2AmoebiasisAmoebiasis 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 countriesPoverty, ignorance, overcrowding, poor sanitation and malnutrition favour transmissionIt is acquired by ingesting food or water contaminated by infected feces.
4Symptoms Mostly they are quite mild and can include loose stools stomach painabdominal crampsAmoebic dysentery – severe formbloody stoolsfeverjaundiceanorexiaweight lossRarely the parasite invades liver and forms an abscess and spread to other parts of the body, such as lungs or brain
5Diagnosis of Amoebiasis Medical history, physical examination, lab tests and stool examinationBlood test to reveal antibodies against the organismSigmoidoscopy to evaluate the intestinal wallRadiological studies including ultrasound and CT scans to detect liver abscesses
6Treatment of Amoebiasis The choice of drug depends on the severity of the symptomDrugs includeMetronidazoleEmetineChloroquineDiloxanide furoate8 - hydroxyquinolineTetracycline
7Classification Tissue amoebicides For both intestinal and extra intestinal amoebiasis:Nitroimidazoles: Metronidazole, Tinidazole, Secnidazole, Ornidazole, Satranidazole.Alkaloids: Emetine, DehydroemetineFor extraintestinal amoebiasis only:ChloroquineLuminal amoebicidesAmide: Diloxanide furoate8-Hydroxyquinolines: Quiniodochlor, DiiodohydroxyquinAntibiotics: Tetracycline
8Metronidazole MOA Prototype nitromidazole.(1959) Highly active amoebicide.Broad spectrum cidal activity against protozoa.It is selectively toxic to anaerobic microorganism.MOANitro group is reduced to highly reactive nitro radical that causes damage to DNA and other critical biomolecules by cytotoxicityIt disrupts energy metabolismDNA helix destabilization and strand breakage are observedFound to inhibit cell mediated immunity to induce mutagenesis and to cause radiosensitization
9Pharmacokinetics ADR Completely absorbed from small intestine Metabolized in liver by oxidation and glucoronide conjucationExcreted in urinePlasma t1/2 is 8hrsADRFrequent- Anorexia, Nausea, Metallic taste, Abdominal crampsLess frequent-Headache, Glossitis, Dizziness, RashesPeripheral neuropathy and CNS effectsSeizuresThromboflebitis
11Tinidazole Secnidazole Equally efficacious as metronidazole Metabolism is slower, t1/2 approx.12hrsBetter toleratedLower incidence of side effectsADRs- Nausea, Rash, Metallic tasteSecnidazoleCongener of metranidazoleSame spectrum of activity and potencyAbsorption rapid after oral administrationSlow metabolism (17-29hrs)
12Ornidazole Satranidazole Activity similar to metronidazole Slowly metabolized (12-14hrs)Dose and duration resemble those for TinidazoleSide effect profile is also similarSatranidazoleLonger t1/2 (14hrs)Better tolerabilityNo nausea, vomiting or metallic taste, absence of neurological diseases
13Contradictions Neurological diseases Blood dyscrasia First trimester of pregnancyChronic alcoholism
14EMETINE 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.
15ADR: 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 muscleHypotension, tachycardia, ECG change, mayocarditis.Contraindicated in presence of cardiac or renal disease and during pregnancy.
16USES:Seldom used as Reserve drug in intestinal and extra intestinal amoebiasisPatients 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.
17ChloroquineMOABy accumulating in the acidic vesicle of amoeba it raises the vesicular PH interfere with degradation of haemeoglobin by parasitic lyzosomes.PHARMACOKINETICSOral absorbtionHave the high affinity for melanin and nuclear chromatinPartly metabolised in liver50% bound in the plasma
18Side effects Uses Anorexia Epigastric pain Loss of vision due to retinal damageLoss of hearingMental disturbanceUsesRhematoid arthritisLepra reactionPhotogenic reaction
19Diloxanide furoate MOA Luminal amoebicidal Furoate ester hydrolysed in intestineThen released diloxanide which gets largely absorbedDiloxanide is weaker amoebicide than furoate ester.PharmacokineticsIts is metabolised by glucoronidation.Excreted in urine.
20Uses Mild intestinal/asymptomatic amoebiasis Combined with metroniadazole or tinidazole.ADROccasional nauseaItchingRarely urticaria
218-Hydroxyquinolines PHARMACOKINETIC MOA Widely employed in past. Active against ENTAMOEBAKill cyst forming tropozoids in intestineEradicate cyst from asymptomatic carrierPHARMACOKINETICAbsorption from intestine (10-30%)Absorbed fraction conjugate in liver with glucoronic acid.Excreted in urine.½ life is 12 hour.
22Uses ADR Giardiasis Trichomonas Vaginitis Non specific diarrhoea Dietry indiscretion.Fungal and bacterial skin infectionADRSMON-sub acute myelo optic neuropathy in JapanGoitreTransient loose and green stool
23TETRACYCLINE 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 casesTetracycline lessen risk of opportunistic infection, perforation, peritonitis.When given along with systemic amoebicide.Not good for acute dysentery and for hepatic amoebiasis.
24RECENT RESEARCH Drugs for treating amoebic colitis 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.
25References Essential of medical pharmacology by K. D. Tripathi Journal of Ethano pharmacology