Antiprotozoal and Anthelmintic Drugs PDF

Antiprotozoal and Anthelmintic Drugs Prof. Dr. Süreyya Barun  Protozoal infections may be one or more infection results from the following: 1) amoebiasis 2) trichomoniasis 3) giardiasis 4) leishmaniasis 5) trypanosomiasis 6) malaria 7) toxoplasmosis. Amebiasis is an infect...

Antiprotozoal and Anthelmintic Drugs Prof. Dr. Süreyya Barun  Protozoal infections may be one or more infection results from the following: 1) amoebiasis 2) trichomoniasis 3) giardiasis 4) leishmaniasis 5) trypanosomiasis 6) malaria 7) toxoplasmosis. Amebiasis is an infection of the intestinal tract caused by Entamoeba Histolytica Chemotherapy of Amebiasis This organism can cause; Asymptomatic infection Mild to moderate colitis Severe intestinal infections (dysentery) Ameboma Liver abscess Other extraintestinal infections Ameboma Mimicking Submucosal Tumor of the Colon in an Elderly Chemotherapy of Amebiasis  The disease can be acute or long term showing varying degrees of illness from no symptoms to fulminating dysentery  Therapy is aimed not only at the acutely ill patients but also at carriers Traetment of specific forms of amebiasis 1. Asymptomatic Intestinal Infection Asymptomatic carriers are treated with a luminal amebicide Standart luminal amebicides are diloxanide furoate, iodoquinol, and paromomycin Each drug eradicates carriage in about 80-90 %of patients with a single course of treatment Traetment of specific forms of amebiasis 2. Amebic Colitis Metranidazole plus a luminal amebicide is the treatment of choice for amebic colitis and dysentery Emetine and dehydroemetine can also be used 3. Extraintestinal infections The treatment of choice for extraintestinal infections is metronidazole plus a luminal amebecide Chemotherapy of amebiasis 1. Metronidazole 2. Emetine, dehydroemetine 3. Chloroquine 4. Iodoquinol 5. Antibiotics 6. Diloxanide furoate Classification of antiprotozal drugs 1. Mixed amebicide: Metronidazole, tinidazole 2. Luminal amebecide: Diloxanide furoate, paromomycin, iodoquinol 3. Systemic amebicide: Chloroquine, emetine and dehydroemetine Metronidazole  It is selectively toxic not only for ameba but also for anaerobic organisms (including bacteria)  The nitro group of metronidazole is able to serve as an electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA to result in cell death Metronidazole  It is used in the treatment of all tissue infections with E. Histolytica  It is not effective against luminal parasites so must be used with a luminal amebicide to ensure eradication of the infection  Metronidazole is the treatment choice for giardiasis and trichomoniasis Metronidazole: Adverse Effects  Nausea, hedache, dry mouth or a metallic taste in the mouth occurs commonly  Pancreatitis and severe CNS toxicity are rare  Metronidazole is a disulfiram-like effect, so-that nausea and vomiting can occur if alcohol is ingested during therapy  I.v. infusions may cause seizures or peripheral neuropathy  Metronidazol potentiates anticoagulant effect of coumarin-type anticoagulants  Lithium toxicity may occur when it is used with metronidazole Diloxanide furoate  It is useful in the treatment of asymptomatic passers of cysts  It is hyrolyzed in the intestinal mucosa and it is about 90 % absorbed  Adverse effects include flatulance, dryness of mouth, pruritus and urticaria Paromomycin  It is an aminoglycoside antibiotic  It is not significantly absorbed from the GI tract  It is hyrolyzed in the intestinal mucosa and it is about 90 % absorbed  Its direct amebicidal action is probably due to the effects it has on cell membrabes to cause leakege  Adverse effect includes abdominal distress and diarrhea Iodoquinol  It is a halogenated hydroxyquinoline  It is an effective luminal amebicide that is commonly used with metronidazole to treat amebic infections  It is effective in the bowel lumen but not against trophozoites in the intestinal wall or extraintestinal tissues  Infrequent adverse effects include GIS symptoms, headache, rash and pruritis  The drug should be discontinued if it produces persistant diarrhea or signs of iodine toxicity (dermatitis, urticaria, pruritis, fever) Chloroquine  It is used in combination with metronidazole and diloxanide furoate to treat and prevent liver abcessess  It reaches high liver concentrations and may be used for amebic abcesess that fail initial therapy with metronidazole  Rare reactions include hemolysis in glucose-6- phosphatedehydrogenase (G6PD)-deficient persons, impaired hearing, confusion, psychosis Chloroquine  Large i.m. İnjections or rapid i.v. İnfusions can result in severe hypotension, cardiac and respiratory arrest  It is contraindicated in patients with psoriasis or porphyria Emetine, Dehydroemetine Emetine is an alcaloid derived from ipeca Dehydroemetine is a synthetic analog of emetine Both are effective against tissue trophozoites of E. Histolytica Because of major toxicity concerns their use is limited Serious toxicities inlude cardiac arrhytmias, heart failure, and hypotension Other Antiprotozoal Agents Pentamidine  Pentamidine has activity against trypanosomatid protozoans, but toxicity is significant  It is only used parenterally Clinical Uses  Pneumocystosis  African trypanosomiasis  Leishmaniasis Adverse effects  It is a highly toxic drug  Rapid i.v. administration may lead to hypotension, tachycardia, dizziness and dyspnea  Pancreatic toxicity is common  Leishmaniasis Phlebotomus argentipes Sodium stibogluconate  Pentavalent antimonials, including sodium stibogluconate and meglumin antimonate, are first- line agents for cutaneous and visceral leishmaniasis  Their mechanism of action is unknown Adverse effects  Toxicity of the stibogluconate increases over the course of therapy  Most common are GIS symptoms  Hemolytic anemia, serious liver, renal and cardiac effects are rare Other drugs for trypanosomiasis and Leishmaniasis Nitazoxamide  It is approved for against Giardia Lamblia  Their mechanism of action is unknown  It appears to have activity against metronidazole- resistant protozoal strains Other drugs for trypanosomiasis and Leishmaniasis SURAMIN It is the first line therapy for early hemolymphatic east african trypanosomiasis Adverse effects are common Immediate reactions can include GIS symptoms, seizures and death Later reactions include fever, rush, paresthesias, agranulocytosis Other drugs for trypanosomiasis and Leishmaniasis MELARSOPROL It is trivalent arsenicals It is first line therapy for advanced CNS East African trypanosomiasis It is extremely toxic The most important toxicity is a reactive encephalopathy and is probably due to disruption of trypanosomes in the CNS Other drugs for trypanosomiasis and Leishmaniasis EFLORNITIN It is an inhibitor of ornithine decarboxylase It is the first line drug for advanced West African Tryphanomiasis Adverse effects include GIS symptoms, anemia, trombocytopenia, leukopenia and seizures Other drugs for trypanosomiasis and Leishmaniasis NIFURTIMOX It is a nitrofuran It is the most commonly used drug for American trypanosomiasis (Chaga’s disease) BENZNIDAZOLE It is an orally administered nitroimidazole It is used in the treatment of Chaga’s disease AMPHOTERICIN It is an antifungal drug It is an alternative drug for the treatment of visceral leishmaniasis Other drugs for trypanosomiasis and Leishmaniasis MILTEFOSINE It is the first effective oral drug for visceral leishmaniasis It has excellent efficacy PAROMOMYCIN Paromomycin sulfate is an aminoglycoside antibiotic It is approved for visceral leishmaniasis Atihelminthic Drugs  Helminths (worms) are multicellular organisms that infect very large numbers of humans and cause a broad range of diseases Atihelminthic Drugs ALBENDAZOLE It is a broad-spectrum oral anthelminthic drug It is a benzimidazole carbamate Benzimidazoles are thought to act against nematodes by inhibiting microtubule synthesis Clinical Uses It is administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites Albendazole  Clinical Uses  Ascariasis , Trichuriasis, and hookworm and pinworm infections  Hydatid disease  Neurocysticercosis Adverse effects:  When used 1-3 days, mild and transient adverse effects occur (GIS symtoms, dizziness, insomnia)  In long term use, blood counts and liver function studies should be monitored Bithionol  It is an alternative treatment for fascioliasis (sheep liver fluke) Adverse effects:  AE are generally mild and transient and include diarrhea, nausea, vomitting, dizziness and headache DIETHYLCARBAMAZINE CITRATE It is a synthetic piperazine derivative Clinical Uses It is used for the treatment of Wuchereria bancrofti, brugia malayi, brugia timori and loa loa ADVERSE REACTIONS AE are mild and transient, include headache, malaise, anorexia, and dizziness DOXYCYCLINE It is a tetracycline antibiotic It has significant macrofilaricidal activity against W. Bancrofti IVERMECTIN It paralyzes nematodes and arthropodes by intensifying GABA-mediated transmission of signals in peripheral nerves It is indicated for the treatment of onchocerciasis and strongyloidiasis Some patients may develop corneal opacities MEBENDAZOLE It is a synthetic benzimidazole that has a wide spectrum of antihelminthic activity It acts by inhibiting microtubule synthesis Clinical uses It is indicated for use in ascariasis, trichuriasis, hookworm and pinworm infections Mild GIS symptoms may occur as AE METRIFONATE It is a low-cost alternative drug for the treatment of Schistosoma haematobium Its action is related to cholinesterase inhibition AE:Mild and transient cholinergic symptoms may occur (nausea, vomiting, diarrhea, bronchospasm, fatigue, vertigo) NICLOSAMIDE It is a second-line drug for the treatment of most tapeworm infections It is used for T.saginata, T.solium Mild GIS symptoms may occur as AE OXAMNIQUINE It is an alternative to praziquantel for the treatment of Schistosoma mansoni AE: CNS symptoms are most common (dizziness, headache, drowsiness PIPERAZINE It is an alternative for the treatment of ascariasis It causes paralysis of ascaris by blocking acetylcholine at the myoneural junction Occasional mild AE include GIS symptoms PRAZIQUANTEL It is effective in treatment of schistosome infections of all species It increases the permeability of cell membranes to calcium, resulting in death It is also used for Taeniasis, Neurocysticercosis and hydatid disease AE: Mild and transient AE are common PYRANTEL PAMOATE It is a broad spectrum antihelminthic drug It is used for the treatment of pinworm, ascaris infections It has neuromuscular blocking effect that causes release of Ach; this results in paralysis of worms AE are infrequent and GIS symptoms are most common THIABENDAZOLE It is an alternative to ivermection or albendazole for the treatment of strongyloidiasis cutaneous larva migrans THANKS!!!