antiparasitics Flashcards
metronidazole- MOA
•Pro-drug targets enzyme unique to the parasite. Active form is free radical that damages DNA and causes oxidative stress that kills parasite.
metronidazole uses
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.
Metronidazole adverse rxns/ contraindications
disulfiram like rxn with alcohol (flushing, tachycardia, hypotension), headache, metallic taste. Contraindicated in hepatic dz, renal dz, CNS abnormalities
Paromomycin- MOA, uses
aminoglycoside Abx (inhibits 30S).Concentrates in parasite in the gut. Little systemic absorption. Uses: asymptomatic lumenal amebiasis, cryptosporidiosis (AIDS), visceral and cutaneous Leishmanias.
Toxoplasmosis treatment
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
Pneumocystis jirovecii treatment
TMP-SMX
Pentamide MOA
disrupts DNA structure/ function (inhibits SAM decarboxylase), inhibits protein synthesis (binds minor groove of DNA), inhibits DNA replication (type II topoisomerase)
Pentamide uses
PCP pneumonia alternative to TMP-SMX, West African Trypanosomiasis (T. brucei gambiense), Visceral Leishmanias
Pentamide adverse rxns
histamine release (dying orgnaisms), drop in BP, hypoglycemia, elevates LFTS, impaired renal function. Few side effects when inhaled for PCP
Benzimidazoles MOA
inhibit microtubule formation - selectively binds to parasite tubulin.
Benzimidazoles uses
Mebendazole: nematodes - enterobiasis (pinworm), ascariasis, trichuriasis (whipworm), hookworm. Albendazole: nematodes- ascariasis, enterobiasis, hookworm. Invasive cestodes- cystic hydatid dz, cysticercosis (pork tapeworm).
mebendazole vs albendazole
mebendazole: poor absorption, excreted in bile, uncomplicated nematode infections. Albendazole better absorption, excreted in urine, cysticercosis, used in kids >4yrs. Both are teratogens
Pyrantel Pamoate MOA
concentrates in parasite- Ach receptor agonists cuases complete spastic paralysis of worm.
Pyrantel Pamoate uses
ascariasis (roundworm), enterobiasis (pinworm) DOC, hookworms
Pyrantel Pamoate contraindications
liver dysfunction.
Praziquantel MOA
Ca2+ ionophore - induces paralysis, detachment, excretion. Induces tegmental damage - activates immune system
Praziquantel uses
Cestodes (tapeworms), and trematodes (flukes) EXCEPT: pork tapeworm cysticercosis, cystic hydatid dz, and sheep liver fluke
Praziquantel adverse rxns
If neurocysercicosis is present: meningismus, seizures, CSF pleocytosis
treatment of Leishmanias
sodium stibogluconate
treatment of African trypanosomiasis
Hemolymphatic stage: suramin, pentamidine. Late stage with CNS involvement: melasporol, eflornithine (west)
Chloroquine MOA
Concentrates in food vacuoles. Inhibits heme polymerization, causing heme accumulation which is toxic to plasmodium. Inhibits peroxidase and catalase activity, generates oxidative stress.
Chloroquine uses
Plasmodium vivax, ovale and malariae. P. falciparum is mostly resistant.
Chloroquine adverse rxns
retinopathy, pruritis. Also hypotension, cardiac arrest, confusion, coma with IV. May cause hemolysis in G6PD deficiency.
Quinine MOA
inhibits parasite feeding mechanism, generates oxidative stress
Quinine uses
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
multi drug resistant malaria treatment
quinine plus Pryimethamine-sulfadoxine, TMP-SMX, clindamycin, doxycycline or tetracycline
Quinine adverse rxns
Cinchonism- visual defects, auditory defects (tinnitus, deafness), GI (nausea, vomiting). Stimulates pancreatic beta cells (hyperinsulinemia), hypotension, hemolysis in G6PD deficiency.
quinine drug interactions
may raise plasma levels of anti-coagulants (warfarin) and cardiac glycosides (digitoxin)
Mefloquine MOA
generates oxidative stress
Mefloquine MOA
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
Mefloquine adverse rxns
CNS toxicity inn 50% (ataxia, visual/auditory disturbances), neuropsychiatric disturbances
Malarone components
Proguanil with Atovaquone
Malarone uses
Malaria caused by P. falciparum (safe for children), PCP (alternative to TMP-SMX), Toxoplasma gondii
malarone adverse rxns
rash. Interacts with rifampin
Malarone MOA
•DHFR Inhibitor. Increases efficacy of Atovaquone to collapse proton gradient
Primaquine MOA and uses
MOA unknown. Latent forms of P. vivax and P. ovale. Only drug active against latent hepatic forms
primaquine adverse rxns
hemolytic anemia in G6PD deficiency
Artemisinin
Component of Chinese herbal remedies. Used in conjunction with lumefantrine (chloroquine analogue), sulfadoxine-pryimethamine for MDR P. falciparum. Generates ROS by interacting with heme.
list drugs used for sensitive P. falciparum, P. vivax, P. malaria and P. Ovale
Chloroquine plus primaquine (for vivax and ovale)
List drugs used for treatment of MDR P. falciparum and P. vivax
mefloquine prophylaxis (use doxycyclie now). Mefloquine plus primaquine OR artemisinin plus lumefantrine OR quinidine. Plus tetracyline OR pyrimethamine-sulfadoxine OR clindamycin
