antiprotozoal drugs are very commonly usedin the tropical area with anibiotics and diarrhea and loss of mineral and water is fatal

1. Dr. Muhammad Saleh Faisal
PIMC, Peshawar
ANTI-AMOEBIC DRUGS

2. Amoebiasis is an acute or chronic infection caused by
Entamoeba histolytica.
Occurs due to ingestion of their cysts.
The parasite exist in two form:
 Trophozoites or active form: does not persist outside the
body.
 Cyst or inactive form: can survive outside the body &
labile.

4. Outcomes:
The outcome infection is variable.
 Asymptomatic but excrete the infectious cyst form,
making them a source for further infections.
 Amebic dysentery :
Trophozoites invade into the colonic mucosa with resulting
colitis and bloody diarrhea .
 Amebic liver abscess:
Trophozoites invade through the colonic mucosa, reach the
portal circulation, and travel to the liver and cause liver
abscess.

5. CLASSFICATION
Tissue Amoebicidals
Both intestinal & extra intestinal
 Nitroimidazoles – Metronidazole, Tinidazole, Secnidazole, Ornidazole
 Alkaloids - Emetine, Dehydroemetine
Extra intestinal amoebiasis only - Chloroquine
Luminal Amoebicidals
 Amide –Diloxanide furoate
 8-Hydroxy quinolones –Iodoquinol
 Antibiotics – Tetracycline, Paromomycin

6. TISSUE AMOEBICIDALS

7. Pharmacokinetics:
 Well absorbed after oral administration
 Distributed in sufficient concentration in the liver, gut,
pelvic tissues, CNS, lungs & other tissues. Reaches high
concentration in body fluids including CSF
 Metabolized by oxidation & glucoronide conjugation in
the liver
 It is eliminated mainly by the kidney
 Plasma protein binding is low (<20%)
 T½ = 8 hours
Metronidazole

8. Spectrum:
Bactericidal against :
 Entamoeba histolytica, Giardia lamblia, trachoma vaginalis
 Anaerobic bacteria - Anaerobic Streptococci, Bacteroide
fragilis, Clostridium perfringes/difficile, Fusobacterium,,
Helicobacter pylori
 Does not affect aerobic bacteria.

9. Mechanism of action
 Metronidazole is a pro-drug.
 Susceptible microorganisms including anaerobic bacteria &
certain protozoa reduces the nitro group of metronidazole by
(PFOR) pyruvate ferredoxin oxido-reductase also known as
nitro-reductase & convert it to active cytotoxic derivative
which binds covalently to DNA, disrupts its helical structure
and thus preventing bacterial nucleic acid synthesis = death.
 Aerobic bacteria lacks this nitro-reductase & are therefore
not susceptible to metronidazole

10. Clinical Indications:
 All symptomatic forms of amoebiasis
 Giardiasis
 Trichomoniasis of urogenital tract in both genders
 Balantidiasis
 Most of Anaerobic infections (clostridial)
 Pseudomembranous colitis
 Helicobacter pylori
 Acute ulcerative gingivitis
 Acute dental infection
 Osteomyelitis
 Abscess of brain & lungs

11.  Prophylaxis of endocarditis by bacillus fragilis
 Prophylaxis of post-surgical abdominal & pelvic
infection
 Treatment of sepsis: post surgical infection, intra-
abdominal infection & septicemia

12. Toxicities:
 Common: Dry mouth, metallic taste, stomatitis, nausea,
headache
 Occasional: vomiting, diarrhea, abdominal distress
 Rare: Urticaria, Flushing, Pruritis
 Serious CNS toxicities warrant discontinuation:
Encephalopathy, Ataxia, vertigo, Dizziness, Convulsion,
Incoordination.

13.  Disulfiram like reaction:
In alcoholic patient:
o Due to inhibition of Acetyldehyde dehydrogenase
enzyme = Acetyldehyde = severe hang over
↑
o Symptom: throbbing headache, visual disturbance,
shortness of breath, nausea, vomiting, Flushing of
the skin, palpatataions, circulatory collapse.
o So to avoid, should not take 12 hours after alcohol
consumption.

14. Tinidazole
 long t ½ , slower metabolism, long DOA= OD dosing.
 Higher cure rates in amoebiasis.
 Lower ADR metallic taste ,nausea, rash.
USES
 Amoebiasis (2g od ---- 3 days)
 Trichomoniasis, giardiasis (2g od ---- single dose)
 Anaerobic infections:
 Px - 2 g od ---- single dose (for colorectal surgeries)
 Tx – 500 mg bd ---- 5 days
 H pylori (500 mg bd ---- 2 wks in triple therapy)

15. Ornidazole
 long t ½
 similar to Tinidazole
Secnidazole
 longest t ½ [17-29 hrs]
 For intestinal amoebiasis = 2 g - od - single dose
 But for hepatic amoebiasis = 1.5 gm - od - 5 days

16.  Emetine, an alkaloid derived from ipecac
 Dehydroemetine, a synthetic analog
 Active against tissue trophozoites
 No action on cysts
MOA
Inhibiting peptidyl-tRNA translocation → inhibiting
elongation of peptide chain → inhibiting protein synthesis
→ interfering cleavage and breeding of trophozoites
Emetin & Dehydroemetine

17. Uses:
 Both are effective against tissue trophozoites of E histolytica, but
because of its major ADR they have been almost completely replaced
by metronidazole.
 Use in circumstances where severe amebiasis warrants effective
therapy and metronidazole cannot be used.
 Dehydroemetine is preferred because of its somewhat better toxicity
profile.
 Should be used for the minimum period to relieve severe symptoms
(usually 3–5 days).

18. Routes of administration:
SC or IM in a supervised setting.
Adverse effect:
 Pain and tenderness in the area of injection are frequent
and sterile abscesses may develop.
 Serious toxicities include cardiac arrhythmias, heart
failure, and hypotension
 Muscle weakness due to neuromuscular blockage.
 Diarrhea, Nausea, vomiting and abdominal discomfort

19. Chloroquine
 Because of complete absorption from Small gut, much
lower concentration in gut wall so less effect on luminal
ameobas.
 Effective in Hepatic amoebiasis bcz concentrated in liver
 Use only when metronidazole is not effective or
contraindicated. Highly effective when combine with
emetine/ dehydroemetine
Dose
• Adults 1g/day x 02 days then 500mg/day x 02 weeks

20. LUMINAL AMOEBICIDALS

21. Diloxanide furoate
 A dichloroacetamide derivative.
 It is an effective luminal amebicide but is not active
against tissue trophozoites.
 It is used with a tissue amebicide, usually metronidazole,
to treat serious intestinal and extraintestinal infections.
 In the gut, diloxanide furoate is split into diloxanide and
furoic acid. Diloxanide is absorbed but has got no
amoebicidal activity. The unabsorbed diloxanide is the
active antiamebic substance.

22. Mechanism of action
is unknown.
Adverse effects:
 Diloxanide furoate does not produce serious adverse
effects.
 Flatulence is common.
 Sometimes nausea and abdominal cramps and rashes are
seen.

23. Iodoquinol
It is effective against organisms in the bowel lumen.
Not useful against trophozoites in the intestinal wall or
extraintestinal tissue.
Pharmacokinetics:
 Pk profile is Poorly understood
 90% of the drug is retained in the intestine & excreted in
the feces.
 The remainder enters the circulation and has a t½ of 11-
14 hours which later excreted in the urine.

24. Mechanism of action:
Unknown
Adverse effects:
Anorexia, nausea, vomiting, abdominal pain.
Headache, rash & pruritus
Contra-indications:
 It should be carefully used in patients with thyroid problems
because the drug may increase serum iodine by displacing
from protein bound.
 It is contraindicated in patients with intolerance to iodine

25. Paromomycin sulfate
 An aminoglycoside antibiotic that is not significantly absorbed from
the GIT
 It is used only as a luminal amebicide.
 No effect against extraintestinal amoebic infections
 In a recent study, it was superior to diloxanide furoate in clearing
asymptomatic infections.
MOA:
 Inhibits protein synthesis → kill trophozoites.
 Also, inhibits the bacterial flora with which Entamoebae live
symbiotically.
Adverse effects:

26. Tetracyclines
 Older tetracyclines are incompletely absorbed in the small
intestine, reach the colon in large amounts and inhibit the
bacterial flora with which Entamoebae live symbiotically.
Thus, they indirectly reduce proliferation of
entamoebae in the colon.
 At high conc, directly inhibit amoebae.

27. Asymptomatic cyst passers
 DOC= Diloxanide furoate
 A paromomycin or tetracycline with tissue amoebicide
in cases which fail to clear completely.
SUMMARY OF AMOEBIASIS TREATMENT

28. Invasive intestinal amoebiasis
 DOC= Metronidazole/ Tinidazole
 Alternatives= Secnidazole, ornidazole,satranidazole
 Symptomatic measures for diarrhea and abdominal pain.

29. Hepatic amoebiasis
 Complete eradication of trophozoites from the liver is
essential to avoid relapses.
 Abscess  aspirated.
 DOC= Metronidazole / Tinidazole
 Dehydroemetine is to be used only if metronidazole
cannot be given for one reason or the other.
 Addional luminal amoebicide must be given later to
finish the intestinal reservoir of infection.

30. THANK YOU