Chapter 36: Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis, Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other Protozoal Infections
A 36-year-old woman with the diagnosis of Trichomonas vaginalis returns to your office one day after receiving a 2 g oral dose of metronidazole with complaints of flushing, headache, vomiting, and abdominal pain. She states that her symptoms began after she and her husband celebrated their 10th wedding anniversary at a restaurant. The most likely cause of her symptoms is
Answer is b. Patients taking metronidazole may have a disulfiram-like reaction (see Chapter 9) if they drink alcohol. The symptoms often include flushing, headache, vomiting, and abdominal pain.
A 24-year-old man with the diagnosis of late stage trypanosomiasis caused by T. brucei gambiense is being treated with eflornithine. Eflornithine is an inhibitor of ornithine decarboxylase. The parasite and human enzyme are equally susceptible to inhibition by eflornithine. The selective toxicity of eflornithine in parasites is because the
a. human enzyme is protected within vacuoles.
b. parasite accumulates the drug in high concentrations.
c. human enzyme is turned over more rapidly than the parasitic enzyme.
d. human enzyme contains a different molecular site of binding of eflornithine.
e. product of the enzyme in parasites is putrescine.
Answer is c. The molecular mechanism of eflornithine clearly is inhibition of ornithine decarboxylase. Eflornithine irreversibly inhibits both mammalian and trypanosomal ornithine decarboxylases, thereby preventing the synthesis of putrescine, a precursor of polyamines needed for cell division. Eflornithine inactivates the enzyme through covalent binding of an active-site cysteine residue. The mammalian enzyme is turned over rapidly, whereas the parasite enzyme is stable, and this difference likely plays a role in the drug’s selective toxicity. In addition, mammalian cells may be able to replenish polyamine pools through uptake of extracellular polyamines. The parasite lacks efficient polyamine transport mechanisms.
Miltefosine is the first orally active drug for the treatment of visceral leishmaniasis. However, because of its teratogenic potential, miltefosine is contraindicated in pregnant women. A suitable alternative in a pregnant woman might be
d. sodium stibogluconate.