Antimalarial and Antiparasitic Drugs Flashcards by Alexa Carnahan

What is pediculosis?

lice - feed on human blood
often asymptomatic; sx: allergic rxn to bites, may take 4-6weeks for itching to appear

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What is the life cycle of lice?

spread by direct contact and move by crawling
adults live ~30 days on head, females lay ~6eggs/day - firmly attaached to hair shaft clost to base
nits hatch in 6-9days

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What are the treatment considerations for lice?

only kill live lice!! not unhatched eggs - spinosad the only exception
usually require 2nd tx 9-10 days later to kill newly hatched lice

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What are the OTC options for lice?

naturally occurring pyrethrins - use with caution is h/o ragweed or chrysanthemum allergy
synthetic pyrethoids

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What are prescription treatments for lice?

spinosad 0.9% topical suspension!!
benzyl alcohol lotion, ivermectin lotion, malathion lotion

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What is the MOA of spinosad?

nicotinic acetylcholine receptor agonist
rapid excitation of the insect nervous system causes death

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What is the MOA of perethrins?

piperonyl butoxide synergistically enhances activity
nerve membrane sodium channel toxins that do not affect potassium channels; disrupting nerve function in insects and mites, specifically targeting sodium channels, leading to paralysis and ultimately death
rapidly metabolized if absorbed - relatively nontoxic b/c rapidly turned over

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Home remedies for lice?

DO NOT WORK

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What are helminth infections?

worm infections
worms multiply outside their definitive host in contrast to other parasites; evade immune system
infections chronic, last for lifetime of host

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What are the effects of helminths on human health?

compromised nutritional status, reduced cognitive processes, tissue reactions, intestinal obstruction or rectal prolapse
in kids: stunted growth, diminished physical fitness, impaired memory + cognition leading to educational deficits

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What is entorobiasis?

pinworm infection - most common helminthic infection worldwide
fecal-oral transmission

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What is the diagnosis for entorobiasis?

tape test

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What is the drug therapy for helminths?

benzimidazoles - broad spectrum activity
mebendazole, thiabendazole, albendazole!!, triclabendazole

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What is the MOA of benzimidazoles?

binds to tubulin and inhibits formation of microtubules
benzimidazoles cap microtubules, microtubules also are shortened from minus end, now have both ends shortening
inhibits cell division, secretion of parasite molecules, glucose uptake
can bind mammalian tubulin, but binds higher affinity to helminth tubulin

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What is the DOC for pinworms?

albendazole - rapidly converted to albendazole sulfoxide (active metabolite with increased activity)

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Albendazole is contraindicated in?

pregnant women

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What is pyrantel pamoate?

broad-spectrum antihelminth; highly effective for treating pinworms, also treats ascariasis
available OTC
highly insoluble (improves utility for intestinal infections)

What is the MOA of pyrantel pamoate?

depolarizing neuromuscular blocking agent –> causes release of acetylcholine and inhibition of cholinesterase –> worms paralyzed and expelled

What are the 5 human malaria parasites?

plasmodium falciparum (infects RBCs of any age, more infections), plasmodium vivax (one in the US, caused by hypnozoites in liver), plasmodium ovale, plasmodium malariae, plasmodium knowlesi

What is the life cycle of plasmodium falciparum?

infected mosquito injects sporozoites –> sporozoites migrate to liver, where they form merozoites –> merozoites are released and invade RBCs –> in RBC, merozoite becomes trophozoite –> in RBC, trophozoite multiplies, producing new merozoites; released when RBC ruptures and can infect other RBCs –> some merozoites become gametocytes

What are the classes of antimalarial drugs?

tissue schizonticides - kill liver stage parasites
blood schizonticides - killy erythrocytic forms
gametocytocides - kill sexual stages, block transmission
no single drug is active against all stages

What are the antimalarial drugs?

artemisinin, 4-aminoquinolines, 8-aminoquinolines, atovaquone, antifolates, antibiotics

Artemisinin

blood schizonticide
sesquiterpene lactone endoperoxide - endoperoxide is the active group (endoperoxide bridge critical for activity!!)
potent and fast acting; low toxicity

What is the MOA of artemisinin?

must be activated - likely via heme-iron in food vacuole
activated artemisinin may form free radicals - alkylated parasite proteins, lipids, DNA; triggers unfolded protein response; inhibits translation, proteasome, mitochondria
may inhibit phosphatidylinositol-3-kinase (PfPl3K)

What is artemisinin not active against?

not active against liver stage or hypnozoites

What is artemisinin commonly paired with?

longer half-life drugs b/c artemisinin has short half-life artemisinin provides rapid knockdown, longer half-life component eliminates remaining parasites - lumefantrine most common, amodiaquine, mefloquine, piperaquine

Is artemisinin soluble?

no - insoluble, can only be used orally!! semisynthetic artemisinins are available with different routes of administration, all converted to dihydroartemisinin (active form)

What is the MOA of artemisinin resistance?

mutations in Kelch 13 gene --> delays progress through the life cycle - remains in ring stage longer

What are the aminoquinolines?

quinine, chloroquine, mefloquine chloroquine structure: weak bases assist in drug accumulation via pH trapping; planar structure allows it to bind to heme

What is hemoglobin metabolism?

malaria parasites ingest hemoglobin from host cell --> degrade hemoglobin to amino acids and free heme in food vacuole, free heme is toxic --> parasite polymerizes heme into hemozoin, which is nontoxic chloroquine accumulates in food vacuole and inhibits heme polymerization, leading to accumulation of toxic heme to kill the parasite

What is the MOA of 4-substituted quinolines?

interfere with heme polymerization resistance associated with lack of accumulation in food vacuole

Chloroquine

DOC oral use; very long half-life hydroxychloroquine more commonly stocked - same thing but with hydroxyl at end of sidechain

What is the primary mechanism of chloroquine resistance?

mutations in PfCRT1 - transmembrane protein localized to food vacuole --> causes reduced accumulation of chloroquine can also get resistance from over-expression of PfMDR1 (multidrug transporter)

What drug is an 8-aminoquinoline?

primaquine

Primaquine

DOC for liver stages (actively growing and hypnozoites (dormant form)) of P. vivax and P. ovale (in combo with chloroquine) metabolized by CYP450 2D6, metabolism required for activity

What is the MOA of primaquine?

2 step process: 1. hydroxylation by CYP2D6 2. not too sure - production of toxic H2O2 (hydrogen peroxide) which kills the parasites

What is primaquine contraindicated in?

high risk of hemolysis in pts with G6PD deficiency do not use in pregnant women contraindications: granulocytopenia, concurrent use of other potentially hemolytic drugs or drugs that suppress myeloid cell development

What antibiotics are used as antimalarial drugs?

tetracycline, doxycycline, and clindamycin are blood schizonticides tetracycline/doxycycline: inhibit protein syntesis; clindamycin: inhibits peptide bond formation

What do the antibiotics target?

components of the apicoplast - carries out many essential biochemical processes

What is doxycycline used for?

commonly paired with quinine or quinidine for treatment of falciparum malaria used for chemoprophylaxis in areas with high resistance to mefloquine