Exam 1 Study Guide Antifungals ● ● ● Signs of drug allergy or sensitivity ○ Amphotericin infusion frequently causes fever, chills, rigors, nausea and headache wheezing, hypoxia; rarely causes rash, seizures, anaphylaxis (PRETREATMENT WITH DIPENHYDRAMINE PLUS AN ANALGESIC CAN REDUCE MILD SYMPTOMS) Basic difference between azoles and polyene antifungals ○ Polyene (Amphotericin B) are highly toxic and must be given IV ■ Amphotericin B binds to components of the fungal cell membrane, specifically ergosterol (member of the sterol family), increasing permeability. Cell’s cytoplasmic membrane becomes susceptible due to sterols. ○ Azoles are broad-spectrum antifungal drugs with lower toxicity and can be given by mouth (represent an alternative to Amphotericin B ■ Used for systemic mycoses: itraconazole, ketoconazole, fluconazole, voriconazole, isavuconazole, and posaconazole ■ Disadvantage is that azoles inhibit hepatic cytochrome P450 drugmetabolizing enzymes and increase the levels of many other drugs Adverse effects of systemic antifungals ○ Amphotericin B Adverse effects: ■ Infusion reactions: ● Frequently produces fever, chills, rigors, nausea, and headache caused by the release of proinflammatory cytokines from monocytes and phagocytes ● Symptoms begin 1 to 3 hrs after starting infusion and persist about an hour ● Reactions can be reduced by pretreatment with diphenhydramine plus acetaminophen (aspirin can also help but it may increase nephrotoxicity) ● IV meperidine or dantrolene can be given if rigors occur ● Glucocorticoids should be avoided as they reduce patient’s ability to fight infection ● Produces high incidence of phlebitis, can be minimized by changing peripheral venous sites often or using a large central vein ● Reactions are less intense with lipid-based amphotericin formulations than w/ conventional formulation ■ Nephrotoxicity ● Toxic to cells of the kidneys; renal impairment occurs in all patients ● Extent of kidney damage is related to total dose administered over full course of treatment ● ■ ■ In most cases, renal function normalizes after ceasing use of amphotericin; if total dose exceeds 4gm residual impairment is likely ● Kidney damage can be minimized by infusing 1 L of saline when amphotericin is administered ● Other nephrotoxic drugs must be avoided (aminoglycosides, cyclosporine, NSAIDs) ● Kidney function tests should be performed every 3 to 4 days and intake + output should be monitored ● If plasma creatinine content is above 3.5mg/dL dosage should reduced Hypokalemia ● Low potassium levels caused by damage to the kidneys ● Potassium supplements may be needed ● Potassium and creatinine levels should monitored often Hematologic effects ● Amphotericin can cause bone marrow suppression leading to normocytic, normochromic anemia ● Hematocrit determination should be done to monitor RBCs status Antivirals ● ● ● Why we do not treat viral infections with antibacterials ○ Antibacterials are ineffective against viruses because viruses impact the cell by hijacking the cells replicative abilities and using it in order to replicate viral DNA Acyclovir ○ 1st line drug for the treatment of HSV ○ Principal adverse effects include ■ Renal failure ■ SJS ■ Phlebitis Oseltamivir ○ “Tami flu” ○ Used for Flu A & B ○ Used as a prophylactic therapy ○ Common adverse effects include ■ Headache ■ Nausea ■ vomiting Antiprotozoals – focus on Malaria ● Chloroquine ○ 1st line drug for many forms of malaria ○ Used in both active infection and as a prophylaxis ○ Adverse effects include GI effects (nausea, diarrhea) ● ■ Visual disturbances ■ Hepatotoxicity ■ pruritus Malaria information ○ Life threatening parasitic disease ○ Two forms P.Vivax, P. Falciparum (less common, more severe) ○ Symptoms peak, decline, and peak again every 48 hours (Vivax)