Anti-Parasitix Flashcards
Metronidazole
MOA: inhibits Pyruvate:Ferrodoxin Oxidoreductase I (**unique enzyme target only found in parasite)–>↑toxic radicals–>damage to DNA and ↓nucleic acid synthesis
“GETGAP on the METRO”
Giardia, Entamoeba, Trichomonas, Gardneralla, Anaerobes (e.g. Bacteroides, C. diff), H. pylori all treated by METROnidazole
ADME:
ADE: Metallic taste Disulfiram reaction Discolored urine Teratogen (CI in pregnancy and nursing) Neurologic toxicity DDI w/ Lithium and Warfarin-->CYP inhibitor
Atovaquone
MOA: inhibition of mitochondrial electron transport–>↓ATP and pyramidine synthesis
ADME: lipophilic; ↓bioavailability and efficacy with ↓GI absorption
ADE: hardly any
Iodoquinol
MOA: unknown
ADME: 90% remains in intestine and effective against luminal trophozoites
ADE: Thyroid disease, optic neuropathy, renal
NO neurotoxicity
Paromomycin
MOA: inhibits initiation complex of protein synthesis; requires O2 uptake
DOC for Amebiasis, Crypto HIV+, and pregnant Giardia pt (avoid metro in pregnancy)
ADME:
ADE: is an Aminoglycoside–>avoid in renal disease
Diarrhea
Pentamidine
MOA: unknown. Possibly inhibits DNA ATP topoisomerase, SAM carboxylae, and folate activity
ADME: delivered IV or inhalation (good for lung infection)
ADE: hypotension (↑histamine release)
hypoglycemia (toxic to pancreatic cells
blood dyscrasias
nephrotoxic (inhibition of renal DHFR)
cardiotoxicity
Melarsoprol
MOA: metabolized by melarsen oxide–>inhibits TRYPATHIONE REDUCTASE
ADME:
ADE: “ars”=arsenic
febrile reaction–>reactive encephalopathy, peripheral neuropathy
Eflornithine
MOA: irreversibly inhibits ORNITHINE DECARBOXYLASE (enzyme in both human and parasite, but in much higher concentration in parasite)
ADME: renally excreted unchanged
ADE: pancytopenia, diarrhea, alopecia
Stibogluconate
MOA: Prodrug (pentavalent form)–>toxic (trivalent form)–>changes/inhibits trypanothione reductase and phagolysosomes–>↑efflux of glutathione and trypanothione from cells
ADME: slow release from tissue, then sequestration in macrophages
ADE: chemical pancreatitis
bone marrow suppression
Chloroquine
MOA: unknown; PREVENTS POLYMERIZATION OF HEME–>↑accumulation of heme–>toxic to parasite
***Mech of resistance: ↑pumping of drug out of cell (via P-gp) AND out of food vacuole where the heme accumulates
[Used in areas without resistant P. falciparum. Good tx/prophylaxis of P. vivax and ovale]
ADME: metabolized in liver, slow excretion from extensive tissue stores (present for months to years)
ADE: toxic to skin, hair, blood, eyes. Also, ototoxicity and peripheral neuropathy
Quinine
MOA: binds DNA and inhibits DNA separation–>blocks DNA replication and transcription
**NOT effective on prophylaxis
ADME: Higher plasma levels in malaria pts due to ↓ liver fxn (can co-adminsiter with rifampin to INDUCE CYP and increase clearance of Quinine)
ADE: ***Hemolytic anemia in pts with G6PD deficiency (just like w/ Primaquine)
Cinchonism (tinnitus, blurred vision, ↓hearing)
Blackwater fever
GI distress
Cardio-depressive + smooth muscle relaxer
Uterine contraction (CI in pregnancy)
Quinidine Gluconate
MOA: D-isomer of Quinine–>same MOA
***also a Class IA Antiarrhythmic
ADME: concentrates in high blood flow areas–>heart, liver, skeletal muscle
ADE: Anticholinergic effects (avoid in AV block)
Mefloquine
MOA: unknown
***DOC for chloroquine resistance prophylaxis (i.e. even good against P. falciparum)
ADME: concentrates in RBCs where it is highly protein bound
ADE: GI distress, vertigo, visual disturbances, nightmares
CI in B blockers, hx of seizures, other -quines, and pregnancy
Lumefantrine
MOA: unknown, similar to mefloquine, coformulated with Artemether (effective against falciparum)
ADME: ↑absorption w/ fatty foods
CYP3A4 interaction
ADE: ↑QT interval
Artemisinins
MOA: reacts with ↑Fe in plasmodia in heme–>↑carbon radicals–>alkylate plasmodial molecules
(coadministration w/ lumefantrine effective against falciparum)
ADME: CYP inducer–>↑its own metabolism
ADE: ??…brain, liver, marrow, fetus (avoid in pregnancy and kids)
Primaquine
MOA: unknown. Destroys late hepatic stage and latent tissue stage of Vivax/Ovale AND gametocytes of P. falciparum–>can cure relapsing malaria
ADME:
ADE: ***Hemolytic anemia w/ G6PD deficiency (just like Quinine)
GI distress
Methemoglobinemia