique antimycobacterial, approved by FDA in 2012
For tx of multidrug resistant TB
Inhibits mycobacterial adenosine triphosphate (ATP) synthesis
Active against replicating and dormant mycobacteria
Black-box warning: increased mortality as compared with a placebo tx
group.
Only to be used when an effective tx regimen cannot otherwise be
provided.
o Para-aminosalicylic acid- structurally similar to PABA and sulfonamides
Folate synthesis antagonist
Active almost exclusive against M. tuberculosis.
Bacteriostatic
Not used frequently – primary resistance is common, and other drugs are
better tolerated and less expensive.
Pharmacokinetics
o Oral antimycobacterials are rapidly and well absorbed in GI tract after PO
administration.
o Isoniazid- 90% bioavailable but should be taken on an empty stomach
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
Sensitive to M. avium and M. kansasii; resistant to all mycobacterium
Irreversible inhibitor of protein synthesis.
Penetrates cells poorly
o Ethionamide- similar binding site and mechanism of action as isoniazid.
Ultimately blocks the synthesis of mycolic acids.
Bacteriostatic – M. tuberculosis
Can inhibit some other Mycobacterium species.
o Capreomycin – peptide abx
Bactericidal to susceptible mycobacteria.
Inhibits RNA synthesis -> decreasing replication of M. tuberculosis.
Resistance easily develops when given as monotherapy (should be given
as part of multidrug regimen)
o Bedaquiline – unique antimycobacterial, approved by FDA in 2012
For tx of multidrug resistant TB
Inhibits mycobacterial adenosine triphosphate (ATP) synthesis
Active against replicating and dormant mycobacteria
Black-box warning: increased mortality as compared with a placebo tx
group.
Only to be used when an effective tx regimen cannot otherwise be
provided.
o Para-aminosalicylic acid- structurally similar to PABA and sulfonamides
Folate synthesis antagonist
Active almost exclusive against M. tuberculosis.
Bacteriostatic
Not used frequently – primary resistance is common, and other drugs are
better tolerated and less expensive.
Pharmacokinetics
o Oral antimycobacterials are rapidly and well absorbed in GI tract after PO
administration.
o Isoniazid- 90% bioavailable but should be taken on an empty stomach
