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Antiparasitic drugs Flashcards

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1
Q

Most roundworms can be treated with _______, though alternative therapies include pyrantel pamoate, oxantel pamoate, and piperazine.

A

Benzimidazoles: mebendazole or albendazole

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2
Q

Threadworms are most effectively treated with _______

A

ivermectin

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3
Q

Th larvae (but not adult stages) of filarial worms can be treated with __________ or diethylcarbamazine

A

ivermectin

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4
Q

What adverse reactions can be seen when treating heavy worm infections?

A

massive worm expulsions have been
known to cause rectal prolapses, intestinal blockages, and intense hypersensitivity reactions can be generated in response to worm debris.

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5
Q

Ascaris lumbricoides is almost always treated with:

A

mebendazole, albendazole, or pyrantel pamoate

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6
Q

What drugs are useful in treatment of mixed infection with hookworms and ascaris?

A

albendazole or mebendazole

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7
Q

How is hookworm (Necator americanus) treated?

A

albendazole or mebendazole

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8
Q

What is cutaneous larva migrans?

A

creeping eruption on skin due to larvae of dog hookworm (Ancylostoma duodenale)

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9
Q

How is cutaneous larva migrans treated?

A

oral or topical thiabendazole, albendazole

NOT mebendazole

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10
Q

How is whipworm (Trichuris trichiura) treated?

A

Benzimidazoles or oxantel pamoate

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11
Q

How are threadworms (Strongyloides stercoralis) treated?

A

ivermectin

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12
Q

How is pinworm (Enterobius vermicularis) treated?

A

mebendazole, albendazole, pyrantel pamoate

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13
Q

Strict personal hygiene is critical in treatment of ______

A

pinworm (Enterobius vermicularis)

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14
Q

How is trichinella spiralis treated?

A

Albendazole and mebendazole effective against early intestinal stage but ineffective against larvae that have migrated to the muscle

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15
Q

How are filarial worms treated?

A

Ex Wuchereria bancrofti, Brugia malayi

Treated with diethylcarbamazine or ivermectin

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16
Q

In very general terms, describe what drugs are used to treat roundworms vs flatworms

A

Roundworms: nematodes

  • intestinal: mebendazole or albendazole
  • filarial: ivermectin

Flatworms: platyhelminths

  • tapeworms: praziquantel
  • flukes: praziquantel
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17
Q

What is the drug of choice for treatment of onchocerciasis

A

ivermectin

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18
Q

What is the drug of choice for treatment of loiasis

A

diethylcarbamazine

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19
Q

With the exceptions of echinococcosis and cysticercosis, ________ is the drug of choice for treating all tapeworm infections

A

praziquantel

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20
Q

How is echinococcus granulosus treated?

A

surgical resection and long term albendazole

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21
Q

What is the drug of choice for all schistosomal infections?

A

Praziquantel

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22
Q

What is the drug of choice for lung, liver, and intestinal flukes?

A

Praziquantel

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23
Q

What is the mechanism of action of benzimidazoles (albendazole, mebendazole)?

A

Binds to worm B tubulin which inhibits microtubule polymerization

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24
Q

List toxicities of mebendazole and albendazole

A

Few systemic toxicities

Not for use in pregnant women

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25
Describe the indications for use of mebendazole
nematode infections including roundworm, hookworm, and whipworm.
26
List indications for use of albendazole
roundworm, hookworm, pinworm, and whipworm. zoonotic tapeworm infections (echinococcosis) such as cystic hydatid and alveolar hydatid disease, cysticercosis It has an advantage over mebendazole in that very often treatment can be effected with only a single dose of drug.
27
_____ has low oral bioavailability and remains largely in the gut, which is advantageous for treatment
Mebendazole
28
Oral bioavailability of ______ is increased with eating a fatty meal
albendazole
29
Describe the disease caused by the filarial worm Onchocerca volvulus
Cutaneous filariasis African river blindness transmitted by black flies, causes lymphatic involvement, dermatitis, blindnesss caused by an endosymbiont (Wolbachia pipientis)
30
What is the mechanism of action of ivermectin
direct activation of avermectin-sensitive glutamate-gated chloride channels; tonic paralysis of the worm pharyngeal musculature.
31
Describe the targets of ivermectin
not active against adult filarial worms, but affects developing larvae and prevents egress of microfilariae from the uterus of the adult worm. By decreasing microfilariae in the skin, it prevents transmission to the black fly vector
32
Why is ivermectin not effective against cestodes and trematodes
Do not have glutamate gated chloride channels that the drug targets
33
Describe indications for ivermectin use
Most filarial worm infections- kills larval form drug of choice to treat, but not cure onchocerciasis. Can treat strongyloides in one dose Effective as single dose once or twice a year
34
What disease is caused by lymphatic filarial roundworms (ex Wuchereria bancrofti, Brugia malayi)
elephantiasis
35
_______ is a drug with strong activity against cestodes and trematodes but not nematodes
Praziquantel
36
Describe the mechanism of action of praziquantel
Causes calcium-dependent changes that include the “blebbing” of the surface tegument Increased susceptibility to host immune response. NOT direct killing
37
What infections are treated with praziquantel
Most cestode and trematode infections, including all Schistosomal species Three dose regimen taken in one day for flukes, single dose for most tapeworm infections
38
What treatment is used for scabies?
permethrin | neurotoxin- prolonged sodium channel activation
39
What is the mechanism of action of metronidazole?
Forms reactive intermediates that cause free radical damage and covalently bind to parasite proteins and DNA.
40
What conditions is metronidazole used to treat?
T vaginalis, amebiasis, giardiasis
41
List side effects of metronidazole
Produces a disulfuram like reaction and should not be used with alcohol. Contraindicated in the first trimester of pregnancy
42
What drug is used to treat the first stage of Trypaonsoma brucei rhodesiense
Suramin
43
What is the mechanism of action of suramin
endocytosed by trypanosomes, inhibits glycolytic enzymes Indication: Effective against primary blood stages. Used primarily to treat T. brucei rhodesiense
44
What drug is used to treat the first stage of Trypanosoma brucei gambiense
Pentamidine
45
What is the mechanism of action of pentamidine
uptake through trypanosome purine receptors; achieves micromolar concentrations within the parasite Binds to mitochondrial (kinetoplast) DNA; disrupts DNA metabolism
46
The drug _____ is first line for treatment of advanced HAT
Melarsoprol
47
What is the mechanism of action of melarsoprol
Arsenic compound that chelates with the essential thiol trypanothione which is comprised of two glutathiones and spermidine`
48
_______ is a drug that can be used to treat West African form of trypanosomiasis and is greatly preferred over melarsoprol
Eflornithin | Marginal efficacy for East African for
49
What is the mechanism of action of eflornithine
Suicide inhibitor of ornithine decarboxylase, rate limiting enzyme in polyamine synthesis. Blocks cell division
50
What are blood schizonticides
Anti-malarial drugs that act on the erythrocytic stage of the infection to block schizogeny and terminate a clinical attack (clinical cure). These drugs are also used for chemoprophylaxis.
51
What are tissue schizonticides?
Primary tissue schizonticide - acts within the liver to prevent initiation of clinical malaria (chloroguanide). Latent tissue schizonticide - acts on latent forms in the liver to prevent relapse of P. vivax and P. ovale (primaquine).
52
What are gametocytocides and sporontocides
Drugs that show activity against malaria parasite sexual forms
53
Describe the mechanism of action of quinine
raises vacuolar pH. This inhibits the polymerization of heme into hemozoin, an important detoxification reaction that is essential for Plasmodium survival in erythrocytes
54
What are specific toxicities of quinine?
Cinchonism – A cluster of dose related symptoms seen after multiple dosing, includes ringing in the ears, headaches, nausea, blurred vision. Hypersensitivity – Some people develop flushing, pruritis, hemoglobinuria after low doses. Blackwater fever – A rare form of hypersensitivity that produces massive hemolysis, hemoglobinemia, hemoglobinuria, and renal failure. Hypoglycemia- quinine induced insulin release from pancreas
55
What is the mechanism of action of chloroquine
Choroquine is a quinoline ring-containing compound with the same mechanism of action as quinine. However, chloroquine is more effective and less toxic
56
What are toxicities of chloroquine?
cardiovascular effects including hypotension, ECG abnormalities
57
Chloroquine and primaquine are contraindicated in people with ________
G6PD deficiency
58
What is the reason for widespread chloroquine resistance?
energy-dependent efflux mechanism.
59
What is the mechanism of mefloquine?
Does not inhibit heme polymerization. It may form toxic heme-mefloquine complexes
60
What are indications for mefloquine?
Drug of choice for prophylaxis of malaria in regions of chloroquine resistance. High doses can be used to treat CQR malaria
61
_______ is an anti-malarial drug that targets latent tissue schizonts
Primaquine
62
Describe unique factors of P vivax
Infects reticulocytes; becomes dormant in the liver; cannot be cultured in vitro Treatment must target liver schizonts or infection will relapse
63
What is the mechanism of action of primaquine
may involve generation of ROS. | Ineffective against erythrocytic stages; cannot terminate an acute clinical attack.
64
What is the mechanism of action of chloroguanide
Prodrug that must be rearranged by a two step process into cycloguanil (active form). It is a folate antagonist that inhibits bifunctional dihydrofolate reductase-thymidylate synthetase causing inhibition of DNA synthesis
65
Describe resistance to chloroguanide
Mutation in the enzyme complex near dihydrofolate reductase binding site which decreases drug affinity. Mutation may also confer resistance to pyrimethamine.
66
Describe uses of chloroguanide
Prophylaxis of malaria, active against tissue schizonts, but will also terminate clinical attacks. Used in combination with atavoquone (Malarone)
67
List anti-folate drugs used to treat malaria
pyrimethamine-sulfadoxine
68
Describe the mechanism of action of atovaquone
may function as inhibitory analogue of ubiquinone; inhibition of mitochondrial electron transport. Ineffective against erythrocytic stages; cannot terminate an acute clinical attack
69
Describe the therapeutic use of atovaquone
prophylaxis and treatment of chloroquine-resistant malaria in combination with chloroguanide (Malarone).
70
What is the mechanism of action of artemisinin
Endoperoxide bridge “warhead” is essential for activity Complexes with ferrous non-heme iron Generation of free radicals and damage of macromolecules and membranes Kills all stages of the parasite in mammals
71
Describe therapeutic use of artemisinin
Very fast and potent; active against chloroquine-resistant forms of malaria. Not used for prophylaxis. Use with other agents- short half life
72
_______ are now the recommended treatment for uncomplicated P falciparum malaria
artemisinin based combination therapies (ACTs) | Use artemisinin + another drug to reach complete cure by using drugs with different mechanisms of action
73
Describe malaria therapy in the first trimester of pregnancy
chloroquine if susceptible, quinine plus clindamycin for 7 days
74
Describe malaria therapy in the second/third trimester of pregnancy
Mefloquine, ACTs known to be effective in the country/region
75
Describe what is known about the mechanism of malaria resistance to chloroquine
CQR strains of P. falciparum do not display characteristic vacuolar swelling following treatment with CQ. Energy-dependent efflux of CQ from food vacuoles is a common denominator linking all drug-resistant Plasmodium strains. Mutation: K76T mutation is never found in isolation; therefore K76T is necessary, but not sufficient for CQR.
76
Efflux of chloroquine from CQR strains of P. falciparum is blocked by the drug __________
Ca2+ channel blocker verapamil

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