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Block 6 Week 5 > Parasite Chemotherapy > Flashcards

Parasite Chemotherapy Flashcards

1
Q

What are the characteristics of protozoa?

A
  • Eukaryotic
  • 80S ribosome
  • metabolic pathways similiar to other animal cells
  • cell membrane sterol- cholesterol
  • no cell walls
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2
Q

What are the antimalarial antiprotozoal drugs?

A

quinone
chloroquine
primaquine
anitmetabolites

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3
Q

What are other antiprotozoal drugs (other than antimalarial)?

A

metronidazole
diloxanide
nifurtimox
suramin

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4
Q

(blank) is a mjor cause of death and illness throughout much of the world, particularly in Africa and Asia. Incidence is greater than 100 million cases per year.

A

Malaria

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5
Q

What is the parasite that causes malaria?

A

plasmodium sp.

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6
Q

What drugs are used to kill plasmodium?

A

it depends on the stage that the parasite is in.

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7
Q

What drug is used to kill plasmodium when it is in the tissues? (i.e exoerythrocytic stage)

A

primaquine

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8
Q

What drug is used to kill plasmodium when it is in the blood? (i.e erythrocytic stage)

A

chloroquine
quinine
diaminopyrimidines
mefloquine

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9
Q

Name the most common to least common forms of plasmodium?

A

P. vivax > P. falciparum > P. malariae > P. ovale (rare)

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10
Q

Why do the symptoms of malaria occur?

A

as a result of release of parasites into the blood stream.

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11
Q

What are the clinical signs of malaria?

A

fever, hemolysis, anemia, hypotension.

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12
Q

Malaria pathogenicity is a function of the degree of (blank) involvement.

A

erythrocyte

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13
Q

(bank) is highly pathogenic because it affects all erythrocytes. These infections are potentially lethal.

A

P. falciparum

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14
Q

P. vivax and P. malariae, which affect fewer red blood cells are (lethal/not lethal)

A

not usually lethal

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15
Q

In the mosquite, how do you kill sporontocides of malaria?

A

primaquine
proguanil
pyrimethamine

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16
Q

In humans, how do you kill tissue shizontocides (its in the liver) of malaria?

A

primaquine
proguanil
pyrimethamine
tetracycline

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17
Q

In humans, how do you kill hypozoiticides?

A

primaquine

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18
Q

In humans, how do you kill gametocytocides?

A

primaquine

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19
Q

How should you treat clinical malaria that has invaded your red blood cells as bood schizontocides?

A 
chloroquine
quinin, quinidine
mefloquine
artesunate
sulfadozine and pyrimethamine
halofantrine
tetracycline
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20
Q

What was the first antimalarial drug?

A

Quinine (it was derived from the bark of the cinchona tree)

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21
Q

How do quinine work?

A

heme polymerization is blocked thus increasing heme concentrations to toxic levels (heme is toxic to parasites)The m

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22
Q

What are the adverse reactions of quinine?

A 
cinchonism (a syndrome similiar to salicylate toxicity)
curare effect
myocarial depression
vasodilation
hemolytic anemia
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23
Q

When should you use quinine?

A

Used to treat chloroquine-resistant plasmodium falciparum

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24
Q

How does chloroquine work?

A

blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!

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25
Q

The mechanism of action is similar for all antimalarial quinolones except (blank).

A

Primaquine

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26
Q

Quinolines are weak (blank) that concentrate in food vacuoles of schizonts.

A

bases

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27
Q

(blank) forms of the malaria parasite are sensitive to chloroquine

A

erythrocytic forms

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28
Q

T or F

Resistant strains of falcparum have arisen and are vary common in Asia

A

T

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29
Q

How do malaria drugs get resistance to quinolines?

A

polygenetic mechanisms involving expression of transpot proteins that excrete the drug.

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30
Q

What is the clinical use of chloroquines?

A

used for prophylaxis (most common drug used) and treatment of acute attacks

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31
Q

What malarial parasites does chloroquine work on?

A

P. falciparum

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32
Q

Why doesn’t P. vivax get killed by chloroquine?

A

because P. vivax exists latent as exoerythrocyticin which is insensitive to drug

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33
Q

What are the adverse effects of chloroquine when you take it prophylactically?

A

prophylactic doses-little toxicity

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34
Q

What are the adverse effects of chloroquine when you take it in acute doses?

A

anorexia, nausea, vomiting, headaches, hemolytic anemia

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35
Q

What are the adverse effects of chloroquine when you take it in high doses (amebicidal)?

A

photosensitization, retinopathy, leukopenia

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36
Q

What are the clinical uses of chloroquine?

A

acute malarial attacks
prophylaxis of malaria
amebiasis

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37
Q

How does primaquine work?

A

binds to DNA, damages mitochondria, inhibits protein synthesis

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38
Q

What do you use primaquine for?

A

used to treat latent liver forms of P. vivax and P. ovale

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39
Q

What are the adverse reactions of primaquine?

A

same as chloroquine

hemolytic anemia

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40
Q

What is this:
Mechanism of action probably involves intercalation into DNA as well as oxidation of macromolecules. It induces oxidative stress in parasites and in host cells.

A

primaquine

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41
Q

Does primaquine work on erythrocytic forms of P. falciparum or P. malariae?

A

No

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42
Q

Why can primaquine cause hemolytic anemia?

A

cuz it is an oxidative stressor and when combined with a G6PD will cause hemolytic anemia

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43
Q

Where does primaquine work at?

A

oxidizes GSH to GSSG

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44
Q

(blank) and (blank) can be used alone or in combination to treat drug-resistant P. falciparum.

A

Artesunate

artemether

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45
Q

What is made up of the active components of a traditional chinese herbal antipyretic that is increasingly used outside the USA to treat drug-resistant P. falciparum. Not available in the US.

A

Aresunate and artemether (qinghaosu)

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46
Q

What is this?

a. Structurally similar to chloroquine and primaquine. Mechanism of action is similar to chloroquine.
b. Useful in treating chloroquine- and Fansidar-resistant strains of malaria. Effective against erythrocytic forms of the parasite.

A

mefloquinine

blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!

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47
Q

What are the adverse reactions of mefloquine (lariam)?

A

nausea, vomiting, bradycardia. Serious psychiatric disturbancese can occur (1:1000)

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48
Q

What are three antimetabolites used to treat malaria?

What are they effective against?

A

Chloroguanide
Pyrimethamine-sulfadoxine (fansidar)
Dapsone
erythrocytic forms of parasite

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49
Q

(blank) is a prodrug metabolized by the liver to dihydrotriazine which is a dihydrofolate reductase inhibitor.

A

chloroguanide

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50
Q

(blank) is a fixed dose combination of a dihydrofolate reductase inhibitor and a very long acting sulfonamide (t1/2 7-9 days).

A

Pyrimethamine-sulfadoxine (fansidar)

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51
Q

What is Pyrimethamine-sulfadoxine used on?

A

chloroquine resistant P. falciparum.

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52
Q

(blank) is a PABA analog also used to treat leprosy.

A

dapsone

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53
Q

What step gets inhibited by sulfadoxine?
What step does pyrimethamine inhibit?

What do these prevent from happening?

A
  • pteridine and PABA becoming dihyropteroic acid
  • dihydrofolic acid reduction to make dTMP

making folic acid for DNA production

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54
Q

(blank) inhibits folic acid synthesis.

A

pyrimethamine-sulfadoxine (fansidar)

55
Q

What do you use pyrimethamine-sulfadoxine (fansidar) for?

A

to treat chloroquine-resistant P. falciparum

56
Q

(blank) is used for multi-drug resistant P. falciparum.

A

mefloquine

57
Q

What is the MOA of mefloquine?

A

similiar to chloroquine (blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!)

58
Q

What are the adverse effects of mefloquine?

A

neurologic, acute psychosis, transient encephalopathy with convulsions

59
Q

(blank) are used for multi-drug resistant P. falciparum.

A

atovaquone and chloroguanide

60
Q

What is the mode of action of chloroguanide?

A

inhibits malaria dihydrofolate reducatse

61
Q

What are the adverse effects of atovaquone and chloroguanide?

A

diarrhea, vomiting and kidney failure

62
Q

What is standard in the treatment of P. falciparum?

A

aremisinin derivatives

63
Q

How do armesinin derivatives work?

A

cause oxidative stress in the malarial parasite.

64
Q

What are the adverse effects of artemisinin derivatives?

A

nausea, vomiting, anorexia, and dizziness. Rare but serious allergic reactions

65
Q

Doxycycline (type of tetracycline) is commony used as (blank)

A

prophylaxis

66
Q

What are the adverse effects of tetracycline?

A

due to effects on bone and tooth growth, it is not used in children under 8, pregnant or lactating women and patients with known hepatic dysfunction

67
Q

How does metronidazole (flagyl) work?

A

ETC activates it in anaerobes to create metabolites to bind to and damage DNA

68
Q

What are the adverse reactions to metronidazole (flagyl)?

A 
Gi distress
CNS seizure
peripheral neuropathy
Disulfiram effect
Potential mutagen
69
Q

Why isnt metronidazole (flagyl) not recommended for pregnant women?

A

Because of the potential for mutagenic effects on the fetus, particularly in the first trimester

70
Q

What are the clinical uses of metronidazole?

A

amebiasis, trichomoniasis, giardiasis, anaerobic bacterial infection

71
Q

(blank) is an amebicide that is the most effective and most important antiprotozoal drug.

A

metronidazole

72
Q

(blank) is an effective luminal amebacide used to treat both symptomatic individuals and asymptomatic carriers of Entamoeba histolytica.

A

Iodoquinol

73
Q

(blank) is an aminoglycoside

A

paramomycin

74
Q

(blank) is an luminal amebicide used to treat Entamoeba histolytica infections, mechanism of action is unknown. Kills cysts in asymptomatic carriers.

A

diloxanide furoate

75
Q

What are 2 combos of dihydrofolate reducate inhibitors and sulfonamides?

A

trimethoprim-sufamethoxasole (septra)

pyrimethamine-sulfadoxine (fansidar)

76
Q

(blank) is used to treat Chagas disease. Reduction of this drugs leads to production of toxic oxygen species which damage DNA

A

nifurtimox

77
Q

What are the adverse reactions to nifurtimox?

A 
there is a high incidence of adverse reactions:
Gi distress
headache
vertigo
imsomnia
rash
78
Q

(blank) causes oxidative damage to DNA and treats Chagas disease

A

Nifurtimox

79
Q

(blank) inhibits multiple enzymes and treats african trypanosomiasis

A

suramin

80
Q

This drug is phagocytized by the parasite and inhibits a variety of enzymes, including enzymes important in energy metabolism.

A

Suramin

81
Q

What are the adverse reactions of suramin?

A

they are infrequent;

include GI distress, neurologic complications and blood dyscrasias

82
Q

What is the most common helminth infection? least common?

A 
anclyostoma necator (roundworm)
strongyloides
83
Q

What are the antihelminth therapeutic strategies?

A

inhibit muscle contraction
inhibit energy metabolism
limit distribution of generally toxic drugs

84
Q

What is quinicrine?

A

an alternative drug for treating giardiasis

85
Q

(blank) is a pentavalent antimonial that may inhibit phosphofructokinase, the rate liminiting enzye in glycolysis. Used to treat leishmaniasis

A

stibogluconate

86
Q

What are the 2 types of arsenicals?

A

melasoprol and tryparsamide.

87
Q

What do melasoprol and tryparasamide do?

A

bind to sulfhydry groups and inhibit pyruvate kinase. Used to treat trypanosomiasis (but replaced now by suramin and nifurtimox)

88
Q

What are platyhelminthes?

A

flatworms

89
Q

What are cestodes?

A

a type of flatworm called a tapeworm

90
Q

what 2 drugs do you use to treat cestodes (tapeworms)?

A

Praziquantel

paromomycin

91
Q

What does praziquantel attack?

A

cestodes and flukes

92
Q

How does praziquantel work?

A

causes a massive influx of calcium and a tetanic contraction of the parasites musculature

93
Q

What are the side effects of praziquantel?

A

nausea
vomiting
abdominal pain
effects are mild and short lived (48 hr)

94
Q

What is the drug of choice for cestode (tapeworm) and trematode (fluke) infections.

A

praziquantel

95
Q

(blank) is an alternative to praziquantel in treating liver and lung fluke infections

A

praziquantel

96
Q

How does bithionol work?

A

uncouples oxidative phosphorylation

97
Q

What are the adverse effects of bithionol?

A

nausea, vomiting, diarrhea, rashes, skin photosensitization

98
Q

What are nematodes?

A

intestinal roundworms

99
Q

What are the four types of nematodes?

A

ascaris, enterobius, trichuris, hookworm

100
Q

What is a benzimidazole derivate that is a broad spectrum antihelminithic agent.

A

Mebendazole

101
Q

How does mebendazole work?

A

binds tubulin and inhibits formation of mitotic spindle. Inhibits glucose uptake.

102
Q

What does metrifonate do?

A

it is an alternative drug for fluke infections and a cholinesterase inhibitor that attacks s. hematobium

103
Q

What does oxamaquine kill?

A

S. mansoni

104
Q

What does niridazole kill?

A

S. mansoni

S. hematobium

105
Q

What is the common name for nemathelmniths?

A

roundworms

106
Q

What is the common name for ancylostoma duodenale and necator americanus?

A

hookworms

107
Q

What is the common name for strongyloids stercoralis?

A

threadworm

108
Q

What is the common name for tricuris trichuria?

A

whipworm

109
Q

WHat is a broad spectrum antihelminithic that is chemically similiar to mebendazole.

A

Albendazole

110
Q

What is the spectrum of mebendazole?

A

broad

111
Q

What is mebendazole used to treat?

A

trichuriasis, capillariaisis, hookworm, echinococcosis, enterobiasis, ascariasis

112
Q

Does mebendazole have high toxicity? Whats scary about mebendazole?

A

no it has low toxicity, cuz its poorly absorbed in GI tract.

it is potentially teratogenic

113
Q

Why shouldnt you give mebendazole in pregnancy?

A

exhibits embryotoxicity

114
Q

What is albendazole used to treat?

A

strongyloidiasis, trichurasis, capillariasis, ascariasis, filariasis, toxocariasis, taenium solium, cysticerus cellulosis; echinococcosis (hydatid disease)

115
Q

How does albendazole work?

A

disrupts microtubules

116
Q

What are the adverse effects of albendazole?

A

transient GI discomfort and headache

117
Q

Can you use albendazole in pregnancy?

A

no (patients should be advised not become pregnant for one month after taking the drug)

118
Q

What is thiabendazole used to treat?

A

strongyloidiasis, nematode larva infections

119
Q

How does thiabendazole work?

A

blocks helminth specific enzyme fumarate reductase and binds tubulin

120
Q

What does thiabendazole have a high incident of?

A

nausea, vomiting, anorexia

121
Q

(blank) is an older drug, produces a hyperpolarizing neuromuscular blockad and flaccid paralysis of the worms.

A

piperazine

122
Q

What is the fancy name for tissue roundworms?

A

filarial worms (wuchereria, brugia, oa loa, onchocerca)

123
Q

What are the tissue roundworms?

A 
trichinella spiralis
wicheria bancrofti
brugia malayi
loa loa
onchocerca volvulus
124
Q

How does diethylcarbamazine (DEC) work?

A

enchances the immune response of the host to the parasite; by releasing antigenic components of the parasites cuticle or by affecting lymphokine production.

125
Q

Diethylcarbamizine (DEC) inhibits (blank)

A

lipoxygenase

126
Q

What is the clinical use of diethylcarbamazine (DEC)?

A

tissue and blood nematodes

127
Q

What are the adverse reactions of diethylcarbamzine (DEC)?

A

headache malaise, weakness, nausea, inflammatory reactions secondary to breakdown of dead microfilariea (mazotti reaction)

128
Q

How does ivermectin work?

A

paralyzes a number of helminths by activating glutamate-activated chloride channels in nerves and muscle cells.

129
Q

Is ivermectin well tolerated?

A

yes :)

130
Q

What can you use ivermectin against?

A

nematodes: onchocerciasis, enterobius, strongyloides, trichuris, ascaris

131
Q

Is ivermectin effective against cestodes and trematodes?

A

NO

132
Q

What is ivermectin recommended for?

A

strongyloides infections

133
Q

Is it more or less safe than diethlycarbamazine in treatment of filarial worm infections (onchocerca)?

A

more safe and more effective

Block 6 Week 5 (10 decks)

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