This chapter will be most useful after having a basic understanding of the material in Chapter 50, Chemotherapy of Protozoal Infections in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, the 12th Edition contains:
A detailed discussion of protozoal infections, including amebiasis, giardiasis, toxoplasmosis, trichomoniasis, cryptosporidiosis, trypanosomiasis, leishmaniasis, babesiosis, balantidiasis, Isospora belli, and microsporidia
Understand the most common protozoal infections, the clinical symptoms, and the mainstays of therapy.
Describe the mechanisms of action of antiprotozoal drugs.
Understand the treatment of giardiasis, amebiasis, and cryptosporidiosis.
Identify the therapeutic uses of antiprotozoal drugs.
Describe the toxicities and precautions to the use of antiprotozoal drugs.
DRUGS INCLUDED IN THIS CHAPTER
Amphotericin B (see Chapter 43)
8-Hydroxyquinolines (iodoquinol; YODOXIN)
PROTOZOAL INFECTIONS DISCUSSED IN THIS CHAPTER
MECHANISMS OF ACTION AND RESISTANCE OF ANTI-PROTOZOAL DRUGS ||Download (.pdf) MECHANISMS OF ACTION AND RESISTANCE OF ANTI-PROTOZOAL DRUGS
|DRUG ||MECHANISM OF ACTION ||MECHANISM OF RESISTANCE |
|Amphotericin ||Binds ergosterol in protozoal membranes to form pores and increase membrane permeability ||No significant protozoal resistance |
|Eflornithine ||Inhibition of ornithine decarboxylase ||Mutations in ornithine decarboxylase |
|Fumagillin ||Inhibition of methionine-aminopeptidase-2 || |
|Melarsoprol ||Inhibition of many enzymes ||Mutations in drug transporters |
|Metronidazole || |
Forms highly reactive nitro radical anion that targets DNA and other vital biomolecules
Interferes with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron-transfer reaction, which is essential to anaerobic metabolism in protozoan and bacterial species
Impaired O2 scavenging capabilities leading to higher local O2 concentrations and decreased activation of metronidazole
Also mutations in nitroreductase
|Miltefosine ||Not completely known ||Point mutations in transporter which leads to decreased drug uptake |
|Nitazoxanide ||Nitazoxanide (like metronidazole) interferes with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron-transfer reaction, which is essential to anaerobic metabolism in protozoan and bacterial species ||Resistance to nitazoxanide has been induced in Giardia in vitro, but resistant clinical isolates have not been reported |
|Nifurtimox ||Nifurtimox is activated by an NADH-dependent mitochondrial nitroreductase, leading to the intracellular generation of nitro radical anions that are thought to account for trypanocidal effects; these radicals form covalent attachments to macromolecules leading to cellular damage that kills the parasites ||Reduced nitroreductase expression |
|Benznidazole ||Same as nifurtimox ||Same as nifurtimox |
|Paromomycin ||Paromomycin binds to the 30S ribosomal subunit similar to neomycin and kanamycin (see Chapter 40) and shares their spectrum of antibacterial activity || |
|Pentamidine ||In Trypanosoma brucei pentamidine is concentrated via an energy-dependent high-affinity uptake system in cells where it is thought to react with a variety of negatively charged intracellular targets ||Although failure to concentrate pentamidine is the usual cause of resistance, other mechanisms also may be involved |
|Sodium Stibogluconate ||Pentavalent antimonials act as prodrugs being reduced to ...|