This document summarizes tissue amoebicides and drugs used to treat various protozoan infections. It discusses the mechanisms of action, pharmacokinetics and side effects of various nitroimidazoles like metronidazole, tinidazole, and secnidazole. It also covers other luminal amoebicides like diloxanide furoate, iodoquinol, and paromomycin. Treatment options discussed for specific protozoan infections include giardiasis, trichomoniasis, leishmaniasis, African trypanosomiasis, and Chagas disease. The document provides a comprehensive overview of antiprotozoal drugs and their use in treating different

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. TISSUE AMOEBICIDES
INTESTINAL AND EXTRA INTESTINAL AMOEBICIDES
METRONIDAZOLE, TINIDAZOLE, ORNIDAZOLE,
SECNIDAZOLE, NIMORAZOLE,
EMETINE, DIHYDROEMETINE
NITAZOXANIDE
EXTRA INTESTINAL AMOEBICIDES
CHLOROQUINE

3.  AMIDES-DILOXANIDE FUROATE
 8-HYDROXYQUINOLINES-
DIIODOHYDROXYQUIN(IODOQUINOL)
 ANTIBIOTICS- TETRACYCLINES, PAROMOMYCIN

5. It is protype nitro imidazole, highly active amoebicide.
selectivity of nitro group containing antibacterial,
antiamoebic, antitrypanosomal arises from absence of
nitroreductase in human and presence of it in the
invading organism.
Metronidazole, tinidazole, secnidazole nitro group
cause both the activity and selectivity.
It has broad spectrum cidal activity against protozoa,
including Giardia lamblia.

6. Metronidazole is selectively toxic to anaerobic
microorganisms.
It enters the cell by diffusion then its nitro group is
reduced by redox proteins to highly reactive nitro radical
which exerts cytotoxicity by damaging DNA & other
critical biomolecules, by inhibiting PFOR(Pyruvate
Ferrodoxin Oxido Reductase)

7. Completely absorbed from intestine.
Widely distributed in the body.
Metabolized in liver & excreted in urine.
Plasma t1/2 is 8 hrs.
Uses
1. Amoebiasis-E.histolytica-DOC
2. Giardiasis-TOC
3. Trichomoniasis-2g single dose
4. Anaerobic bacterial infections
5. Pseudomembranous enterocolitis

8. 1. Anorexia
2. Nausea
3. Metallic taste
4. Abdominal cramps
5. Loose stool is
occasional
6. Headache
7. Dryness of mouth
Contraindications
1. Neurological disorder
2. Blood dyscrasias
3. Ist trimester of
pregnancy
4. Chronic alcoholism

9. A disulfiram like intolerance to alcohol occurs; patients
should avoid drinking abdominal distress, nausea,
vomiting, flushing, or headache, tachycardia,
hyperventilation
aldehyde
dehydrogenase
Ethanol ------  Acetaldehyde ----- Acetate
Enzyme inducer(Phenobarbitone, Rifampicin)
Cimetidine reduce metabolism.
Lithium toxicity can occur on co-administration
Potentiate the anti-coagulant effect of coumarin
derivatives

10. 1. It is potent & directly acting amoebicide
2. Mechanism Act on tissue trophozoites causing
irreversible block of protein synthesis.
3. Metabolized & Excreted slowly via kidney so it has
a cumulative effect.
4. It is not given orally as it is vomited out.
5. Dehydroemetine is less toxic than emetine
6. cardio toxicity

11. 1. It is used for extraintestinal Amoebiasis only.
2. It kills trophozoites of E.histolytica. & highly conc.
in liver.
3. Antimalarial drug
4. Used in combination with metronidazole as luminal
amoebicide for amoebic liver diseases.

12. 1. It is highly effective luminal amoebicide.
2. Drug of choice for mild intestinal/asymptomatic
amoebiasis. Less effective in invasive dysentery.
3. Given orally Split in the intestine, most of
diloxanide is absorbed, conjugated to form a
glucuronide which is excreted in urine (90%).
4. The unabsorbed diloxanide is the amoebicidal
agent (10%) asymptomatic luminal infections,
used with metronidazole
Side Effects-Well tolerated
Flatulence, nausea, urticaria.

13. It is a salicylamide congener of antihelminthic niclosamide
Introduced for treatment of giardiasis and
cryptosporidiosis is active against E.histolytica, T.vaginalis,
ascaris, H.nana.
It is a prodrug which on absorption is converted to active
form tizoxanide, an inhibitor of PFOR enzyme that is
essential pathway of electron transport energy
metabolism in anaerobic organisms
Nitazoxanide is most effective drug for Cryptosporidium
parvum infection which causes diarrhoea in children and
AIDS patients

14. Halogenated 8-hydroxyquinoline
Effective luminal amoebicide, commonly used with
metronidazole
It kill the cyst forming trophozoites in the intestine.
These are used for prophylaxis & treatment of
nonspecific diarrhoea, travellers diarrhoea, dietary
indiscretion.
Not effective against trophozoites in the intestinal wall
and extra-intestinal tissues
T1/2-11-14hrs
Should be taken with meals-avoid GI side effects

15. 1. Nausea, transient loose & green stool
2. Goiter occurs on prolonged use.
3. Iodism ( furunculosis, inflammation of mucous
membrane) occur due to chronic iodine overload.
4. Repeated use of high doses causes a neuropathic
syndrome called ‘sub acute myelo-optic
neuropathy’.
5. Sensitive individuals may develop acute reaction,
chills, fever, angioedema and cutaneous
haemorrhages
C/I-optic neuropathy, renal disease, thyroid disease,
non- amoebic hepatic disease

16. Aminoglycoside antibiotic, not significantly absorbed
from GIT
Luminal amoebicide
Drug accumulates in renal tissue-toxicity
Superior to diloxanide furoate in asymptomatic cases
parenteral  visceral leishmaniasis
ADR- abd. Distress, diarrhea

17. Giardia lamblia lives as commensal
in the intestine.
It sometimes invades the mucosa & causes diarrhoea.
TREATMENT:
1. Metronidazole- 400 mg TDS for 7days
2. Nitazoxanide -500mg BD for 3 days
3. Mepacrine -100 mg TDS for 5days
4. Quinidochlor- 250 mg TDS for 7 days.
5. Furazolidone -100 mg TDS for 5-7 days.

18. Trichomonas vaginalis is a protozoon
causing vulvovaginitis.
TREATMENT:
Drugs used orally;
Metronidazole 400 mg TDS for 7 days
Nimorazole 2 g single dose with meals
Drugs used intravaginally;
Diiodohydroxyquin 200 mg /2wks
Quiniodochlor 200 mg/2wks
Povidine-iodine 400mg/2wks

19. African Tripanosomiasis-t.Brucei
Suramin, Pentamidine,
Melarsoprol,
Eflornithine
American Tripanosomiasis-t.Cruzi
Nifurtimox
Benznidazole

20. ANTIMONIALS- Sodium stibogluconate
Meglumine antimonate
DIAMIDINE- Pentamidine
OTHERS- Amphotericin B, Ketoconazole
Miltefosine, Allopurinol
Leishmania donovani causes visceral leishmaniasis
(kala-azar).
It occur in subtropical regions of world.
It is transmitted by bite of female sand-fly phlebotomus

21. SODIUM STIBOGLUCONATE:
1. It is drug of choice for kala-azar.
2. Mechanism of action is inhibition of –SH
dependent enzymes & blockage of glycolytic &
fatty acid oxidation pathways.
Adverse effects are nausea, vomiting
Metallic taste, cough, abdominal pain etc.

22. Aromatic diamidine
Parentral only
It interacts with kinetoplast DNA & inhibits
topoisomerase II or interfere with aerobic
glycolysis.
Not effective in CNS infection
USES
Pneumocystosis
African trypanosomiasis
leishmaniasis

23. Toxicity is high-acute reaction: sharp fall in BP,
cardiovascular collapse, dyspnoea,
liver & kidney damage, myelosuppression,
Few cases of shock.
Liver & kidney damage, mental confusion,
ECG changes, arrhythmias.
It causes cytolysis of pancreatic b cells Pancreatitis

24. Used in the early treatment and prophylaxis of African
trypanosomiasis.
The drug binds to the host plasma proteinsenters
trypanosome by endocytosis liberated by lysosomal
proteases harmful to parasite
It does not cross BBB and is not effective against
advanced CNS infection
Given by slow IV administration
Suramin + Melarsoprol –in advanced CNS infection
ADR-vomiting, shock, urticaria, proteinuria,
haematuria

25. Trivalent arsenical reserved for treating meningo-
encephalitic stage of African trypanosomiasis
Mainly used to treat trypanosoma infections with CNS
involvement.
The drug acts by reacting with SH groups in protozoal
enzymes and proteins, thereby altering their cellular
structure and inhibiting their functions
ADR- reactive encephalopathy with cerebral edema
seizures coma and death
peripheral neuropathy, hypertension, myocardial
damage

26. Leishmania have high percentage of ergosterol and AMB
has high affinity and binds to it
AMB has highest cure rate in kala-azar up to 99% clinical
and parasitological cure rate
AMB is second line drug due to need of hospitalization,
repeated slow IV infusions
AMB is drug of choice in pregnant women and breast
feeding mothers
L-AMB is best suited as it delivers the drug inside
reticuloendothelial cells in spleen and liver where
amastigotes live.
It is also used in cutaneous leishmaniasis

27. Derivative of alkyl phosphocholine
Potent antileishmania activity
First orally active drug for kala-azar
MOA- interfering with lipid metabolism of parasite or
prevent synthesis of some cell surface anchor
molecules or alter signal transduction
T1/2- 7days-4weeks
ADR-anorexia, vomiting, diarrhoea, skin allergy,
reversible kidney dysfunction, teratogenic

28. Used in the treatment of acute form of Trypanosoma
cruzi infection and T. brucei-gambiense
It acts by generating superoxide and hydrogen peroxide
radicals – toxic as they lack catalase.
Mammalian cells are protected by catalase, glutathione
peroxidase and superoxide desmutase
Orally well absorbed
In chronic infection it fails to prevent progression to GIT
and cardiac manifestations. A combination of gamma-
interferon+ nifurtimox is more efficacious
ADR-hypersensitivity reactions, such as dermatitis,
icterus, GI symptoms

29. THANKYOU
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