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ANTIAMOEBIC DRUGS

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

CLASSIFICATION

TISSUE AMOEBICIDES INTESTINAL AND EXTRA

INTESTINAL AMOEBICIDES METRONIDAZOLE, TINIDAZOLE,

ORNIDAZOLE, SECNIDAZOLE, NIMORAZOLE,

EMETINE, DIHYDROEMETINEEXTRA INTESTINAL AMOEBICIDES CHLOROQUINE

LUMINAL(INTESTINAL)AMOEBICIDES

AMIDES-DILOXANIDE FUROATE 8-HYDROXYQUINOLINES-

DIIODOHYDROXYQUIN(IODOQUINOL) ANTIBIOTICS- TETRACYCLINES,

PAROMOMYCIN

AMOEBICIDES

METRONIDAZOLE

It is protype nitroimidazole, highly active amoebicide.

selectivity of nitro group containing antibacterial, antiamoebic, antitrypanosomal arises from absence of nitroreudctase in human and presence of it in the invading organism.

2) so we can say that in metronidazole, tinidazole, secnidazole, nitro group cause both the activity and selectivity.

It has broad spectrum cidal activity against protozoa, including Giardia lamblia.

Mechanism of Action

Metronidazole is selectively toxic to anaerobic microorganisms.

It enters the cell by diffusion then its nitro group is reduced by redox protiens to highly reactive nitro radical which exerts cytotoxicity by damaging DNA & other critical biomolecules.

Pharmacokinetics

Completely absorbed from intestine.Widely distributed in the body.Metabolized in liver & excreted in urine.Plasma t1/2 is 8 hrs.

Adverse Effects

1. Anorexia2. Nausea 3. Metallic taste4. Abdominal cramps5. Loose stool is occasional6. Headache7. Dryness of mouth

Contraindications

1. Neurological disorder2. Blood dyscrasias3. Ist trimester of pregnancy4. Chronic alcoholism

Interactions

1. A disulfiram like intolerance to alcohol occurs; patients should avoid drinking.

When metronidazole is given with alcohol abdominal distress, nausea, vomiting, flushing, or headache, tachycardia, hyperventilation

aldehyde dehydrogenase Ethanol Acetaldehyde Acetate1. Enzyme inducer(phenobarbitone,rifampicin)2. Cimetidine reduce metabolism.3. It decrease renal metabolism of lithium.

Uses

1. Amoebiasis2. Giardiasis3. Trichomonas vaginitis4. Anaerobic bacterial infections5. Pseudomembranous enterocolitis

ALKALOIDS- EMETINE, DEHYDROEMETINE

1. It is potent & directly acting amoebicide2. MechanismAct on tissue trophozoites causing

irreversible block of protein synthesis.3. Metabolized & Excreted slowly via kidney so it has

a cumulative effect.4. It is not given orally as it is vomited out.5. Dehydroemetine is less toxic than emetine6. cardiotoxicity

CHLOROQUINE

1. It is used for extraintestinal amoebiasis only.2. It kills trophozoites of E.histolytica. & highly conc.in

liver.3. Antimalarial drug4. Used in combination with metronidazole as luminal

amoebicide for amoebic liver diseases.

DILOXANIDE FUROATE

1. It is highly effective luminal amoebicide.2. Drug of choice for mild intestinal/asymptomatic

amoebiasis. Less effective in invasive dysentery.3. Given orallySplit in the intestine, most of

diloxanide is absorbed, conjugated to form a glucoronide which is excreted in urine (90%).

4. The unabsorbed diloxanide is the amoebicidal agent (10%).

5. Well tolerated

Side Effects are flatulence, nausea, urticaria.

8-HYDROXYQUINOLINES-Iodoquinol

1. It kill the cyst forming trophozoites in the intestine.2. These are used for prophylaxis & treatment of

nonspecific diarrhoeas, travellers diarrhoea, dietary indisecretion.

3. Its side effects are few-nausea, transient loose & green stool

4. Goitre occurs on prolonged use.5. Iodism occur due to chronic iodine overload.6. Repeated use of high doses causes a neuropathic

syndrome called ‘subacute myelo-optic neuropathy’.

DRUGS FOR GIARDIASIS

1. Giardia lamblia lives as commensal in the intestine.

2. It sometimes invades the mucosa & causes diarhoea.

TREATMENT:1. Metronidazole- 200 mg TDS for 7days2. Mepacrine - 100 mg TDS for 5days3. Quinidochlor- 250 mg TDS for 7 days.4. Furazolidone -100 mg TDS for 5-7 days.

DRUGS FOR TRICHOMONIAISIS

1. Trichomonas vaginalis is a protozoon causing vulvovaginitis.

2. TREATMENT:Drugs used orally;

Metronidazole 400 mg TDS for 7 days Nimorazole 2 g single dose with meals

Drugs used intravaginally;Diiodohydroxyquin 200 mg Quiniodochlor 200 mgClotrimoxazole 100 mg

DRUGS FOR TRIPANOSOMIASIS

AFRICAN TRIPANOSOMIASIS-T.BRUCEISURAMIN, PENTAMIDINE,

MELARSOPROL, EFLORNITHINE AMERICAN TRIPANOSOMIASIS-

T.CRUZI NIFURTIMOX BENZNIDAZOLE

DRUGS FOR LEISHMANIASIS

1. Leishmania donovani causes visceral leishmaniasis(kala-azar).

2. It occur in subtropical regions of world.3. It is transmitted by bite of female sandfly

phlebotomus.

LEISHMANIASIS DRUGS

ANTIMONIALS1. Sodium stibogluconate2. Meglumine antimonate

DIAMIDINE PentamidineOTHERS

Amphotericin B, KetoconazoleMiltefosine, Allopurinol

ANTIMONIALS

SODIUM STIBOGLUCONATE:1. It is drug of choice for kala-azar.2. Mechanism of action is inhibition of –SH

dependent enzymes & blockage of glycolytic & fatty acid oxidation pathways.

Adverse effects are nausea, vomiting Metallic taste, cough, abdominal pain etc.Pancreatitis,liver & kidney damage,

myelosuppression, ECG changes are possible.Few cases of shock.

DIAMIDINE-Pentamidine

It interacts with kinetoplast DNA & inhibits topoisomerase II or interfere with aerobic glycolysis.

Toxicity is high-acute reaction: sharp fall in BP, cardiovascular collapse, dyspnoea,

Liver & kidney damage, mental confusion, ECG changes, arrythmias.

It causes cytolysis of pancreatic b cells.USES: Kala-azar Pneumocystis carinii Trypanosomiasis

Pentamidine

Liver & kidney damage, mental confusion, ECG changes, arrythmias.

It causes cytolysis of pancreatic b cells. USES: Kala-azar Pneumocystis carinii Trypanosomiasis

Suramin

Used in the early treatment and prophylaxis of African trypanosomiasis.

It acts by inhibiting enzymes of energy metabolism including glycerol phosphate dehydrogenase – for trypanocidal activity

Melarsoprol

Trivalent arsenical Mainly used to treat trypanosoma infections with

CNS involvement. The drug acts by reacting with SH groups of various

enzymes

Nifurtimox -Chagas disease

Used in the treatment of Trypanosoma cruzi infection.

It acts by generating superoxide and hydrogen peroxide radicals – toxic as they lack catalase.

Orally well absorbed

Thank you