ANTIAMOEBIC DRUGS

PRESENTED BY: Group 8

(PRIST)Sneha Kulkarni

Vinita PillaiSnehal KhedekarUrvashi RajputVijay Bansode

Amoebiasis

Amoebiasis is an infection of the intestine, liver, or other tissues caused by a one-celled parasite called Entamoeba histolytica.

Amoebiasis is most prevalent in tropical and subtropical countries

Poverty, ignorance, overcrowding, poor sanitation and malnutrition favour transmission

It is acquired by ingesting food or water contaminated by infected feces.

Symptoms Mostly they are quite mild and can include

loose stools stomach pain abdominal cramps

Amoebic dysentery – severe form stomach pain bloody stools fever jaundice anorexia weight loss

Rarely the parasite invades liver and forms an abscess and spread to other parts of the body, such as lungs or brain

Diagnosis of Amoebiasis

Medical history, physical examination, lab tests and stool examination

Blood test to reveal antibodies against the organism

Sigmoidoscopy to evaluate the intestinal wall

Radiological studies including ultrasound and CT scans to detect liver abscesses

Treatment of Amoebiasis

The choice of drug depends on the severity of the symptom

Drugs include Metronidazole Emetine Chloroquine Diloxanide furoate 8 - hydroxyquinoline Tetracycline

Classification Tissue amoebicides

For both intestinal and extra intestinal amoebiasis:▪ Nitroimidazoles: Metronidazole, Tinidazole,

Secnidazole, Ornidazole, Satranidazole.▪ Alkaloids: Emetine, Dehydroemetine

For extraintestinal amoebiasis only:▪ Chloroquine

Luminal amoebicides Amide: Diloxanide furoate 8-Hydroxyquinolines: Quiniodochlor,

Diiodohydroxyquin Antibiotics: Tetracycline

Metronidazole Prototype nitromidazole.(1959) Highly active amoebicide. Broad spectrum cidal activity against protozoa. It is selectively toxic to anaerobic microorganism.

MOA Nitro group is reduced to highly reactive nitro radical that

causes damage to DNA and other critical biomolecules by cytotoxicity

It disrupts energy metabolism DNA helix destabilization and strand breakage are

observed Found to inhibit cell mediated immunity to induce

mutagenesis and to cause radiosensitization

Pharmacokinetics Completely absorbed from small intestine Metabolized in liver by oxidation and glucoronide

conjucation Excreted in urine Plasma t1/2 is 8hrs

ADR Frequent- Anorexia, Nausea, Metallic taste, Abdominal

cramps Less frequent-Headache, Glossitis, Dizziness, Rashes Peripheral neuropathy and CNS effects Seizures Thromboflebitis

Uses Amoebiasis

Giardiasis

Trichomonas vaginitis

Anaerobic bacterial infections

Pseudo membranous enter colitis

Ulcerative gingivitis, trench mouth

Peptic ulcer

Tinidazole Equally efficacious as metronidazole Metabolism is slower, t1/2 approx.12hrs Better tolerated Lower incidence of side effects ADRs- Nausea, Rash, Metallic taste

Secnidazole Congener of metranidazole Same spectrum of activity and potency Absorption rapid after oral administration Slow metabolism (17-29hrs)

Ornidazole Activity similar to metronidazole Slowly metabolized (12-14hrs) Dose and duration resemble those for Tinidazole Side effect profile is also similar

Satranidazole Longer t1/2 (14hrs) Better tolerability No nausea, vomiting or metallic taste, absence of

neurological diseases

Contradictions

Neurological diseases

Blood dyscrasia

First trimester of pregnancy

Chronic alcoholism

EMETINE

MOA:

Alkaloid from Cephalis ipecacuanha.

Potent directly acting amoebicide (trophozoites).

Does not kill cysts.

Inhibiting protein synthesis in amoebae.

Cannot given orally, administered by s.c or i.m injection.

ADR:

Cumulative toxicity high

It is an irritant; pain, stiffness, eczematous lession at site of injection.

Nausea and vomiting, abdominal cramp and diarrhoea, Weakness and stiffness of muscle

Hypotension, tachycardia, ECG change, mayocarditis.

Contraindicated in presence of cardiac or renal disease and during pregnancy.

USES:

Seldom used as Reserve drug in intestinal and extra intestinal amoebiasis

Patients not responding / intolerant to metronidazole.

Luminal amoebicide follows emetine to eradicate cysts.

Also effective in liver fluke infestation.

Dihydroemetin = effective but less toxic.

Preferred over emetine.

ChloroquineMOA

By accumulating in the acidic vesicle of amoeba it raises the vesicular PH interfere with degradation of haemeoglobin by parasitic lyzosomes.

PHARMACOKINETICS

Oral absorbtion Have the high affinity for melanin and nuclear chromatin Partly metabolised in liver 50% bound in the plasma

Side effects

Anorexia Epigastric pain Loss of vision due to retinal damage Loss of hearing Mental disturbance

Uses

Rhematoid arthritis Lepra reaction Photogenic reaction

Diloxanide furoate

MOA

Luminal amoebicidal Furoate ester hydrolysed in intestine Then released diloxanide which gets largely absorbed Diloxanide is weaker amoebicide than furoate ester.

Pharmacokinetics

Its is metabolised by glucoronidation. Excreted in urine.

Uses

Mild intestinal/asymptomatic amoebiasis

Combined with metroniadazole or tinidazole.

ADR

Occasional nausea

Itching

Rarely urticaria

8-Hydroxyquinolines

Widely employed in past. MOA Active against ENTAMOEBA Kill cyst forming tropozoids in intestine Eradicate cyst from asymptomatic carrier

PHARMACOKINETIC Absorption from intestine (10-30%) Absorbed fraction conjugate in liver with glucoronic acid. Excreted in urine. ½ life is 12 hour.

Uses

Giardiasis Trichomonas Vaginitis Non specific diarrhoea Dietry indiscretion. Fungal and bacterial skin infection

ADR

SMON-sub acute myelo optic neuropathy in Japan Goitre Transient loose and green stool

TETRACYCLINE Directly Inhibit amoebae at high concentration. Older tetracycline is incompletely absorbed in the small

intestine which reaches colon and inhibits bacterial flora along with Entamoeba living symbiotically.

USES: It is adjuvant in chronic, difficult to treat cases Tetracycline lessen risk of opportunistic infection,

perforation, peritonitis. When given along with systemic amoebicide. Not good for acute dysentery and for hepatic

amoebiasis.

RECENT RESEARCH

This review compares different drugs used against amoebic colitis, alone or in combination, and also assesses single-dose regimens versus longer regimens.

Thirty-seven trials with 4487 participants were included, and only one was of high methodological quality. Tinidazole reduced clinical failure compared with metronidazole and was associated with fewer adverse events. Combination therapy resulted in fewer parasitological failures than metronidazole alone.

Tinidazole appears more effective at reducing clinical failures than metronidazole and has fewer associated adverse events. There is insufficient evidence to draw conclusions regarding the efficacy of the other antiamoebic drugs. The choice of antiamoebic drugs would depend largely on the availability and accessibility of drugs.

Drugs for treating amoebic colitis

References Essential of medical pharmacology

by K. D. Tripathi

http://www.2.cochrone.org/review/en/ab006085.html Journal of Ethano pharmacology

http://www.medlineplus.com/

http://www.drugs.com/multimedia/pdfs.pdf

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