anti-fungals/protozoans/helminth

Question 1

Amphotericin B

Answer 1

-Binds ergosterol & forms pores in membrane
-Use: Serious systemic mycoses: cryptococcus, bastomyces, coccidioides, histoplasma, candida, mucor.
-PK: Intrathecally for fungal meningitis.
*Supplement K+ and Mg2+ because of altered
renal tubule permeability.
-Tox: Fever/chills, hypotension, severe nephrotoxicity (must hydrate), arrhythmia, anemia, IV phlebitis.

Question 2

Nystatin

Answer 2

• Topical form of amphotericin B.

- Use: oral candidasis, topical for vaginal candidiasis (yeast infection) or diaper rash.

Question 3

Azoles

Answer 3

• Inhibit ergosterol synth. by inhibiting the cytochrome P-450 enzyme (14-alpha-demethylase).
• Use: local and less serious systemic mycoses.
• Tox: P450 inhibitor, testosterone synth. inhibition (esp. ketoconazole)

*all weak acids, so do NOT take w/antacids.

Question 4

Fluconazole

Answer 4

-Azole
-Use: Chronic suppression of cryptococcal
meningitis in AIDS pts & all candida infections.
-Tox: Inihibits P450, testosterone synth. inhibition

• Overall very well tolerated.
• only azole that crosses BBB.

Question 5

Itraconazole

Answer 5

• Azole
• Use: Blastomyces, Coccidioides, Histoplasma.
• Tox: Inihibits P450, testosterone synth. inhibition

Question 6

Clotrimazole & miconazole

Answer 6

• Azole
• Use: topical fungal infections
• Tox: Inihibits P450, testosterone synth. inhibition

Question 7

Flucytosine

Answer 7

• Converted to 5-FU by viral cytosine deaminase.
• 5-FU: inhibits DNA synth (thymidilate synth inhib) and RNA synth. (nonfunctional uracil analog).
• Use: Systemic mycoses (esp. Cryptococcus meningitis) in combo with amphotericin B.
• Tox: Bone marrow suppression

Question 8

Echinocandins. “fungin”s

-Caspofungin, micafungin, anidulafungin

Answer 8

• inhibits beta-glucan synthesis
• Use: Invasive aspergillosis, Candida.
• Tox: GI upset, flushing (by histamine release).

Question 9

Terbinafine

Answer 9

• Inhibits ergosterol synth via squalene epoxidase.
• Use: dermatophytes (esp. onychomycosis-finger/toenail)
• Tox: GI upset, headaches, hepatotoxicity, taste disturbance.

Question 10

Griseofulvin

Answer 10

• Interferes w/MTs & disrupts mitosis. Deposits in keratin-containing tissues.
• Use: dermatophytes. Superficial infections (tinea, ringworm).
• PK: given orally.
• Tox: Teratogenic, carcinogenic, confusion, headaches,  inc. P-450 and warfarin metabolism.

Question 11

Trichomonas vaginalis Tx:

Answer 11

-metronidazole, treat both partners

Question 12

Giardia lamblia Tx:

Answer 12

-metronidazole

Question 13

Entamoeba histolytica Tx:

Answer 13

-metronidazole

Question 14

Toxoplasma gondii Tx:

Answer 14

-Sulfadiazine (dihydropteroate synthase inhibitor)
AND
-pyrimethamine (DHF reductase inhibitor)

Question 15

Leishmania donovani Tx:

Answer 15

-Amphotericin B, sodium stibogluconate (similar to arsenic).

Question 16

Trypanosoma cruzi Tx:

Chagas disease

Answer 16

-Benznidazole or nifurtimox

Question 17

Plasmodium Tx:

Answer 17

-Chloroquin.
-If resistant, mefloquine or atovaquone/proguanil
-If life-threatening, use IV quinidine (test for G6PD deficiency).
-Vivax/ovale—add primaquine for hypnozoite (test for
G6PD deficiency). *primaquine = only one that kills liver-form of the parasite. The other

Question 18

P. falciparum Tx:

Answer 18

-artemether/lumefantrine or atovaquone/proguanil.

Question 19

Most nematodes Tx:

Answer 19

-Bendazoles (inhibit parasite’s glucose uptake, and interferes w/MT structure.
or
-pyrantel pamoate (nicotonic agonist will result in muscle paralysis so worm falls off gut wall and can be pooped out).

Question 20

Most cestodes (tapeworms) and trematodes (flukes) Tx:

Answer 20

-praziquantel (inc Ca influx to cause spasm in bug and also causes vacuolization).