Antimicrobial 6: Antifungals

Question 1

Name the Common Fungal Infections: (4)

Answer 1

• Ringworm
• Jock itch
• Athlete’s Foot
• Fungal Nail Infections

Question 2

What are Fungi?

Answer 2

• Fungi are non-motile eukaryotic cells that are
parasitic or saprophytic in nature

• ~50 species of fungi are pathogenic in humans

• Most fungi only cause systemic infections in
immunocompromised individuals
– ‘dimorphic’ fungi can infect healthy individuals

Question 3

What are 2 types of Antifungals?

Answer 3

• Naturally occurring antifungal antibiotics (polyenes &
echinocandins)

• Synthetic drugs (azoles & fluorinated pyrimidines)

Question 4

Drugs for Fungal Infections

Slide 6 & 7

Answer 4

See slide 6 : Drugs for Fungal Infections

See slide 7 : fungal infections and typical 1st choice of
antifungal drug therapy

Question 5

Amphotericin

Characteristcs

Answer 5

Amphotericin is an antifungal antibiotic that is structurally a very large macrolide (belongs to polyene group of antifungals)

Question 6

Amphotericin

MOA

Oral only if fungal infection in GI tract

Answer 6

• Acts on the fungal cell membrane; its hydrophilic core
creates a transmembrane ion channel resulting in the loss of intracellular K + and disrupting cellular
permeability and transport systems

• Has a high affinity for ergosterol, a fungal membrane
sterol not found in mammalian cells

Question 7

Amphotericin

AE

Oral only if fungal infection in GI tract

Answer 7

• * Hypotension
• * Renal toxicity: 80% individuals renal toxicity - drug binds to prox tubule in kidneys
- 25% hypokalemia and hypomagnesia
• * Hypokalemia
• * Thrombocytopenia

• Rigor, fever, chills and headache
• Local thrombophlebitis

Question 8

Nystatin

MOA

AE

Answer 8

• a polyene antibiotic with similar MOA to amphotericin
• may cause nausea, vomiting, diarrhea

primarily for candida infections of skin, GI tract

Question 9

Griseofulvin

Characteristics

Answer 9

Narrow-spectrum antifungal isolated from Penicillium

griseofulvum

Question 10

Griseofulvin

MOA

Answer 10

Binds to fungal microtubules and interferes with mitosis

Question 11

Griseofulvin

AE

Answer 11

• • Photosensitivity
• GI upset
• Headaches
• Allergy (rashes, fever)
• Contraindicated in pregnancy

Question 12

Echinocandins

Characteristics

Answer 12

Echinocandins are synthetic modifications to echinocandin B ( Aspergillus nidulans ) and include caspofungin, anidulafungin & micafungin

• caspofungin: fungistatic for Aspergillosis infections
• anidulafungin & micafungin: fungicidal invasive candiasis infections

Question 13

Echinocandins

MOA

Answer 13

Inhibit 1,3-β-glucan synthase to impair 1,3-β-glucan production (polymer), which is necessary for structural integrity of the fungal cell wall

IV

Question 14

Echinocandins

AE

Answer 14

• • Hepatotoxicity (micafungin), monitor liver enzymes
• Nausea & vomiting
• Diarrhea
• Rash

Question 15

Azoles

Characteristics, name 4

Answer 15

Azoles are synthetic broad-spectrum fungistatic agents
  – Ketoconazole
  – Fluconazole
  – Itraconazole
  – Miconazole

Question 16

Azoles

MOA

Answer 16

• Azoles inhibit the fungal cytochrome P450 3A enzyme
  (lanosine 14α-demethylase), which prevents ergosterol formation from lanosterol
• Results in impaired replication, fungistatic
• if doing combo therapy, won’t work with amphotericin, no sterol to bind to

Question 17

Azoles

AE

Answer 17

• • Stevens-Johnson syndrome (fluconazole &
    itraconazole)
• • Gynecomastia (ketoconazole), cannot make steroids
• Hepatotoxicity
• GI disturbances (nausea, abdominal pain)
• Headache
• Pruritus

Question 18

Flucytosine

MOA

Answer 18

Orally active antifungal that is converted into 5-
fluorouracil (only within fungal cells), which inhibits
thymidylate synthetase and subsequent DNA synthesis

Question 19

Flucytosine

AE

Answer 19

• • Neutropenia
• • Alopecia: gut microbiota can convert flucytosine to 5-fluorouracil, contribute to alopecia
• • Hepatitis
• GI disturbances
• Anemia

Question 20

Terbinafine

MOA

Answer 20

• Lipophilic fungicidal compound that inhibits squalene
epoxidase, which is required for synthesizing
ergosterol from squalene

• Naftifine is thought to act via a similar mechanism of
action

Question 21

Terbinafine

AE
usually self limiting

Answer 21

• • Arthralgia & myalgia
• • Hepatitis
• GI disturbances
• Rashes & itch
• Headache & dizziness

Question 22

Summary

_____ has affinity for ergosterol and its hydrophilic core creates a transmembrane ion channel resulting in the loss of intracellular K + and disrupting cellular permeability and transport systems

Answer 22

Amphotericin

Question 23

Summary

\_\_\_\_ inhibit 1,3-β-glucan production, which impairs structural integrity of the fungal cell wall 
- Drugs in this class include caspofungin, 
   anidulafungin, and micafungin

Answer 23

Echinocandins

Question 24

Summary

____ inhibit the fungal cytochrome P450 3A enzyme,
which prevents ergosterol formation from lanosterol
- Interferes with fungal replication

Answer 24

Azoles

Question 25

Summary

____ is converted into 5-fluorouracil (only within
fungal cells), which inhibits thymidylate synthetase and
subsequent DNA synthesis

Answer 25

Flucytosine