1. Antiprotozoal drugs
Dr. Naza M. Ali
LEC 15

2. Antiprotozoal drugs:
Amebiasis
Antimalaria
Toxoplasmosis
Leishmaniasis
Trypanosomiasis
Giardiasis

3. 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.

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

5. 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

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

7. 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

8. 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.

9. 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.

10. 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

11. 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

12. 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.

13. 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.

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

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

16. 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.

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

19. 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

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

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

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

23. 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.

24. 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.]

25. 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.

26. 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

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

28. 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

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

30. 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.