Drug card 4: fungal and protozoan

Question 1

Membrane function

Answer 1

Ampho B, nystatin

Question 2

Cell wall synthesis

Answer 2

caspofungin, anidulfungin

Question 3

Nucleic acid synthesis

Answer 3

5-flucytosine

Question 4

Lanosterol synthesis

Answer 4

naftifine, terbinafine

Question 5

Ergosterol synthesis

Answer 5

fluconadole, itraconazole, voriconazole

Question 6

Amphotericin B

Answer 6

Binds ergosterol, forms membrane pores that allow leakage

Clinical: serious, systemic mycoses. Intrathecally for fungal meningitis. SUPPLEMENT K and MG because of altered renal tubule permeability.

Toxicity: fever, chills, hypotension, nephrotoxicity, arrythmias, anemia, IV phlebitis (amphoterrible), hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.

Question 7

Nystatin

Answer 7

MOA: same as amphotercin B, topical form because too toxic for systemic use.

Clinical: swish and swallow for oral candidiasis; topical for rash or vaginal candidiasis

Question 8

Azoles

Answer 8

MOA: inhibit fungal sterol (ergosterol) synthesis, by inhibiting the P450 enzyme that converts lanosterol to ergosterol.

Clinical: local and less serious systemic mycoses. Fluconazole for chronic suppresionof cryoptococcal meningitis in AIDS pts and candidal infection for all types.
Itraconazole for blastomyces, coccidioides, histoplasma.

Clotrimazole and miconazole for topical infection

Toxicity: testosterone synthesis inhibitor (gynecomastia, esp with ketoconazole) liver dysfunciton (inhibits cytochrome P450)

Question 9

Flucytosine

Answer 9

Inhibit DNA and RNA synthesis by conversion to 5-fluorouracil by cytosine deaminase

Clinical: systemic function infection (esp meningiditis caused by cryptococcus), in combo with amphotericin B

Toxicity: bone marrow suppression

Question 10

Caspofungin, micafungi

Answer 10

Inhibit cell wall synthesis by inhibiting synthesis of beta glucan

Clinical: invasive aspergillosis, candida

Toxicity: GI upset, flushing (by histamine release)

Question 11

Terbinafine

Answer 11

Inhibit the fungal enzyme squalene epoxidase

Clinical:dermatophytoeses (esp onychomycosis)- fungal infection of fingers or toe naisl

Toxicity: abnormal LFT, visdual disturbance

Question 12

Griseofulvin

Answer 12

MOA: interferes with microtubule formation, disrupts mitosis, deposits keratin containing tissues (nails)

Clinical: oral treamtne tof superficial infection; inhibits growth of dermatophytes (tinea, ringworm)

Toxicity: teratogenic, carcinogenic, confusion, HA, increase p450 and warfarin metabolism

Question 13

Antiprotozoan therapy

Answer 13

Pyrimethamine (toxo)

Suramin+melarsprol (trypanosoma brucei)

Nifurtimox (T cruzi, Chaga)

Sodium stibogluconate (leishmaniasis)

Question 14

Chloroquine

Answer 14

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

Clinical: treatment of plasmodial species other than F falciparum. Frequency of resistance in P falaciparum is too high. resistance due to membrane pump that reduces intracellular concentration fo drug.

Treat P falciparum with artemether/lumifantrine or atovaquonoe/proquanil.

For life-threatening malaria, use quinidine in US (quinine elsewhere, or artisunate)/

Toxicity: retinopathy

Question 15

Antihelminthic therapy

Answer 15

Mebendazole, pyrantel pamoate
Ivermectin
Diethylcarbamazine,
Praziquantel; immobilizes helminth

Use praziquantel against flucks (trematodeS) such as schistomas