Amoebicial drugs

1. Amebiasis
Two morphologically identical but genetically
and biochemically distinct species of
Entamoeba:
E. histolytica in 10% is pathogenic,
and E. dispar in 90%

2. ?
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3. May cause:
mild to severe colitis ( acute or chronic )
- amebic dysentery.
In some instances, these trophozoites also
invade extraintestinal tissues,
chiefly the liver where they produce
amebic abscesses and systemic disease

4. Anti-amoebics
Drugs used in Amebiasis

5. Classification

6. Chemical Classification
Nitroimidazoles:
 Metronidazole
 Tinidazole
 Ornidazole
Dichloroacetamides:
 Diloxanide furoate
Halogenated
hydroxiquinolines
 Iodoquinol

7. Emetines:
 Emetine
 Dehydroemetine
Quinolines:
 Chloroquine
Antibiotics /
Antimicrobials:
 Tetracyclines
 Paromomycin
 Erythromycin

8. Clinical Classifications
Luminal:
Diloxanide furoate
Iodoquinol
Paromomycin
Tissue:
DehydroEmetine or
Emetine
Chloroquine (for liver only)
Tissue:
( Nitroimidazoles )
Metronidazole,
Tinidazole,
Ornidazole
Alternatives
Antibiotics:
Tetracycline
Erythromycin

9. Asymptomatic
Intestinal Infection:
Luminal_Diloxanide or
Iodoquinol, or
Paromomycin or
antibacterials.
Mild to Moderate
Intestinal Infection
Metronidazole etc.
and Luminal
Severe Intestinal
Infection:
Metronidazole and
Luminal or
Dehydroemetine or
Tetracycline
Hepatic Amebiasis:
Metronidazole and
Luminal or D Emetetine
Chloroquine (Liver)

11. Luminal
Amoebicides
Tissue
Amoebicides
Mixed_ ?
Amoebicides

12. What may be the preferred initial drug?

13. Metronidazole:
Metronidazole
enters an aerobic
bacterium where, via
the electron transport
protein ferrodoxin, it is
reduced.
The drug then binds to
DNA, and DNA…..
breakage occurs.
Bacterium

14. Mechanism of action:
Metronidazole is amebicidal,
bactericidal,
and trichomonicidal.

15. Unionized metronidazole is readily taken
up by anaerobic organisms and cells.
Its selectivity for anaerobic bacteria is a
result of the ability of these organisms to
reduce metronidazole to its active form
intracellularly.

16. The electron transport proteins
necessary for this reaction are found
only in anaerobic bacteria.
Reduced metronidazole then disrupts
DNA's helical structure, thereby
inhibiting bacterial Nucleic Acid
Synthesis.

17. Cell death.
Metronidazole is equally effective
against dividing and non-dividing
cells.

18. Spectrum of activity:
Metronidazole and related
nitroimidazoles are active in vitro against a
wide variety of
anaerobic protozoal parasites
and anaerobic bacteria.
It is:
amebicidal, trichomonacidal and
bactericidal.

19. The spectrum of activity of metronidazole
includes the following:
Anaerobic gram-negative bacilli,
including :
Bacteroides species,
Fusobacterium
and Veillonella;

20. Anaerobic gram-positive cocci
including:
Clostridium,
Eubacterium,
Peptococcus
and Peptostreptococcus.

21. Metronidazole is also active against:
H. pylori,
E. histolytica
G. vaginalis & lamblia.
T. vaginalis

22. Metronidazole acts primarily against
the trophozoite forms of E. histolytica
and has limited activity against the
encysted forms.

23. Pharmacokinetics:
Preparations of metronidazole are available
for oral, intravenous, intravaginal,
and topical administration.
The drug usually is completely and promptly
absorbed after oral intake

24. With the exception of placenta,
metronidazole penetrates well into body
tissues and fluids, including vaginal
secretions, seminal fluids, saliva, and breast
milk.
Therapeutic concentrations also are achieved
in cerebrospinal fluid.

25. After an oral dose, over 75% of labeled
metronidazole is eliminated in the urine, largely as
metabolites;
only about 10% is recovered as unchanged drug.
The liver is the main site of metabolism, and this
accounts for over 50% of the systemic clearance
of metronidazole.

27. Therapeutic Indications:
Protozoal Infections:
1. Amoebiasis…Hepatic and intestinal
2. Trichomonal infections in men and
women.
3. Giardiasis.

28. 4. Susceptible Anaerobic Bacteria:
Serious Infections such as caused by
Bacteroide fragilis (and other species),
Clostridium, Fusobacterium, Peptococcus, and
Peptostreptococcus species.
5. Antibiotic-induced Diarrhea:
Colitis, including mild to moderate cases of
Pseudomembranous Colitis caused by C. difficile.

29. 6. In Mixed Aerobic And Anaerobic Infections:
with concomitant administration of an antibiotic
appropriate for the treatment of the Aerobic
Infection.
7. H. Pylori-associated Peptic Ulcer Disease:
in multiple-drug regimens
8. Bacterial Vaginosis:

30. 9. Periodontal Infections:
10. As An Adjunct: in the treatment of Acute
Necrotizing Ulcerative Gingivitis (ANUG) caused
by spirochetes, fusobacteria, and Bacteroides
species.
11. Rosacea: Topically for Inflammatory
papules, pustules and Erythema of Rosacea.

31. Adverse Effects:
Side effects to discontinue therapy are
rarely severe enough.
The most common are headache, nausea,
dry mouth, and a metallic taste.
Vomiting, diarrhea, and abdominal distress
occasionally are experienced.

32. Furry tongue, glossitis, and stomatitis occurring
during therapy.
Dizziness, vertigo, and, very rarely encephalopathy,
convulsions, incoordination, and ataxia are
neurotoxic effects that warrant discontinuation of
metronidazole.

33. Temporary Neutropenia:
reversible after discontinuation of therapy.

35. Contraindications:
The drugs should be used to treat amebic
dysentery or amebic liver abscess for the
minimum period needed to relieve severe
symptoms
They should not be used for more than 10
days.

36. Precautions:
The drug should be withdrawn if numbness
or paresthesias of the extremities occur.
Urticaria, flushing, and pruritus are
indicative of drug sensitivity that can
require withdrawal of metronidazole.

37. Metronidazole should be used with caution
in patients with Active Disease of the CNS
because of its potential neurotoxicity.
The dosage of metronidazole should be
reduced in patients with Severe Hepatic
Disease.

38. Drug Interactions:
Alcohol:
Disulfiram-like Effect.
abdominal distress, vomiting, flushing, or
headache if they drink alcoholic beverages
during or within 3 days after therapy with this
drug.

39. Lithium Toxicity:
May precipitate CNS signs of lithium toxicity.
Cimetidine:
Plasma levels of metronidazole can be elevated by
inhibition its hepatic microsomal metabolism.
Coumarin Anticoagulants.
metronidazole can prolong the prothrombin time

40. DILOXANIDE FUROATE
Diloxanide is a dichloroacetamide derivative,
furoate ester
proved to be appreciably
more active
than
the parent compound.

41. Pharmacological Effects.
Diloxanide is directly amebicidal when
tested in vitro.
The furoate ester is more potent.
Mechanism of Action:
Little is known

42. Pharmacokinetics:
After oral ingestion, the ester is largely
hydrolyzed in the lumen or mucosa of the
intestine to diloxanide and furoic acid;
only diloxanide appears in the systemic
circulation.
10 % remain in lumen
60% to 90% is excreted in the urine
within 48 hours

43. Therapeutic Uses
Given alone, diloxanide furoate is effective
for treatment of Asymptomatic Passers of
amoebic cysts
Diloxanide is ineffective when
administered alone in the treatment of
extra intestinal amoebiasis.

44. Diloxanide furoate is used
along with or after an appropriate
systemic or mixed amoebicide to affect a
cure of invasive and extra intestinal
amoebiasis.

45. Orally recommended Adult Dose:
500 mg three times daily for 10 days.
If necessary, treatment can be extended to
20 days.
Children Dose: 20 mg/kg per day in three
divided doses for 10 days.

46. Adverse Effects:
Diloxanide furoate generally is well
tolerated and side effects are mild.
Flatulence is most commonly reported;
nausea, vomiting, diarrhea, pruritus, and
urticaria occur occasionally

47. Iodoquinol
(di-iodo-hydroxyquin)
Iodoquinol (diiodohydroxyquin) is a
halogenated hydroxyquinoline.
An effective luminal amebicide
used with metronidazole to treat amoebic
infections.

48. Pharmacokinetics &
Pharmacological effects:
90% of the drug is retained in the intestine
and excreted in the feces.
10% enters the circulation, has a half-life of
11-14 hrs,
Excreted in the urine as glucuronides.

49. The Mechanism Of Action of iodoquinol
against trophozoites is unknown.
It is effective against organisms in the
bowel lumen
but not against trophozoites in the
intestinal wall or extra intestinal tissues.

50. Precautions:
Iodoquinol should be taken with meals to
limit gastrointestinal toxicity.
It should be used with caution in patients
with optic neuropathy, renal or thyroid
disease, or nonamoebic hepatic disease.

51. Contraindications:
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

52. Paromomycin
Paromomycin sulfate is an aminoglycoside
antibiotic
Not significantly absorbed from the GIT
.
Used only as a luminal amebicide and has no
effect against extraintestinal amebic infections.
The small amount absorbed is slowly excreted
unchanged, mainly by glomerular filtration.
The drug may accumulate with renal
insufficiency and contribute to renal toxicity.

53. • Paromomycin is an effective luminal amebicide
similar efficacy and probably less toxicity than
other agents;
In a recent study, it was superior to
diloxanide furoate in clearing asymptomatic
infections.
(Parenteral paromomycin is under investigation in
the treatment of visceral leishmaniasis.)

54. Adverse Effects:
Occasional Abdominal Distress and Diarrhea.
Paromomycin should be avoided in patients
with Significant Renal Disease
used with caution in persons with
gastrointestinal ulcerations.

55. Emetine, Dehydroemetine:
Emetine:
an alkaloid derived from ipecac
"Brazil root"
Direct-acting, systemic amebicidal
Dehydroemetine:
similar pharmacological properties
but is considered to be less toxic.

56. Pharmacokinetics:
The drugs are administered parenterally because
oral preparations are absorbed erratically.
Emetine and dehydroemetine should be
administered subcutaneously (preferred) or
intramuscularly (but never intravenously) in a
supervised setting
They accumulate in tissues and are eliminated
slowly via the kidneys.

57. Therapeutic Indications:
Limited to unusual circumstances in which
severe amebiasis warrants effective therapy
and metronidazole cannot be used.
Dehydroemetine is preferred over emetine
because of its somewhat better toxicity
profile.

58. Adverse Effects:
Adverse effects are generally mild when the drugs
are used for 3-5 days but increase with prolonged
use
Pain and tenderness in the area of injection are
frequent, and sterile abscesses may develop.

59. Diarrhea is common.
nausea, vomiting
, muscle weakness and discomfort
minor electrocardiographic changes.
Serious toxicities :
cardiac arrhythmias,
heart failure,
hypotension

60. Although both drugs have been widely used
to treat severe invasive intestinal amebiasis
and extraintestinal amebiasis
but they largely have been replaced by the
mixed amebicide metronidazole, which is as
effective and far safer
Emetine and Dehydroemetine should not
be used unless metronidazole is ineffective
or contraindicated.

61. Precautions:
The drugs should not be used in patients of
cardiac or renal disease,
in young children,
in pregnancy
unless absolutely necessary.

62. Asymptomatic Luminal Agent:
Intestinal Diloxanide Furoate,
Infection 500 mg TID
for 10 days
or
Iodoquinol,
650 mg TID
for 21 days
or
Paromomycin,
10 mg/kg TID
for 7 days
Clinical Setting Drugs of Choice Alternative Drugs
and Adult Dosage and Adult Dosage

63. Mild to Metronidazole, Luminal
Moderate 800 mg TID as above
Intestinal for 10 days plus either
Infection or Tetracycline.
Tinidazole, 250 mg TID
2 G daily for 10 days
for 3 days. or
plus Erythromycin,
Luminal 500 mg QID
as above for 10 days

64. Metronidazole, Luminal
Severe 800 mg TID as above
Intestinal for 10 days plus either
Infection or Tetracycline.
Tinidazole, 250 mg TID
2 G daily for 10 days
for 3 days. or
plus Dehydroemetine,
Luminal or Emetine
as above 1 mg / kg SC or IM
for 3–5 days

65. Hepatic Metronidazole, Dehydroemetine
Abscess, 800 mg TID or Emetine
Amoeboma, for 10 days 1 mg / kg SC or IM
And Other for 8-10 days
Extra intestinal or followed by
Disease Tinidazole Chloroquine (liver only)
2 G daily 500 mg BID
for 5 days for 21 days
plus plus
Luminal Luminal
as above as above