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NR 565 Week 6 Study Guide, NR 565: Advanced Pharmacology Fundamentals, Chamberlain
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NR 565 Week 6 Study Guide, NR 565: Advanced Pharmacology Fundamentals, Chamberlain
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NR 565 Week 6 Study Guide,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
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
Readily diffuses into all body fluids including CSF (90% of serum levels), pleural,
and ascitic fluids
Readily diffuses into tissues, organs, saliva, sputum, and feces
Crosses placenta and breastmilk
Metabolism is extensive and highly variable and dependent on acetylator status.
Primarily acetylated by the liver
50% of both blacks and whites are slow acetylators
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