MICRO - Antifungals

Question 1

Amphotericin B (Mechanism, Clinical use, Toxicity)

Answer 1

Forms Membrane Pores

Mechanism:

• Binds ergotsterol in fungal cell membrane
• Creates pores –> cell leakage of electrolytes

Clinical use:

• Severe fungal infections
  
  • Cryptococcus, Histoplasma, Coccidiodies, Mucor, Blastomyces, Candida
• Intrathecal for meningitis

Toxicity:

• Nephrotoxicity
  
  • Low K+ –> Arrythmias
  • Low Mg²⁺
  • Hypotension
  • Supresison of EPO –> anemia
• IV phlebitis
• Fevers / chills

Tox. treat: Hydration

** Can give alternative (Liposomal Amphotericin) with less toxicity

Question 2

Amphotericin B (Mechanism, Clinical use, Toxicity)

Answer 2

Forms Membrane Pores

Mechanism:

• Binds ergotsterol in fungal cell membrane
• Creates pores –> cell leakage of electrolytes

Clinical use:

• Severe fungal infections
  
  • Cryptococcus, Histoplasma, Coccidiodies, Mucor, Blastomyces, Candida
• Intrathecal for meningitis

Toxicity:

• Nephrotoxicity
  
  • Low K+ –> Arrythmias
  • Low Mg²⁺
  • Hypotension
  • Supresison of EPO –> anemia
• IV phlebitis
• Fevers / chills

Tox. treat: Hydration

** Can give alternative (Liposomal Amphotericin) with less toxicity

Question 3

Amphotericin B (Mechanism, Clinical use, Toxicity)

Answer 3

Forms Membrane Pores

Mechanism:

• Binds ergotsterol in fungal cell membrane
• Creates pores –> cell leakage of electrolytes

Clinical use:

• Severe fungal infections
  
  • Cryptococcus, Histoplasma, Coccidiodies, Mucor, Blastomyces, Candida
• Intrathecal for meningitis

Toxicity:

• Nephrotoxicity
  
  • Low K+ –> Arrythmias
  • Low Mg²⁺
  • Hypotension
  • Supresison of EPO –> anemia
• IV phlebitis
• Fevers / chills

Tox. treat: Hydration

** Can give alternative (Liposomal Amphotericin) with less toxicity

Question 4

Nystatin (MOA, Use)

Answer 4

Forms Membrane Pores

MOA:

• Binds ergosterol in cell membrane
• Creates pores –> electrolyte leakage

USE:

• Topical use:
  
  • Diaper rash
  • Vaginal candidiasis
• Oral candidiasis (swish and swallow)
  
  • not absorbed from GI tract

Question 5

Nystatin (MOA, Use)

Answer 5

Forms Membrane Pores

MOA:

• Binds ergosterol in cell membrane
• Creates pores –> electrolyte leakage

USE:

• Topical use:
  
  • Diaper rash
  • Vaginal candidiasis
• Oral candidiasis (swish and swallow)
  
  • not absorbed from GI tract

Question 6

Flucytosine (MOA, USE, TOX)

Answer 6

Nucleic acid synthesis

MOA:

• –>[Cytosine Deaminase] –> 5-FU –| DNA/RNA synthesis

USE:

• Systemic mycosis with Amphotericin B
  
  • (especially cryptococcal meningitis)

TOX:

• Bone marrow suppression

Question 7

Flucytosine (MOA, USE, TOX)

Answer 7

Nucleic acid synthesis

MOA:

• –>[Cytosine Deaminase] –> 5-FU –| DNA/RNA synthesis

USE:

• Systemic mycosis with Amphotericin B
  
  • (especially cryptococcal meningitis)

TOX:

• Bone marrow suppression

Question 8

Flucytosine (MOA, USE, TOX)

Answer 8

Nucleic acid synthesis

MOA:

• –>[Cytosine Deaminase] –> 5-FU –| DNA/RNA synthesis

USE:

• Systemic mycosis with Amphotericin B
  
  • (especially cryptococcal meningitis)

TOX:

• Bone marrow suppression

Question 9

Azoles (MOA, USE, TOX)

Answer 9

Ergosterol Synthesis

MOA:

• Inhibits CYP450
  
  • Lanosterol –> [CYP450] –> Ergosterol

USE:

• Local and less serious systemic
• Fluconazole:
  
  • AIDS + Cryptococcal Meningitis
  • Candida (any kind)
• Itraconazole:
  
  • Blastomyces
  • Coccidiodes
  • Histoplasma
• Cotrimazole and Miconazole:
  
  • Topical

TOX:

• Inhibition of testosterone synth
  
  • Gynecomastia (especially ketoconazole)
• Liver dysfunction (CYP450 inhibition)

[Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole]

Question 10

Azoles (MOA, USE, TOX)

Answer 10

Ergosterol Synthesis

MOA:

• Inhibits CYP450
  
  • Lanosterol –> [CYP450] –> Ergosterol

USE:

• Local and less serious systemic
• Fluconazole:
  
  • AIDS + Cryptococcal Meningitis
  • Candida (any kind)
• Itraconazole:
  
  • Blastomyces
  • Coccidiodes
  • Histoplasma
• Cotrimazole and Miconazole:
  
  • Topical

TOX:

• Inhibition of testosterone synth
  
  • Gynecomastia (especially ketoconazole)
• Liver dysfunction (CYP450 inhibition)

[Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole]

Question 11

Azoles (MOA, USE, TOX)

Answer 11

Ergosterol Synthesis

MOA:

• Inhibits CYP450
  
  • Lanosterol –> [CYP450] –> Ergosterol

USE:

• Local and less serious systemic
• Fluconazole:
  
  • AIDS + Cryptococcal Meningitis
  • Candida (any kind)
• Itraconazole:
  
  • Blastomyces
  • Coccidiodes
  • Histoplasma
• Cotrimazole and Miconazole:
  
  • Topical

TOX:

• Inhibition of testosterone synth
  
  • Gynecomastia (especially ketoconazole)
• Liver dysfunction (CYP450 inhibition)

[Clotrimazole, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole]

Question 12

Terbinafine (MOA, USE, TOX)

Answer 12

Lanosterol synthesis

MOA:

• –| Squalene Epoxidase
  
  • Squalene –> [SE] –> –> Lanosterol

USE:

• Dermatophytes (especially onchomycosis)

TOX:

• GI upset
• Headaches
• Taste disturbance
• Hepatotoxicity

Question 13

Terbinafine (MOA, USE, TOX)

Answer 13

Lanosterol synthesis

MOA:

• –| Squalene Epoxidase
  
  • Squalene –> [SE] –> –> Lanosterol

USE:

• Dermatophytes (especially onchomycosis)

TOX:

• GI upset
• Headaches
• Taste disturbance
• Hepatotoxicity

Question 14

Terbinafine (MOA, USE, TOX)

Answer 14

Lanosterol synthesis

MOA:

• –| Squalene Epoxidase
  
  • Squalene –> [SE] –> –> Lanosterol

USE:

• Dermatophytes (especially onchomycosis)

TOX:

• GI upset
• Headaches
• Taste disturbance
• Hepatotoxicity

Question 15

Echinocandins (MOA, USE, TOX)

Answer 15

Cell wall synthesis

MOA:

• –| Beta-glucan synthesis

USE:

• Invasive Aspergillosis
• Candida

TOX:

• GI upset
• Histamine release –> flushing

[Anidulafungin, caspofungin, micafungin]

Question 16

Echinocandins (MOA, USE, TOX)

Answer 16

Cell wall synthesis

MOA:

• –| Beta-glucan synthesis

USE:

• Invasive Aspergillosis
• Candida

TOX:

• GI upset
• Histamine release –> flushing

[Anidulafungin, caspofungin, micafungin]

Question 17

Echinocandins (MOA, USE, TOX)

Answer 17

Cell wall synthesis

MOA:

• –| Beta-glucan synthesis

USE:

• Invasive Aspergillosis
• Candida

TOX:

• GI upset
• Histamine release –> flushing

[Anidulafungin, caspofungin, micafungin]

Question 18

Griseofulvin (MOA, USE, TOX)

Answer 18

Microtubles

MOA:

• –| Microtubules –> disrupted mitosis

USE:

• Dermatophytes
  
  • Oral drug concentrated in keratin containing tissues

TOX:

• –>⁺ CYP450 (and wafarin metabolism)
• Teratogenic, carcinogenic
• Confusion
• Headaches

Question 19

Griseofulvin (MOA, USE, TOX)

Answer 19

Microtubles

MOA:

• –| Microtubules –> disrupted mitosis

USE:

• Dermatophytes
  
  • Oral drug concentrated in keratin containing tissues

TOX:

• –>⁺ CYP450 (and wafarin metabolism)
• Teratogenic, carcinogenic
• Confusion
• Headaches

Question 20

Griseofulvin (MOA, USE, TOX)

Answer 20

Microtubles

MOA:

• –| Microtubules –> disrupted mitosis

USE:

• Dermatophytes
  
  • Oral drug concentrated in keratin containing tissues

TOX:

• –>⁺ CYP450 (and wafarin metabolism)
• Teratogenic, carcinogenic
• Confusion
• Headaches