keywords:
Bookmark and Share



Front Back
Mycobacteria structure
  • CW have high lipid content that makes them acid fast
  • long chain FA mycolic acid contributes to acid fastness
MDR = multi drug resistant
  • Resistant to Isoniazid and Rifampin
  • results from misuse of first line agents
XDR = extremely drug resistant
  • resistant to Isoniazid, Rifampin, and SLD's
  • results from misuse of second line agents
FLD's of TB
  • Isoniazid
RIPE:
  • Rifampin (Rifapentine, rifabutin if taking retroviral drugs) 6 months
  • Isoniazid
  • Pyrazinamide 2 months
  • Ethambutol
SLD's
  • 2 year regimen
  • amikacen
  • cipro
  • ethionamide
  • streptomycin (used to be FL)
  • kanamycin
  • clarithromycin
TB treatment
must use at least 2 drugs to prevent resistance
FLD:
  • Isoniazid (aka INH)
  • v narrow spectrum, only indication is TB
  • inhibits synthesis of enzymes needed for mycolic acid synthesis, mediated via oxygen dependent pathways (catalase-peroxidase reaction
  • INH-NADH complex inhibit ketoenoyl reductase enzyme
  • used in combo therapy, or as a prophylaxis of +PPD tests
  • hepatotoxicity
FLD:
  • Rifampin
  • fat soluble macrocyclic antibiotic
  • bactericidal
  • blocks bacterial RNA synth by binding/inhibiting DNA dep RNA polymerase
  • also prophylactic in INH intolerant pts
  • oral! distr well (incl CNS)
  • elderly/alcoholics develop hepatitis
Rifampin and HIV
In HIV infections, rifampin can't be used with protease inhibitors - because it inhibits the metabolism of rifampin, making it very toxic!
FLD: (for retroviral combo)
  • Rifamycins: Rifapentine
  • Mechanism like Rifampin (inhibits RNA polymerase)
  • Has longer half life than rifampin
  • also CI with protease inhibitors
FLD: (for retroviral combo)
  • Rifamycins: Rifabutin
  • used for rifampin intolerant patients
  • useful in prophylaxis of MAI infection
  • Mech like rifampin (inhibits RNA polymerase)
FLD: 
  • Ethambutol
  • Bacteriostatic
  • blocks arabino-galactin (component of myco CW)
  • adverse: visual disturbance "green blindness", retinal damage
FLD: 
  • Pyrazinamide
  • use only 2 months because it enters macrophages and increases concentration intracellularly, bactericidal
  • Inhibits mycolic acid synthesis
Leprosy tx
  • DOC: dapsone
  • prevalent drugs: Sulfones (dapsone, acedapsone) and Clofazimine
  • dapsone in low doses can allow resistance to emerge
Atypical Mycobacterial infections
  • tx with Ethambutol, Rifampin (both FL TB drugs)
  • NOT PZA or INH
  • used with SLD's
Classes of antifungal drugs
  • Polyene's
  • Flucytosine (only base analog)
  • MT synthesis inhibitor
  • Azoles
  • Echinocandins
Polyene antibiotics:
  • Amphotericin B
  • Nystatin
Polyene antibiotics:
  • Amphotericin B
  • Mechanism: forms pores/channels by interacting with ergosterol, a membrane lipid, and renders the preformed membrane permeable.
  • used systemically
  • IV in fungal meningitis, intrathecal in coccidioides meningitis
  • adverse: nephrotoxic
  • similar to Nystatin
Polyene antibiotics:
  • Nystatin
  • oral use
  • for oral infections (pharyngitis, etc, many Candida infections)
  • never used systemically due to nephrotoxicity
  • similar to ampho B
Flucytosine
  • is the only base analog antifungal drug! fluorinated pyridine
  • is deaminated to 5-FU, inhibits thymidylate synthase enzyme
  • inhibits replication
Griseofulvin
  • Inhibitor of MT synthesis (gets in the way of spindle formation during mitosis!)
  • good for hair and nail fungal infections
  • oral (systemic drug) or topical
Azoles
Mechanism: stops cell membrane synthesis by inhibiting 14-alpha demethylase
  • Clotrimazole
  • Miconazole
  • Itraconazole
  • Fluconazole
  • Ketoconazole
  • Econazole
Azoles:
  • Clotrimazole
  • topical
  • mucosal and cutaneous infections
  • oral candidiasis
Azoles: 
  • Miconazole
  • Topical or IV
  • Cutaneous candidiasis and vulvovaginitis
  • deep or derm
Azoles: 
  • Itraconazole
  • oral and parenteral
  • broad spec
  • long half life up to 20 hr
Azoles: 
  • Fluconazole
  • oral, parenteral, water soluble
  • in IC patients (HIV+)
  • broad spec, resists first pass metab
  • in AIDS pts tx cryptococcalmeningitis
Azoles: 
  • Ketaconazole
  • Deep and derm
  • no CNS, oral, topical, used systemically
  • very wide spectrumeffective against oral/pharyngeal candidiasis in AIDS patients
  • adverse: endocrinological abnorm d/t inhibition of steroid biosynthesis, hepatitis in some after long term tx
Azoles: 
  • general adverse effects
  • N/V
  • effects on host steroids
  • hepatotoxicity (mild, may lead to fatal necrosis)
Echinocandins
  • Anidulafungin
  • micafungin
  • caspofungin
Echinocandins
  • Anidulafungin
  • against candida and aspergillus
  • inhibits fungal specific enzyme: glucan synthase - req for synthesis of cw component (beta 1-3D glucan
  • use IV for serious fungal infections
Echinocandins 
  • Micafungin
  • used IV.  Approved for esophageal candidiasis, candidemia, etc.
Terbinafine
  • Inhibits fungal squalene monooxygenase for membrane synthesis
  • granulated suspended tablets
  • approved for tinea
  • oral, ok for kids.
x of y cards