Anti-protozoal drugs

Dr. Mozna Talpur

 Protozoal infections
• Amebiasis
• Malaria
• Giardiasis
• Leshmaniasis
• Toxoplasmosis
• Trypanosomiasis
 Protozoal infections
• Difficult to be treated than bacterial infections.
• Protozoal cells (Eukaryotes) have metabolic
processes closer to human host than prokaryotic
bacterial pathogens.
• Many of antiprotozoal drugs cause toxic effects on the
host.
• Cells with high metabolic processes in the host are
susceptible.
– Examples: bone marrow stem, renal tubular cells, intestinal
& neuronal cells.
• Antiprotozoal are not safe during pregnancy.
 Amebiasis
• Amebiasis is a protozoal infection of the
intestinal tract that occurs due to ingestion
of foods or water contaminated with
Entameba Histolytica cysts
 LIFE CYCLE
• Entamoeba histolytica exists in two forms:
– Cysts (infective):
– can survive outside the human body.
– transform to trophozoites.
– Trophozoites (non-infective; invasive):
• They may feed on intestinal bacteria or
invade and ulcerate wall of large
intestine, and may migrate to liver or other
tissues.
• transform to cysts which are excreted in
feces.
 Life Cycle
• Cysts ingestion.
• Formation of trophozoites
• Penetration of intestinal wall
• Multiplication of trophozoites within colon
wall.
• Systemic invasion.
• Cyst formation in rectum and excretion in
feces.
• Clinical presentations:
– Asymptomatic Intestinal infection (Carriers,
passing cysts)
– Mild to moderate intestinal disease
(Nondysenteric Colitis)
– Severe Intestinal infection (Dysentery)
– Hepatic abscess, ameboma (localized
granulomatous lesion of colon) and other
extraintestinal disease
 ANTIAMEBIC DRUGS
• Luminal Amebicides
– Diloxanide Furoate
– Iodoquinol
– Paromomycin (aminoglycoside)
– Tetracyclines
– Erythromycin (aminoglycoside)
• Systemic amebicides
– Emetine
– Dehydroemetine
– Chloroquine (liver only)
• Mixed Amebicides
– Metronidazol
– Tinidazole
 DILOXANIDE FUROATE
• Diloxanide furoate is an effective luminal
amebicide but it is not effective against tissues
trophozites. In the gut diloaxanide furoate is split
in to diloxanide and furoate acid; 90% of the
diloxanide is rapidly absorbed and conjugated to
form glucuronide which is later on excreted in the
urine. The unabsorbed diloxanide is the active
antiamebic substance.
• It is commonly used with a tissue
amebicide like metronidazole.
• Flatulence, nausea and abdominal
cramps are rare adverse effects. The drug
is not recommended in pregnancy
 Metronidazole
• Mixed amoebicide.
• Drug of choice for intestinal &
extraintestinal amoebiasis.
• Acts on trophozoites.
• Has no effect on cysts.
 MOA
• Nitro group of metronidazole is reduced by
protozoan leading to cytotoxic reduced
product that binds to DNA and proteins
resulting into parasite death.
• Tindazole, a related nitroimidazole, appears to
have similar activity and a better toxicity
profile then metronidazole.
 Clinical Uses
• Extraluminal amoebiasis (combined with
luminal amebicide).
• Giardiasis
• Trichomoniasis
• Broad spectrum of Anaerobic bacteria e.g.,
– Helicobacter pylori infection
– Pseudomembranous colitis (Clostridium
defficile).
 Adverse reaction
• GIT:
– Nausea
– Vomiting
– Dry mouth
– Metallic taste
– Diarrhoea
– Oral Thrush (Moniliasis, yeast infection).
• CNS: Neurotoxicological effect
– Insomnia, dizziness
– Peripheral neuropathy, paresthesia
– Encephalopathy, convulsion ( IV infusion,
rare).
• Dysuria, dark urine.
• Neutropenia
• Disulfiram-like effect if taken with alcohol.
 CONTRAINDICATIONS /
PRECAUTIONS:
• Pregnancy and nursing women.
• Alcohol intake
• CNS diseases
• Severe hepatic disease
• Severe renal disease
 EMETINE AND DEHYDROEMETINE: 
• Emetine hydrochloride is a plant alkaloid derived from
Cephaelis ipecacuanha. Dehydroemetine is a synthetic
analogue
• Pharmacokinetics : Erratic oral absorption. Given preferably
subcutaneously but could be given by IM, NEVER I.V .
Plasma half life is 5 days. 
• Concentrated in Liver, Lungs, Spleen, Kidney, Cardiac muscle
and Intestinal wall. Metabolized & Excreted slowly via
kidney so it has a cumulative effect. Trace amounts could be
detected in urine 1-2 month after last dose. Should not be
used for more than 10 days (usually 3-5 days). 
• Mechanism of action:
– It is directly acting amoebicide. Act on tissue
trophozoites but has no effect on cysts. It act by
inhibiting protein synthesis in amoebae by arresting
intraribosomal translocation of t-RNA amino acid
complex, causing irreversible block of protein synthesis.
• Clinical Uses: 
– Amoebic liver abscess.
– Intestinal wall infections.
– Severe forms of amebiasis
– Acute amoebic dysentery
– dehydroemetine is preferable due to less toxicity (3-5
days).
 Adverse Effects: 
• Dehydroemetine is less toxic than emetine
– Pain at site of injection, abcesses.
– GIT: nausea, vomiting, diarrhoea.
– Neuromuscular weakness
– Serious toxicities :
• Cardiotoxicity - cardiac arrhythmias
• Hypotension - heart failure
• Contraindications: 
– Heart disease
– Kidney disease
– Pregnancy
– Children
 Chloroquine
• Chloroquine Antiamebic drug Antimalarial drug
Used in combination with metronidazole and
luminal amebicide for amebic liver diseases.
• LUMEN AMOEBICIDES: 
– Acts on the parasites in the lumen of the bowl
– Used for treatment of asymptomatic amebiasis.
– Include Amide- Diloxanide Furoate & Nitazoxanide
8-Hydroxyquinoline- Iodoquinol & Quiniodochlor
Antibiotics- - Paromomycin
 HYDROXYQUINOLINES
• Iodoquinol
• Mechanism of action:
– Unknown
– Effective against organisms in GIT only
– Not intestinal wall or liver 
• Clinical Uses:
– Lumen amoebicide.
– For eradication of infection given along with tissue amoebicide
(metronidazole).
• Adverse Effects:
– Peripheral neuropathy including optic neuritis
– GIT: Nausea, vomiting, diarrhea.
– Enlargement of the thyroid gland. Interference with thyroid function
tests (increase protein-bound serum).
– Agranulocytosis.
 Contraindications:
– Optic neuropathy
– Thyroid disease
– Severe liver disease
– Severe kidney disease
– Discontinued if it produces persistent diarrhea or signs of iodine
toxicity (dermatitis, urticaria, pruritus, fever) 
• Mixed amoebicides: 
– Effective against both luminal and systemic forms of the
disease. Although luminal concentration is too low for single
drug – treatment. Metronidazol Tinidazole

• Drugs for Giardiasis:

– Metronidazole, Nitazoxanide, Quiniodochlor, Furazolidone
• Drugs for Trichomoniasis:
– Oral Drug- Metronidazole
– Intravaginally- Quiniodochlor, Diiodohydroxyquin, Clotrimazole,
Hamycine, Natamycine