Anti Fungal

Question 1

What is the mechanism of Amphotericin B?

Answer 1

Binds ergosterol (unique to fungi) and forms membrane pores, allowing leakage of electrolytes.

Mnemonic: Amphotericin ‘tears’ holes in the fungal membrane by forming pores.

Question 2

What are the clinical uses of Amphotericin B?

Answer 2

• Serious systemic mycoses:
  
  • Cryptococcus (with or without flucytosine for cryptococcal meningitis)
  • Blastomyces
  • Coccidioides
  • Histoplasma
  • Candida
  • Mucor
• Intrathecally for coccidioidal meningitis.

Question 3

What are the adverse effects of Amphotericin B?

Answer 3

• Fever/chills (‘shake and bake’)
• Hypotension
• Nephrotoxicity
• Arrhythmias
• Anemia
• IV phlebitis (‘amphoterrible’)
• Supplement K+ and Mg2+ due to altered renal tubule permeability
• Hydration reduces nephrotoxicity
• Liposomal amphotericin reduces toxicity.

Question 4

What is the mechanism of Nystatin?

Answer 4

Same as amphotericin B: Binds ergosterol and forms membrane pores, allowing leakage of electrolytes.

Question 5

What are the clinical uses of Nystatin?

Answer 5

• Topical use only (too toxic for systemic use)
• ‘Swish and swallow’ for oral candidiasis (thrush)
• Topical for diaper rash or vaginal candidiasis.

Question 6

What is the mechanism of Flucytosine?

Answer 6

Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil (5-FU) by cytosine deaminase.

Question 7

What are the clinical uses of Flucytosine?

Answer 7

• Systemic fungal infections (especially meningitis caused by Cryptococcus) in combination with amphotericin B.

Question 8

What are the adverse effects of Flucytosine?

Answer 8

Myelosuppression.

Question 9

Name some drugs classified as Azoles.

Answer 9

• Clotrimazole
• Fluconazole
• Isavuconazole
• Itraconazole
• Ketoconazole
• Miconazole
• Voriconazole.

Question 10

What is the mechanism of Azoles?

Answer 10

Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol.

Question 11

What are the clinical uses of Azoles?

Answer 11

• Local and less serious systemic mycoses.
• Fluconazole: Chronic suppression of cryptococcal meningitis in people living with HIV and all types of candidal infections.
• Itraconazole: Blastomyces, Coccidioides, Histoplasma, Sporothrix schenckii.
• Clotrimazole and miconazole: Topical fungal infections.
• Voriconazole: Aspergillus and some Candida.
• Isavuconazole: Serious Aspergillus and Mucor infections.

Question 12

What are the adverse effects of Azoles?

Answer 12

• Testosterone synthesis inhibition (gynecomastia, especially with ketoconazole)
• Liver dysfunction (inhibits cytochrome P-450)
• QT interval prolongation.

Question 13

What is the mechanism of Terbinafine?

Answer 13

Inhibits the fungal enzyme squalene epoxidase.

Question 14

What are the clinical uses of Terbinafine?

Answer 14

Dermatophytoses, especially onychomycosis (fungal infection of finger or toenails).

Question 15

What are the adverse effects of Terbinafine?

Answer 15

GI upset, headaches, hepatotoxicity, taste disturbance.

Question 16

Name some drugs classified as Echinocandins.

Answer 16

• Anidulafungin
• Caspofungin
• Micafungin.

Question 17

What is the mechanism of Echinocandins?

Answer 17

Inhibit cell wall synthesis by inhibiting synthesis of β-glucan.

Question 18

What are the clinical uses of Echinocandins?

Answer 18

Invasive aspergillosis, Candida infections.

Question 19

What are the adverse effects of Echinocandins?

Answer 19

GI upset, flushing (caused by histamine release).

Question 20

What is the mechanism of Griseofulvin?

Answer 20

Interferes with microtubule function, disrupting mitosis. Deposits in keratin-containing tissues (e.g., nails).

Question 21

What are the clinical uses of Griseofulvin?

Answer 21

Oral treatment of superficial infections; inhibits growth of dermatophytes (e.g., tinea, ringworm).

Question 22

What are the adverse effects of Griseofulvin?

Answer 22

• Teratogenic
• Carcinogenic
• Confusion
• Headaches
• Disulfiram-like reaction
• Induces cytochrome P-450 and warfarin metabolism.

Question 23

Name some drugs used in Antiprotozoal Therapy.

Answer 23

• Pyrimethamine-sulfadiazine: Toxoplasmosis
• Suramin and melarsoprol: Trypanosoma brucei
• Nifurtimox: Trypanosoma cruzi (Chagas disease)
• Sodium stibogluconate: Leishmaniasis.

Question 24

Name some drugs used in Anti-Mite/Louse Therapy.

Answer 24

• Permethrin: Blocks sodium channels causing paralysis of mite/louse
• Malathion: Acetylcholinesterase inhibitor
• Topical or oral ivermectin.
• Used to treat scabies (Sarcoptes scabiei) and lice (Pediculus and Pthirus).

Question 25

What is the mechanism of Chloroquine?

Answer 25

Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia.

Question 26

What are the clinical uses of Chloroquine?

Answer 26

Treatment of plasmodial species other than P. falciparum (due to drug resistance from a membrane pump that reduces intracellular drug concentration).

Question 27

What are the adverse effects of Chloroquine?

Answer 27

Retinopathy (cumulative dose-dependent), pruritus (especially in dark-skinned individuals).