Treatment of amoebiasis & giardiasis

1. TREATMENT OF AMOEBIASIS & GIARDIASIS

2. It is the infection caused by protozoa Entamoeba histolytica. It is usually transmitted by faecal transmission of food & water. Mostly present in the areas with poor environmental sanitation. AMOEBIASIS

3. Tissue Amoebicides For both Intestinal & Extraintestinal Amoebiasis: Nitroimidazoles: Metronidazole, Tinidazole, Secnidazole, Ornidazole, Satranidazole Alkaloids: Emetine, Dehydroemetine For extraintestinal amoebiasis only: Chloroquine Luminal Amoebicides Amide : Diloxanide furoate, Nitazoxanide 8-Hydroxyquinolines: Quiniodochlor, Diiodohydroxyquin Antibiotics: Tetracyclins Classification Of Drugs

4. It has broad spectrum cidal activity against protozoa including Giardia lamblia & Amoeba. Many anaerobic bacteria are sensitive. Anaerobic bacteria & G. lamblia also can develop metronidazole resistance, but this is a clinical problem only in the case of H.pylori. Metronidazole

5. Metronidazole is selectively toxic to anaerobic microorganisms. After entering the cell by diffusion, its nitro gp. i s reduced by certain redox proteins operative only in anaerobic microbes to highly reactive nitro radical which exerts cytotoxicity. The nitro radical of metronidazole acts as an electron sink which competes with the biological electron acceptors of the anaerobic organism for the electrons generated by the pyruvate:ferredoxin oxidoreductase(PFOR) enzyme pathway of pyruvate oxidation. The energy metabolism of anaerobes, is thus, disrupted.

6. Aerobic environment attenuates cytotoxicity of metronidazole by inhibiting its reductive activation. Anaerobes which develop metronidazole resistance become deficient in the mechanism that generates the reactive nitro radical from it.

7. Metronidazole is almost completely absorbed from the small intestines; little unabsorbed drug reaches the colon. It is widely distributed in the body, attaining therapeutic concentration in vaginal secretion, semen, saliva & CSF. It is metabolized in liver primarily by oxidation & glucoronide conjugation & excreted in urine. Plasma t-half is 8hrs. PHARMACOKINETICS

8. Side effects to metronidazole are:- Anorexia, nausea, metallic taste & abdominal cramps. Less frequent are– Headache, glossitis, dryness of mouth, dizziness, rashes & transient neutropenia. Prolonged administration may cause peripheral neuropathy and CNS effects . Adverse Effects

9. It is contraindicated in:- Neurological diseases Blood dyscrasias First trimester of pregnancy Chronic alcoholism CONTRAINDICATIONS

10. A disulfiram-like intolerance to alcohol occurs in some patients taking metronidazole; they should be instructed to avoid drinking. Enzyme inducers may reduce its therapeutic effect. Cimetidine can reduce metronidazole metabolism. Metronidazole enhances warfarin action by inhibiting its metabolism . interactions

11. Amoebiasis : Metronidazole is a first line drug for all forms of amoebic infections. For invasive dysentery & liver abscess- 800mg TDS( children 30-50 mg/kg/day) for 7-10 days. For mild intestinal disease—400mg TDS for 5-7 days. USES

12. Trichomonas vaginitis Anaerobic bacterial infections Pseudomembranous enterocolitis Ulcerative gingivitis, trench mouth Peptic ulcer disease Also used in…

13. It is an equally efficacious congener of metronidazole, similar to it in every way except: Metabolism is slower; t1/2 is—12hr; duration of action is longer; dosage schedules are simpler. Thus it is more suited for single dose or once daily therapy. Better tolerated Side effects are lower: metallic taste, nausea, rash. For Amoebiasis: 2g OD for 3 days( children 30-50mg/kg/day). tinidazole

14. A congener of metronidazole. Absorption after oral administration is rapid & complete. Metabolism is slower resulting in a plasma t1/2 of 17-29 hrs. Dose-- 2g stat. secnidazole

15. It is slowly metabolized. Has longer t1/2(12-14hr). Dose & duration of regimens for amoebiasis, giardiasis, trichomoniasis,anaerobic infections & bacterial vaginosis resemble those for tinidazole. ornidazole

16. Another nitroimidazole having longer t1/2(14hr). Advantages are: better tolerability– no nausea, vomiting or metallic taste, absence of neurological & disulfiram-like reactions & that it does not produce the acetamide metabolite which is a weak carcinogen. Dose– 300mg BD for 3-5 days in Amoebiasis . satranidazole

17. It is potent & directly acting amoebicide– kills trophozoites but has no effect on cysts. It acts by inhibiting protein synthesis in amoeba by arresting intraribosomal translocation of t-RNA-amino acid complex. Toxic Effects Of Emetine Nausea & vomiting are frequent. Abdominal cramps & diarrhoea Weakness & stiffness of muscles Hypotension, tachycardia, ECG changes & myocarditis. emetine

18. It kills trophozoites of E.histolytica Highly concentrated in liver. Used in hepatic amoebiasis only. Because it is completely absorbed from the upper intestine & not so highly concentrated in intestinal wall– it is neither effective in invasive dysentry nor in controlling the luminal cycle. Dose for amoebic liver abscess: 600mg for 2 days followed by 300mg daily for 2-3 weeks. chloroquine

19. It is highly effective luminal amoebicide Directly kills trophozoites responsible for production of cysts. Furoate ester is hydrolyzed in intestine & the released diloxanide is largely absorbed. Diloxanide is a weaker amoebicide than its furoate ester & is primarily metabolized by glucuronidation & is excreted in urine. Diloxanide furoate is less effective in invasive amoebic dysentery, bcoz of poor tissue amoebicidal action. However, a single course produces high(80-90%) cure rate in mild intestinal amoebiasis. Diloxanide furoate

20. Diloxanide furoate is very well tolerated Side effects are flatulence, occasional nausea, itching & rarely urticaria. It is the drug of choice for mild intestinal/ asymptomatic amoebiasis. Combined use with metronidazole/ tinidazole is quite popular. Dose: 500mg TDS for 5-10 days; children 20mg/kg/day.

21. Recently introduced for the treatment of giardiasis but is also active against E.histolytica, T.vaginalis, Cryptosporidium, Ascaris. It is a prodrug which on absorption is converted to the active form tizoxanide, an inhibitor of PFOR enzyme that is an essential pathway of electron transport energy metabolism in anaerobic organisms. Tizoxanide produced in the body is conjugated & excreted in urine and bile. nitazoxanide

22. Nitazoxanide is indicated in giardiasis, cryptosporidiosis, as well as in amoebic dysentery as luminal amoebicide. Abdominal pain, vomiting & headache are mild & infrequent side effects. Dose: 500mg (children 7.5 mg/kg) BD for 3 days .

23. They directly inhibit amoebae only at higher concentrations. The older tetracyclins are incompletely absorbed in the small intestine, reach the colon in large amounts Inhibit the bacterial flora with which Entamoebae live symbiotically. Thus, they indirectly reduce proliferation of Entamoebae in the colon. They are not good for acute dysentery & for hepatic amoebiasis. tetracyclines

24. Giardia lamblia is a flagellate protozoon which mostly lives as a commensal in the intestine. Invades the mucosa Causes diarhhoea requiring treatment. DRUGS:- Metronidazole :- 200mg TDS (children 15mg/kg/day) for 7 days or 2g daily for 3 days Or Tinidazole 0.6g daily for 7 days or 2g single dose Or Secnidazole 2g single dose may be considered as the drugs of choice. Drugs for giardiasis

25. Nitazoxanide:- This prodrug of the PFOR enzyme inhibitor tizoxanide has recently become available for the treatment of diarrhoea & dysentery caused by Giardia lamblia, E.histolytica, C.parvum . The dosage schedule is convenient– 500mg (children 7.5mg/kg) twice daily for 3 days, efficacy high(80-90%) & tolerability good. Quiniodochlor :- 250mg TDS for 7 days is a somewhat less effective alternative.

26. Furazolidone:- It is a nitrofuran compound active against many gram –ve bacilli including Salmonella & Shigella , also Giardia & Trichomonas . For Giardiasis 100mg TDS for 5-7 days is inferior to metronidazole or tinidazole. It has also been used in bacterial enteritis, food poisoning diarrhoeas & bacillary dysentery, but is not a first line treatment for any of these. Furazolidone is partly absorbed from intestines & excreted in urine which turns orange. Side effects are mild & infrequent– nausea, headache, dizziness.

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