Antifungals

Question 1

Amphotericin B MECH

Answer 1

binds ergosterol (unique to fungus); forms membrane pores that allow leakage of electrolytes. “AmphoTEARicin” - tears holes in fungal membrane

Question 2

Amphotericin B USE

Answer 2

Serious, systemic mycoses. Cryptococcus (amphotericin B w/or w/o flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis. Supplement K & Mg b/c of altered renal tubule permeability.

Question 3

Amphotericin B TOX

Answer 3

Fever/Chills “shake & bake,” hypOTN, nephrotox, arrythmias, anemia, IV phlebitis “amphoterrible.” Hydration reduces nephrotox. Liposomal amphotericin reduces toxicity.

Question 4

Nystatin MECH

Answer 4

Same as amphotericin B. Topical b/c too toxic for systemic use.

Question 5

Nystatin USE

Answer 5

“Swish & swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.

Question 6

Azoles

Answer 6

Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole

Question 7

Azoles MECH

Answer 7

Inhibit fungal sterol (ergosterol) synth, by inhibiting P450 (can’t convert lanosterol to ergosterol)

Question 8

Azoles USE

Answer 8

Local & less serious systemic mycoses.

Question 9

Fluconazole USE

Answer 9

chronic suppression of cryptococcal meningitis in AIDS patients & candidal infections of all types.

Question 10

Itraconazole USE

Answer 10

Blastomyces, Coccidioides, Histoplasma

Question 11

Clotrimazole & miconazole USE

Answer 11

topical fungal infections

Question 12

Azoles TOX

Answer 12

Testosterone sythesis inhibition (gynecomastia, esp ketocon), liver dysfx (inhibits cytochrome P450)

Question 13

Flucytosine MECH

Answer 13

Inhibits DNA & RNA biosynth by conversion to 5-FU by cytosine deaminase.

Question 14

Flucytosine USE

Answer 14

Used in systemic fungal infections (esp. meningitis caused by cryptococcus) in combo w/Amphotericin B

Question 15

Flucytosine TOX

Answer 15

Bone marrow suppression

Question 16

Caspofungin, micafungin MECH

Answer 16

Inhibits cell wall synth by inhibiting Beta-glucan synth

Question 17

Caspofungin, micafungin USE

Answer 17

invasive aspergillosis, Candida

Question 18

Caspofungin, micafungin TOX

Answer 18

GI upset, flushing (by histamine release)

Question 19

Terbinafine MECH

Answer 19

Inhibits fungal enzyme squalene epoxidase

Question 20

Terbinafine USE

Answer 20

Tx dermatophytoses (onychomycosis)

Question 21

Terbinafine TOX

Answer 21

Abnormal LFTs, visual disturbances

Question 22

Griseofulvin MECH

Answer 22

Interferes w/microtubule fx. disrupts mitosis. deposits in keratin-containingtissues (ie-nails)

Question 23

Griseofulvin USE

Answer 23

Oral Tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)

Question 24

Griseofulvin TOX

Answer 24

Teratogenic, carcinogenic, confusion, headaches, increased P450 & warfarin metabolism

Question 25

Antiprotozoan therapy

• Toxoplamosis
• Trypanosoma brucei
• T. cruzi
• Leishmaniasis

Answer 25

• Toxoplamosis - pyrimethamine
• Trypanosoma brucei - suramin & melarsoprol
• T. cruzi - nifurtimox
• Leishmaniasis - sodium stibogluconate

Question 26

Chloroquine MECH

Answer 26

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

Question 27

Chloroquine USE

Answer 27

Tx of plasmodial species other than P. falciparum (due to resistance).

Question 28

Chloroquine RESIST

Answer 28

membrane pump decreases intracellular [ ] of drug.

Question 29

Chloroquine TOX

Answer 29

Retinopathy

Question 30

Malaria tx

Answer 30

Chloroquine
P. falciparum - artemether/lumifantrine or atovaquone/proguanil.
Life-threatening malaria - quinidine in US, quinine, artisumate elsewhere

Question 31

Antihelminthic Therapy

Answer 31

Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel (against flukes (trematodes) -> Schistosoma