1. ANTI-PROTOZOAL DRUGS

2. ANTI-AMEBIC DRUGS

3. Life cycle of E. histolytica

5. Therapeutic Classification of Anti-Amebic Drugs
I. Luminal Amebicides (Drugs effective in Luminal Infection only)
1. Dichloroacetamides
Diloxanide Furoate
2. Halogenated Hydroxyquinolines
Idoquinol (Diiodohydroxyquine)
3. Antibiotics: Tetracyclines, Paromomycin
4. Oral Bismuth Salt : Emetine Bismuth Iodide

6. II. Extra-Luminal Amebicides
A: Systemic or Tissue Amebicides
1. Chloroquine
2. Emetines : Emetine, Dehydroemetine
B: Mixed Amebicides /Drugs effective in systemic & Intestinal
Amebiasis . (Not reliably effective against luminal infections as
luminal concentrations are too low for single drug treatment)
Nitroimidazoles
Metronidazole
Tinidazole
Secnidazole.

7. Metronidazole (Flagyl)
Most commonly used
Mixed tissue amebicide (Intestinal & extra Intestinal) not reliably
effective against amebae in the lumen as luminal concentrations are
too low for single drug treatment.
Kills only trophozoits in intestinal wall but not the cysts of E.
histolytica.

8. Chemically --- Nitroimidazole

9. Pharmacokinetics:
Prep: Oral, I/V infusion, topical gel, cream.
Abs. well & almost complete from GIT, some unabsorbed drug reaches
colon.
PPL:1- 3 hrs
Dist Rapid & wide. Distributed to all tissues & high concentrations in
body fluids– CSF & brain. Also in Vaginal secretions ,saliva.
t ½: 7.5 hrs
Met: in the liver; may accumulate in hepatic insufficiency
Excretion: urine.

10. MOA
Metronidazole kills protozoa & is bactericidal for anaerobic bacteria.
• Metronidazole is a pro drug.
It requires reductive activation of the NITRO group.
This occurs in sensitive anaerobic protozoa & anaerobic
bacteria by Ferredoxins; which are electron transport
proteins.
• These proteins can donate electrons to Metronidazole ,which serves
as electron acceptor.
• The reduced product is cytotoxic, it targets DNA & other
biomolecules / proteins, resulting in cell death.
Hence it kills the micro-organisms .

11. Resistance:
Not a therapeutic problem.
Some strains of T. vaginalis are becoming resistance.

12. Antimicrobial Spectrum
Kills anaerobic protozoa & bacteria
• Entameba Histolytica (Trophozoits only)
Trichomona Vaginalis
Giardia Lamblia
Clostridia – C . difficile
B. fragilis
Helicobacter pylori.
Also toxic to hypoxic / anoxic cells

13. Therapeutic Uses
Versatile drug
1. Amebiasis: DOC in all tissue infections
Acute intestinal Amebiasis / Amebic colitis with
dysentery. 10 d course with a luminal amebicide
Not reliably effective against parasites in lumen,
Hepatic Amebiasis :10 d course cures 95 % cases
For cases in which initial therapy fails –
Aspiration of abscess & addition of Chloroquine /
Dehydroemetine or Emetine--- toxic

14. 2. Trichomoniasis : Treatment of choice single dose of 2g.
Vaginal & urethral Trichomoniasis. Can be used topically.
3. Giardiasis Treatment of choice--- single dose 90 % efficacy.
4. Bacterial vaginosis: Can be used topically as a gel.
5. Eradication of H. Pylori in Peptic ulcer--a component of 14
days triple therapy regimen. Metronidazole 500mg BD along
with a proton pump inhibitor BD, Clarithromycin 500mg BD
6. Pseudomembranous enterocolitis by Clostridium difficile.
DOC. (Vancomycin is the drug of second choice)

15. 1. Anaerobic/ mixed intra abdominal infections.
2. Component of prophylaxis specially for colorectal
surgery.
3. Brain abscess.
4. Acute Ulcerative Gingivitis.
5. Facilitates extraction of adult guinea worm in
Dranculosis
6. Acne rosacae.

16. Adverse Effects
GIT:
Dry mouth, metallic taste --- most common.
Nausea, vomiting, abdominal cramps , Diarrhea.
Oral thrush--stomatitis
Rarely Pancreatitis.
Neurotoxicity: Headache, Insomnia, numbness or paraesthesias,
weakness , dizziness.
Rarely Ataxia, encephalopathy & seizures.

17. III. OTHER A/E:
2. Disulfiram like action with alcohol.
3. Dysuria ,Dark urine.
4. Mutagenic in bacteria.
5. Carcinogenic in Rodents.
6. Hypersensitivity reactions--- rash, neutropenia
IV. Drug interactions
- Potentiate Anticoagulant effect of Warfarin.
- Metabolism of Metronidazole induced by Phenytoin &
Phenobarbitone & Cimetidine may inhibit it.
- Metronidazole increases Lithium toxicity.

19. Contraindications
Patient with active disease of the CNS.
Hepatic Disease/Renal disease, dose adjustment should
be done.
Pregnancy/ Nursing Mothers.

20. Tinidazole :
• It is a second- generation Nitroimidazole.
• Congener of Metronidazole
• It is similar to Metronidazole in spectrum of activity, MOA ,
absorption , A/E & D/I.
• It is also effective against cysts of E.histolytica.
• It is longer acting –once daily dose.
• Short course– 2gm daily, single dose-- for 3 days.
Secnidazole: Longer acting
Single 2gm dose is given

21. Emetines
Source: Emetine --- Alkaloid of Ipecacuanna (Ipecac)
Dehydroemetine---Synthetic analog
Effective against the trophozoits of Entameba histolytica.

22. Therapeutic Uses :Limited use: Only when Metronidazole can not be
used in :
Severe Amoebic dysentry
Hepatic Amebiasis
Dehydroemetine is preferrd– better toxic profile
Drug should be used S/C or I/M injection in a supervised setting
Never given I/V
Used only for minimum period to relieve severe symptoms. Usually 3-5
days.

23. Adverse Effects
Mild when used for 3-5 days, increase with time
Diarrhea .
Central nausea & vomiting
Pain & tenderness at site of injection/ sterile abscess.
Muscle weakness & discomfort.
Minor ECG changes
Serious toxicity:
Hypotension, Cardiac arrhythmias, Cardiac failure.
Contraindications:
Cardiac /renal disease
Young children , pregnancy.

24. Chloroquine
Antimalarial drug –already discussed.
Tissue Amebicide specially against Amoebic Hepatitis &
Liver Abscess.
Concentrated in liver; kills trophozoits of E. histolytica
Not effective for amebic colitis or luminal amebae
because absorbed in upper intestine.
TH.use: Hepatic amebiasis / abscess; not responding to
Metronidazole

25. Diloxanide Furoate (Luminal amebicide)
Dichloroacetamide derivative
Pharmacokinetics: Given orally, in gut splits into Diloxanoid
& furoic acid. 90% Diloxanoid is absorbed & conjugated
to form glucuronide -- excreted in urine
MOA: Not understood.
Unabsorbed Diloxanoid is directly amebicidal
against amebea in lumen but not those in intestinal wall.

26. Therapeutic uses:
Drug of choice for Asymptomatic Luminal Amoebiasis
(cyst passers)
Alongwith tissue amebicide in severe intestinal & extra
intestinal amebiasis.
Adverse effects
Flatulence
Nausea, abdominal cramps
Skin rashes rarely.
Precautions: Pregnancy

27. IODOQUINOL
Iodoquinol (Diiodohydroxyquine) is a halogenated hydroxyquinoline.
An effective luminal amobecide used with metronidazole to treat
amebic infections.
Only effective against trophozoits in lumen.
Pharmacokinetics :-Poorly understood
90% unabsorbed → amebicide.
10% absorbed →Metabolized to Glucronides ,excreted in urine. Half
life 11-14 hrs.

28. ADVERSE EFFECTS
Diarrhoea, anorexia, nausea, vomiting, abdominal pain.
Headache
Iodism: Dermatitis, urticaria , pruritis ,fever.
Increased in protein bound iodine --- decreased 131I measurement.
Some idoquinol can produce severe neurotoxicity on prolonged use
& high doses--- so used with caution
CAUTIONS
Taken with meals.
With caution in: optic neuropathy , Non-amebic Hepatic disease ,
Renal or Thyroid disease.
C/I in intolerance to Iodine.

29. ANTIBIOTICS
.
Paromomycin
Tetracyclines
Uses: Luminal amebicides
5. Asymptomatic infection (Carriers).
6. Along with extra luminal amebicides in serious
infections.

30. Paromomycin sulphate:
An aminoglycoside antibiotic.
Not significantly absorbed from the gut.
Used as Luminal amebicide.
Less toxic than other agents.
Superior to Diloxanide furoate in clearing asyptomatic
infections.
No effect on extra-intestinal amebic infections.
Also used in visceral leishmeniasis paenterally.
A/E: Abd. Distress & diarrhea.

31. Tetracyclines:
Used as Luminal amebicide.
Does not kill bacteria directly but disturbs the symbiosis
between normal intestinal flora & E .histolytica . The
amebae grow at expense of normal intestinal flora .
Tetracyclines are broad spectrum antibiotics & kill these
flora leading to death of E .histolytica also.
Used in resistant cases.

32. Treatment of specific forms of Amebiasis:
Asymptomatic intestinal infection.
Generally not treated in endemic area.
In non-endemic area treated with luminal amebicide.
– Dolixanide furoate
– Iodoquinol
– Paromomycin.
May be combined with tetracyclines.

33. Amebic Colitis with dysentery:
Mild to moderate intestinal infection:
DOC ---- Metronidazole & Luminal agent.
Alternative ---- Dolixanide furoate, Iodoquinol,
Paromomycin + Tetracycline / Erythromycin.
Severe intestinal infection
DOC ---- Metronidazole & Luminal agent
Alternative ---- Dolixanide furoate, Iodoquinol,
Paromomycin + Tetracycline / dehydroemetine or
emetine.

34. Hepatic abscess, ameboma & other Extra intestinal
Infections:
DOC ---- Metronidazole & luminal agent.
For unusual cases--- not responding to Metronidazole
– Chloroquine + Luminal agent.
– Dehydroemetine or emetine.