Antimalarial & Antiparasitic Flashcards

(38 cards)

1
Q

Three parasitic infections associated with HIV in the US

A

Pneumocystic jirovecii - Pneumonia
Toxoplasma gondii - Encephalitis
Cryptosporidium - Cryptosporidosis

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2
Q

Three parasitic infections associated with HIV Globally

A

Malaria, Leshmania

Trypanosoma cruzi - Chagas

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3
Q

Who is most likely to contract fatal malarial cases?

A

African children < 5 years old. If they make it past 5, they developed preventative immunity.

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4
Q

What is the Plasmodium responsible for most malarial deaths and why?

A

P. falciparum. Africa, SE Asia, South America. P. falciparum can infect RBCs of all ages (vs. others can only infect reticulocytes).

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5
Q

Regions here P. vivax and P. ovale are found. What type of malaria do they cause and why?

A

vivax - subtropics and temperate regions.
ovale - West Africa.
relapsing - hypnozoites in the liver

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6
Q

What are the time courses of the erythrocytic lytic cycle of P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi?

A

P. falciparum - continuous
P. malariae - 72 hrs. (quartan)
P. vivax and ovale - 48 hours (tertian)
P. knowlesi - 24 hrs. (secondary) - RAPID DISEASE progression

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7
Q

What are the names of the different stages of the malaria parasite life cycle? Which stage is infectious? which stage is latent? Which stages are sexual vs. asexual?

A

Sporozoites injected by mosquito, Schizonts and Hypnozoites (latent) formed in the LIVER. Schizonts are asexual. Schizonts invade RBCs, divide, rupture RBC, release Merozoites that re-invade. Merozoites are sexual and produce gametocytes. Gametocytes taken up by mosquito.

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8
Q

What do most malarial drugs target? What are there NO drugs for, and why is this significant?

A

Target parasite lifecycle and NOT the inflammatory response. No drugs for sporozoite form - therefore cannot prevent infection of cells.

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9
Q

What is a schizonticide? An exoerythrocytic schiznocide? An erythrocytic schizonticide?

A

Attacks the liver forms (exoerythrocytic) and early blood stages (erythrocytic).

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10
Q

What is a gametocide?

A

Kills sexual stages and prevents transmission to mosquito.

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11
Q

What is cinchonism? What can cause these?

A

Tinnitis, headache, nausea, dizziness, flushing, & visual disturbances. Quinine adverse effect.

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12
Q

What constitutes a severe malarial infection? How do you treat this?

A

Impaired consciousness/coma, severe normocytic anemia, renal failure, pulmonary edema, etc. Quinidine gluconate IV + antibiotic w/ cardiologist & infectious diseases consult OR Artesunate IV from CDC (IND) with Malarone, Doxy/Clinda, or Melfloquine

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13
Q

Which drugs act on the gametocyte stages of plasmodium?

A

Artemisin (dihydroartemisinin, aresunate, artemether), melfloquine, primaquine

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14
Q

What drugs act on the liver stages of plasmodium?

A

Primaquine and Atovaquone. Only primaquine acts on the hypnozoites.

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15
Q

Which drugs can be used for malaria prophylaxis? What are their dosing regimens?

A

Melfloquine - >2wks before, 4 wks after
Chloroquine - 1-2 wks before, 4 wks after
Doxycycline/Tetracycline - 1-2 days before, 4 wks after
Primaquine - 1-2 days before, 7 days after

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16
Q

Which anti-malarial is first line treatment?

A

Chloroquine/Hydroxychloroquine - ONLY IN SENSITIVE AREAS. High levels of resistance.

17
Q

G6PDH Deficiency is a contraindication for the use of which anti-malarials and why?

A

Quinine, Quinidine, Primaquine. Can cause severe hemolytic anemia.

18
Q

What two anti-malarials can be given IV? Why is this significant?

A

Quinine/Quinidine and Aresunate. They are both agents used for severe malarial infections.

19
Q

What two anti-malarials cannot be used prophylactically and why?

A

Artemisinins and Quinine/Quinidine - They are rapid acting and don’t stay around long enough to be prophalactic.

20
Q

What three anti-malarials also have activity against other parasites?

A

Quinine/Quinidine - Babesiosis
Atovaquone - Pneumocystis jiroveci
Pyrimethamine/Proguanil - Toxoplasmosis

21
Q

Which anti-protozoal drugs are contraindicated in pregnancy

A

Artemisinin - in the 1st trimester
Doxycycline/Tetracycline - Use Chloroquine alternatively
Meltifosine

22
Q

What anti-malarial is contraindicated in patients with psoriasis, porphyrias, retinal/visual field abnormalities, or myopathies?

A

Chloroquine, Hydroxychloroquine

23
Q

What are 3 Artemisinin antimalarial drugs? What is their mechanism of action?

A

Artemisinins: Artemisinin, dihydroartemisinin, aresunate, artemether.

Artemisinins - Endoperoxide generates toxic free radicles that damage ATPase in ER (PfATP6). CONCENTRATION DEPENDENT KILLING

24
Q

What are five 4-aminoquinoline antimalarial drugs? What is their mechanism of action

A

4-Aminoquinolines: Chloroquine, Hydroxychloroquine, quinine, Quinidine, Melfloquine.

4-Aminoquinolines: Prevent heme polymerization and detoxification to hemozoin in plasmodium food vacoule. TIME-DEPENDENT KILLING

25
What is the mechanism of Atovaqone?
Antimalarial - Binds CytC and disrupts electron transport
26
What anti-folates can be used for malaria treatment? What are their mechanisms?
Pyrimethamine/Proguanil - Inhibits plasmodium dihydropteroate synthase Sulfadoxine - Inhibits plasmodium dihydrofolate reductase Should be taken in combination
27
What 6 Anti-Malarial Drugs should be taken in combination?
1. Artemisinins - Lumefantrine, melfloquine (slower acting pair prevents recrudescence) 2. Dihydroartemisinin - + piperaquine 3. Atovaquone - prevent resistance 4. Pyrimethamine/Proguanil - + Sulfadiazine or clinda if treating toxoplasma 5. Pyrimethamine/Proguanil + sulfadoxine - prevent resistance 6. Doxy/Tetra - w/ quinine/quinidine
28
Which drug puts patients at risk for cnincohonisms, hypotension, and Blackwater Fever?
Quinine/Quinidine Hypotension - w/ rapid infusion Blackwater fever - in G6PD deficient
29
What drug has P. falciparum developed widespread resistance to and how? How does P. Vivax resistance to this drug differ?
Chloroquine - efflux pump (PfMDR1) from mutation in PFCRT1 prevents accumulation in food vacoule P. vivax - different mechanism, ONLY in Papua guinea and Indonesias
30
Which antimalarial can cause neuropsychiatric toxicity?
Melfloquine
31
What can be used to treat Anaerobic protozoa & bacteria (Giardia, Entamoeba, Trichomonas)?
Metronidazole (flagyl) or TInidazole - Activated by e- donation from microbe ETC. Treat EXTRAINTESTINAL infection - combine w/ luminal durg
32
What luminal agent can be used to treat Entamoeba histolytica dysentry?
Iodoquinol Combo for systemic infections. Solo for asymptomatic infections.
33
What can pentamidine be used to treat?
T. brusi (Gambiense - West African) Acute Visceral leishmania Pneumocystis jirovecii
34
What are the acute and late (CNS) treatments for Trypanosoma brusi (African Sleeping Sickness) - both East (Rhodesiense) and west (Gambiense)?
Rhodesiense - East: Acute - Suramin, Late - Melarsoprol | Gambiense - West: Acute - Pentamidine, Late - Eflornithine
35
What is used to treat T. cruzi (Chagas)
Nifurtimox or Benznidazole - Acute phase only, does not prevent disease progression
36
``` What are the toxicities of the following non-malarial antiprotozoal drugs: Metronidazole Tinidazole Pentamidine Melarsoprol Nifurtimox Miltefosine ```
``` Metronidazole & Tinidazole - Neurotoxicity, Antabuse w/ alcohol Pentamidine - Hypoglycemia, nephrotoxic Melarsoprol - Encephalopathy, 50% death Nifurtimox - Hypersensitivity, GI upset Miltefosine - Tetratogen ```
37
What two drugs are contraindicated in alcoholics?
Metronidazole and Tindazole - Inhibit Acetaldehyde DH
38
What are these drugs? Fandisar Lariam Coartem
FANDISAR - combination pyrithamine + sulfadoxine LARIAM - Melfloquine COARTEM - Artemeter + Lumefantrin