Antiparasitic Flashcards
How many species of Plasmodium (malaria parasites) infect humans?
5
What are the the species of Plasmodium that infect humans?
Falciparum
Vivax
Ovale
Malariae
Knowlesi
What is the most common form of malaria?
Falciparum malaria
What is the most severe form of malaria?
falciparum malaria
What form of malaria is often lethal?
Cerebral form
Vivax malaria is…?
a milder but common form of malaria
Which form of malaria can relapse due to dormant hypnozoites that remain in the liver and are NOT affected by blood-stage antimalarials?
Vivax malaria
What are the two types of antimalarial chemotherapy?
Prophylaxis
Treatment of active or latent infection
What antimalarial agents are used for prophylaxis?
Cholorquine
Primaquine
What antimalarial agents are used to treat active or latent infections?
Chloroquine
Primaquine
Artemether/lumefantrine
What is another term for antimalarials?
Schizonticides
What are the two stages of malaria that drugs target?
Liver stage
Blood stage
During what stage of malaria do patients experience symptoms?
Blood Stage
Malaria drugs that target the blood stage produce a ____ cure
Clinical
Malaria drugs that target the liver stage produce a ____ cure
radical
(of relapsing malaria)
Are blood stage antimalarial effective against liver stage parasites?
No
What antimalarial drugs disrupts disease transmission? And by what activity?
Artemether and Primaquine
gametocidial activity
Chloroquine and Artemisinins are antimalarial drugs that target the ____ stage of malaria
Blood stage
Primaquine is an antimalarial drug that target the ____ stage of malaria
Liver stage
Orally effective, long half-lives and low toxicity are properties of what type of antimalarial agent?
Prophylactic
What does chemoprophylaxis treatment for malaria prevent?
symptomatic blood stage
How is antimalarial drug for a US traveler selected?
dependent on the resistant pattern of the intended destination
Since no regimen is fully protective for malaria, what else is important?
prevention of mosquito bites
Chloroquine is a weak organic acid/base?
base
inhibition of biocrystalization is the MOA of what antimalarial drug?
Chloroquine
what are the therapeutic uses of chloroquine?
clinical cure and prophylaxis against sensitive strains
what is used for prophylaxis and treatment of malaria during pregnancy
chloroquine
chloroquine is effective/ineffective against most strains of P. falciparum in Africa, Asia and s. America?
ineffective
Adverse reactions of chloroquine depend on …
low-dose (prophylaxis) vs. high-dose (clinical cure)
Cholorquine targets the blood/liver stage of malaria?
blood
True or False: chloroquine is generally well-tolerated at lower doses?
true
At higher-doses, adverse reactions of chloroquine include:
pruritus
headache
GI
CV toxicity
Artemether route of administration is…
oral
artemether is derived from …
medicinal Chinese plant quinghao
the MOA of artemether is
unclear
(drugs may form toxic free radicals in the presence of heme)
what property of artemether makes the drug NOT useful for prophylaxis?
short half-life
what is artemether used with in a fixed-dose combination
lumefantrine
what is important about lumefantrine?
it is long acting, half life of 4.5 days, it sustains antimalarial activity during the frequent sub-therapeutic trough levels or artemether
what is an important therapeutic use of artemether-lumefantrine?
first line oral of MDR falciparum malaria
inactive counterfeits that closely mimic genuine drugs for malaria are common/uncommon
common
artemether adverse reactions are
not well characterized, generally safe
adverse reactions of artemether (in animal studies) include
neurotoxicity (in animals) and potent embryo toxicity (in animals)
artemether is used to treat ____ stage of malaria
blood stage
Why is it important that chloroquine is a weak organic base?
it becomes ionized in acidic environment which allows ion trapping in parasite food vacule (an infected RBC)
what is the food source for malaria parasites?
globin from hemoglobin
hematin is ____ to malaria parasites
toxic
what is biocrystallization and why is it important for malaria parasites?
malaria parasites:
hematin —(biocrystallization) —> non-toxic hemozoin
resistance to chloroquine is due to ….
mutated efflux transporter (PfCRT) that prevents drug accumulation
Primaquine targets ____ stage of malaria
liver stage
what is the MOA of primaquine?
it is unknown
what are the three therapeutic uses of primaquine (oral)?
- with chloroquine to achieve clinical and radical cure of vivax/ovale malaria
- for terminal prophylaxis AFTER completion of travel to vivax/ovale endemic areas
- for primary prophylaxis against all species if other agents are inappropriate
what are the two types of prophylaxis that are uses of primaquine?
primary and terminal
primaquine is well tolerated but causes hemolytic anemia in _____ deficient patients
G6PD
Besides G6PD-deficient patients, primaquine is contraindicated for
pregnant females (fetal G6PD status cannot be determined)
What is a common genital STI protozoal infection in the US?
trichomoniasis
giardiasis, amebiasis and cryptosporidiosis are …
all GI protozoal infections that are common in the US
amebiasis infection occurs mainly in the GI and the infection can ….
be asymptomatic, mild-mod (colitis) or severe (dysentery)
antiprotozoal agents for GI protozoal infections are classified as ____ or ______
systemic or GI luminal
what is a systemic antiprotozoal agent?
metronidazole
what is a luminal antiprotozoal agent?
paromomycin
metronidazole MOA
prodrug converted to DNA-damaging metabolite in anaerobic organisms
two therapeutic uses of metronidazole are …
- treat amebiasis (given in combo with a luminal amebicide to eradicate luminal survivors)
- anaerobic bacterial infections
why is metronidazole given in combination with a luminal amebicide?
to eradicate luminal survivors because metronidazole levels in the GI tract are low due to its complete oral absorption
what class is parmomycin?
aminoglycoside
MOA of paromomycin
binds to 30S subunit to inhibit protein synthesis
is paromymycin absorbed from the GI tract?
No, it is a luminal antiprotozoal agent
what is the prototype drug for benzimidazoles?
albendazole
MOA of albendazole
inhibits polymerization of parasite B-tubulin, preventing formation of cytosolic microtubules
Antihelminthics include …
albendazole, ivermectin
uses for albendazole and how is it used?
- enterobiasis infection, single 400 mg dose repeated 2 weeks later
- cestode and roundworm infections
adverse effects of albendazole
teratogenic effect in animal, long term–liver toxicity, bone marrow suppression
immobilization by tonic muscle paralysis is the MOA of what antihelminthic drug?
Ivermectin
how does ivermectin cause tonic muscle paralysis in helmniths?
(+) glutamate-gated Cl- channels only found in invertebrate neurons, causes hyperpolarization of neuronal membrane
how is ivermectin kept out of the CNS in the host?
P-glycoprotein efflux transporter in host BBB
three uses of ivermectin include:
- broad spectrum agent to treat ticks, fleas, mites in vet medicine
- onchocerciasis (river blindness)
- scabies, head lice
adverse effects of ivermectin
mazzotti reaction
teratogenic potential (cleft palate in animals)
what is a mazzotti reaction and when does it occur?
adverse reaction of ivermectin that occurs in onchocerciasis. It is an immune reaction to drying worms. Includes: pruritus, rash, fever, lymphedema
