Lecture 4 - Fungus and how to treat Flashcards
Name the four main classes of antifungals and what they target
azoles - cell membrane (cytp450 prevent ergosterol)
polyenes - cell membrant
echinocandidins - cell wall via glucan
5-flucytosine - nucleic acids
Why are Antifungals not 100% selective to only fungal cells
- sterols present in host plasma membranes (cholesterol not ergosterol)
- cytochrome p450 in host hepatocytes
- nucleic acids same as ours (5-flucytosine)
Name three ways selective toxicity can be achieved with antifungals
- topical application
- target specificity
- for serious infections accept degree of toxicity
Describe the acute reaction associated with Ampohtericin B
peaks 30 minutes after an infusion lasts 4 hours
-chills, fever, SOB, drop in BP, aches
Why does the acute reaction of Amphotericin B happen? What should you do to prevent this?
1) induction of Prostaglandin E
2) -tiny dose first then escalate
- pre med with paracetamol brufen or steroids
1) Describe the effect of Amphotericin B on the kidneys
2) How would you manage this?
1) causes vasodilation therefor loss of electrolytes
less EPO produced
less nephron units
2) regular renal monitoring, electrolyte replacement, amiloride can counteract loss
Name the effects of Amphotericin toxicity (aside from renal and acute)
- anorexia, nausea, vomiting, phlebitis, gradual anaemia related to decreased erythropoietin
- thrombocytopenia, leucopaenia, coagulopathy. tinnitus, vertigo, seizures, encephalopathy, anaphylaxis and allergy
Why does the composition of Amphotericin B formula affect dosage?
if use lipid formulation use a higher dose as cant expect all lipids to disperse
Describe the prevelance of resistance in Azoles and 5-flucytosine and amphotericin B
azoles - increasing resistance in C. albicans etc…
5-flucytosine - resistance is rare when used in combination therapy but common with monotherapy (lower permeability and lower phosphorylation)
Amphotericin B - low resistance as ergosterol has to change - this also reduces fungal fitness so fungus not as likely to survive either
Which antifungals have higher toxicity and which have highest resistance?
high toxicity in effective drugs
high resistance in low toxicity drugs ( and low affectivity)
What are Caspofungin and Micafungin examples of?
Echinocandins
How must Echinocandins be given?
iv as lipopepdite in side chain - break down if taken orally
Which fungi do Echinocandins affect
Candida spp (cidal) (equally effective as AmB), Aspergillius spp (static) - responce rate ~45%
side effects of Echinocandins?
phlebitis, fever, headache, hepatotoxicity, haemolysis (often patients v v ill anyway)
what fungal infections are these?
onychomycosis
cadidiasis
superficial mycoses:
nails
mucous membranes
