This document discusses anti-amoebic drugs used to treat infections caused by Entamoeba histolytica. It focuses on nitroimidazoles like metronidazole, tinidazole, secnidazole, and ornidazole which are the first-line treatment for amoebiasis. It also discusses luminal amoebicides like diloxanide furoate and nitazoxanide that kill intestinal trophozoites. Treatment involves the use of nitroimidazoles to eliminate tissue infection combined with luminal agents to clear the intestinal form for a full cure.

1. ANTIAMOEBIC DRUGS

4. NITROIMIDAZOLES
Metronidazole
• prototype nitroimidazole
• amoeba , Trichonomas vaginalis, anaerobic protozoa (Giardia lamblia)
• Many anaerobic bacteria, Bacteroids fragilis, Fusobacterium,
Clostridium perfringens, Cl. difficile, helicobacter pylori,
Campylobacter;
• spirochetes and anaerobic Streptococci
• does not affect aerobic bacteria.

5. NITROIMIDAZOLES
Metronidazole
Mechanism of action
• nitro group of metronidazole is reduced by certain redox proteins
present only in anaerobic microbes to a highly reactive nitro radical
which exerts cytotoxicity
• metronidazole acts as an electron sink which competes with the
biological electron acceptors of the anaerobic organism for the
electrons generated by the pyruvate : ferredoxin
oxidoreductase(PFOR) enzyme pathway of pyruvate oxidation.
• Aerobic environment does not cause reduction of nitro group no
activation

6. NITROIMIDAZOLES
Metronidazole
pharmacokinetics
• Almost completely absorbed from the small intestines
• widely distributed in the body
• Metabolism occurs in liver (oxidation and glucuronide conjugation)
• renal excretion
• t½ is 8 hrs

7. NITROIMIDAZOLES
Metronidazole
Adverse effects
• Anorexia, nausea, metallic taste and abdominal cramps (most
common)
• headache, glossitis, dryness of mouth
• flushing, heat, itching, rashes and fixed drug eruption
• Peripheral neuropathy and CNS effects ( c/I in neurological diseases)
• mutagenic potential ( c/I in pregnancy )
• Disulfiram like reactions in alcoholics ( inhibit acetaldehyde
dehydrogenase )

8. NITROIMIDAZOLES
Metronidazole
Uses
• Amoebiasis: Metronidazole is a first line drug
• Giardiasis
• Trichomonas vaginitis
• Anaerobic bacterial infections after colorectal or pelvic surgery,
appendicectomy, etc
• Pseudomembranous enterocolitis caused by Cl. Difficile
• Acute necrotizing ulcerative gingivitis (ANUG/ trench mouth) :
Metronidazole/ tinidazole are the drugs of choice ; caused by mixed flora
of anaerobes like fusobacteria, spirochetes and bacteroides.
• Helicobacter pylori gastritis/peptic ulcer

9. NITROIMIDAZOLES
Tinidazole
Similar to metronidazole except:
• Metabolism is slower; t½ is ~ 12 hr;
• Duration of action is longer;
• dosage schedules : once daily therapy/ single dose
• Higher cure rates in amoebiasis
• better tolerated

10. NITROIMIDAZOLES
Secnidazole
Similar to metronidazole except:
• Metabolism is slower; t½ of 17- 29 hours

11. NITROIMIDAZOLES
Ornidazole
Similar to metronidazole except:
• Metabolism is slower; t½ ( 12-14 hr).

12. NITROIMIDAZOLES
Satranidazole
Similar to metronidazole except:
• Metabolism is slower; t½ ( 14 hr).
• better tolerability

13. Emetine
• potent and directly acting amoebicide
• MOA: inhibiting protein synthesis in amoebae by arresting
translocation
• administered by s.c. or i.m. injection
• ADR: local irritant and has high systemic toxicity, viz, nausea, vomiting
(due to CTZ stimulation and gastric irritation), abdominal cramps,
diarrhoea, weakness, ECG changes and myocarditis
• Use: only in patients not tolerating metronidazole.

14. Dehydroemetine
• equally effective
• Less toxicity overall and less toxic to the heart

15. Chloroquine
• kills trophozoites of E. histolytica and is highly concentrated in liver.
Therefore, it is used in hepatic amoebiasis only.

16. LUMINAL AMOEBOCIDE
Diloxanide furoate
• kills trophozoites responsible for production of cysts
• No systemic antiamoebic activity is evident despite its absorption.
• metabolized by glucuronidation and is excreted in urine
• No/less action on bacteria, invasive amoebic dysentery
• ADR: very well tolerated; flatulence, occasional nausea, itching and
rarely urticaria.
• Use: mild intestinal and asymptomatic amoebiasis/cyst passers
• given after or along with any tissue amoebicide

17. LUMINAL AMOEBOCIDE
Nitazoxanide
• protozoa including E. histolytica, T vaginalis, giardia
• helminths- Ascaris, H. nana,
• MOA: inhibitor of PFOR enzyme that is an essential pathway of
electron transport energy metabolism in anaerobic organisms.
• ADR: Abdominal pain, vomiting and headache

18. LUMINAL AMOEBOCIDE
8-HYDROXYQUINOLINES
• Entamoeba, Giardia, Trichomonas, some fungi ( dermatophytes,
• Candida) and some bacteria.
• Liver glucuronide conjugation excreted in urine; t½ is ~ 12 hours
• rarely prescribed now, except in some poor localities ( inexpensive)
• ADR: nausea, transient loose and green stools, pruritus
• lodism (furunculosis, inflammation of mucous membranes) and goiter
may develop o n prolonged intake.

19. LUMINAL AMOEBOCIDE
Tetracyclines
• MOA: direct inhibitory action on Entamoeba. inhibit the bacterial
flora with which Entamoebae live symbiotically. Thus, they indirectly
reduce proliferation of entamoebae in the colon
• Use: chronic cases who have only the luminal cycle with little mucosal
invasion; adjuvant role ( used with a more efficacious luminal
amoebicide)

20. LUMINAL AMOEBOCIDE
Paromomycin
• Entamoeba, Giardia,, Trichomonas, l.eishmania and some tape
worms,

21. Treatment
Acute amoebic dysentery
• Metronidazole/tinidazole are the drugs of choice kill the
trophozoites in 5- IO days.
• followed by a course of luminal amoebicide to ensure eradication
• Metronidazole 800 mg oral TDS x 7-1 0 days/Tinidazole 2.0 g oral daily
x 3-6 days
+ Diloxanide furoate 500 mg TDS x 5-10 days

22. Treatment
Mild Intestinal amoebiasis/Asymptomatic cyst
passers
• Metronidazole 400 mg oral TDS x 5-7 days/Tinidazole 2.0 g oral OD x
2-3 days
+Diloxanide furoate 500 mg TDS x 5-10 days
• Asymptomatic cyst passers are mostly treated with only luminal
amoebicide.

23. Treatment
Amoebic liver abscess
• Metronidazole and tinidazole + luminal amoebicide
• Large abscesses : take months to resolve,. may require aspiration