Step 1 Antiparasite_fungals

Question 1

Chloroquine MOA, Use, Resistance

Answer 1

MOA - inhibits heme polymerase activity (accumulate free heme - toxic to parasites) Use - Oral tx for all types of malaria (Except chloroquine resistant P. falciparum)

Question 2

Primaquine MOA, Use, Side Effects

Answer 2

MOA - Kills intrahepatic P. vivax and P. ovale (prevents development of erythrocytic forms) Use - Oral agent to kill tissue form of P. vivax and P. ovale Side Effects - Hemolytic anemia when admin w/G6PD

Question 3

Quinine MOA, Use, Side Effects

Answer 3

MOA - Inhibit heme polymerase (accumulate free heme = toxic to parasites) Use - Chloroquine-resistance species of Plasmodia (used in combo w/pyrimethamine/sulfonamide), Babesia (w/Clindamycin) Side Effects - Cardiotoxic

Question 4

Pyrimethamine MOA, Use, Resistance

Answer 4

MOA - Inhibits parasitic DHFR (inhibit folate met) Use: Chloroquine-resistant P. falciparum - used w/quinine and sulfadoxine (Fansidar - combo sulfadoxine/Pyrimethamine) Prophylaxis/tx of toxoplasmosis (combined w/sulfadiazine) Resistance - Occurs via pt mutation in parasite DHFR-thymidylate synthase enzyme that decreases drug binding

Question 5

Ivermectin MOA, Use

Answer 5

MOA - Potent agonist at GABA receptors (In nematodes/arthopods GABA sends inhibitory signal to motor neurons - Ivermectin potentiates these inhibitory signals which paralyzes parasite) NOTE - Ivermectin does NOT cross BBB (GABA confined to CNS) so does not cause paralysis in humans Use: Intestinal form of Strongyloides stercoralis Larval form of nematode Onchocerca volvulus

Question 6

Amphotericin B MOA, Use, Side Effects, Administration

Answer 6

MOA - Binds ergosterol in fungal membrane, forms membrane pores that allow leakage of electrolytes Use: Serious, systemic mycoses (Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor). Intrathecally for fungal meningitis (doesn’t cross BBB) Side Effects - Fever/chills, hypotension, nephrotoxic (cumulative, dose related damage, reduced by hydration), Anemia, Arrhythmias Administration - Liposomal amphotericin reduces toxicity

Question 7

5-Flucytosine (5FC) MOA, Use, Side Effects

Answer 7

MOA - Fluorine analog deaminated to 5-FU which acts as noncompetitive inhibitor of thymidylate synthetase and DNA synthesis Use - Tx systemic infections of Candida or Cryptococcus neoformans (often co-admin w/Amphotericin B b/c synergism and to reduce resistance) Side Effects - Myelosuppression, vomit, diarrhea, nausea

Question 8

Azoles MOA, Side Effects

Answer 8

MOA - Inhibit fungal Cyp-dependent lanosterol to ergosterol reaction (inhibits fungal sterol synthesis) Side Effects: Antagonistic w/Amphotericin B b/c they decrease synthesis of sterol target Hormone synthesis inhibition (gynecomastia) Liver dysfunction (inhibits Cyps) Fever/chills

Question 9

Fluconazole Class, Use

Answer 9

Class - Triazole Use - Cryptococcal meningitis in AIDS pts, candidal infections of all types

Question 10

Clotrimazole, Miconazole Class, Use

Answer 10

Class - Imidazoles Use - cutaneous and vulvovaginal infections

Question 11

Caspofungin, Micafungin MOA, Use, Side Effects

Answer 11

MOA - Prevent glucan synthesis in fungal cell wall Use - Aspergillus Side Effects - GI upset, flushing, cost

Question 12

Ketoconazole Class, Use, Side Effects

Answer 12

Class - Imidazole Use - Blastomyces, Coccidioides, Histoplasma, Candida albicans, Hypercortisolism Side Effects - Hormone synthesis inhibition -< Adrenal suppression, gynecomastia, hypocholesterolemia and hypothyroidism

Question 13

Terbinafine MOA, Use

Answer 13

MOA - Inhibit fungal enzyme squalene epoxidase Use - Treat dermatophytoses (especially onchymycosis - fungal infection of finger or toe nails)

Question 14

Griseofulvin MOA, Use, Side Effects

Answer 14

MOA - Interferes w/microtubule function to disrupt mitosis (deposits in keratin-containing tissues (hair, nails and inhibits fungal growth) Use - Oral tx of superficial infections, inhibits growth of dermatophytes Side Effects - (rare) Teratogenic, carcinogenic, confusion, headaches, increase Cyps (warfarin metabolism increased)

Question 15

Nystatin MOA, Use

Answer 15

MOA - Binds ergosterol and forms pores that allow leakage of cellular contents (like Amphotericin B) Use: (topical only - too toxic for systemic use) Topical tx of diaper rash and vaginal candidiasis “swish and swallow” for oral candida

Question 16

Suramin MOA, Use, Bioavailability

Answer 16

MOA - Inhibits enzymes involved in energy metabolism (No CNS involvement) Use - Trypanosoma brucei (African sleeping sickness)

Question 17

Melarsoprol MOA, Use, Bioavailability

Answer 17

MOA - Inhibits sulfhydryl groups in parasite enzymes (w/CNS involvement) Use - Trypanosoma brucei (African sleeping sickness)

Question 18

Nifurtimox MOA, Use

Answer 18

MOA - Forms intracellular oxygen radicals toxic to organisms Use - Trypanosoma cruzi (Chagas)

Question 19

Sodium stibogluconate MOA, Use

Answer 19

MOA - Inhibit glycolysis at PFK reaction Use - Leishmania donavani

Question 20

Mefloquine MOA, Use

Answer 20

MOA - Unknown Use - Chloroquine resistant malaria

Question 21

Mebendazole MOA, Use

Answer 21

MOA - Inhibit glucose uptake and microtubule synthesis Use - Intestinal nematodes (Enterobius, Ascaris, Trichinella, Strongyloides, hookworms), Echinococcus

Question 22

Pyrantel pamoate MOA, Use

Answer 22

MOA - Stimulates nicotinic receptors at NMJ, contraction occurs, followed by depolarization-induced paralysis Use - Nematodes (Enterobius, Ascaris, hookworms)

Question 23

Diethycarbamazine MOA, Use

Answer 23

MOA - unknown Use - Tissue nematodes (Loa loa, Wucheria bancrofti, Toxocara canis)

Question 24

Praziquantel MOA, Use

Answer 24

MOA - Increases membrane permeability to calcium causing contraction/paralysis of tapeworms/flukes Use - Cestodes (Taenia, Diphyllobothrium) and Trematodes (Schistosoma, Clonorchis, Paragonimus)