Antifungals lecture Flashcards

Question

Itraconazole - Route - Considerations - Spectrum of activity - Uses/ limitations

Answer 1

- Available in PO capsules, suspension, IV formuation; IV & PO suspension made w/ cyclodextrin --> LIMITED USE IN RENAL INSUFFICIENCY D/T RISK FOR NEPHROTOXICITY - Should be taken with food to increase absorption (acidic enviro); AVOID taking with acid reducers (H2 antags, PPIs) - Covers Candida spp & Aspergillus (spp): replaced by voriconazole d/t better bioavailability & penetration of CNS - In Onychomycosis: high recurrence rate; not covered by insurance - Histplasmosis, Blastomycosis

Answer 2

- Available in PO tablets, sol'n & IV formulation - Dosed according to indication/ severity: e.g. VVC vs. CNS/ candidemia - Very well-tolerated, good volume of distribution (incl CSF) - DOSE ADJUST in renal insufficiency (CrCl <50 ml) - TREATMENT AND PROPHYLAXIS of coccidiodal & cryptococcal meningitis - TREATMENT of Candidemia, candiduria, esophageal candidiasis, VVC, other systemic candidiasis - PROPHYLACTIC for neutropenic pts (i.e. chemo pts) NO ACTIVITY AGAINST ASPERGILLUS -resistance seen in C. krusei/ glabrata

Answer 3

- PO tablets, sol'n, IV formulations - Loading dose for 1 day to get to therapetuic [ ] faster; then maintenance dose (typically, PO is ~200 mg b.i.d) - EXCELLENT PO bioavailability; requires dose adjustment in HEPATIC IMPAIRMENT (not renal) - ADEs incl: hepatic toxicity, rash (uncommon), visual changes (mostly involving color; goes away) - CANDIDA SPP (INCL FLUCONZAOLE-RESISTANT spp) - ASPERGILLUS SPP. - Rare spp seen in HIV, leukemia (Scedosporium, Fusarium) -TREATMENT OR PROPHYLAXIS OF INVASIVE FUNGAL INFECTIONS (esp in oncology)

Answer 4

- PO sol'n, tablets, IV - Doses differ by formulation, indication: e. g. higher dose for prophylaxis vs. oral thrush: SUSPENSION ONLY, lower dose x 13 days; REFRACTORY oral thrush: suspension only, higher dose -Increased bioavailabilty after a FULL meal or with an acidic carbonated drink - BROAD SPECTRUM AGAINST: CANDIDA SPP, ASPERGILLUS SPP, other molds - PROPHYLAXIS of fungal infxn for immunosuppressed pts: acute leukemia, stem cell transplant - SALVAGE THERAPY in systemic fungal infections

Answer 5

- Oxiconazole, butoconazole, clotrimazole, miconazole, econazole, etc. - Similar activity against common dermatophytoses - Available in OTC preparations that vary in potency (affects duration of tx); commonly used as creams, powders - VVC - Athlete's foot - Diaper rash - Other topical yeast infections

Answer 6

-Caspofungin, micafungin, anidulafungin - ACTIVE AGAINST CANDIDA (fungicidal) & ASPERGILLUS (fungistatic) - May be combined with another drug to completely cover Aspergillus (ID specialist) - IV FORMULATION ONLY (destroyed by stomach acid; must be through IV line, not a push) - Inhibits B-1,3 glucan synthase; inhibits creation of fungal cell wall component; disrupts fungal cell integrity --> cell death

Answer 7

- Typically, well-tolerated - G.I effects; flushing reactions if infused too fast (follow guidelines) - Increased LFTs (esp for at-risk pts) - Reduced potential compared to azoles - Increases [drug] of: immunosuppressants, antihypertensives, etc.

Answer 8

- Limited by IV formulation - Often for REFRACTORY CASES (can't tolerate or didn't resp to azoles); pts with RENAL OR HEPATIC IMPAIRMENT - Caspofungin: disseminated dz, SALVAGE TX of ASPERGILLOSIS, empiric tx of possible fungal infection - Micafungin: esophageal candidiasis, candidemia, PROPHYLAXIS for CANDIDA in SCT pts - Anidulafungin: esophageal candidiasis, invasive candidiasis

Answer 9

-Binds to keratin in skin & prevents spread of fungal infection -POOR PO absorption; INCREASED with high-fat meal Takes weeks for effects to be seen as skin cells turnover RISK OF LIVER TOXICITY (monitor LFTs qmonthly) -Sometimes used for treatment of fungal skin & nail infections (dermatophytoses)

Answer 10

- Interferes with ergosterol synthesis --> leads to fungicidal buildup of squalene epoxidase - Available as topical cream or PO tablets: dosed over several months - RISK OF HEPATIC TOXICITY WITH PO TABLETS: monitor LFTs - Used for dermatophytoses, ESP ONYCHOMYCOSIS

Answer 11

- Similar action to terbinafine (lower potency) - Risk of skin irritation in sensitive individuals - NO ACTIVITY AGAINST CANDIDA SPP INFECTIONS!! -Commonly used in TOPICAL CREAMS, SPRAYS Treatment of ATHLETE'S FOOT (tinea pedis) and other superficial fungal infections ; usually INEFFECTIVE for onychomycosis

Answer 12

- Polyene macrolide antifungal (same as amphoterecin) - Powder, cream, vaginal suppository, PO suspension -Active against MOST CANDIDA SPP!! Oral thrush -- PO suspension -- "swish & spit" VVC -- cream or suppository -- azoles are more common Candidal skin infections -- cream or powder Generally well-tolerated topically

Answer 13

- Identify pt at risk for or with a fungal infection (immunosuppressed, chemo, neutropenic, etc) - Consider level of tx: prophylaxis vs. empiric (broad) vs. targeted (narrow) - Consider possible fungi involved/ severity of infection - Select Rx from available agents based on: route, spectrum of activity, availability, cost, tolerability

Answer 14

-No need to consider potent antifungals like amphoterecin, azoles, echinocandins -Topical antifungal: -Creams are more potent than powders (greater absorption) Options: Lotrimin (clotrimazole) or Lamisil (terbinafine) -Counsel pt with directions -Non-pharmaceutical tx: keep feet dry, change socks frequently, avoi walking around with bare feet, esp near water

Answer 15

- Pt is at risk for systemic fungal infection like Candidemia - Want to select an agent that covers Candida but minimize potential for ADEs - Options: fluconazole, voriconazole, echinocandins, ampho - Fluconazole: best-tolerated, lost cost - Others would not be wrong, but may be more expensive (vori) or more toxic (ampho) - MONITOR DRUG INTERACTIONS

Answer 16

-Invasive aspergillosis; would need tissue bx - Empiric antifungal tx needed!! Should cover Aspergillus, Candida (& other) - Options: Vori, itraconazole, posaconazole, amphoterecin (+ lipid form), echinocandins - Ampho: most toxic - Lipid amphos are expensive - Posa: only approved for prophylaxis, OPC - Echinocandins: NOT COMMON as 1st line - Vori: better bioavailability & broader spectrum than itroconazole!! (multiple options, vori seems best)

Antifungals lecture Flashcards

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