Antifungal Agents

Question 1

Anti fungals have great selective toxicity. What are the problems with this

Answer 1

Steroid present in host - cholesterol versus ergosterol , can attach onto both

Cytochrome P450 system in host hepatocytes -action in humans to be affected

Nucleic acids

Question 2

How should you manage the dosages of Amphotericin B

Answer 2

Test dose then escalate if not problems
Pre-medicate with paracetamol, brufen or steroid

Can cause chills, fever, sob, drop in BP, aches in acute reactions

Question 3

What does amphotericin do?

Answer 3

Induction of prostaglandin E2

Question 4

List Amphotericin B toxicity main

Answer 4

Vasoconstriction renal arteriolar
Potassium,magnesium and bicarbonate loss
Decreased erythropoietin production
=loss of nephron units

Must monitor renal, electrolyte replacement and amiloride

Question 5

What other toxicity can AmpB have?

Answer 5

Anorexia, nausea, vomiting, phlebitis, gradual anaemia related to decreased erythropoietin

Question 6

What is so good about lipid formulations of Amphotericin B

Answer 6

Match with lipid vehicles to help decrease renal toxicity. Because of less free ampB to go into kidneys ,

Question 7

Describe the three different lipid formulations of AmpB

Liposomal AmB
AmB colloidal dispersion
AmB lipid complexes

Answer 7

Liposomal AmB are small vesicles

ABCD are slightly bigger discs

ABLC are much bigger ribbons, AmB is released by affinity to ergosterol and action of phospholipase

Question 8

Even though AmB is toxic, why do we like it?

Answer 8

Very broad spectrum of fungals

Question 9

How do fungals gain resistance against
AmB
Azoles
5-Flucytosine

Answer 9

AmB - alters ergosterol, also worsens fungal fitness though
Azoles- altered c14 alpha demethylase
5-flucytosine - rare in combination therapy but common with mono therapy, decreased permeability

Question 10

Echinocandins
E.g caspofungin, micafungin and anidulafungin
Are equi-effective with AmB and side chains determine solubility

All targetwhat?
IV or oral?
Restricted to?
Side effects?

Answer 10

Beta-1,3-D-glucan synthase

IV only
Restricted to candida spp, aspergillus spp,

Side effects- phlebitis, fever, headache, hepatotoxicity, haemolysis

Question 11

Superficial mycoses and deep mycoses

List them

Answer 11

Superficial
Skin: dermatophytosis
Nails: onychomycosis
Mucous membranes: candidiasis

Deep
Invasive candidiasis
Aspergillosis
Cryptococcosis

Question 12

List examples of dermatophytosis

Answer 12

Tinea pedis - athletes foots) predisposition to cellulitis

Need topical terbinafine and clotrimazole

Tinea cruris
Tinea corporis - ring worm need clotrimazole
Tinea manum
Tinea capitis - kerion

Molds
.trichophyton
.microsporum
.epidermophyton

Question 13

List examples of dermatophytosis

Answer 13

Serborrheic dermatitis
Pityriasis versicolor- variation in skin colour

Yeast
.malassezia

Question 14

What would you give for oral flush.

Answer 14

Topical nystatin and oral fuconazole

Question 15

How can invasive candidiasis happen and what is it

Answer 15

Can happen from in dwelling devices

Mucosae damaged
Immunocompromised

Need to give Amphotericin B and fluconazole

Question 16

What is aspergillosis and what do you give

Answer 16

Local disease e.g. lungs

AmB, iraconazole, echinocandin

Question 17

What happens in crypto coccus and how do you treat?

Answer 17

Meningitis in HIV

Give Amphotericin B +/- 5 flucytosine

Question 18

List some examples of endemic mycoses and what is the treatment for them all?

Answer 18

Histoplasmosis
Sporotrichosis
Eumycetoma
Madura foot

Treatment
AmB and itraconazole