1) Metronidazole is the drug of choice for treating infections caused by Entamoeba histolytica, the parasite that causes amebiasis. It kills the trophozoites of E. histolytica. 2) Pentavalent antimonials like sodium stibogluconate are the conventional treatment for leishmaniasis, though pentamidine and amphotericin B are also used. 3) For malaria, chloroquine remains a first-line treatment for non-falciparum and chloroquine-sensitive falciparum malaria, though resistance has emerged. Artemisinin derivatives combined with other drugs are now recommended for falciparum

1. Antiamoebic and Other
Antiprotozoal Drugs
Dr. Muhammad Fahd Mushtaq
M.Phil pharmacology (GCUF)

2. General View
These are drugs useful in infection caused by the anaerobic
Entamoeba histolytica. Other Entamoeba species are generally
nonpathogenic.

3. Classification

4. Chemotherapy For Amebiasis
Amebiasis (also called amebic dysentery) is an infection of the
tract caused by Entamoeba histolytica. Th disease can be acute or
chronic, with patients showing varying degrees of illness, from no
symptoms to mild diarrhea to fulminating dys
Life cycle of Entamoeba histolytica

5. Mixed amebicides (metronidazole and tinidazole)
Metronidazole a nitroimidazole, is the mixed amebicide of choice for
treating amebic infections; it kills the E. histolytica trophozoites. [Note:
Metronidazole also finds extensive use in the treatment of infections
caused by Giardia lamblia, Trichomonas vaginalis, anaerobic cocci, and
anaerobic gram-negative bacilli (for example, Bacteroides species).
Mechanism of action

6. Adverse effects
metallic taste and abdominal cramps, glossitis, dryness of mouth and
dizziness, Urticaria, flushing, heat, itching, rashes, Prolonged
administration may cause peripheral neuropathy and CNS effects like
Seizures.
Interactions
A disulfiram-like intolerance to alcohol occurs in some patients taking
metronidazole
Clinical Uses
Amoebiasis, Pseudomembranous enterocolitis, Trichomonas vaginitis,
Giardiasis, Helicobacter pylori gastritis/peptic ulce

7. Tinidazole
Tinidazole [tye-NI-da-zole] is a second-generation nitroimidazole
is similar to metronidazole in spectrum of activity.
Luminal amebicides
IODOQUINOL
It is an effective luminal amebicide that is commonly used with
metronidazole to treat amebic infections.
M.O.A
UNKNOWN
A.D.R’S
skin reactions, thyroid enlargement, and interference with thyroid
function studies. Headache and diarrhea also occur.

8. Diloxanide Furoate
Diloxanide furoate (Furamide) is an amebicide that is effective against
trophozoites in the intestinal tract. In mild or asymptomatic infections,
cures of 83 to 95% have been achieved;
A.D.R’S
flatulence, abdominal distention, anorexia, nausea, vomiting, diarrhea,
pruritus, and urticaria occur
PAROMOMYCIN SULFATE
aminoglycoside antibiotic It is used only as a luminal amebicide and
has no effect against extraintestinal amebic infections it was superior
diloxanide furoate in clearing asymptomatic infections.

9. Systemic amebicide
These drugs are useful for treating liver abscesses or intestinal wall
infections caused by amebas.
EMETINE & DEHYDROEMETINE
effective against tissue trophozoites of E histolytica, but because of
major toxicity concerns their use is limited to unusual circumstances in
which severe amebiasis requires effective therapy and metronidazole
cannot be used. drugs should be used for the minimum period
to relieve severe symptoms (usually 3–5 days).
Adverse effects
pain, tenderness, and sterile abscesses at the injection site;muscle
weakness and discomfort; and minor electrocardiographi changes,
cardiac arrhythmias, heart failure, and hypotension

10. Chloroquine
It kills trophozoites of E. histolytica and is highly concentrated in liver.
Therefore, it is used in hepatic amoebiasis only. Because it is
absorbed from the upper intestine and not so highly concentrated in
the intestinal wall—it is neither effective in invasive dysentery nor in
controlling the luminal cycle.
Though chloroquine is relatively safe,

11. Chemotherapy for Malaria
Malaria is an acute infectious disease caused by four species of the
protozoal genus Plasmodium. The parasite is transmitted to humans
through the bite of a female Anopheles mosquito, which thrives in
humid, swampy areas. Plasmodium falciparum is the most dangerous
species,
P. falciparum infection can lead to capillary obstruction and death if
treatment is not instituted promptly. Plasmodium vivax causes a
milder form of the disease. Plasmodium malariae is common to many
tropical regions, but Plasmodium ovale is rarely encountered

12. Life cycle of the malarial parasite

13. tissue schizonticides
Drugs that eliminate developing or dormant liver forms
blood schizonticides
that act on erythrocytic parasites
Gametocides
that kill sexual stages and prevent transmission to mosquitoes

14. Tissue schizonticide
Primaquine
eradicates primary exoerythrocytic forms of P. falciparum and P. vivax
and the secondary exoerythrocytic forms of recurring malarias (P.
and P. ovale). only agent that can lead to radical cures of the P. vivax
and P. ovale malarias, which may remain in the liver in the
exoerythrocytic form after the erythrocytic form of the disease is
eliminated.
Mechanism of action
Metabolites of primaquine are believed to act as oxidants that are
responsible for the schizonticidal action as well as for the hemolysis
methemoglobinemia encountered as toxicities.

15. Adverse effects
drug-induced hemolytic anemia, abdominal discomfort,
methemoglobinemia, lupus or arthritis.
Blood Schintizides
Chloroquine
Chloroquine has been the drug of choice for both treatment and
chemoprophylaxis of malaria but its usefulness against P falciparum
been seriously compromised by drug resistance.
M.O.A
Chloroquine appears to work by intercalation with DNA, inhibition of
heme polymerase or by interaction with Ca–calmodulinmediated
mechanisms. It also accumulates in the parasite’s food vacuoles, where it
inhibits peptide formation and phospholipases, leading to parasite

16. Resistance
In P falciparum, mutations in a putative transporter, PfCRT, have been
correlated with resistance. Chloroquine resistance can be reversed by
agents, including verapamil, desipramine, and chlorpheniramine, but the
clinical value of resistance-reversing drugs is not established.
Clinical Uses
Chloroquine is the drug of choice in the treatment of non-falciparum and
sensitive falciparum malaria. It rapidly terminates fever (in 24–48 hours) and
clears parasitemia (in 48–72 hours) caused by sensitive parasites.
Adverse Effects
Pruritus, abdominal pain, headache, anorexia, malaise, blurring of vision,
urticarial, impaired hearing, confusion, psychosis, seizures, agranulocytosis,

17. Mefloquine
Mefloquine [MEF-lo-kween] appears to be promising as an effective
single agent for suppressing and curing infections caused by
resistant forms of P. falciparum.
apparently damage the parasite's membrane.
Adverse reactions
dizziness to disorientation,hallucinations, and depression.
Electrocardiographic abnormalities and cardiac arrest are possible
Quinine and quinidine
interfere with heme polymerization, resulting in death of the
erythrocytic form of the plasmodial parasite. lkalinization of the urine
decreases its excretion. cinchonism—a syndrome causing nausea,
vomiting, tinnitus, and vertigo.

18. ARTEMISININ & ITS DERIVATIVES
Artesunate, Artemether, dihydroartemisinin
artemisinin monotherapy for the treatment of uncomplicated malaria
now strongly discouraged.
Mechanism of action
endoperoxide bridge in its molecule appears to interact with haeme in
parasite. Ferrous iron-mediated cleavage of the bridge releases a highly
reactive free radical species that binds to membrane proteins, causes
peroxidation, damages endoplasmic reticulum, and ultimately results in
lysis of the parasite.
Adverse effects
bdominal pain, itching and drug fever, headache, tinnitus, dizziness,
bleeding, dark urine

19. Halofantrine & Lumefantrine
Halofantrine hydrochloride, a phenanthrene-methanol, Is effective
against erythrocytic (but not other) stages of all four human malaria
speciesBecause of toxicity concerns, it should not be taken with meals.
Lumefantrine, an aryl alcohol related to halofantrine, is available only
as a fixed-dose combination with artemether which is now the first-
therapy for uncomplicated falciparum malaria in many countries

20. INHIBITORS OF FOLATE SYNTHESIS
Pyrimethamine, Proguanil, Fansidar, sulfadoxine
is frequently employed to effect a radical cure as a blood
It also acts as a strong sporonticide in the mosquito's gut when the
mosquito ingests it with the blood of the human host.
M.O.A
Pyrimethamine inhibits plasmodial dihydrofolate reductase3 at much
lower concentrations than those needed to inhibit the mammalian
enzyme. The inhibition deprives the protozoan of tetrahydrofolate a
cofactor required in the de novo biosynthesis of purines and
pyrimidines and in the interconversions of certain amino acids.

21. Chemotherapy for Leishmaniasis
cutaneous, mucocutaneous, and visceral

22. Leishmaniasis is transmitted from animals to humans (and between
humans) by the bite of infected sandflies. The diagnosis is established
by demonstrating the parasite in biopsy material and skin lesions. The
treatments of leishmaniasis and trypanosomiasis are difficult, because
the effective drugs are limited by their toxicities and failure rates.
Pentavalent antimonials, such as sodium stibogluconate, are the
conventional therapy used in the treatment of leishmaniasis, with
pentamidine and amphotericin B as backup agents. Allopurinol has also
been reported to be effective (it is converted to a toxic metabolite by
the amastigote form7 of the organism)