Anti-TB starting regimen drugs
- rifampin
- isoniazid
- pyrazinamide
- ethambutol
- streptomycin
Standard tx: RIPE (take 4 drugs for 2 mo; then 2 drugs for 4-7 mo)
Rifabutin and rifapentine also considered first-line drugs in some circumstances
Streptomycin formerly first line drug but
ethambutol
Anti-TB agent
MECH: interferes with the biosynthesis of cell wall arabinogalactan; active against multiplying bacilli
RESIST: embCAB operon encodes arabinosyl transerases and a mutation in embB associated with 50% of resistant strains
TOX: optic neuritis;
isoniazid (INH)
Anti-TB agent
USED AS A SINGLE DRUG IN LATENT TB
MECH: inhibits cell wall synthesis; passive penetration of intra and extracellular bacteria; PRODRUG that is activated by catalase peroxidase in bacteria; kills actively growing bacteria
RESIST: mutation in
pyrazinamide
Anti-TB agent
MECH: works better in slowly-metabolizing (persistent) bacteria because it is not pumped out as fast; PRODRUG
RESIST: mutation of enzyme to prevent prodrug conversion
rifampin
Anti-TB agent
USE: broad-spectrum; also used to tx leprosy
MECH: inhibits prokaryotic RNA polymerase: binds to Beta subunit to prevent transcripton of mRNA; readily penetrates most tissues and phagocytic cells; active against both rapidly growing and slow
streptomycin
USE: Streptomycin formerly first-line drug for TB but now less useful due to increasing resistance; used in combo with rifampicin to tx Buruli ulcer caused by M. ulcerans
MECH: binds IRREVERSIBLY to the 30S ribosomal subunit; inhibits initiation, elongati
Drugs for tx of leprosy
- dapsone
- rifampin
Treat pauci-bacillary (PB) leprosy (1-5 skin lesions) with rifampicin and dapsone for 6 mo
Treat multi-bacillary (MB) leprosy (>5 lesions) with rifampicin, dapsone, and cofazimine for 12 mo
dapsone
Anti-leprosy agent
MECH (not covered in class): works similarly to sulfonamides by competing with PABA for the active site of active site of dihydropteroate synthetase, thereby blocking synth of DHF.
rifabutin
Anti-MAC (M. avium complex) agent
MECH (not covered in class): works by blocking bacterial RNA pol
polyenes
anti cell mem
- amphotercin B
- nystatin
Bind ergosterol; compromise fungal cell membrane
imidazoles
anti cell mem
- clotrimazole
- ketoconazole
- miconazole
USE: effective orally and topically: important for tx of local infections; fungistatic
MECH: inhibit ergosterol synthesis by blocking fungal CYP enzyme lanosterol 14-alpha-demethylase; impair fungal
triazoles
anti cell mem
- fluconazole
- itraconazole
- posaconazole
- voriconazole
USE: effective orally and parenterally: important in both local and SYSTEMIC infections; fungistatic
MECH: inhibit ergosterol synthesis by blocking fungal CYP enzyme lanosterol 14-al
allylamines
anti cell mem
- terbinafine
Block ergosterol synthesis at a different step from that inhibited by azoles (squalene epoxidase)
echinocandins
anti cell wall
- anidulafungin
- capsofungin
- micafungin
flucytosine
anti-fungal (targets cell replication/division)
USE: orally effective in the tx of systemic fungal infections, particularly severe Candida and Cryptococcus meningitis; poor therapeutic index if used alone (resistance common); used in combo with ampho B fo
griseofluvin
Anti-fungal agent (targets cell replication/division)
USE: oral admin/systemic treatment of dermatophytosis (hair, nails, skin); however, its use has been supplanted by terbinafine and itraconazole
MECH: fungistatic; interacts with polymerized microtubule
amphotericin B
Polyene antibiotic (anti-fungal that targets cell membrane)
USE: broadest spectrum antifungal; drug of choice for most life-threatening systemic infections including Candida, Aspergullus, Cryptococcus
Usually fungicidal, but may be static depending on pH,
nystatin
Polyene antibiotic (anti-fungal that targets cell membrane)
USE: oral or topical use only (TOO TOXIC TO BE USED PARENTERALLY); used to tx candidal infections of mucosa (thrush, denture stomatitis), skin, intestinal tract, and vagina
SPECTRUM: somewhat mor
clotrimazole
anti-fungal (targets cell membrane)
IMIDAZOLE
USE: restricted to oral/topical admin for local distribution (highly effective against local candida infections and more palatable than nystatin); drug of choice for oropharyngeal candidsis in AIDs pts; admin
ketoconazole
anti-fungal (targets cell membrane)
IMIDAZOLE
USE: limited b/c of availablilty of safer drugs
MECH: inhibits ergosterol synthesis by blocking fungal CYP enzyme, lanosterol 14-a-demethylase (NOTE: does not bind directly to ergosterol); impairs fungal cell
miconazole
anti-fungal (targets cell membrane)
IMIDAZOLE
USE: effective topically against cutaneous candidiasis (oropharyngeal and vaginal candidiasis); systemic use limited by toxicity and availability of less toxic drugs
MECH: inhibits ergosterol synthesis by bloc
fluconazole
anti-fungal (targets cell membrane)
TRIAZOLE
USE: most commonly-used systemic antifungal agent for local and systemic infections; 1st line agent for invasive Candida (except C. krusei) and refractory mucocutaneous candidiasis; used for prophylaxis in immu
itraconazole
anti-fungal (targets cell membrane)
TRIAZOLE
USE: to treat infections by Aspergillus and some fluconazole-resistant Candida spp. (esophageal candidiasis); use for many serious infections has been supplanted by voriconazole
SPECTRUM: broader than fluconazo
posaconazole
anti-fungal (targets cell membrane)
TRIAZOLE
USE: prophylactically against invasive fungal infections in BMT with graft-vs-host disease; hematologic malignancy and prolonged neutropenia
SPECTRUM: similar to voriconazole (can tx Aspergillus and some flucon
voriconazole
anti-fungal (targets cell membrane)
TRIAZOLE
USE: to tx invasive molds in immunocompromised pts; Aspergillosis (improved survival compared to ampho B; so new standard of care for inital tx of invasive aspergillosis); Fusarium infections; fluconazole-resis
terbinafine
anti-fungal (allylamine)
USE: mainstay tx for skin/nail infections; also used to tx unusual / refractory mold infections
SPECTRUM: primarly effective against dermatophytes (same as griseofulvin)
MECH: inhibits ergosterol synthesis by blocking the activity
anidulafungin
anti-fungal (glucan synthesis inhibitor)
USE: to tx invasive candidiasis resistant to other antifungals; invasive aspergillosis/mold infections
SPECTRUM: Aspergillus, azole-resistance Candida
ADMIN: given by IV only
MECH: inhibits the synthesis of glucan,
capsofungin
anti-fungal (glucan synthesis inhibitor)
USE: to tx invasive candidiasis resistant to other antifungals; invasive aspergillosis/mold infections
SPECTRUM: Aspergillus, azole-resistance Candida
ADMIN: given by IV only
MECH: inhibits the synthesis of glucan,
micafungin
anti-fungal (glucan synthesis inhibitor)
USE: to tx invasive candidiasis resistant to other antifungals; invasive aspergillosis/mold infections
SPECTRUM: Aspergillus, azole-resistance Candida
ADMIN: given by IV only
MECH: inhibits the synthesis of glucan,