Antifungal and Antihelminths

Question 1

Amphotericin B

Answer 1

Binds ergosterol (unique to fungi); forms membrane pores -> leakage of electrolytes

Use: Serious systemic mycoses. Cryptococcus (Amphotericin +/- flucytosine for cryptococcal meningitis), Blastomyces, Histoplasma, Candida, Mucor
Supplement K and Mg.
Tox: Fever, chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (amphoterrible)
Hydration decreases nephrotoxicity.

Question 2

Nystatin

Answer 2

Same as Amphotericin B. Topical use

Swish and swallow for oral candidiasis(thrush); Topical for diaper rash or vaginal candidiasis

Question 3

Flucytosine

Answer 3

Inhibits DNA/RNA synthesis. Cytosine deaminase converts it to 5-Fluouracil

Systemic fungal infections esp if Cryptococcal meningitis + Amphotericin B

Bone marrow suppression

Question 4

Azoles

Answer 4

Ketoconazole

Inhibit fungal sterol synthesis by inhibiting Cyt P450 that converts lanosterol to ergosterol

Local and less serious systemic mycoses.

Tox: Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction (inhibits cyt p450)

Question 5

Fluconazole, Itraconazole use

Answer 5

Fluconazole - chronic suppression of cryptococcal meningitis in AIDS patients
Also for candidal infections of all types

Itraconazole: Blastomyces, Coccidoides, Histoplasma

Miconazole and clotrimazole - topical fungal infections

Question 6

Terbinafine

Answer 6

Inhibits fungal enzyme squaline epoxidase

Dermatohytoses (esp onchomycosis - fingal infection of finger or toe nails)
GI upset, headaches, hepatotoxicity, taste disturbance

Question 7

Eichinocandins

Answer 7

Caspofungin
inhibit cell wall synthesis by inhibiting B glucan synthesis

Use: invasive Aspergillosis, Candida
GI upset, flushing (histamine release)

Question 8

Griseofulvin

Answer 8

interferes with Microtubule function; disrupts mitosis; Deposits in keratin containing tissues - nails
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
Teratogenic, carcinogenic, confusion, headaches, increases Cyt P450 and warfarin metabolism

Question 9

Antiprotozoan therapy:

Answer 9

pyrimethamine - toxoplasmosis
Suramin and melarsoprol - Tryp. Brucei
Nifurtimox - T cruzi

Question 10

Anti mite/louse therapy

Answer 10

Permethrin (blocks Na channels -> neurotoxicity), malathion (Ache inhibitor), Lindane (blocks GABA channels -> neurotoxicity)
Treat Scabies and lice

Question 11

Chloroquine

Answer 11

Blocks heme detoxification into hemozin
Heme accumulates and is toxic to plasmodia

Tx plasmodial species. Resistance due to membrane pump that decrease intracellular concentration of drug
Treat P. falciparum with Atovaquone

Malaria: quinidine
Tox: retinopathy, pruritis esp in dark skinned people

Question 12

Antihelminthic therapy

Answer 12

Mebendazole, pyrantel pamoate, ivermectin, praziqantel