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Pharmacology Exam 2 > Anti-Parasitics > Flashcards

Anti-Parasitics Flashcards

1
Q

Are there vaccines for parasites?

A

No

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2
Q

What is constantly a problem in dealing with parasites?

A

Resistance

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3
Q

From what genus is malaria from?

A

Plasmodium

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4
Q

What are the 5 malaria parasites?

A

1) Falciparum
2) Vivax
3) Ovale
4) Malariae
5) Knowlesi

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5
Q

Which malaria is responsible for most deaths?

A

Falciparum

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6
Q

Which malaria is known to be “relapsing” due to hypozoites in the liver?

A

Vivax

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7
Q

What is a hypnozoite?

A

Dormant form of malaria

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8
Q

What is a second type of “relapsing” malaria found primarily in West Africa?

A

Ovale

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9
Q

Which malaria has a 24 hour life cycle and causes zoonotic infections?

A

Knowlesi

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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).

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11
Q

After injection (stage 1) where do the sporozoites go and what do they become?

A

Liver and they form merozoites

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12
Q

What do merozoites do after stage 2?

A

Invade red blood cells

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13
Q

What happens after the merozoites infects the RBC?

A

It becomes a trophozoite (growing stage where it saps nutrients)

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14
Q

What happens to the trophozoites in the RBCs?

A

They multiply producing new merozoites.

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15
Q

What happens when the multiplied merozoites cause the RBC to rupture?

A

They infect other RBCs

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16
Q

What else can merozoites do besides infect new cells?

A

Become gametocytes

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17
Q

What do the gametocytes do?

A

Get picked up by new mosquito where they grow into sporozoites.

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18
Q

Classic symptoms of uncomplicated malaria?

A

Cold stage, hot stage, sweating stage, 48 hour periodicity for Falciparum and Vivax

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19
Q

More usual symptoms of uncomplicated malaria?

A

Fever and flu symptoms, anemia and jaundice

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20
Q

Signs of cerebral malaria?

A

Abnormal behavior, consciousness impairment, seizures, coma, and other neurologic complications

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21
Q

In severe malaria what will be seen in the urine?

A

Hemoglobinuria

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22
Q

When and how can malaria affect pregnancy?

A

Especially first pregnancy and causes low birth weight and miscarriage.

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23
Q

What are the 3 types of drug classification for malaria?

A

Tissue schizonticides, blood schizonticides, and gametocytocides.

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24
Q

What do tissue schizontices do?

A

Kill liver stage parasites

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25
Q

What do blood schizontices do?

A

Kill erythrocytic forms

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26
Q

What do gametocytocides do?

A

Kill sexual stages and block transmission.

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27
Q

Best option to deal with malaria?

A

Prevention

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28
Q

When should chemoprophylaxis be taken?

A

Before, during, and after travel

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29
Q

What should you consider before traveling?

A

Species the area, level/type of resistance, and time before travel

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30
Q

Prevention 1-2 days prior and 7 days after

A

Malarone: Atovaquine + Proguanil

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31
Q

Prevention 1-2 days prior and 4 weeks after

A

Doxycycline

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32
Q

Prevention 1-2 weeks prior and 4 weeks after

A

Chloroquine

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33
Q

Prevention more than 2 weeks before and continue 4 weeks after

A

Mefloquine

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34
Q

Prevention if >90 Vivax in area w/ 1-2 days prior and 7 days after

A

Primaquine

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35
Q

Main treatment for complicated malaria?

A

Quinidine gluconate plus doxycycline, tetracycline, or clindamycin.

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36
Q

Drawbacks of quinidine gluconate?

A

Hypotension, wide QRS/long QTc interval, and hypoglycemia

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37
Q

If quinidine gluconate doesn’t work what then?

A

Artsunate followed by malarian, doxycycline, or mefloquine

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38
Q

How is Artsunate administered?

A

IV only

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39
Q

3 characteristics about Artemisinin drug?

A

1) Potent and fast acting (10,000 fold reduction of parasites in 48 hours)
2) Low Toxicity
3) Resistance observed in SE Asia

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40
Q

How is Artemisinin activated?

A

Via heme iron

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41
Q

How does Artemisinin function?

A

Forms free radicals that target parasite proteins and lipids

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42
Q

How is Artemisinin shut down/resisted?

A

Mutations in Kelch 13 gene

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43
Q

What parasites does Artemisinin work on?

A

Blood schizonticide, not liver stages

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44
Q

How long is the half life of Artemisinin?

A

1-2 hours

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45
Q

How can Artemisinin be taken?

A

Only orally so low bioavailability

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46
Q

What do you do to correct for the low bioavailability of Artsemisinin?

A

Administer a semisynthetic via different route of transmission.

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47
Q

What pharmacologically association determines the effectiveness of Artemisinin?

A

Cmax

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48
Q

What is another way to counteract the short acting characteristic of Artemisinin?

A

Combine it with a drug with a longer half life.

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49
Q

When can artemisinin affect pregnancy?

A

First trimester

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50
Q

What are adverse side effects of Artemisinin?

A

Nausea, vomiting, diarrhea, and dizziness.

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51
Q

How does Chloroquine work?

A

Inhibits hemoglobin metabolism

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52
Q

How do parasites metabolize hemoglobin?

A

Ingestion of HG, breakdown into free heme, heme (toxic) to hemozoin (nontoxic)

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53
Q

What do 4-substituted quinolines interfere with?

A

Heme polymerization

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54
Q

Half life of Chloroquine?

A

3-5 days

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55
Q

How is Chlorquine taken?

A

Orally

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56
Q

Main side effect of Chloroquine?

A

Itching

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57
Q

When do you not use Chloroquine?

A

Psoriasis or prophyria, retina or visual field abnormalities, and myopathy

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58
Q

What interferes with absorption of Chloroquine?

A

Antidiarrheals and antiacids

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59
Q

Which malaria has the most resistance to Chloroquine?

A

Falciparum and Vivax

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60
Q

Where is the mutation that grants the resistance to Chlorquine?

A

PfCRT1 in the food vacuole

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61
Q

What is the mechanism for Quinine?

A

Similar to Chloroquinine with inhibition of heme polymerization

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62
Q

When do we use Quinine?

A

Chloroquinine resistant strains

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63
Q

What specific Quinine do we use for Chloroquinine resistant falciparum?

A

Quinine sulfate via oral

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64
Q

What specific Quinine do we use for severe falciparum malaria?

A

Quinidine gluconate via IV

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65
Q

Why do we not use quinine for prophylaxis?

A

Short half life and toxicity

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66
Q

What is cinchonism?

A

OD of Quinine. Tinting, headache, nausea, dizziness, flushing, and visual problems

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67
Q

How can Quinine affect pregnancy?

A

Stimulate uterine contractions

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68
Q

How can Quinine affect blood?

A

G6PD deficiency and blackwater fever (marked by hemoglobinuria)

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69
Q

What metabolizes Quinine?

A

CYP3A4

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70
Q

How can Quinine cause hypotension?

A

Too rapid infusion.

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71
Q

What does Mefloquine target?

A

Erythrocytic forms of falciparum and vivax

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72
Q

What is Mefloquine used for?

A

Prophylaxis and treatment

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73
Q

Problem with Mefloquine?

A

Neuropsychiatric toxicity: Seizures, toxic psychosis, and sleep disturbance

74
Q

What metabolizes Primaquine?

75
Q

What is Primaquine best used for?

A

Liver stages hypnozoites of Vivax and Ovale

76
Q

What is Primaquine gametocidal against?

A

All 4 malaria parasites

77
Q

When do you not want to use Primaquine?

A

G6PD deficinecy, pregnancy, and breast feeding

78
Q

What drug is very similar to Primaquine?

A

Tafenoquine

79
Q

What is Malarone a combination of?

A

Proguanil and Atavaquone

80
Q

Why did Atavaquone fail solo?

A

Resistance development

81
Q

What does Malarone kill?

A

Liver and blood stages, no hypnozoites

82
Q

What can Malarone be used for?

A

Uncomplicated Malaria and chemoprophylaxs

83
Q

What non malarias can Atavaquone be used to treat?

A

Toxoplasma gondii and Pneumocystis jiroveci

84
Q

How does Atavaquone work?

A

Selective inhibitor of malaria mitochondrial cytochrome bc1 complex.

85
Q

What happens in Atavaquone inhibition?

A

Electron transport doesn’t work, mitochondrial membrane potential collapses.

86
Q

What does electron transport in falciparum mainly do?

A

Regenerate ubiquinone

87
Q

What does Proguanil do?

A

Gets converted to cycloguanil which inhibits parasite purine and pyrimidine synthesis

88
Q

What does Proguanil enhance?

A

Mitochondrial toxicity of Atavaquone

89
Q

What do Pyrimethamine-Sulfadoxine (Fansidar) drugs inhibit>

A

Folate synthesis inhibitors

90
Q

What does Fansidar act on?

A

Slowly acts on erythrocytic schizonticides

91
Q

What else can Fansidar like drugs be used to treat?

A

Toxoplasmosis

92
Q

What does Pyrimethamine act on?

A

Inhibits plasmodia DHF reductase which has 1000 fold selectivity for Plasmodium

93
Q

Two other uses of antifolates?

A

Toxoplasmosis and Pneumocytis

94
Q

Why do we not use single antifolates?

A

Resistances develop quickly

95
Q

Pharmokinetically what is the advantage of antifolateS?

A

Both pieces have long half lives and allow for 20 fold reduction in dose size of each component

96
Q

What class of antimalarial do Tetracycline, doxycycline, and clindamycin fall under?

A

Blood schizonticides

97
Q

What do the antibiotics target of the parasites?

A

Apicoplast (plant like organelle that carries out biochemical processes)

98
Q

What is doxycycline normally paired with?

A

Quinine or Quinidine

99
Q

When is Doxy paired with Quinine or Quinidine?

A

Falciparum

100
Q

When is Doxy used for chemoprophylaxis?

A

Areas with high resistance to mefloquine

101
Q

What is Toxoplasma gone related to>

A

Plasmodium

102
Q

What is the definitive host for Toxoplasmosis?

103
Q

How do you get Toxoplasmosis?

A

Raw meat, cat feces

104
Q

What problems can cause a severe toxoplasmosis case?

A

HIV/AIDs, organ transplant and chemotherapy

105
Q

When can congenital toxoplasmosis become a problem?

A

Via placenta for women who are infected for the first time

106
Q

How do you treat Toxoplasmosis?

A

Pyrimethamine + Sulfadiazine

107
Q

What are main parasites associated with HIV in U.S.?

A

Pneumocystis jirovecii, Toxoplasma gondii, and Cryptosporidium

108
Q

Main parasites and HIV globally?

A

Malaria, Leishmania, and Trypanosome Cruzi (Chagas Disease)

109
Q

Mechanism for Pentamidine?

A

Unknown, speculated to accumulate in parasites

110
Q

Problem with Pentamidine?

A

Highly toxic showing side effects in 50% of patients. Causes hype or hyperglycemia

111
Q

What do you use Pentamidine for?

A

Trypanosomiasis or alternative treatment for visceral leishmania and pneumocystosis

112
Q

What are 3 anaerobic protozoa?

A

1) Entamoeba histolitica
2) Giardia lamblia
3) Trichomonas vaginalis

113
Q

How is Giardia transmitted?

A

Water borne disease

114
Q

How is Trichomonas vaginalis transmitted?

A

Sexually transmitted

115
Q

What is the first stage of Entamoeba histolytica?

A

Ingestion of cysts

116
Q

What happens after you eat the cysts of Entamoeba?

A

They form trophozoites

117
Q

Where do the trophozoites of Entamoeba go?

A

Penetrate intestinal wall

118
Q

Where do the trophozoites multiply in Entamoeba?

A

Colon wall

119
Q

After trophozoites of Entamoeba multiply where do they go>

120
Q

What happens to trophozoites of Entamoeba that don’t invade?

A

Discarded with feces

121
Q

What does Entamoeba cause

A

Diarrhea and cysts on lining of intestine

122
Q

How do you kill cysts of Entamoeba?

A

Boiling, chlorination doesn’t work

123
Q

How does Amebiasis spread?

A

Poor sanitation and fecal contamination of food/water

124
Q

How does Amebiasis usually present?

A

Asymptomatic

125
Q

What symptoms does Amebiasis show when it isn’t asymptomatic?

A

Diarrhea, flatulance, abdominal cramps, and liver abcess

126
Q

What is the most common intestinal parasite in the US?

A

Giardia lamblia

127
Q

Treatment of choice for Giardia?

A

Metronidazole or Nitazoxanide

128
Q

What is the most frequent cause of recreational water related disease outbreaks in US?

A

Cryptosporidium

129
Q

Most common symptom of Cryptosporidium?

A

Watery diarrhea followed by cramps, dehydration, cause/vomiting, fever and weight loss

130
Q

Best way to treat Cryptosporidium?

A

Nitazoxanide

131
Q

Where does Trichomonas reside?

A

Lower female genital tract/Male urethra and prostate

132
Q

How does Trichomonas present in men?

A

Asymptomatic

133
Q

How does Trichomonas present in women?

A

Vaginitis with purulent discharge, vulvar and cervical lesions, dysuria, and dyspareunia

134
Q

Best way to treat Entamoeba, guard, and trichomonas?

A

Metronidazole

135
Q

Concerning anaerobic parasites what does Metronidazole kill?

A

Trophozoites, not cysts

136
Q

What is a drug similar to Metronidazole but less toxic>

A

Tinidazole

137
Q

What is the mechanism of Metronidazole?

A

Not known, but speculated to involve electron transport proteins of anaerobes that activate metronidazole

138
Q

What will interact with Metronidazole to cause Anatabuse effect (nausea, vomiting, and heart rate)?

A

Alcohol. Metronidazole inhibits acetaldehyde dehydrogenase

139
Q

What is the drug you use for intestinal amebiasis?

A

Paromomycin

140
Q

What are 3 characteristics of Paromomycin?

A

1) Not significantly absorbed into GI tract
2) Similar efficacy and less toxicity
3) Also works on Cryptosporidium

141
Q

What is a good alternative to Paromomycin?

A

Iodoquinol with metronidazole

142
Q

What is Nitazoxanide metabolized to?

A

Tizoxanide

143
Q

What is mechanism of Nitazoxanide?

A

Uncertain, inhibits anaerobic metabolism and interferes with pyruvate ferredoxin oxidoreductase

144
Q

What does Nitazoxande inhibit?

A

Growth of sporozoites and oocysts of Cryptosporidium and trophozoites of Giardia

145
Q

What parasites fall under the category of Kinetoplasmids?(3)

A

1) Leishmania
2) African Trypanosomes
3) American Trypanosomes

146
Q

Of the two main African Trypanosomes which is more prevalent?

A

Trypanosoma brucei gambiense (95%)

Rhodesiense (5%) think rhinos extinctish

147
Q

Which Trypanosome is the American version?

A

Cruzi (Americans go on Cruises)

148
Q

What are the unique organelles of the Kinetoplastids?

A

Kinetoplast and glycosome

149
Q

How do you treat Leishmaniasis?

A

Sodium stibogluconate or Amphotericin B

Miltefosine as alternative

150
Q

How do you treat early stage African trypanosomiasis?

A

Pentamidine for West africa, Suramin for East

151
Q

Late stage trypanosomiasis?

A

Melarsoprol or Eflornithine

152
Q

How do you treat American Trypanosomiasis?

A

Nifurtimox or Benznidazole

153
Q

Is Miletefosine to be used during pregnancy?

154
Q

What is Miletefosine used to treat>

A

Leishmania

155
Q

Most commonly used drug for T. cruzi?

A

Nifurtimox and Benznidazole

156
Q

What is the mechanism Nifurtimox and Benznidazole work?

A

Unknown, but activated by NADH dependent mitochondrial nitroreductase. Generates nitro radical anions

157
Q

Side effects of Nifurtimox and Benznidazole?

A

Toxicity common, hypersensitivity, GI complications

158
Q

What is a Helminth infection?

A

Worm infection

159
Q

Where do worms multiply?

A

Outside of definitive host

160
Q

How do worms stay in the body?

A

Evade immune system and stay in host for lifetime

161
Q

Most common helminth infection?

162
Q

What causes cysticercosis?

A

Ingesting eggs of T. solium

163
Q

What happens in systicercosis after ingesting eggs?

A

Hatch in intestine, invade wall, and migrate to striated muscles, brain, liver, and other tissues where they develop into cysticerci

164
Q

How do you treat helminths?

A

Benzimidazoles

165
Q

What are the 3 main benzimidazoles on the market?

A

1) Mebendazole
2) Thiabendazole
3) Albendazole

166
Q

What is the mechanism of Benzimidazoles?

A

Binds to tubulin and inhibits formation of microtubules. Cap plus end of microtubules

167
Q

Drug of choice for Albendazole?

A

Cysticercosis

168
Q

Why is Thiabendazole no longer preferred?

A

Toxicity and teratogen

169
Q

What is Praziquantel effective against?

A

Cestodes and trematodes, not nematodes

170
Q

Mechanism of Praziquantel?

A

Increased muscular activity that detaches worms from blood vessels

171
Q

Drug of choice for all schistosomiasis?

A

Praziquantel, kills 100% of Saginata, Solium, and Latum. Doesn’t kill eggs of Solium

172
Q

Drug of choice for Strongyloidiasis and Onchocerciasis?

A

Ivermectin

173
Q

How does Ivermectin function?

A

Paralyzes microfilariae and blocks progeny, allows cytotoxic cells to adhere. Doesn’t kill adults

174
Q

Primary use of Ivermectin

A

Treatment of Onchocerciasis, can be used for ascariasis, enterobiasis, strongyloidiasis, and filariasis as well

175
Q

What is Pyrantel Pamoate?

A

Antihelminth

176
Q

What is Pyrantel Pamoate used for?

A

Pinworms and ascaris, also hookworms. Not good for migratory stages or ova

177
Q

Mechanism of Pyrantel Pamoate?

A

Inhibits cholinesterase

178
Q

What caused Scabies?

A

Itch mite, sarcoptes scabei

179
Q

How do you treat Scabies?

A

Permethrin cream

180
Q

How do you treat head lice?

A

Permethrin or spinosad

Pharmacology Exam 2 (9 decks)

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