Antimycobacterials Rational Drug Selection
(Answer)- · follow CDC guidelines -many other uses for rifampin that are not
mycobacterial infections
Antimycobacterials Pharmacodynamics
(Answer)- · Isoniazid: most active for TB treatment --interferes w/ lipid and
nucleic acid biosynthesis in growing organisms --bacteriocidal (intracellular and
extracellular)-Isoniazid and ethambutol-inhibit synthesis of mycolic acids
(important for mycobacterial cell walls) -Rifamycins (rifampin, rifabutin,
rifapentine): binds to subunit of mycobacteria DNA-dependent RNA polymerase
and inhibits RNA synthesis -bactericidal -Ethambutol: inhibits synthesis of
arabinogalactan, essential bacterial cell wall component; also stops cell
multiplication causing cell death Drug interactions- -vary by drug -Rifamycins:
potent inducers of CYP450 and speed metabolism of many drugs, causing
therapeutic failure
Antimycobacterials Pharmacokinetics
(Answer)- Rapidly absorbed in GI tract -Isoniazids Need to be taken on empty
stomach-Metabolized in liver -Isoniazid metabolism is highly variable and
dependent on acetylator status Excreted in urine, bile
Antimycobacterials Pharmacotherapeutics (Answer)-
Precautions/Contraindications -Renal and hepatic impairment Ethambutol,
pyrazinamide: Gouty arthritis -pregnant, or immediately postpartum -Rifampin:
CYP450 inducer -Isoniazid=Pregnancy Cat A, most others: C, streptomycin: D
Antimycobacterials Clinical indications & dosing
(Answer)- Tuberculosis infection --four drugs req'd (INH, RIF, PZA, and EMB)
x2months --then continuation drugs (INH and another drug, usually RIF) x4-7
months -HIV has phase protocols -preventative drug therapy w/ INH
, Antimycobacterials ADRs (Answer)-
Hypersensitivity -INH: Peripheral neuropathy (most common for INH);
pyridoxine for prophy while taking INH -INH, rifampin, pyrazinamide:
hepatotoxicity -INH: blood dyscrasias, metabolic acidosis, drug fever,
gynecomastia -Rifamycins: GI, discolored body fluids (orange red), blood
dyscrasias, HA, drowsiness, inability to concentrate, pruritic rash, lupus -
Streptomycin, capreomycin: ototoxic -Rifabutin: neutropenia and
thrombocytopenia -GI reactions -Ethambutol: optic neuritis
Antimycobacterials Pt Education (Answer)- Essential education d/t length of tx -
Report ADRs --take w/ food if GI upset -Rifamycin discolors bodily fluids -
Ethambutol: report vision changes or eye pain
Antivirals Spectrum of Coverage
(Answer)-
drugs target the steps of viral replication:1. absorption to and penetration into
susceptible cells 2. uncoating of viral nucleic acid 3.synthesis of early, regulatory
proteins 4. synthesis of RNA or DNA 5. synthesis of late, structural proteins 6.
assembly of viral particles 7. release from the cell -Many antivirals act on step 4 -
Antivirals must either block entry into the cell or be active inside host cells -they're
nonselective, so damage to host cells occurs
Antivirals Pharmacodynamics
(Answer)- Acyclovir, valacyclovir -Pharmacodynamics -Acyclovir --Converted to
monophosphate derivative by virus-specific thymidine kinase --Then to di- and
triphosphate compounds by host's cellular enzymes --Inhibits viral DNA synthesis
-Valacyclovir --Converted to acyclovir -Famciclovir -metabolized to penciclovir;
similar activity as acyclovir. Antiviral drugs must either block entry into the cells
or be active inside host cells to be effective Acyclovir: active against herpes
simplex viruses 1 and 2 (HSV-1 and HSV-2); varicella-zoster virus (VZV);
Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes virus 6
Valacyclovir is converted to acyclovir after oral administration and is active
against the same viruses Famciclovir: active against HSV-1 and HSV-2, VZV,
EBV, and hepatitis B virus Ganciclovir is active against CMV
Antivirals Rational drug selection (Answer)- Choice based on cost and
convenience
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