Therapeutics ID Nieto Flashcard

Nitazoxanide: MOA

  • Prodrug
  • Converted to active tizoxanide by ester cleavage, which is then reduced to an active intermediate
  • Inhibits the enzyme pyruvate: ferredoxin oxidoreductase and disrupts the bioenergetics of the microorganism

Diloxanide Furoate: MOA

  • Prodrug
  • Hydrolyzed to diloxanide
  • Has the same MOA of 
  • Metabolism via glucuronidation

Atovaquone: MOA

  • Antimalarial Drug
  • Inhibits the mitochondrial respiratory chain
  • Ubiquinone Reductase Inhibitor

 

Atovaquone: PK

  • Poorly absorbed (increased with meals) — very lipophilic drug
  • Highly bound to plasma proteins
  • Not significantly metabolized

Chloroquine: Class
Antimalarial
Halofantrine: Class
Antimalarial
Mefloquine: Class
Antimalarial
Primaquine: Class
Antimalarial
Pyrimethamine: MOA

  • Antimalarial
  • Same MOA as trimethoprim (DHFR inhibitor)

Proguanil: Class
Antimalarial
Albendazole: MOA

  • Benzamidazole
  • Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

Albendazole: ADME

  • Poorly absorbed from GI
  • Metabolized by CYP450 — glucuronidation

Mebendazole: ADME

  • Poorly absorbed from GI
  • Metabolized by CYP450 — glucuronidation

Mebendazole: MOA

  • Benzamidazole
  • Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

Thiabendazole: MOA

  • Benzamidazole
  • Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

Thiabendazole: ADME

  • Poorly absorbed from GI
  • Metabolized by CYP450 — glucuronidation

Ivermectin: MOA

Two Hypotheses


1.  IVM acts as either a GABA agonist (binds irreversibly to glutamate-gated chloride channels — results in rapid decrease of microfilarial concentrations) or as an Inducer of Chloride Ion Influx, leading to hyperpolarization and muscle paralysis –> motility of microfalaria is reduced, which allows cytotoxic cells of the host to adhere to the parasite and parasite is eliminated

2.  Degeneration of microfilariae –> fewer microfilariae released from the female worms –> prevents further fertilization and production of microfilariae

Praziquantel: MOA

More than one mechanism

  • Ca2+ redistribution –> leads to muscle contraction and paralysis –> worm expulsion
  • Inhibits phosphoinositide metabolism –> leads to the worm paralysis
  • Affects glycogen content and energy metabolism

Praziquantel: ADME

  • Rapidly absorbed
  • Metabolized (hydroxylation — NOT on the aromatic ring)

Oxamniquine: MOA

  • Oxamniquine must be metabolically activated by the addition of an ester group to the hydroxy group of the aromatic ring –> the ester is removed and the drug now has a positive charge
  • After obtaining the positive charge, it becomes an intercalating agent that intercalates itself into the DNA

Diloxanide Furoate: Metabolism

  • The ester prodrug is metabolized to diloxanide — results in an OH (polar handle) on the aromatic ring
  • The polar handle is then glucuronidated

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