antiparasitics

Question 1

metronidazole- MOA

Answer 1

•Pro-drug targets enzyme unique to the parasite. Active form is free radical that damages DNA and causes oxidative stress that kills parasite.

Question 2

metronidazole uses

Answer 2

GET GAP: giardia, entamoeba, trichomonas, gardnerella vaginalis, anaerobes (bacteroides, C. diff), H. Pylori. It doesn’t reach lumen so better for systemic dz. Can use with lumenal amebicide (paromomycin/ diloxanide) for amebiasis.

Question 3

Metronidazole adverse rxns/ contraindications

Answer 3

disulfiram like rxn with alcohol (flushing, tachycardia, hypotension), headache, metallic taste. Contraindicated in hepatic dz, renal dz, CNS abnormalities

Question 4

Paromomycin- MOA, uses

Answer 4

aminoglycoside Abx (inhibits 30S).Concentrates in parasite in the gut. Little systemic absorption. Uses: asymptomatic lumenal amebiasis, cryptosporidiosis (AIDS), visceral and cutaneous Leishmanias.

Question 5

Toxoplasmosis treatment

Answer 5

Pyrimethamine + sulfadiazine (or clindamycin if sulfa allergy). Pyrimethamine targets dihydrofolate reductase and sulfadiazine targets dihydropteroic synthase, blocking folic acid synthesis and thus nucleic acid and protein synthesis

Question 6

Pneumocystis jirovecii treatment

Answer 6

TMP-SMX

Question 7

Pentamide MOA

Answer 7

disrupts DNA structure/ function (inhibits SAM decarboxylase), inhibits protein synthesis (binds minor groove of DNA), inhibits DNA replication (type II topoisomerase)

Question 8

Pentamide uses

Answer 8

PCP pneumonia alternative to TMP-SMX, West African Trypanosomiasis (T. brucei gambiense), Visceral Leishmanias

Question 9

Pentamide adverse rxns

Answer 9

histamine release (dying orgnaisms), drop in BP, hypoglycemia, elevates LFTS, impaired renal function. Few side effects when inhaled for PCP

Question 10

Benzimidazoles MOA

Answer 10

inhibit microtubule formation - selectively binds to parasite tubulin.

Question 11

Benzimidazoles uses

Answer 11

Mebendazole: nematodes - enterobiasis (pinworm), ascariasis, trichuriasis (whipworm), hookworm. Albendazole: nematodes- ascariasis, enterobiasis, hookworm. Invasive cestodes- cystic hydatid dz, cysticercosis (pork tapeworm).

Question 12

mebendazole vs albendazole

Answer 12

mebendazole: poor absorption, excreted in bile, uncomplicated nematode infections. Albendazole better absorption, excreted in urine, cysticercosis, used in kids >4yrs. Both are teratogens

Question 13

Pyrantel Pamoate MOA

Answer 13

concentrates in parasite- Ach receptor agonists cuases complete spastic paralysis of worm.

Question 14

Pyrantel Pamoate uses

Answer 14

ascariasis (roundworm), enterobiasis (pinworm) DOC, hookworms

Question 15

Pyrantel Pamoate contraindications

Answer 15

liver dysfunction.

Question 16

Praziquantel MOA

Answer 16

Ca2+ ionophore - induces paralysis, detachment, excretion. Induces tegmental damage - activates immune system

Question 17

Praziquantel uses

Answer 17

Cestodes (tapeworms), and trematodes (flukes) EXCEPT: pork tapeworm cysticercosis, cystic hydatid dz, and sheep liver fluke

Question 18

Praziquantel adverse rxns

Answer 18

If neurocysercicosis is present: meningismus, seizures, CSF pleocytosis

Question 19

treatment of Leishmanias

Answer 19

sodium stibogluconate

Question 20

treatment of African trypanosomiasis

Answer 20

Hemolymphatic stage: suramin, pentamidine. Late stage with CNS involvement: melasporol, eflornithine (west)

Question 21

Chloroquine MOA

Answer 21

Concentrates in food vacuoles. Inhibits heme polymerization, causing heme accumulation which is toxic to plasmodium. Inhibits peroxidase and catalase activity, generates oxidative stress.

Question 22

Chloroquine uses

Answer 22

Plasmodium vivax, ovale and malariae. P. falciparum is mostly resistant.

Question 23

Chloroquine adverse rxns

Answer 23

retinopathy, pruritis. Also hypotension, cardiac arrest, confusion, coma with IV. May cause hemolysis in G6PD deficiency.

Question 24

Quinine MOA

Answer 24

inhibits parasite feeding mechanism, generates oxidative stress

Question 25

Quinine uses

Answer 25

treat/ cure of erythrocytic stages of chloroquine resistant and MDR P. falciparum malaria treat/ cure of erythrocytic stages of chloroquine resistant and MDR P. falciparum malaria

Question 26

multi drug resistant malaria treatment

Answer 26

quinine plus Pryimethamine-sulfadoxine, TMP-SMX, clindamycin, doxycycline or tetracycline

Question 27

Quinine adverse rxns

Answer 27

Cinchonism- visual defects, auditory defects (tinnitus, deafness), GI (nausea, vomiting). Stimulates pancreatic beta cells (hyperinsulinemia), hypotension, hemolysis in G6PD deficiency.

Question 28

quinine drug interactions

Answer 28

may raise plasma levels of anti-coagulants (warfarin) and cardiac glycosides (digitoxin)

Question 29

Mefloquine MOA

Answer 29

generates oxidative stress

Question 30

Mefloquine MOA

Answer 30

Alternative for treatment of erythrocytic stages of chloroquine resistant and MDR P. falciparum. BUT…it is a court martial offence to prescribe nowAlternative for treatment of erythrocytic stages of chloroquine resistant and MDR P. falciparum. BUT…it is a court martial offence to prescribe now

Question 31

Mefloquine adverse rxns

Answer 31

CNS toxicity inn 50% (ataxia, visual/auditory disturbances), neuropsychiatric disturbances

Question 32

Malarone components

Answer 32

Proguanil with Atovaquone

Question 33

Malarone uses

Answer 33

Malaria caused by P. falciparum (safe for children), PCP (alternative to TMP-SMX), Toxoplasma gondii

Question 34

malarone adverse rxns

Answer 34

rash. Interacts with rifampin

Question 35

Malarone MOA

Answer 35

•DHFR Inhibitor. Increases efficacy of Atovaquone to collapse proton gradient

Question 36

Primaquine MOA and uses

Answer 36

MOA unknown. Latent forms of P. vivax and P. ovale. Only drug active against latent hepatic forms

Question 37

primaquine adverse rxns

Answer 37

hemolytic anemia in G6PD deficiency

Question 38

Artemisinin

Answer 38

Component of Chinese herbal remedies. Used in conjunction with lumefantrine (chloroquine analogue), sulfadoxine-pryimethamine for MDR P. falciparum. Generates ROS by interacting with heme.

Question 39

list drugs used for sensitive P. falciparum, P. vivax, P. malaria and P. Ovale

Answer 39

Chloroquine plus primaquine (for vivax and ovale)

Question 40

List drugs used for treatment of MDR P. falciparum and P. vivax

Answer 40

mefloquine prophylaxis (use doxycyclie now). Mefloquine plus primaquine OR artemisinin plus lumefantrine OR quinidine. Plus tetracyline OR pyrimethamine-sulfadoxine OR clindamycin