Antiprotozoal drugs

Antiprotozoal drugs

• Treatment of amoebiasis.
• Treatment of Giardiasis.
• Treatment of malaria.
 CHEMOTHERAPY OF AMOEBIASIS
The major infecting organism is Entamoeba histolytica , which is
ingested in cystic form which pass to the intestine where
trophozoites are liberated , and may invade the intestinal wall
causing dysentery.
Antiamoebic drugs are classified according to their site of action into:
1- Drugs acting on cysts in the intestinal lumen or asymptomatic
amoebiasis (luminal amoebicidal)
a) Dichloroacetamides (diloxanide , etofamide).
b) Halogenated 8-hydroxyquinolines (diiodohydrox-
quin , iodochlorohydroxyquin)
c) Antibiotics:
- Paromomycin and erythromycin are direct amoebicidal.
- Oxytetracyclines are indirect by modifying bacteria
necessary for survival of amoeba
 2- Drugs acting on the vegetative form in the intestinal wall
and other organs (tissue amoebicidal).
a) Nitroimidazoles(metronidazole,tinidazole,seconidazole)
b) Emetines (emetine and dehydroemetine)
c) Chloroquine (for hepatic amoebiasis).
N.B: (A) metronidazole is partially effective as luminal
amoebicidal.
(B) liver amoebic abscess is treated by surgical
drainage and tissue amoebicidal drugs.
Tissue amoebicidal drugs
1- Metronidazole
Mechanism of action:
Reduced by anaerobic bacteria and protozoa into active metabolite
that binds to DNA leading to inhibition of nucleic acid formation.
Clinical uses:
1- Anti-amebic. Direct amebicidal.
▫ Tissue amebicidal

▫ Drug of choice in amoebiasis (for 10 days).

▫ Less effective as luminal amebicide.

2- Anti-trichomoniasis: Drug of choice

3- Anti-Giardiasis: Drug of choice.
3- Powerful Bactericidal against anaerobic bacteria:
• Peptic ulcer associated with H. pylori

• Pseudomembraneous colitis ( clostridium dificile)

• Anaerobic vaginitis.

• Sepsis caused by anaerobic bacteroids.

• Acute ulcerative gingivitis and dental infections (Fusobacterium ).

ADVERSE EFFECTS
1-CNS: Headache, dizziness, vertigo, parathesia , peripheral neuropathy
2-GIT: Nausea, vomiting, diarrhea, abdominal pain & metallic taste
3-Dark or red brown urine
4-Allergy.
5-Carcinogenic in rats , teratogenic
6-Intensification of Moniliasis
7-Thrombophlebitis of the injected vein occurs if the solution is not well
diluted.
2-Tinidazole ,Seconidazole are similar to metronidazole but effective in
shorter courses (3 – 5 days).
3- EMETINE AND DEHYDROEMETINE
• Ipecacuanha alkaloid.
• Direct tissue ambicidal ( gut wall, hepatic & extra-intestinal )
• Mechanism of action: it causes degenerative effects in cytoplasm and
nucleus.
• Uses: Effective against motile vegetative trophozoite rather
than cysts
1-Hepatic amebiasis and amebic abscess.
2-Extra-intestinal amebiasis.
3-Amebic dysentery.
Adverse effects:
1-Local pain & tenderness at site of injection.
2-C.V.S : Toxic myocarditis (shortness of breath (tachycardia , precordial
chest pain) & hypotension
 N.B: Bed rest during emetine therapy with frequent ECG tracings is
needed.
3-G.I.T: Nausea, vomiting & diarrhea.
4-Skeletal muscle stiffness & tenderness.
5-Peripheral neuritis.
N.B: Dehydroemetine: similar to emetine but safer.
4- Chloroquine phosphate
➢ It is amoebicidal for hepatic amoeba and concentrated in
the liver 500 -5000 times than in plasma.
➢ Adverse effects: vomiting, pruritis , depigmentation
of hair , corneal opacity , alopecia , exacerbation of
psoriasis , photophobia , peripheral neuropathy ,
irreversible retinal injury.Parenteral chloroquine can
cause hypotension arrhythmias and convulsions.
 Luminal amoebicidal drugs
1- Diloxanide furoate
• Direct amoebicidal mainly on the cystic luminal forms.
Used in the treatment of asymptomatic cyst carriers
in amoebic dysentery , amoebic hepatitis to eradicate
intestinal infection.
Adverse effects: flatulence , abdominal distension ,
anorexia , nausea, vomiting , diarrhea , pruritis.
2- Paromomycin
• An aminoglycoside antibiotic with amoebicidal action.
• Adverse effect: diarrhea , GIT upset.
3- Diiodohydroxquin:
• Active against both trophozoites and cystic forms.
• Poorly absorbed from GIT , excreted in faeces .
Used in treatment of asymptomatic amoebiasis ,
in combination with other drugs in the treatment
of amoebic dysentery.
Adverse effects: rash , acne , slight enlargement of the
thyroid gland , peripheral neuropathy after prolonged use in
high dode, iodine sensitivity.
N.B: Iodochlorohydroxyquin not used systemically
because it produces subacute myelooptic neuropathy
(SMON) syndrome.

Treatment of Giardia lamblia (Giardiasis)

• Metronidazole (drug of choice for 5-10 days orally)
• Tinidazole : ( one packet for 3 days orally).
• Nitazoxanide (once orally)
 ANTI-MALARIAL DRUGS
Treatment is directed towards different stages of
development of malarial parasite.
4-AMINOQUINOLNES
CHLOROQUINE & AMODIAQUINE
Kinetics:
• Absorption: Well absorbed orally.
• Distribution: all-over the body And Concentrate in liver
500 times plasma.
• Excreted in urine. Acidification of urine increases its
excretion.

Dynamic: Inhibits enzymatic synthesis of D.N.A & R.N.A.

 ACTIONS
• Anti-malarial actions.
▫ (Drug of choice in acute attacks).
▫ In plasmodium falciparum it produces radical cure.
▫ Suppressive (prophylaxis): Suppress merozoites before
infecting RBCs 500 mg once / weeks orally.
• Anti-amebic: only in hepatic amoebiasis, Anti-
giardiasis.
• Anti-inflammatory & anti-rheumatic: rheumatoid
arthritis and lupus erythematosus
• Mild direct myocardial depressant (Mild quinidine-
like action).
 SIDE EFFECTS AND TOXICITY
When used as antimalarial: Small doses for short time,
almost no toxic effects, but when used as antirheumatic:
Large doses for long periods:
• C.N.S & psychological disorders.
• Visual disturbances.
• Ototoxicity.
• Dermatitis: desquamation, Bleaching of hair, alopecia &
thinning of Nails.
• Cardiotoxicity
• G.I.T Upsets.
• Teratogenecity.
• Bone marrow inhibition.
• Allergic Manifestations.