Anti-Parasitics Flashcards
(180 cards)
1
Q
Are there vaccines for parasites?
A
No
2
Q
What is constantly a problem in dealing with parasites?
A
Resistance
3
Q
From what genus is malaria from?
A
Plasmodium
4
Q
What are the 5 malaria parasites?
A
1) Falciparum
2) Vivax
3) Ovale
4) Malariae
5) Knowlesi
5
Q
Which malaria is responsible for most deaths?
A
Falciparum
6
Q
Which malaria is known to be “relapsing” due to hypozoites in the liver?
A
Vivax
7
Q
What is a hypnozoite?
A
Dormant form of malaria
8
Q
What is a second type of “relapsing” malaria found primarily in West Africa?
A
Ovale
9
Q
Which malaria has a 24 hour life cycle and causes zoonotic infections?
A
Knowlesi
10
Q
What is the first stage in the life cycle of falciparum?
A
Mosquito injects sporozoites (motile sporelike organism that is typically the infective agent introduced in the host).
11
Q
After injection (stage 1) where do the sporozoites go and what do they become?
A
Liver and they form merozoites
12
Q
What do merozoites do after stage 2?
A
Invade red blood cells
13
Q
What happens after the merozoites infects the RBC?
A
It becomes a trophozoite (growing stage where it saps nutrients)
14
Q
What happens to the trophozoites in the RBCs?
A
They multiply producing new merozoites.
15
Q
What happens when the multiplied merozoites cause the RBC to rupture?
A
They infect other RBCs
16
Q
What else can merozoites do besides infect new cells?
A
Become gametocytes
17
Q
What do the gametocytes do?
A
Get picked up by new mosquito where they grow into sporozoites.
18
Q
Classic symptoms of uncomplicated malaria?
A
Cold stage, hot stage, sweating stage, 48 hour periodicity for Falciparum and Vivax
19
Q
More usual symptoms of uncomplicated malaria?
A
Fever and flu symptoms, anemia and jaundice
20
Q
Signs of cerebral malaria?
A
Abnormal behavior, consciousness impairment, seizures, coma, and other neurologic complications
21
Q
In severe malaria what will be seen in the urine?
A
Hemoglobinuria
22
Q
When and how can malaria affect pregnancy?
A
Especially first pregnancy and causes low birth weight and miscarriage.
23
Q
What are the 3 types of drug classification for malaria?
A
Tissue schizonticides, blood schizonticides, and gametocytocides.
24
Q
What do tissue schizontices do?
A
Kill liver stage parasites
25
What do blood schizontices do?
Kill erythrocytic forms
26
What do gametocytocides do?
Kill sexual stages and block transmission.
27
Best option to deal with malaria?
Prevention
28
When should chemoprophylaxis be taken?
Before, during, and after travel
29
What should you consider before traveling?
Species the area, level/type of resistance, and time before travel
30
Prevention 1-2 days prior and 7 days after
Malarone: Atovaquine + Proguanil
31
Prevention 1-2 days prior and 4 weeks after
Doxycycline
32
Prevention 1-2 weeks prior and 4 weeks after
Chloroquine
33
Prevention more than 2 weeks before and continue 4 weeks after
Mefloquine
34
Prevention if >90 Vivax in area w/ 1-2 days prior and 7 days after
Primaquine
35
Main treatment for complicated malaria?
Quinidine gluconate plus doxycycline, tetracycline, or clindamycin.
36
Drawbacks of quinidine gluconate?
Hypotension, wide QRS/long QTc interval, and hypoglycemia
37
If quinidine gluconate doesn't work what then?
Artsunate followed by malarian, doxycycline, or mefloquine
38
How is Artsunate administered?
IV only
39
3 characteristics about Artemisinin drug?
1) Potent and fast acting (10,000 fold reduction of parasites in 48 hours)
2) Low Toxicity
3) Resistance observed in SE Asia
40
How is Artemisinin activated?
Via heme iron
41
How does Artemisinin function?
Forms free radicals that target parasite proteins and lipids
42
How is Artemisinin shut down/resisted?
Mutations in Kelch 13 gene
43
What parasites does Artemisinin work on?
Blood schizonticide, not liver stages
44
How long is the half life of Artemisinin?
1-2 hours
45
How can Artemisinin be taken?
Only orally so low bioavailability
46
What do you do to correct for the low bioavailability of Artsemisinin?
Administer a semisynthetic via different route of transmission.
47
What pharmacologically association determines the effectiveness of Artemisinin?
Cmax
48
What is another way to counteract the short acting characteristic of Artemisinin?
Combine it with a drug with a longer half life.
49
When can artemisinin affect pregnancy?
First trimester
50
What are adverse side effects of Artemisinin?
Nausea, vomiting, diarrhea, and dizziness.
51
How does Chloroquine work?
Inhibits hemoglobin metabolism
52
How do parasites metabolize hemoglobin?
Ingestion of HG, breakdown into free heme, heme (toxic) to hemozoin (nontoxic)
53
What do 4-substituted quinolines interfere with?
Heme polymerization
54
Half life of Chloroquine?
3-5 days
55
How is Chlorquine taken?
Orally
56
Main side effect of Chloroquine?
Itching
57
When do you not use Chloroquine?
Psoriasis or prophyria, retina or visual field abnormalities, and myopathy
58
What interferes with absorption of Chloroquine?
Antidiarrheals and antiacids
59
Which malaria has the most resistance to Chloroquine?
Falciparum and Vivax
60
Where is the mutation that grants the resistance to Chlorquine?
PfCRT1 in the food vacuole
61
What is the mechanism for Quinine?
Similar to Chloroquinine with inhibition of heme polymerization
62
When do we use Quinine?
Chloroquinine resistant strains
63
What specific Quinine do we use for Chloroquinine resistant falciparum?
Quinine sulfate via oral
64
What specific Quinine do we use for severe falciparum malaria?
Quinidine gluconate via IV
65
Why do we not use quinine for prophylaxis?
Short half life and toxicity
66
What is cinchonism?
OD of Quinine. Tinting, headache, nausea, dizziness, flushing, and visual problems
67
How can Quinine affect pregnancy?
Stimulate uterine contractions
68
How can Quinine affect blood?
G6PD deficiency and blackwater fever (marked by hemoglobinuria)
69
What metabolizes Quinine?
CYP3A4
70
How can Quinine cause hypotension?
Too rapid infusion.
71
What does Mefloquine target?
Erythrocytic forms of falciparum and vivax
72
What is Mefloquine used for?
Prophylaxis and treatment
73
Problem with Mefloquine?
Neuropsychiatric toxicity: Seizures, toxic psychosis, and sleep disturbance
74
What metabolizes Primaquine?
CYP2D6
75
What is Primaquine best used for?
Liver stages hypnozoites of Vivax and Ovale
76
What is Primaquine gametocidal against?
All 4 malaria parasites
77
When do you not want to use Primaquine?
G6PD deficinecy, pregnancy, and breast feeding
78
What drug is very similar to Primaquine?
Tafenoquine
79
What is Malarone a combination of?
Proguanil and Atavaquone
80
Why did Atavaquone fail solo?
Resistance development
81
What does Malarone kill?
Liver and blood stages, no hypnozoites
82
What can Malarone be used for?
Uncomplicated Malaria and chemoprophylaxs
83
What non malarias can Atavaquone be used to treat?
Toxoplasma gondii and Pneumocystis jiroveci
84
How does Atavaquone work?
Selective inhibitor of malaria mitochondrial cytochrome bc1 complex.
85
What happens in Atavaquone inhibition?
Electron transport doesn't work, mitochondrial membrane potential collapses.
86
What does electron transport in falciparum mainly do?
Regenerate ubiquinone
87
What does Proguanil do?
Gets converted to cycloguanil which inhibits parasite purine and pyrimidine synthesis
88
What does Proguanil enhance?
Mitochondrial toxicity of Atavaquone
89
What do Pyrimethamine-Sulfadoxine (Fansidar) drugs inhibit>
Folate synthesis inhibitors
90
What does Fansidar act on?
Slowly acts on erythrocytic schizonticides
91
What else can Fansidar like drugs be used to treat?
Toxoplasmosis
92
What does Pyrimethamine act on?
Inhibits plasmodia DHF reductase which has 1000 fold selectivity for Plasmodium
93
Two other uses of antifolates?
Toxoplasmosis and Pneumocytis
94
Why do we not use single antifolates?
Resistances develop quickly
95
Pharmokinetically what is the advantage of antifolateS?
Both pieces have long half lives and allow for 20 fold reduction in dose size of each component
96
What class of antimalarial do Tetracycline, doxycycline, and clindamycin fall under?
Blood schizonticides
97
What do the antibiotics target of the parasites?
Apicoplast (plant like organelle that carries out biochemical processes)
98
What is doxycycline normally paired with?
Quinine or Quinidine
99
When is Doxy paired with Quinine or Quinidine?
Falciparum
100
When is Doxy used for chemoprophylaxis?
Areas with high resistance to mefloquine
101
What is Toxoplasma gone related to>
Plasmodium
102
What is the definitive host for Toxoplasmosis?
Cats
103
How do you get Toxoplasmosis?
Raw meat, cat feces
104
What problems can cause a severe toxoplasmosis case?
HIV/AIDs, organ transplant and chemotherapy
105
When can congenital toxoplasmosis become a problem?
Via placenta for women who are infected for the first time
106
How do you treat Toxoplasmosis?
Pyrimethamine + Sulfadiazine
107
What are main parasites associated with HIV in U.S.?
Pneumocystis jirovecii, Toxoplasma gondii, and Cryptosporidium
108
Main parasites and HIV globally?
Malaria, Leishmania, and Trypanosome Cruzi (Chagas Disease)
109
Mechanism for Pentamidine?
Unknown, speculated to accumulate in parasites
110
Problem with Pentamidine?
Highly toxic showing side effects in 50% of patients. Causes hype or hyperglycemia
111
What do you use Pentamidine for?
Trypanosomiasis or alternative treatment for visceral leishmania and pneumocystosis
112
What are 3 anaerobic protozoa?
1) Entamoeba histolitica
2) Giardia lamblia
3) Trichomonas vaginalis
113
How is Giardia transmitted?
Water borne disease
114
How is Trichomonas vaginalis transmitted?
Sexually transmitted
115
What is the first stage of Entamoeba histolytica?
Ingestion of cysts
116
What happens after you eat the cysts of Entamoeba?
They form trophozoites
117
Where do the trophozoites of Entamoeba go?
Penetrate intestinal wall
118
Where do the trophozoites multiply in Entamoeba?
Colon wall
119
After trophozoites of Entamoeba multiply where do they go>
Liver
120
What happens to trophozoites of Entamoeba that don't invade?
Discarded with feces
121
What does Entamoeba cause
Diarrhea and cysts on lining of intestine
122
How do you kill cysts of Entamoeba?
Boiling, chlorination doesn't work
123
How does Amebiasis spread?
Poor sanitation and fecal contamination of food/water
124
How does Amebiasis usually present?
Asymptomatic
125
What symptoms does Amebiasis show when it isn't asymptomatic?
Diarrhea, flatulance, abdominal cramps, and liver abcess
126
What is the most common intestinal parasite in the US?
Giardia lamblia
127
Treatment of choice for Giardia?
Metronidazole or Nitazoxanide
128
What is the most frequent cause of recreational water related disease outbreaks in US?
Cryptosporidium
129
Most common symptom of Cryptosporidium?
Watery diarrhea followed by cramps, dehydration, cause/vomiting, fever and weight loss
130
Best way to treat Cryptosporidium?
Nitazoxanide
131
Where does Trichomonas reside?
Lower female genital tract/Male urethra and prostate
132
How does Trichomonas present in men?
Asymptomatic
133
How does Trichomonas present in women?
Vaginitis with purulent discharge, vulvar and cervical lesions, dysuria, and dyspareunia
134
Best way to treat Entamoeba, guard, and trichomonas?
Metronidazole
135
Concerning anaerobic parasites what does Metronidazole kill?
Trophozoites, not cysts
136
What is a drug similar to Metronidazole but less toxic>
Tinidazole
137
What is the mechanism of Metronidazole?
Not known, but speculated to involve electron transport proteins of anaerobes that activate metronidazole
138
What will interact with Metronidazole to cause Anatabuse effect (nausea, vomiting, and heart rate)?
Alcohol. Metronidazole inhibits acetaldehyde dehydrogenase
139
What is the drug you use for intestinal amebiasis?
Paromomycin
140
What are 3 characteristics of Paromomycin?
1) Not significantly absorbed into GI tract
2) Similar efficacy and less toxicity
3) Also works on Cryptosporidium
141
What is a good alternative to Paromomycin?
Iodoquinol with metronidazole
142
What is Nitazoxanide metabolized to?
Tizoxanide
143
What is mechanism of Nitazoxanide?
Uncertain, inhibits anaerobic metabolism and interferes with pyruvate ferredoxin oxidoreductase
144
What does Nitazoxande inhibit?
Growth of sporozoites and oocysts of Cryptosporidium and trophozoites of Giardia
145
What parasites fall under the category of Kinetoplasmids?(3)
1) Leishmania
2) African Trypanosomes
3) American Trypanosomes
146
Of the two main African Trypanosomes which is more prevalent?
Trypanosoma brucei gambiense (95%)
| Rhodesiense (5%) think rhinos extinctish
147
Which Trypanosome is the American version?
Cruzi (Americans go on Cruises)
148
What are the unique organelles of the Kinetoplastids?
Kinetoplast and glycosome
149
How do you treat Leishmaniasis?
Sodium stibogluconate or Amphotericin B
| Miltefosine as alternative
150
How do you treat early stage African trypanosomiasis?
Pentamidine for West africa, Suramin for East
151
Late stage trypanosomiasis?
Melarsoprol or Eflornithine
152
How do you treat American Trypanosomiasis?
Nifurtimox or Benznidazole
153
Is Miletefosine to be used during pregnancy?
No
154
What is Miletefosine used to treat>
Leishmania
155
Most commonly used drug for T. cruzi?
Nifurtimox and Benznidazole
156
What is the mechanism Nifurtimox and Benznidazole work?
Unknown, but activated by NADH dependent mitochondrial nitroreductase. Generates nitro radical anions
157
Side effects of Nifurtimox and Benznidazole?
Toxicity common, hypersensitivity, GI complications
158
What is a Helminth infection?
Worm infection
159
Where do worms multiply?
Outside of definitive host
160
How do worms stay in the body?
Evade immune system and stay in host for lifetime
161
Most common helminth infection?
Ascaris
162
What causes cysticercosis?
Ingesting eggs of T. solium
163
What happens in systicercosis after ingesting eggs?
Hatch in intestine, invade wall, and migrate to striated muscles, brain, liver, and other tissues where they develop into cysticerci
164
How do you treat helminths?
Benzimidazoles
165
What are the 3 main benzimidazoles on the market?
1) Mebendazole
2) Thiabendazole
3) Albendazole
166
What is the mechanism of Benzimidazoles?
Binds to tubulin and inhibits formation of microtubules. Cap plus end of microtubules
167
Drug of choice for Albendazole?
Cysticercosis
168
Why is Thiabendazole no longer preferred?
Toxicity and teratogen
169
What is Praziquantel effective against?
Cestodes and trematodes, not nematodes
170
Mechanism of Praziquantel?
Increased muscular activity that detaches worms from blood vessels
171
Drug of choice for all schistosomiasis?
Praziquantel, kills 100% of Saginata, Solium, and Latum. Doesn't kill eggs of Solium
172
Drug of choice for Strongyloidiasis and Onchocerciasis?
Ivermectin
173
How does Ivermectin function?
Paralyzes microfilariae and blocks progeny, allows cytotoxic cells to adhere. Doesn't kill adults
174
Primary use of Ivermectin
Treatment of Onchocerciasis, can be used for ascariasis, enterobiasis, strongyloidiasis, and filariasis as well
175
What is Pyrantel Pamoate?
Antihelminth
176
What is Pyrantel Pamoate used for?
Pinworms and ascaris, also hookworms. Not good for migratory stages or ova
177
Mechanism of Pyrantel Pamoate?
Inhibits cholinesterase
178
What caused Scabies?
Itch mite, sarcoptes scabei
179
How do you treat Scabies?
Permethrin cream
180
How do you treat head lice?
Permethrin or spinosad
