Drugs for amebiasis

Solomon M. Abay (PhD)

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• Amebiasis: Infestation with E.hystolytica
– Intestine: principal site of infestation
– Other tissues: liver liver abscesses
• Usually asymptomatic, when symptoms are
present the most characteristics are:
– Diarrhea
– Abdominal pain

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A. Asymptomatic intestinal infection
– In nonendemic areas they are treated by luminal
amebicide
• Diloxanide furoate
• Iodoquinol
• Paramomycin
• Therapy with a luminal amebicide is also required in
the Rx of all other forms of amebiasis

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B. Amebic colitis
– Metronidazole plus luminal amebicide is the Rx of
choice for colitis & dysentery
– TTC & erythromycin are alternative for moderate
colitis
– Dehydroemetine or emetine can also be
used(toxic)

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C. Extraintestinal infections
– Rx of choice are metronidazole + a luminal amebicide
• For unusual cases:
– Initial therapy with metronidazole fails

– Aspiration of abscess (liver)

+
– Chloroquine + repeat metronidazole
• Dihydroemetine or emetine are toxic alternative
drugs
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Classification of antiamebic agents
– Luminal amebicides
• Diloxanide
• Idoquinol
• Paramomycin

– Tissue amebicide
• Both intestinal & extraintestinal
– Metronidazole, tinidazole
– Emetine, Dihdroemetine

• For extraintestinal only

– Chloroquine
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 Metronidazole
• Chemistry: 5-nitroimidazole derivative

• The nitro group accepts electrons from electron transporting

proteins with sufficiently lowSMA
redox potential [ferrodoxin] 7
 Metronidazole
Therapeutic uses
• Amebiasis
– for all symptomatic tissue infections
– must be used with luminal amebicide
• Gardiasis
– highly effective
– lower dosage than for amebiasis
• Trichomoniasis
– highly effective
– can be given topically
• Severe infections due to anaerobic bacteria including
– Bacteriodes
– Clostridium
– Fusobacterium
– H.pylori
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 Metronidazole
• In patients with peptic ulcer infected with H. pylori
• In Rx of pseudomembrane colitis in place of vancomycin
• To facilitate extraction of guinea worm in drancunculiasis

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Adverse effects
• common: head ache, nausea, dryness of
mouth, metallic taste, dizziness
• has a disulfiram like effect
– Disulfiram blocks aldehyde dehydrogenase
• copious vomiting
• flushing
• palpitation
• head ache

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• Used with caution in pts with active disease of CNS
• Its use during 1st trimester is not recommended

Drug Interaction
• With alcohol: disulfiram like effect
• Inhibits inactivation of oral anticoagulant
• Phenobarbitone: enhanced metabolism of
metronidazole
• Cimetidine: reduces metabolism of metronidazole
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 Tinidazole
• similar to metronidazole
• differ in: better toxicity profile & higher t ½

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 Diloxanide furoate
• Useful in the Rx of:
– asymptomatic passers of cyst
– In conjugation with metronidazole in the Rx of
intestinal & systemic amebiasis
– 90% absorbed & the nonabsorbed is effective

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 Emetine & dehydroemetine
• Emetine, an alkaloid derived from ipecac, and
dehydroemetine, a synthetic analog
• Alternative agent
• Mechanism: Inhibit protein synthesis by blocking chain
elongation
• Adverse effects
– Pain at the site of injection
– Transient nausea & vomiting
– Cardiotoxicity [arrhythmia, heart failure, hypotension]

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DRUGS FOR TRYPANOSOMIASIS

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• Trypanosomiasis: refers to chronic & eventually fatal diseases
caused by species of trypanosoma

African sleeping sickness

• caused by:
a. Trypanosoma brucei gambiense
– slow to enter CNS
– Caused sleeping sickness
• Suramine & pentamidine are used in early stage of the
disease[hemolymphatic stage]
• Enflornithine: used in early stage + CNS involvement
b. Trypanosoma brucei rhodesiense
– Early invasion of the CNS
– Usually fatal if not treated
• Melarsoprol: used when there is involvement of CNS in both “a” & “b”.
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• Chaga’s disease[American Trypanosomiasis]
– Caused by Trypanosoma cruzi
– Parasites invade cardiac cells & neurons of
myenteric cell
• Destruction of these cells can cause cardiomyopathy &
megacolon & death
– Drugs used for therapy: Nifurtimox &
Benznidazole

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 Suramine
• Mechanism: unknown; inhibits many trypanosomal
enzyme
• Pharmacokinetics:
– poorly absorbed: administered parenterally
– slowly cleared by renal excretion
• Therapeutic use:
– 1st line of therapy of early hemolymphatic African
trypanosomiasis;
• For chemoprophylaxis against African trypanosomiasis

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 Suramine...
• Adverse effects: common
– Immidiate reaction [fatigue, nausea, vomiting, &
rarely seizure, shock & death]
– Later reaction include:
• Fever, rash, head ache, paresthesias
• Renal abnormality [protein, blood cell, cast]

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 Pentamidine
• Mechanism: not defined; disrupts synthesis of DNA,
RNA, Phospholipid, & proteins
• Pharmacokinetics
– Administered parenterally [im, iv] or by inhalation
• Penetration to brain & CSF is poor

• Therapeutic use
– Rx of PCP/PJP: Injection or inhalation[prophylaxis]
– African sleeping sickness: hemolymphatic stage
– Alternative for Rx of leishmaniasis
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 Pentamidine...
• Adverse effects: highly toxic
– Rapid iv
• Sudden & severe hypotension
• Hypoglycemia due to inappropriate insulin release.
– Pain at i.m. injection site
– Other adverse effect:-
Rash Metallic taste
Fever Hypocalcemia
Thrombocytopenia Cardiac arrhythmia
Hallucinations
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 Eflornithine

• Mechanism: irreversibly inhibits both mammalian &

trypanosomal ornithine decarboxylase, thereby
preventing the synthesis of putrescine;
– the host replaces the inhibited enzyme more rapidly.

• Pharmacokinetics: given p.o or i.v; Penetrate CSF

– Important for late phase trypanosomiasis (West Africa
type)
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 Eflornithine...
• Therapeutic uses: Rx of T. brucei gambiense
• Adverse effects:
– Anemia
– Leukopenia
– Thrombocytopenia
– Alopecia
– Vomiting
– Abdominal pain

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 MELARSOPROL [Trivalent arsenicals]

• Mechanism: react avidly with -SH groups

thereby interacts with & inactivate enzyme
• Mammalian cells may be less permeable
• May act differentially on parasite pyruvate
kinase, which is the terminal glycolytic pathways
• Therapeutic use:
– Drug of choice for late stage trypanosomiasis
[African sleeping sickness]

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MELARSOPROL [Trivalent arsenicals]...
• Adverse effects:
– Quite toxic
• Febrile toxic
• Hypertension
• Albuminuria
• Myocardial damage
• Reactive encephalitis
– Due to rapid release of trypanosoma antigen
– Administration of glucocorticoids can reduce the incidence

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 Drugs for leishmaniasis
• Leishmaniasis:- refers to infestation by a
protozoal species belonging to the genus
Leishmania.
– acquired through a bite of sand flies
• Has three different forms:
• Cutaneous leishmaniasis
• Mucocutaneous leishmaniasis
• Visceral leishmaniasis[kalazar]

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• Drugs include:
– Pentavalent antimony
• Sodium stibogluconate
• Meglumine antimonite
– Allopurinol + sodium stibogluconate
– Amphotericin
– Ketoconazole

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 Sodium stibogluconate
• Mechanism: unknown;
– Nonspecific binding of antimony to -SH group of amastigote
– Both glycolysis & fatty acid oxidation are inhibited
– Pharmacokinetics:
• Poorly absorbed from GIT; used i.m. or i.v.
• Therapeutic use:
– 1st line agent against cutaneous & visceral leishmaniasis
• Adverse effect:
• Muscle pain
• Joint stiffness
• Bradcardia
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 Amphotericin

• Antifungal drug is an alternative therapy for visceral

leishmaniasis, especially in parts of India with high-
level resistance to sodium stibogluconate

• Its use is limited due to cost, and toxicity.

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 Miltefosine
• Treatment of visceral leishmaniasis
• Adverse effects:
– Vomiting and diarrhea but short-lived toxicities.
– Transient elevation of liver enzymes and
nephrotoxicity
– Teratogenic
– Considering the serious limitations of other drugs,
including parenteral administration, toxicity, and
resistance—it may become the treatment of choice.

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• Drugs for Pneumocystis jiroveci pneumonia (PCP/PJP)
– Cotrimethoxazole
– Pentamidine
– Trimethoprim-dapsone
– Primaquine + clindamycin
• Drugs for trichomoniasis
– Metronidazole
– Tinidazole
• Drugs for toxoplasmosis
– Pyrimethamine + sulfadoxine
– Pyrimethamine + sulfadiazine
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Thank you

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