TB and Leprosy drugs Flashcards
Naftifine
Squalene Epoxidase Inhibitors
Antifungals for cutaneous mycoses
Nystatin
Antifungals for cutaneous mycoses
Isoniazid
1st line Antimycobacterial used to treat TB
Most commonly used for latent TB (also active)
9 month treatment or 12 once-weekly doses of Isoniazid + rifapentine
Prodrug; inhibits mycelia acid in bacteria -> disruption in cell wall
M tuberculosis and M kansasii (at higher levels)
Most non-TB mycobacteria are resistant
effective against fast growing bacilli
Active against intracellular organisms
Cross resistance possible with ethionamide
PO- well absorbed (decreased w/ food, esp high fat meals)
Distributes to all body fluids, cells, caseous material, CSF
Metabolism is genetically variated- some faster w/ short 1/2 life, some slower w/ longer 1/2 life
Metabolized in liver
Renal excretion
AE: Hepatitis (can be fatal, MC in >35, + rifampin, or w/ alcohol), peripheral neuropathy (parasthesia of hands/feet = pyridoxine deficient -> supplement w/ pyridoxine (B6), CNS effects (convulsions), Hypersensitivity
*inhibits metabolism of carbamazepine and phenytoin - CYP450, causing nystagmus, ataxia, etc.
Monitor baseline hepatic enzymes
Macrolides
2nd line Antimycobacterial used to treat TB
Used in several non-TB mycobacterial infections (MAC)
Clofazimine
Anytimycobacterial used to treat Leprosy
Phenazine dye
MOA not fully known, may bind to bacterial DNA and/or cause generation of toxins
Some anti-inflammatory and anti-immune activity
Covers M leprae and maybe M tuberculosis and non-TB mycobacterium
PO- absorbed
Distribution: accumulates in tissues and allow intermittent therapy
No CSF
AE: typical to develop pink to brownish-black discoloration of skin, eosinophilic and other form of enteritis (sometimes surgery, rare)
Butoconazole
Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia
AE: contact dermatitis, vulvar irritation, edema
Pyrazinamide
1st line Antimycobacterial used to treat TB
MOA unclear, but covers TB
Prodrug
Most benefit early in Tx, d/c after 2 months
Combo with Isoniazid, Rifampin, or Ethambutol
Covers tuberculosis bacilli in acidic lesions and macrophages
PO- distributes through body + CSF
Monitor baseline hepatic enzymes and uric acid levels
AE: liver toxicity, hepatitis, hyperuricemia, nausea, rash, joint ache, uric acid retention (but does not cause gout)
Capreomycin
2nd line Antimycobacterial used to treat TB
Inhibits protein synthesis
Only MDR-TB Tx
Parenteral only
Monitor vestibular, auditory, and renal toxicity
Risks of ototoxicity, nephrotoxicity
Sertaconazole
Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia
AE: contact dermatitis, vulvar irritation, edema
Flucytosine (5-FC)
Antimetabolite Antifungal
(5-FC)
Use for candida UTI if fluconazole not appropriate.
Usually only used in combo.
Combo with Amphotericin B- covers systemic mycoses, meningitis caused by C. neoformans and C albicans, and cryptococcosis.
Combo with itraconazole- chromoblastomycosis.
Enters cell w/ fungal-specific enzyme, then is converted to compounds (5-FU and others) disrupt nucleic acid and protein synthesis.
Fungistatic
Amp B increases cell permeability through pores, allowing more 5-FC into cell.
Metabolized by converting to 5-FU in fungal cell.
Renal elimination- adjust dose w/ dys.
AE: reversible neutropenia or thrombocytopenia, dose-related bone marrow suppression (caution w/ radiation or chemo), reversible hepatic dysfunction + elevation of serum transaminases and alkaline phosphatase, Gi disturb, severe enterocolitis
Tioconazole
Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia
AE: contact dermatitis, vulvar irritation, edema
Dapsone
Anytimycobacterial used to treat Leprosy
Similar structure to sulfonamides
Caution if sulfa allergy
Inhibits folate synthesis, interfering with bacterial cell growth/replication
Covers M leprae, Pneumocystis jirovecii (pneumonia in immunosuppressed patients)
PO
Distributes widely, and has high concentrations in the skin
Hepatic metabolism
Renal elimination
AE: Hemolysis (esp if G6P deficient), methemoglobinemia, peripheral neuropathy
Itraconazole
Triazoles Azole Antifungal
M. Tuberculosis, M avian-intracellulare, M chelonae, M abscesses, M kansasii, M fortuitous, M leprae
Types of mycobacteria
Rod shaped, aerobic
Multiply slowly (q18-24h)
Streptomycin (Aminoglycosides), Para-aminosalicylic acid, capreomycin, cycloserine, ethionamide, fluoroquinolones, macrolides
2nd line against TB
Sulconazole
Imidazoles Antifungals for cutaneous mycoses Topical Tinea corporis, cruris, pedis Oropharyngeal candida Vulvovaginal candida Trichophyton,epidermophyton, microsporum, candida, malassezia
AE: contact dermatitis, vulvar irritation, edema
Terbinafine
Squalene Epoxidase Inhibitors
Antifungals for cutaneous mycoses
Amphotericin B Anidulafungin Caspofungin Fluconazole Flucytosine Intraconazole Ketoconazole Micafungin Posaconazole Voriconazole
Antifungals for systemic/subcutaneous mycoses