Antiprotozoal drugs Dr. Naza M. Ali LEC 15 23-1-2017

Antiprotozoal drugs: Amebiasis Antimalaria Toxoplasmosis Leishmaniasis Trypanosomiasis Giardiasis

Is an infection caused by Entamoeba histolytica. Chemotherapy of Amebiasis Is an infection caused by Entamoeba histolytica. Can be acute or chronic, with patients showing varying degrees of illness, from no symptoms to mild diarrhea to fulminating dysentery. Diagnosis by isolating E. histolytica from fresh feces. Therapy is aimed not only at the acutely ill patient but also at those who are asymptomatic carriers, because dormant E. histolytica may cause future infections.

Life cycle of Entamoeba histolytica, showing the sites of action of amebicidal drugs.

Classification of amebicidal drugs Mixed amebicides are effective against both the luminal and systemic Luminal amebicides act on the parasite in the lumen of the bowel 3. Systemic amebicides are effective against amebas in the intestinal wall and liver

Mixed amebicides: Metronidazole Tinidazole Luminal amebicide Iodoquinol Paromomycin Diloxanide furoate Systemic amebicide Chloroquine Emetine and dehydroemetine

Mixed amebicides: Metronidazole: It is nitroimidazole use for Amebic infections E. histolytica trophozoites Giardia lamblia, Trichomonas vaginalis, Anaerobic cocci, Anaerobic gram negative bacilli Pseudomembranous colitis In brain abscesses

Mechanism of action: The nitro group of metronidazole is able to serve as an electron acceptor, forming reduced cytotoxic compounds that bind to proteins and DNA, resulting in cell death.

Pharmacokinetics: Completely ,rapidly absorbed / orally Distributes well to body tissues & fluids. Therapeutic levels can be found in vaginal , seminal fluids, saliva, breast milk, and CSF . Metabolism by hepatic oxidation Accumulates in patients with severe hepatic disease.

Tinidazole: Is a second-generation nitroimidazole Is similar to metronidazole in spectrum of activity, absorption, adverse effects, and drug interactions. Tinidazole is as effective as metronidazole, with a shorter course of treatment

Luminal amebicides After treatment of invasive intestinal or extraintestinal amebic disease is complete Luminal drugs should be administered for treatment of the asymptomatic colonization state. Iodoquinol Paromomycin Diloxanide furoate

The mechanism of action of iodoquinol against trophozoites is unknown. Paramomycin An aminoglycoside antibiotic Is directly amebicidal action Act by reducing the population of intestinal flora.

Diloxanide furoate In the gut, it split into diloxanide and furoic acid about 90% of the diloxanide is rapidly absorbed and then conjugated to form the glucuronide, which is excreted in the urine. The unabsorbed diloxanide is the active antiamebic substance. The mechanism of action of diloxanide furoate is unknown. Diloxanide furoate is the drug of choice for asymptomatic luminal infections.

Systemic amebicides are useful for treating liver abscesses and intestinal wall infections Chloroquine Emetine and dehydroemetine

Chloroquine: Is used in combination with metronidazole and diloxanide furoate Emetine and dehydroemetine: They inhibit protein synthesis by blocking chain elongation.

Chemotherapy of Malaria Malaria is an acute infectious disease Plasmodium falciparum is the most dangerous species, causing an acute, rapidly fulminating disease That is characterized by persistent high fever, orthostatic hypotension, and massive erythrocytosis (an abnormal elevation in the number of red blood cells accompanied by swollen, reddish limbs). P. falciparum infection can lead to capillary obstruction and death if treatment is not instituted promptly.

Blood Schizonticide Tissue Schizonticide 2. Mefloquine 3. Quinine 1. Chloroquine 2. Mefloquine 3. Quinine 4. Pyrimethamine 5. Artemisinin Tissue Schizonticide Primaquine

Blood Schizonticide Drug Uses MOA Side effects 1. Chloroquine Prophylaxis & treat in area non resistant P Falciparum , P vivax , P Ovale Accumulates in the food vacuole of plasmodia , prevents polymerization of hemoglobin high dose: Retinal damage, auditory impairment 2. Mefloquine Prophylaxis & treat in area with resistant P Falciparu Damage the parasite membrane NV , hallucination 3. Quinine Treatment of multidrug- resistant Malaria Complexes with double stranded DNA to prevent strand separation Cinchonsim, hemolysis in G6PD, Fetotoxic 4. Pyrimethamine Prophylaxis and treatment of multidrug- resistant Inhibit dihydrofolate reductase 5. Artemisinin Treatment of multidrug- resistant Metabolite in food vacuole of parasite forming toxic free radicals safe

Drug Uses MOA Side effects Tissue Schizonticide Primaquine Eradicate of liver stage P vivax, P Ovale As cellular oxidants hemolysis in G6PD

Action of chloroquine on the formation of hemozoin by Plasmodium species.

Primaquine side effect: drug-induced hemolytic anemia in patients with genetically low levels of glucose-6-phosphate dehydrogenase

Chemotherapy of Toxoplasmosis: Toxoplasma gondii, is transmitted to humans when they consume raw or inadequately cooked infected meat. An infected pregnant woman can transmit the organism to her fetus. Cats are the only animals that shed oocysts, which can infect other animals as well as humans. The treatment of choice is a combination of sulfadiazine and pyrimethamine. Leucovorin is administered to protect against folate deficiency.

Chemotherapy of Leishmaniasis: There are three types of leishmaniasis: Cutaneous, Mucocutaneous, Visceral. [ The visceral type (liver , spleen), the parasite is in the bloodstream and can cause very serious problems.]

Leishmaniasis is transmitted from animals to humans by the bite of infected sandflies. The diagnosis by demonstrating the parasite in biopsy material and skin lesions.

Treatment: Sodium stibogluconate used in the treatment of leishmaniasis, with pentamidine and amphotericin B as backup agents Sodium stibogluconate Inhibition of glycolysis in the parasite at the phosphofructokinase reaction. not absorbed orally, administered parenterally

Chemotherapy of Trypanosomiasis African sleeping sickness and American sleeping sickness, two chronic and fatal diseases

A. Melarsoprol The drug reacts with sulfhydryl groups of various substances, including enzymes in both the organism and host. The parasite’s enzymes may be more sensitive than those of host. is the agent of choice in the treatment of T. brucei which rapidly invades the CNS

B. Pentamidine / T. Brucei The drug binds to the parasite’s DNA interferes with its synthesis of RNA

C. Nifurtimox use only in the treatment of acute T. cruzi infections D. Suramin used in the early treatment and the prophylaxis of African trypanosomiasis.