Antiparasitic Drugs and Helminths Classification

Anthelmintics

• Anthelmintics are drugs with the property of ridding the body of parasitic worms and act by either destroying the helminths or expelling them from the infested patient.
• There are two main classes of helminths: Nematodes (roundworms, hookworms, whipworms, and threadworms) and Platyhelminthes (flatworms, including tapeworms).

Sources of Infestations

• Contact with infected animals
• Ground contaminated by human or animal excrement
• Water infested with cercariae
• Ingestion of infested meat

Treatment

• Selection of drug is important due to attendant side effects
• Stool examination is crucial for identification of the worm
• Hygiene is the most important key to prevention

Chemotherapy Classes of Anthelmintics

• Chlorinated Hydrocarbons (e.g., tetrachloroethylene)
• Phenol and derivatives (e.g., Niclosamide)
• Piperazine and derivatives (e.g., Diethylcarbamazine)
• Heterocyclic compounds (e.g., Mebendazole, thiabendazole)

Piperazine Derivatives

• Piperazine is used to treat threadworms and roundworms
• It blocks the response of ascaris muscle to acetylcholine, causing flaccid paralysis of the worm
• Diethylcarbamazine (DEC), a piperazine derivative, is used for filariasis, ascaris, and river blindness

Mebendazole

• Mebendazole is a broad-spectrum anthelmintic effective against various nematode infestations
• It irreversibly blocks glucose uptake in susceptible helminths, depleting glycogen stored in the parasite

Albendazole

• Albendazole is a broad-spectrum anthelmintic
• It is effective as a single-dose treatment for ascariasis
• It undergoes rapid and extensive first-pass metabolism to the sulfoxide, which is the active form in plasma

Thiabendazole

• Thiabendazole is a broad-spectrum anthelmintic with activity against enterobiasis, threadworm, ascariasis, hookworm, and whipworm infections
• It inhibits the helminth-specific enzyme fumarate reductase

Niclosamide

• Niclosamide is a potent taeniacide that causes phosphorylation in the mitochondria, interfering with vital life processes
• It is used to treat tapeworm infections

Pyrantel

• Pyrantel is the drug of choice against infestations with ascaris and enterobius
• It inhibits worm's acetylcholinesterase, causing spastic paralysis in susceptible helminths

Amoebicides

• Amoebiasis is a protozoal infection of the intestine (Intestinal amoebiasis) and sometimes the liver (Hepatic amoebiasis) caused by Entamoeba histolytica
• The parasite exists in two forms: the active parasite (trophozoite) and the dormant parasite (cyst)

Chemotherapy for Amoebiasis

• Nitroimidazoles are the drugs of choice for both intestinal and systemic amoebiasis
• They are also useful in trichomoniasis, schistosomiasis, giardiasis, cutaneous leishmaniasis, acute ulcerative gingivitis, and Trichomonas vaginalis
• Examples include Metronidazole, Tinidazole, Ornidazole, Secnidazole, Nimorazole, and Niridazole

Mechanism of Action of Nitroimidazoles

• Antibacterial and antiprotozoal, with microbicidal activity against most obligate anaerobic bacteria and protozoa
• Mechanism is mediated through oxidative reactive species
• Reduced metronidazole (2-hydroxy metabolite) interacts with DNA to cause a loss of helical structure, strand breakage, and resultant inhibition of nucleic acid synthesis and cell death