Pharm II Exam 2 (Chapter 92 Antifungal Agents)Antifungal Agents

•Immunocompromised host •Candidiasis, aspergillosis, cryptococcosis, mucormycosis •Nonopportunistic •Can occur in any host •Sporotrichosis, blastomycosis, histoplasmosis, coccidioidomycosis

•Broad-spectrum antifungal agent (also used against some protozoa) •Important, but dangerous drug…Highly toxic!!
•Infusion reaction and renal damage occur in all patients to varying degrees •Must be given IV – no oral administration (Infusion given daily or every other day for several months)

•Drug of choice for most systemic mycoses •Before ampho B, systemic fungal infections were usually fatal

•Binds to ergosterol (much more than cholesterol) in fungal cell membrane •Bacterial cell membranes lack sterols •Fungi damaged more than human cells •Increases the permeability

•Infusion reactions •Nephrotoxicity •Hypokalemia

•Fever, chills, rigors, nausea, and headache •Caused by release of proinflammatory cytokines •Symptoms begin 1-3 hours after starting infusion and last for about 1 hour •Less intense with lipid-based ampho B formulations
•Mild reactions – pretreatment options•Diphenhydramine plus acetaminophen•Aspirin can help – may increase renal damage•IV meperidine or dantrolene can be given if rigors occur.
•Hydrocortisone can be given with caution.

•Extent of kidney damage related to total dose administered over the full course of treatment •If total dose >4 g, residual impairment likely •Damage minimized by infusing 1 L of saline on days of treatment •Avoid other nephrotoxic drugs concurrently. •Aminoglycosides, cyclosporins •NSAIDs should also be avoided. •Monitor serum creatinine q 3-4 days. •Reduce dosage if >3.5 mg/dL

•Results from damage to the kidneys •May need potassium supplements •Monitor serum levels

•Can cause bone marrow suppression •Anemia – monitor hematocrit

•Broad-spectrum antifungal drugs •Only 5/14 – can be an alternative to ampho B for most systemic mycoses •Lower toxicity •Can be given orally ***Disadvantage compared to Amphotericin B ***inhibit P450 drug-metabolizing enzymes and can increase the levels of many other drugs

•Azole group of antifungal agents •Lower toxicity level

•Dose: PO capsules or suspension…administration with a cola beverage enhances absorption! J Usually 200mg 1-2x/day •Uses •Systemic mycoses (alternative to ampho B)

•Inhibits the synthesis of ergosterol •Inhibits fungal cytochrome P450-dependent enzymes

Well tolerated in usual doses
•Cardiosuppression •Transient decrease in ventricular ejection fraction •Liver damage •Watch for signs of liver dysfunction •Can inhibit drug metabolizing enzymes •GI effects •Nausea, vomiting, diarrhea

•Azole group of antifungal agents •Fungistatic •Same mechanism of action as itraconazole •Oral absorption good •IV and oral dosage the same