L19 Antifungal drugs

Question 1

List factors that contribute to the increased prevalence of fungal infections

Answer 1

• immunocompromised individuals where a nonpathogenic drugs can become pathogenic to them
• Immune system damage increase the risk of fungal infections
• widespread use of broad-spectrum antibiotics - eliminate nonpathogenic bacterial competitors (so fungal can grow)
• use of immunosuppressant

Question 2

Describe the classification of mycoses (4) and the relevant site of infection

Answer 2

Superficial: outermost epidermal layer of skin.
Cutaneous:epidermal layer of skin, hairshafts, and nails.
Subcutaneous:dermal and underlying layers of skin.
Systemic: serious infections of internal organs gain access via the respiratory tract, the GI tract, or blood vessels

Question 3

Most fungal infections are ___ infections

Answer 3

opportunistic

Question 4

4 antifungal drug classes

Answer 4

echinocandins (se-synthetic)
polyenes (natural occurring)
allylamines (synthetic)
azoles (synthetic)

Question 5

Inhibit cell wall synthesis for Fungal

Answer 5

echinocandins

Question 6

Alter cell membrane integrity or permeability for fungal

Answer 6

Polyenes
Allylamines
Azoles

Question 7

Antifungal (antimycotic) drugs standard info/challenges

Answer 7

• biological similarities between humans and fungi as eukaryotes
• can be toxic to host (oral antifungal drugs must be strictly monitored)
• distinctive sterols: ergosterol in fungal cell membranes vs. cholesterol in human cells

Question 8

Fungal cell wall glucan we know

Answer 8

ß-1,3-glucan

Question 9

Echinocandins mech of action as an antifungal

Answer 9

Bind to β-1,3-glucan synthase for inhibition of β-1,3-glucan synthesis

• nausea, vomiting and diarrhoea
• infusion-related reactions

Question 10

Echinocandin B

Answer 10

• poor oral absorption - i.v. administration
• concentration-dependent activity - Cmax:MIC
• fungicidal for Candida species - treat invasive candidiasis
• fungistatic for Aspergillus species
• nausea, vomiting and diarrhoea
• infusion-related reactions

Question 11

Polyenes as an antifungal

Answer 11

Directly interact with ergosterol to alter membrane stability and fluidity

Question 12

Antifungal Polyenes info

Answer 12

Broad spectrum
* form pores/ion channels for leakage of K+ ions
* interact at cell membrane surface like a sponge.

Question 13

Amphotericin B

Answer 13

Polyene
*broad spectrum
*Poor absorption is fine bc it treats upper GI tract
*Slow I.V
*minimal hepatic metabolism and effects renal function

• infusion-related - inflammatory response
• nephrotoxicity - interactions with cell membranes
• liposomal formulations - ↓ toxicity

Question 14

Antifungal allylamines inhibit what to prevent what

Answer 14

squalene monooxygenase
lanosterol in formation of ergosterol (altered cell membrane stability and fluidity)

Question 15

Antifungal azoles inhibit what to prevent what

Answer 15

14(a)-demethylase
ergosterol (altered cell membrane stability and fluidity)

Question 16

Terbinafine drug

Answer 16

allylamine
* treats onychomycosis (nail bed fungal infections)
* highly lipophilic and keratinophilic - dermatophytes require keratin for growth
* oral/topical administration - rapid absorption - taken up by skin/nails
CYP2D6 inhibitor

• GI disturbance
• rash
• muscle pain

Question 17

Itraconazole

Answer 17

• can be administered orally but absorption is variable
• extensive hepatic metabolism
• CYP3A4 inhibition and may cause d-d interactiosn

Question 18

Cutaneous cause what drug related toxicities

Answer 18

Rash

Question 19

Azoles cause what drug related toxicities

Answer 19

Hepatic
GI tract
QTc prolongation

Question 20

Amphotericin B cause what drug related toxicities

Answer 20

Nephrotoxocity:Renal Toxicity
Infusion reactions

Question 21

Echinocandins cause what drug related toxicities

Answer 21

Infustion reactions