NR565 Week 6 Study Guide Antimycobacterials Spectrum of Coverage (Answer)- · Isoniazid Rifamycins (rifampin, rifabutin, rifapentine) Ethambutol Pyrazinamide Streptomycin Ethionamide Capreomycin Bedaquiline Para- aminosalicylic acid -monotherapy causes resistance -cross-resistance w/ INH and ethionamide 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 1 / 2
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 Monitoring (Answer)- Directly observed therapy 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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