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Chapter: Biology of Disease: Infectious Diseases and Treatments

Antifungal, Antiprotozoal and Antihelminthic Drugs - Treatment of Infectious Diseases

Fungi, protozoa and helminth parasites are responsible for many infections, particularly in the developing world.

ANTIFUNGAL, ANTIPROTOZOAL AND ANTHELMINTHIC DRUGS

Fungi, protozoa and helminth parasites are responsible for many infections, particularly in the developing world. Given that they are all eukaryotic, then drugs to treat them are prone to act against host cells and they often have side effects. These drugs may kill the parasite or simply inhibit its growth. In the latter case, therapy must be continued for sufficient time to allow the host immune system to eradicate the organism.

Most antifungal drugs are not fungistatic but are fungicidal. One fungistatic drug, griseofulvin, inhibits intracellular transport and mitosis in fungi by interfering with the functions of their microtubules. A comparatively large number of fungicidal drugs suppress the synthesis of the essential cell membrane constituent, ergosterol. These include the allylamine antifungals, terbinafine and naftifine; the imidazoles, clotrimazole, econazole, ketoconazole and miconazole and the triazoles fluconazole and itraconazole. Ciclopiroxolamine inhibits the synthesis of fungal cell membrane proteins. The polyene antifungals, amphotericin and nystatin insert into plasma membranes of susceptible fungi. This increases the permeability of the membranes, allowing water and ions to leak and kill the parasite. Fluorocytosine inhibits the synthesis of fungal DNA.

In many cases, the precise biochemical mechanisms of antiprotozoal drugs are not known in any great detail. However, atovaquone inhibits electron transport in mitochondria. Pentamidine and isethionate interfere with the synthesis of protozoal macromolecules, while metronidazole, nifurtimox and tinidazole are thought to denature existing macromolecules. A number of other antiprotozoal therapeutic drugs are in clinical use. These variously affect protozoal enzymes, inhibit glycolysis and fatty acid oxidation or inhibit the synthesis of precursors of nucleic acids.

In general, the therapeutic bases of anthelminthic drugs are poorly understood. A number of commonly used drugs interfere with muscle contractions in the worms producing flaccid or spastic paralysis. This kills the parasite or makes it susceptible to attack by the host immune system. Paralysis is achieved by several overlapping mechanisms. Metriphonate inhibits cholinesterase leading to spastic paralysis while ivermectin potentiates inhibitory F aminobutyric acid mediated peripheral neurotransmission and levamisole and pyrantel block nerve transmission at the neuromuscular junction. Diethylcarbamazine and piperazine cause hyperpolarization of muscle membranes. Praziquantel acts directly on muscle cells and increases the permeability of muscle membranes to Ca2+.

Other anthelminthic agents act through different mechanisms. Oxamniquine interacts with helminth DNA and disrupts its structure. Niclosamide inhibits mitochondrial oxidative phosphorylation in helminth parasites. The anthelminthic agents albendazole, mebendazole and thiabendazole disrupt the microtubules of the cytoskeleton of the helminth.


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Biology of Disease: Infectious Diseases and Treatments : Antifungal, Antiprotozoal and Antihelminthic Drugs - Treatment of Infectious Diseases |


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