Anti-Amoebic drugs

1. Antiamoebic Drugs

2. • Amebiasis affects about 10% of the world's
population, causing invasive disease in about 50
million people and death in about 100,000 of
these annually.
• Amoebiasis is an acute or chronic infection with
Entamoeba histolytica produced by ingestion of
cysts of this organism.
• 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. • 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. • Choice of drug depends upon:
– Clinical presentation
– Desired site of action
• Asymptomatic carriers generally are not
treated in endemic areas but in nonendemic
areas they are treated with a luminal
amebicide.
• Luminal agents used to treat asymptomatic
individuals found to be infected with E.
histolytica.
- Diloxanide furoate
- The nonabsorbed aminoglycoside
paromomycin & the 8-hydroxyquinoline
compound iodoquinol

6. • Metronidazole and Tinidazole are the only
nitroimidazoles are the drugs of choice for the
treatment of amebic colitis, amebic liver abscess,
and any other extraintestinal form of amebiasis.
• Metronidazole is so well absorbed in the gut, levels
may not be therapeutic in the colonic lumen, and it
is less effective against cysts.
• Patients with amebiasis (amebic colitis or amebic
liver abscess) also should receive a luminal agent to
eradicate any E. histolytica trophozoites residing
within the gut lumen.

7. • Nitatzoxanide an oral synthetic broad-spectrum
antiparasitic agent , effective against a number
of intestinal helminths and protozoans.
• Other agents, dehydroemetine and chloroquine,
rarely used in Rx of amebic colitis or amebic liver
abscess and are reserved for only very unusual
cases where metronidazole is contraindicated.
• Tetracyclines and erythromycin are alternative
drugs for moderate colitis but are not effective
against extraintestinal disease.

9. Con’d

10. Metronidazole
• Metronidazole is a nitroimidazole antiprotozoal
drug, Kills the E. histolytica trophozoites.
• Has antibacterial activity against anaerobes,
including bacteroides & clostridium species.
• It is the drug of choice for the
pseudomembranous colitis caused by the
anaerobic, gram-positive bacillus cl difficile & is
also effective in the treatment of brain abscess
caused by these organisms

11. • Antiparasitic & antimicrobial spectrum
– Obligate anaerobic bacteria
– Helicobacter pylori
– Bacteroids
– Clostridia
– -E histolytica
– Giardia lumblia
– -Trichomona vaginalis

12. • P/K:
– Well absorbed after oral & rectal administration
– Distributed in sufficient concentration in the liver,
gut, pelvic tissues, CNS, lungs & other tissues like
bone tissue. Reaches high concentration in body
fluids including CSF
– Metabolized by oxiadation & glucoronide conjugation
in the liver
– It is eliminated mainly by the kidney (urine) in
unchanged & some as metabolized from
– Plasma protein binding low (<20%)
– t½ 8 hours

13. Mechanism of action
– Metronidazole is a prodrug.
– Susceptible microorganisms including
anaerobic bacteria & certain protozoa reduce
the nitro group of metronidazole by a
nitroreductase & convert it to a cytotoxic
derivative.
– Aerobic bacteria lacks this nitroreductase &
are therefore not susceptible to metronidazole

14. • Metronidazole diffused into anaerobic bacterial or
sensitive protozoal cells
↓
In electron transport chain, the nitro group of
metronidazole is reduced by ferridoxine (by
accepting electron from transport protein)
↓
The reduced product appear to be responsible for
killing the organism probably reacting with cellular
macromolecules such as DNA, protein & membrane .
↓
Inactivation of DNA
↓
Death of protozoa & susceptable bacteria.

15. Indications:
– All symptomatic forms of amoebiasis
– Giardiasis
– Trichomoniasis of urogenital tract in both sex
– Anaerobic infection (clostridial)
– Prophylaxis of post-surgical abdominal &
pelvic infection
– Helicobacter pylori

16. – Acute ulcerative gingivitis
– Acute dental infection
– Balantidiasis
– Osteomylitis
– Abscess of brain & lungs
– Pseudomembranous colitis
– Prophylaxis of endocarditis by bacillus fragilis
– Treatment of sepsis: post surgical infection,
intraabdominal infection & septicemia

17. • Toxicities:
– Common: headache, nausea, dry mouth,
metallic taste
– Occasional: vomiting, diarrhea, abdominal
distress
– Serious warrant discontinuation:
Dizziness, vertigo, Encephalopathy,
Convulsion, Incoordination, Ataxia

18. – Rare are: Urticaria, Flushing, Pruritus, Cystitis
– Disulfiram like reaction: Severe nausea &
vomiting ,Due to inhibition of Acetyldehyde
dehydrogenase enzyme.
Disulfirum:
– In alcoholic patient
– Severe Hangover: Due to ↑Acetyldehyde
dehydrogenase.
– Symptom: Flushing of the skin, Accelerated HR,
shortness of breath, nausea,vomiting, throbbing
headache, visual disturbance, circulatory
collupse. Should not take 12 hours after alcohol
consume.

19. • Disulfiraum is used in cocaine dependence as it
inhibit Dopa decarboxylase → Prevent
breakdown of dopamine. ( A NT whose release
is stimulated by cocaine)
• The excess dopamine results in increase anxiety,
high BP, restlessness.

20. • Contraindication:
– Active disease of CNS
– Evidence of blood dyscariasis
– 1st trimester of pregnancy
– Any type of carcinoma

21. Tinidazole
• A nitroimidazole, appears to have similar
activity and a better toxicity profile than
metronidazole
• Has a longer half-life of 13 hours.
• Excreted in urine in unchanged (mainly) form
• Indication:
– Anaerobic and protozoal infections:
– Very effective in case of – Giardiasis,
trichomoniasis, ulcerative gingivitis
– Helicobacter pylori eradication

22. Secnidazole
• Indication: It is used in the treatment of amoebiasis,
& has also been tried in giardiasis, & trichomoniasis
• Dose:
– Given in giardiasis by mouth, usually as a single
dose of 2 gm in adult; for child, the dose is 30
mg/kg
– In invasive hepatic amoebiasis a dose of 1.5 g/ day
is given single or in divided doses for 5 days
• Trade name: Secnid Susp. 500 mg, Tab. 1 gm;
Secnidal, Sezol DS.

23. • Emetine, an alkaloid derived from ipecac
• Dehydroemetine, a synthetic analog
• Both are effective against tissue trophozoites of E
histolytica, but because of major toxicity concerns
they have been almost completely replaced by
metronidazole.
• use is limited to unusual circumstances in which
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 needed to relieve severe
symptoms (usually 3–5 days).
Emetin & Dehydroemetine

24. • 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.
Diarrhea is common.
nausea, vomiting, muscle weakness and
discomfort
• Serious toxicities include cardiac arrhythmias,
heart failure, and hypotension

25. Iodoquinol
• Effective luminal amoebicide that is commonly used
with metronidazole to treat amebic infections
• Pharmacokinetics:
– Poorly understood
– 90% of the drug is retained in the intestine &
excreted in the feces. The remainder enters the
circulation, has a t½ of 11-14 hours, & is excreted
in the urine as glucoronides

26. • Mechanism of action:
– unknown. It is effective against organisms in the
bowel lumen but not against trophozoites in the
intestinal wall or extraintestinal tissue
• Adverse effects:
– anorexia, nausea, vomiting, abdominal pain,
headache, rash, & pruritus
• The drug may increase protein-bound serum iodine,
leading to a decrease in measured 131I uptake that
persist for months

27. • Should be taken with meal to limit GI toxicity
• Should be taken with caution in patient with
optic neuropathy, renal or thyroid disease. Di-
iodo chlorhydroxyquinoline causes subacute
myelo optic neuropathy, so it is not used now
• The drug should be discontinued if it produces
persistent diarrhea or signs of iodine toxicity
(dermatitis, urticaria, pruritus, fever)
• It is contraindicated in patients with intolerance
to iodine

28. Diloxanide furoate
• A dichloroacetamide derivative.
• It is an effective luminal amebicide but is not active
against tissue trophozoites.
• In the gut, diloxanide furoate is split into diloxanide
and furoic acid
• About 90% of the diloxanide is rapidly absorbed and
then conjugated to form the glucuronide, which is
promptly excreted in the urine.The unabsorbed
diloxanide is the active antiamebic substance.

29. • The mechanism of action of diloxanide furoate is
unknown.
• Diloxanide furoate is the drug of choice for
asymptomatic luminal infections.
• It is used with a tissue amebicide, usually
metronidazole, to treat serious intestinal and
extraintestinal infections.
• Diloxanide furoate does not produce serious adverse
effects. Flatulence is common, but nausea and
abdominal cramps are infrequent and rashes are
rare.
• The drug is not recommended in pregnancy.

30. Paromomycin sulfate
• It is an aminoglycoside antibiotic that is not
significantly absorbed from the GIT
• It is used only as a luminal amebicide & has no
effect against extraintestinal amebic infections
• The drug may accumulate with renal insufficiency &
contribute to renal toxicity
• Have similar efficacy & probably less toxicity than
other agents; in a recent study, it was superior to
diloxanide furoate in clearing asymptomatic
infections
• Adverse effects:
– Occasional abdominal distress & diarrhea
• Should be avoided in patients with significant renal
disease & GI ulceration.

31. Nitazoxanide
• An oral synthetic broad-spectrum
antiprotozoal agent
• It was found initially to have activity against
a number of intestinal helminths &
protozoans

32. • Spectrum of activity:
– Cryptosporidium parvum; G.lumblia;
– E.histolytica
– A lumbricoides; Fasciola hepatica
– H. pylori
• Nitazoxanide appears to have activity against
metronidazole-resistant protozoal strains & is well
tolerated

33. • M/A:
Nitazoxanide is a nitrothiazolyl-salicylamide prodrug.
It is rapidly absorbed & converted to active metabolite
tizoxanide which inhibits the pyruvate:ferredoxin
oxidoreductase (PFOR) enzyme-dependent electron-
transfer reaction.
This reaction is essential in anaerobic glucose energy
metabolism.This results in cell swelling, mem. Damage
causing dysfunction of parasite.

34. • Therapeutic uses:
• Treatment of G. intestinalis infection & treatment of
diarrhea caused by cryptosporidia
• Dose:
– Children between 12 & 47 months
• 100 mg 12 hourly for 3 days
– Children between 4-12 years
• 200 mg 12 hourly for 3 days
– Children over 12 years & adults
• 500 mg 12 hourly for 3 days

35. • Adverse effects:
– Rare. Abdominal pain, diarrhea, vomiting &
headache have been reported. A greenish tint
to the urine is seen in most individuals taking
nitazoxanide
• Nitazoxanide is considered a category B agent for
use in pregnancy based on animal teratogenicity &
fertility studies, but there is no clinical experience
with its use in pregnant women or nursing
mothers