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NR 565 Week 6 Study Guide, NR 565: Advanced Pharmacology Fundamentals, Chamberlain $12.49   Add to cart

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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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  • May 22, 2023
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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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