Parasite Chemotherapy Flashcards
(133 cards)
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
2
Q
What are the antimalarial antiprotozoal drugs?
A
quinone
chloroquine
primaquine
anitmetabolites
3
Q
What are other antiprotozoal drugs (other than antimalarial)?
A
metronidazole
diloxanide
nifurtimox
suramin
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
5
Q
What is the parasite that causes malaria?
A
plasmodium sp.
6
Q
What drugs are used to kill plasmodium?
A
it depends on the stage that the parasite is in.
7
Q
What drug is used to kill plasmodium when it is in the tissues? (i.e exoerythrocytic stage)
A
primaquine
8
Q
What drug is used to kill plasmodium when it is in the blood? (i.e erythrocytic stage)
A
chloroquine
quinine
diaminopyrimidines
mefloquine
9
Q
Name the most common to least common forms of plasmodium?
A
P. vivax > P. falciparum > P. malariae > P. ovale (rare)
10
Q
Why do the symptoms of malaria occur?
A
as a result of release of parasites into the blood stream.
11
Q
What are the clinical signs of malaria?
A
fever, hemolysis, anemia, hypotension.
12
Q
Malaria pathogenicity is a function of the degree of (blank) involvement.
A
erythrocyte
13
Q
(bank) is highly pathogenic because it affects all erythrocytes. These infections are potentially lethal.
A
P. falciparum
14
Q
P. vivax and P. malariae, which affect fewer red blood cells are (lethal/not lethal)
A
not usually lethal
15
Q
In the mosquite, how do you kill sporontocides of malaria?
A
primaquine
proguanil
pyrimethamine
16
Q
In humans, how do you kill tissue shizontocides (its in the liver) of malaria?
A
primaquine
proguanil
pyrimethamine
tetracycline
17
Q
In humans, how do you kill hypozoiticides?
A
primaquine
18
Q
In humans, how do you kill gametocytocides?
A
primaquine
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
20
Q
What was the first antimalarial drug?
A
Quinine (it was derived from the bark of the cinchona tree)
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
22
Q
What are the adverse reactions of quinine?
A
cinchonism (a syndrome similiar to salicylate toxicity) curare effect myocarial depression vasodilation hemolytic anemia
23
Q
When should you use quinine?
A
Used to treat chloroquine-resistant plasmodium falciparum
24
Q
How does chloroquine work?
A
blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!
25
The mechanism of action is similar for all antimalarial quinolones except (blank).
Primaquine
26
Quinolines are weak (blank) that concentrate in food vacuoles of schizonts.
bases
27
(blank) forms of the malaria parasite are sensitive to chloroquine
erythrocytic forms
28
T or F
| Resistant strains of falcparum have arisen and are vary common in Asia
T
29
How do malaria drugs get resistance to quinolines?
polygenetic mechanisms involving expression of transpot proteins that excrete the drug.
30
What is the clinical use of chloroquines?
used for prophylaxis (most common drug used) and treatment of acute attacks
31
What malarial parasites does chloroquine work on?
P. falciparum
32
Why doesn't P. vivax get killed by chloroquine?
because P. vivax exists latent as exoerythrocyticin which is insensitive to drug
33
What are the adverse effects of chloroquine when you take it prophylactically?
prophylactic doses-little toxicity
34
What are the adverse effects of chloroquine when you take it in acute doses?
anorexia, nausea, vomiting, headaches, hemolytic anemia
35
What are the adverse effects of chloroquine when you take it in high doses (amebicidal)?
photosensitization, retinopathy, leukopenia
36
What are the clinical uses of chloroquine?
acute malarial attacks
prophylaxis of malaria
amebiasis
37
How does primaquine work?
binds to DNA, damages mitochondria, inhibits protein synthesis
38
What do you use primaquine for?
used to treat latent liver forms of P. vivax and P. ovale
39
What are the adverse reactions of primaquine?
same as chloroquine
| hemolytic anemia
40
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.
primaquine
41
Does primaquine work on erythrocytic forms of P. falciparum or P. malariae?
No
42
Why can primaquine cause hemolytic anemia?
cuz it is an oxidative stressor and when combined with a G6PD will cause hemolytic anemia
43
Where does primaquine work at?
oxidizes GSH to GSSG
44
(blank) and (blank) can be used alone or in combination to treat drug-resistant P. falciparum.
Artesunate
| artemether
45
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.
Aresunate and artemether (qinghaosu)
46
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.
mefloquinine
| blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!
47
What are the adverse reactions of mefloquine (lariam)?
nausea, vomiting, bradycardia. Serious psychiatric disturbancese can occur (1:1000)
48
What are three antimetabolites used to treat malaria?
| What are they effective against?
Chloroguanide
Pyrimethamine-sulfadoxine (fansidar)
Dapsone
erythrocytic forms of parasite
49
(blank) is a prodrug metabolized by the liver to dihydrotriazine which is a dihydrofolate reductase inhibitor.
chloroguanide
50
(blank) is a fixed dose combination of a dihydrofolate reductase inhibitor and a very long acting sulfonamide (t1/2 7-9 days).
Pyrimethamine-sulfadoxine (fansidar)
51
What is Pyrimethamine-sulfadoxine used on?
chloroquine resistant P. falciparum.
52
(blank) is a PABA analog also used to treat leprosy.
dapsone
53
What step gets inhibited by sulfadoxine?
What step does pyrimethamine inhibit?
What do these prevent from happening?
- pteridine and PABA becoming dihyropteroic acid
- dihydrofolic acid reduction to make dTMP
making folic acid for DNA production
54
(blank) inhibits folic acid synthesis.
pyrimethamine-sulfadoxine (fansidar)
55
What do you use pyrimethamine-sulfadoxine (fansidar) for?
to treat chloroquine-resistant P. falciparum
56
(blank) is used for multi-drug resistant P. falciparum.
mefloquine
57
What is the MOA of mefloquine?
similiar to chloroquine (blocks plasmodial heme polymerization, increases heme concentrations. Heme is toxic to parasites!!!!)
58
What are the adverse effects of mefloquine?
neurologic, acute psychosis, transient encephalopathy with convulsions
59
(blank) are used for multi-drug resistant P. falciparum.
atovaquone and chloroguanide
60
What is the mode of action of chloroguanide?
inhibits malaria dihydrofolate reducatse
61
What are the adverse effects of atovaquone and chloroguanide?
diarrhea, vomiting and kidney failure
62
What is standard in the treatment of P. falciparum?
aremisinin derivatives
63
How do armesinin derivatives work?
cause oxidative stress in the malarial parasite.
64
What are the adverse effects of artemisinin derivatives?
nausea, vomiting, anorexia, and dizziness. Rare but serious allergic reactions
65
Doxycycline (type of tetracycline) is commony used as (blank)
prophylaxis
66
What are the adverse effects of tetracycline?
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
How does metronidazole (flagyl) work?
ETC activates it in anaerobes to create metabolites to bind to and damage DNA
68
What are the adverse reactions to metronidazole (flagyl)?
```
Gi distress
CNS seizure
peripheral neuropathy
Disulfiram effect
Potential mutagen
```
69
Why isnt metronidazole (flagyl) not recommended for pregnant women?
Because of the potential for mutagenic effects on the fetus, particularly in the first trimester
70
What are the clinical uses of metronidazole?
amebiasis, trichomoniasis, giardiasis, anaerobic bacterial infection
71
(blank) is an amebicide that is the most effective and most important antiprotozoal drug.
metronidazole
72
(blank) is an effective luminal amebacide used to treat both symptomatic individuals and asymptomatic carriers of Entamoeba histolytica.
Iodoquinol
73
(blank) is an aminoglycoside
paramomycin
74
(blank) is an luminal amebicide used to treat Entamoeba histolytica infections, mechanism of action is unknown. Kills cysts in asymptomatic carriers.
diloxanide furoate
75
What are 2 combos of dihydrofolate reducate inhibitors and sulfonamides?
trimethoprim-sufamethoxasole (septra)
| pyrimethamine-sulfadoxine (fansidar)
76
(blank) is used to treat Chagas disease. Reduction of this drugs leads to production of toxic oxygen species which damage DNA
nifurtimox
77
What are the adverse reactions to nifurtimox?
```
there is a high incidence of adverse reactions:
Gi distress
headache
vertigo
imsomnia
rash
```
78
(blank) causes oxidative damage to DNA and treats Chagas disease
Nifurtimox
79
(blank) inhibits multiple enzymes and treats african trypanosomiasis
suramin
80
This drug is phagocytized by the parasite and inhibits a variety of enzymes, including enzymes important in energy metabolism.
Suramin
81
What are the adverse reactions of suramin?
they are infrequent;
| include GI distress, neurologic complications and blood dyscrasias
82
What is the most common helminth infection? least common?
```
anclyostoma necator (roundworm)
strongyloides
```
83
What are the antihelminth therapeutic strategies?
inhibit muscle contraction
inhibit energy metabolism
limit distribution of generally toxic drugs
84
What is quinicrine?
an alternative drug for treating giardiasis
85
(blank) is a pentavalent antimonial that may inhibit phosphofructokinase, the rate liminiting enzye in glycolysis. Used to treat leishmaniasis
stibogluconate
86
What are the 2 types of arsenicals?
melasoprol and tryparsamide.
87
What do melasoprol and tryparasamide do?
bind to sulfhydry groups and inhibit pyruvate kinase. Used to treat trypanosomiasis (but replaced now by suramin and nifurtimox)
88
What are platyhelminthes?
flatworms
89
What are cestodes?
a type of flatworm called a tapeworm
90
what 2 drugs do you use to treat cestodes (tapeworms)?
Praziquantel
| paromomycin
91
What does praziquantel attack?
cestodes and flukes
92
How does praziquantel work?
causes a massive influx of calcium and a tetanic contraction of the parasites musculature
93
What are the side effects of praziquantel?
nausea
vomiting
abdominal pain
effects are mild and short lived (48 hr)
94
What is the drug of choice for cestode (tapeworm) and trematode (fluke) infections.
praziquantel
95
(blank) is an alternative to praziquantel in treating liver and lung fluke infections
praziquantel
96
How does bithionol work?
uncouples oxidative phosphorylation
97
What are the adverse effects of bithionol?
nausea, vomiting, diarrhea, rashes, skin photosensitization
98
What are nematodes?
intestinal roundworms
99
What are the four types of nematodes?
ascaris, enterobius, trichuris, hookworm
100
What is a benzimidazole derivate that is a broad spectrum antihelminithic agent.
Mebendazole
101
How does mebendazole work?
binds tubulin and inhibits formation of mitotic spindle. Inhibits glucose uptake.
102
What does metrifonate do?
it is an alternative drug for fluke infections and a cholinesterase inhibitor that attacks s. hematobium
103
What does oxamaquine kill?
S. mansoni
104
What does niridazole kill?
S. mansoni
| S. hematobium
105
What is the common name for nemathelmniths?
roundworms
106
What is the common name for ancylostoma duodenale and necator americanus?
hookworms
107
What is the common name for strongyloids stercoralis?
threadworm
108
What is the common name for tricuris trichuria?
whipworm
109
WHat is a broad spectrum antihelminithic that is chemically similiar to mebendazole.
Albendazole
110
What is the spectrum of mebendazole?
broad
111
What is mebendazole used to treat?
trichuriasis, capillariaisis, hookworm, echinococcosis, enterobiasis, ascariasis
112
Does mebendazole have high toxicity? Whats scary about mebendazole?
no it has low toxicity, cuz its poorly absorbed in GI tract.
| it is potentially teratogenic
113
Why shouldnt you give mebendazole in pregnancy?
exhibits embryotoxicity
114
What is albendazole used to treat?
strongyloidiasis, trichurasis, capillariasis, ascariasis, filariasis, toxocariasis, taenium solium, cysticerus cellulosis; echinococcosis (hydatid disease)
115
How does albendazole work?
disrupts microtubules
116
What are the adverse effects of albendazole?
transient GI discomfort and headache
117
Can you use albendazole in pregnancy?
no (patients should be advised not become pregnant for one month after taking the drug)
118
What is thiabendazole used to treat?
strongyloidiasis, nematode larva infections
119
How does thiabendazole work?
blocks helminth specific enzyme fumarate reductase and binds tubulin
120
What does thiabendazole have a high incident of?
nausea, vomiting, anorexia
121
(blank) is an older drug, produces a hyperpolarizing neuromuscular blockad and flaccid paralysis of the worms.
piperazine
122
What is the fancy name for tissue roundworms?
filarial worms (wuchereria, brugia, oa loa, onchocerca)
123
What are the tissue roundworms?
```
trichinella spiralis
wicheria bancrofti
brugia malayi
loa loa
onchocerca volvulus
```
124
How does diethylcarbamazine (DEC) work?
enchances the immune response of the host to the parasite; by releasing antigenic components of the parasites cuticle or by affecting lymphokine production.
125
Diethylcarbamizine (DEC) inhibits (blank)
lipoxygenase
126
What is the clinical use of diethylcarbamazine (DEC)?
tissue and blood nematodes
127
What are the adverse reactions of diethylcarbamzine (DEC)?
headache malaise, weakness, nausea, inflammatory reactions secondary to breakdown of dead microfilariea (mazotti reaction)
128
How does ivermectin work?
paralyzes a number of helminths by activating glutamate-activated chloride channels in nerves and muscle cells.
129
Is ivermectin well tolerated?
yes :)
130
What can you use ivermectin against?
nematodes: onchocerciasis, enterobius, strongyloides, trichuris, ascaris
131
Is ivermectin effective against cestodes and trematodes?
NO
132
What is ivermectin recommended for?
strongyloides infections
133
Is it more or less safe than diethlycarbamazine in treatment of filarial worm infections (onchocerca)?
more safe and more effective
