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28 Cards in this Set
- Front
- Back
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Polyenes |
-bind to ergosterol in cell membrane -form transmembrane chanel, allow ions to leak out ->amphotericin B ->nyastatin ->flucytosine |
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Amphotericin B |
fungi, protozoa, mammalian ACTIVITY: candidia, aspergillus, cryptococcus, neoformans, histoplasma, mucormycoses ADME: no oral absorption, IV, 1/2L: 24 hours, daily dosing terminal 1/2= 15 d, slow kidney excretion, 2-5% urine, most sequestered in tissues (liver, spleen) but NOT in brain, joints |
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Amphotericin B- Indications |
Oral: prophylaxis of candida IV: systemic fungal infections, liver transplant prophylaxis, 1st line crytococcal meningitis DOSE: 1mg/kg (60% normal dose with flucytosine to assist into CNS) |
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Amphotericin B Adverse Effects |
-serious: renal toxiciyt -25% hypokalemia -linked to rapid onsest hypotension -chills, fever, tinnitus, headache -20% emetic repsonse RARE: anaphylactoid |
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Nyastatin |
-no GIT or skin absorption -toxic -non toxic when topical INDICATIONS: mucocutaneous candidiasis -> skin, mouth, oesophagus, GIT, vagina Prophylaxis immunocompromised -dosage forms: creams, ointments, suspensions, tablets, lozenges |
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Flucytosine ADME |
-affects DNA synthesis, converts to 5-Fu -IV(20-40min) -1/2L 3-6 hrs -renal excretion -widely distributed including CNS -80% unchanged in urine -resistance can develop |
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Flucytosine Indications |
-use with other antifungals -crytococcal meningitis with amp B DOSE: 25-37.5mg/kg qid -gut flora will also convert to 5-Fu |
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Flucytosine Adverse Effects |
-anaemia, leucopenia, thrombocytopenia, NVD RARE: agranulycytosis, hepatic necrosis, convulsions, GI haemorrhage, B3 |
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IMIDAZOLES |
-ketoconazole -inhibit lanosine 14-d demethylase -depletion of ergosterol -alters fluidity of membrane -interferes with membrane bound enzyme activity -results in loss of replication |
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Ketoconazole ADME |
-acidic PH -1/2L 8 hours -metabolised in liver -body distribution extensive except CNS |
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Ketoconazole INDICATIONS |
-tinea versicolour -dermatophytes -candida -2nd line deep and systemic mycoses -shampoo for dandruff -active fungi (not moulds) |
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Ketoconazole Adverse |
-incr. liver enzymes -hepatic necrosis -itch and pruritis -NV -abdominal pain -dizziness HIGH DOSE: -gynaecomastia, decr. libido, decr. coritsol, menstrual irregularities, alopecia, decr. testosterone B3 but miconazole can be used |
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Ketoconazole Interactions |
-Inhibits CYPs: CYP3A4 -inhibits metabolism of: warfarin, benzodiazepines, cyclosporin A, phenytoin INHIBITS RITINOVIR: alcohol goes down diff. pathways |
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Triazoles |
-fungistatic -wider spectrum of activity -candida -cryptococcus neoformans -histoplasma capsulation -replacement for ketoconazole: systemic use and wider spectrume -reduced adverse effect profile -increased efficacy -still CYP3A4 inhibition -fluconazole, itraconazole, voriconazole and posaconazole |
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Fluconazole |
INDICATIONS: 2nd line cryptococcal meningitis, severe mucocutaneous candida, prophylaxis in immunocompromised, sever systemic mycoses, little effect on mould ADVERSE: NVD, reversible alopecia, dark urine, fatigue, hepatic failure, SJS ADME: 94% bioavailability, 11% protein bound, CNS conc therapeutic, renally unchanged, 1/2L: 25-30hours DOSE: 50-200mg/d IV or Oral |
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Itraconazole |
INDICATIONS: severe mucucutaneous candida and dermatophyte tinea, vulvovaginal candida, 2nd line histoplasmosis and blastomycosis, prophylaxis neutropenia, 2nd pro HIV ADV EFF: dyspepsia, constipation, headache, incr. ALT/AST, dizziness, hepatic damage, hypokalemia, impotence, SJS, oedema ADME: 55% bioavailable, 99.8% protein bound -incr. food -inc. BA acid PH -cns conc nil -elimination liver 0.1.%urine P 40%urine M -1/2L 30-40 hours DOSE: 50-200mg/d |
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Voriconazole |
INDICATIONS: invasive aspergillosis, lung infections, serious systemic mucocutaneous ADV EFF: visual, confusino, hypokalemia, fever, NVD, inc. ALT/AST, tachycardia, respiratory distress, infusions ADME: 96% bioav, 58% protein bound, decr. food, therapeutic CNS, liver metab, 2% urine P, 98% urine M, 1/2L: 6-7h Interact: warfarin, omeprazole, rifamycins DOSE: IV: 6mg/kg bd O: 200-400mg bd |
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Posaconazole
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INDICATIONS: invasive aspergillosis, zygomycetes ADME: variable bioav, 99% protein bound, incr. food, therapeutic CNS conc, elimination liver metab 77% faeces 14% urine, 1/2L= 20-31hrs -inhibits Cyp3a4 ADV EFF: fatigue, headache, somnolence, dizziness, confusion, fevers, NVD, muscle pain, hypokaleamia, neutropenia DOSE: 400mg bd cc |
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Griseofulvin |
-fungistatic -binds to fungal microtubulin -inhibits mitosis and nucleic acid synth -tinea capitis |
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Griseofulvin: ADME, DOSE, ADV EFFECTS |
ADME: deposits in keratin, skin inf only, 50% oral abs, 1/2L 10-12hrs, high fat meal inc. abs, urine excretion (metabolites) DOSE: 500mg-1g d ADV EFF: well tolerated, CNS, thirst, reflux, photosensitivity, NVD, rash Interacts warfarin and alcohol! |
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Terbinafine |
-inhibits squalene epoxidase, combo of fungistatic and fungicidal -used for nail infections, dermatophytes, candida, tinea, some moulds |
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Terbinafine ADME, ADV, DOSE |
ADME: rapid abs, 40% bioav, 99% protein bound, Human CYP inhibits CYP2D6, 1/2 12 hours (200-400h steady state), urine excretion DOSE: topical: bd oral: 250mg/d rapid action ADV EFF: well tolerated, redness, burning, stinging, NVD, GI pain, rash, incr. ALT/AST, liver failure, loss of taste |
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OTHER ANTIFUNGALS |
-amorolfine -ciclopirox -tolnaftate -echinocandins (caspofungin and anidulgfungin) |
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Amorolfine |
-decr. ergosterol -5% nail lacquer -dermatophytes, candida, other yeast -6-12month duration |
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Ciclopirox |
shampoo, iron chelator |
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Tolnaftate |
-unknown mechanism -dermatophytes only -cream, spray, sol, gel -2-6week dose |
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Echinocandins: Caspofungin and Anidulfungin |
-inhibit synth of B(1-3) D glucan, cell wall component |
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Echinocandins |
ADME: slow IV infusion, little oral abs, 1/2L 9-10h, 70mg 1st daily, 50mg d -35% faecal, 41% urine excretion INDICATIONS: candida, aspergillosis, immunocompromised oesophagal candida, patients intolerant to other agents ADVERSE: incr. liver enzymes, NVD, inflammation, pain and inj, incr. urine protein, decr. plasma K, eosinophilia, anaemia |
