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PHRM 865: Theraputics V > Lecture 37: Antimalarial & Antiparasitic > Flashcards

Lecture 37: Antimalarial & Antiparasitic Flashcards

1
Q

What are the two parasites that are the most common to cause Malaria?

A
  • Plasmodium Falciparum [most malaria deaths; in tropics]
  • Plasmodium Vivax [causes relapse & hypnozoites in liver; 50% of infections in asia & 80% in americas]
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2
Q

What is the Life Cycle of Plamodium Falciparum?

A
  • Mosquito injects sporozoites
  • then moves to liver to make merozolites
  • released to invade RBC
  • trophozolite divides making merozolites
  • merozolites into gametocytes
  • female mosquito sucks up gametocytes to remake the sporozoites
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3
Q

When should you do Prophylaxis for Malaria and what are some of the options for it?

A
  • Should be taken before, during and after traveling
  • Atovaquone-Proguanil is most common; Cholorquine [sensitive parasites]; Mefloquine [longer trips]; Primaquine [high P. Vivax in area]
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4
Q

What are the Drug Classifications of Antimalarial Drugs?

A
  • Tissue Schizonticides [kills liver parasites]
  • Blood Schizonticides [Kills erythrocytics]
  • Gametocytocides [no pathogen]
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5
Q

What is the MOA for Artemisinin?

A
  • Activated by Heme-Iron to form free radicals [breaks the lactone endoperoxide bridge]
  • Maybe inhibits [PfPI3K]??
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6
Q

What is important to know about Artemisinin?

A
  • For Blood Schizonticide
  • NOT Active for Liver Stage
  • Short half life [1-2h] = needs longer half life drugs to help kills rest of parasites
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7
Q

What is the Resistance towards Artemisinin?

A
  • Mutations in Kelch 13; causes drug to eliminate and parasite to regrow
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8
Q

What is important to know about Hemoglobin Metabolism in Parasites?

A
  • Malaria Parasites eat up the Hemoglobin from host; which makes it to Free Heme =Toxic
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9
Q

What is the MOA of Chloroquine?

Resistance?

A
  • Builds up in Food Vacuole and inhibits heme polymerization

RESISTANCE: Mutations in PfCRT1

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10
Q

What is the MOA of Quinine?

A
  • Builds up in Food Vacuole and inhibits heme polymerization
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11
Q

What are some of the Adverse Effects for Quinines?

A
  • Tinnities, Headache, Nausea, Dizziness, Flushing, Visual Problems
  • Hemolysis [G6PD Deficiency]
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12
Q

What is Primaquine good for when it becomes Active?

A
  • DOC for liver stages [actively growing and hypnozoites] of P. Vivax and Ovale
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13
Q

What is the MOA for Primaquine?

A
  • Hydoxylated by 2D6 = [OH-PQm]
  • Then oxidation of OH-PQm to make H2O2
  • Then CPR reduces H2O2 back to OH-PQm to then make H2O2 again by oxidation
  • REPEAT
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14
Q

What is important to know about Primaquine?

A
  • HIGH RISK for Hemolysis in G6PD Deficiency
  • NOT used in Pregnancy
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15
Q

What are the Two Drugs that make up Malarone and what is it good against??

A
  • Atovaquone + Proguanil
  • Kills Liver and Blood stages

Atovaguone helps with Toxo and PJP [duh]

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16
Q

What is the MOA of Atovaquone?

A
  • Inhibitor of malaria mitochondrial cytochrome bc1 complex; which inhibits electron transport and collapses the membrane potential [indirect way to block DNA synthesis]
17
Q

What is the MOA of Proguanil?

A
  • Inhibitor of DHFR-TS; needed for Parasite purine and pyrimidine synthesis
18
Q

What is the MOA for Albendazole & Mebendazole?

A
  • Binds to tubulin to inhibit the elongation of plus end of microtubules [caps end]; which shortens minus end = inhibition of cell division
19
Q

What is the MOA for Praziquantel?

what electrolyte does it change?

A
  • Binds to the Helminth Transietn receptor potential ion channel [TRPMpzq]
  • Ca influx
20
Q

What is the MOA for Liposomal Amphotericin B?

A
  • Inhibits ergosterol formation within Leishmaniasis
21
Q

What is the MOA of Benznidazole and Nifurtimox?

A
  • unknown but; Activated by NADH-dependent mitochonrail nitroreductase to generate nitro radical anions
22
Q

What is the MOA for Ivermectin?

A
  • Binds to GABA and glutamate Cl channels in Nematode Nevres; causing hyperpolarization by increasing Cl conc.; doesnt kill the worms
23
Q

What is the MOA of Pyrantel Pamote?

A
  • Depolarizing Neuromuscular Blocking agents that causes release of Ach and inhibits cholinesterase; paralyzing the worms and expelling them
24
Q

What is considered to be the Revival Drug for African Trypanosomiasis?

A
  • Eflornitine + Nifurtimox
25
Q

What is the first oral antileishmanisais drug and what is its MOA?

A
  • Miltefosine
  • Inhibits phospolipids and sterol productions
26
Q

What is the MOA for Eflornitine?

A
  • Only good for West African Trypanosomiasis that inhibits ornitine decarboxylase

PHRM 865: Theraputics V (42 decks)

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