PROTOZOAL INFECTION IN ADVANCE PHARMACOLOGY BY SEJAL AGRAWAL

PROTOZOAL INFECTION BY SEJAL AGRAWAL M PHARMA

1. PROTOZOAL INFECTION PRESENTED BY : SEJAL AGRAWAL

2. INDEX : Introduction Anti-amoebic Life cycle Classification Anti-amoebic drug Giardiasis

3. INTODUCTION : PROTOZOA : the term protozoa implies “ fist animal” . As the primary hunters of the microbial world , protozoa help in countinuing the equilibrium of bacteria , algal and other microbial life forms. Protozoa are single-celled organisms without cell walls. Protozoa vary in size and shape . Their sizes range from 10 to 55 micrometer , but they can be as large as 1 mm. Protozoa groups are : amoeboid, flagellates , ciliates , sporozoans .

4. ANTI-AMOEBIC DRUS: Amoebiasis is a protozoal infection caused by protozoa ENTAMOEBA HISTOLYTICA. These are the drugs useful in infection caused by the anaerobic protozoa. Amoebiasis has a wordwide distribution (over 50million people suffer invasive disease,but many more harbour it) Poor environmental sanitation and low socio-economic status are the important factors in the spread of disease , occur by fecal contamination of food and water. Entamoeba Histolytica exists in two forms : Cysts form ( that can survive out side the body ) Trophozoites ( that are labile and don’t persist outside the body)

5. LIFE CYCLE INGESTION OF CYSTS : Cysts are ingested through feces, contaminated food or water. FORMATION OF TROPHOZOITES : Cysts are passed into the lumen of intestine, where the trophozoites are liberated . PENETRATION AND MULTIPLICATION OF TROPHOZOITES : Trophozoites are penetrated in intestinal wall and multiply within colon wall. They either invade and ulcerate the mucosa of large intestinal or simply feed on intestinal bacteria. SYSTEMIC INVASION LARGE NUMBER OF TROPHOZOITES Within the colon wall can also lead to systemic invasion and caused liver abscess. CYSTS DISCARDED The trophozoites within the intestine are slowly carried towards the rectum, where they retrun to cysts and are excreated in feces

6. CLASSIFICATION

7. NITROIMIDAZOLES : METRINIDAZOLE : Metronidazole is having broad spectrum activity. Effective against most anaerobic bacteria and several protozoa, such as E.histolytica , Giardia lambia and Vaginalis. It helps in the extraction of gunea worm ( Dranunculus medinensis) Metronidazole and diloxanide drug useful in the treatment of both intestinal and extraintestinal symptoms of amoebiasis in orally .

8. MECHANISM OF ACTION : Metrinidazole Microorganism Nitrogroup is reduced by ferrodoxins Death of the organism Damage microbes DNA Active metabolite NOTE : in presence of oxygen (aerobes) metronidazole can’t be reduced to its active metabolite,hence it is ineffective aerobes.   PHARMACOKINETICS: The drugs are well absorbed from the gastrointestinal tract, maximum plasma levels generally being obtained 1 to 4 h after oral intake.

9. Clinical use and Adverse effect : CLINICAL USES : A – Amoebiasis and Anaerobic infection . G – Giardiasis and guinea worm infection . T – Trichomoniasis , trench mouth , ulcerative gingivitis. ADVERSE EFFECT : A – Anorexia , Abdominal crams , Alcohol intolerances. G – Glossitis , Giddiness . T – Metallic , Thrombophlebitis , Teratogenic potential

10. ALKALOIDS : Examples : Emetin , Dehydroemetin Emetin is an alkaloid , derived from ipecac (Brazil root). Dehyroemetine is a semisynthetic analog. MECHANISM OF ACTION Directly affect the trophozoites but not cysts. Inhibit protein syn in amoeba by arresting intraribosomal translocation of t-RNA amino acid complex. Can be used only in sever amoebiasis for 3-5 days in patients , but generally not preferred due to toxicity.

11. Clinical uses and Adverse effect : CLINICAL USES Acute amoebic dysentery Amoebic liver abscess Liver fluke infection ADVERSE EFFECT Emesis Muscle weakness ECG change Tachcardia Itching

12. EXTRA INSTENTINAL AMOEBIASIS : EXAMPLE : Chloroquine . Used in hepatic amoebiasis . It kill trophozoites of E.histolytica and highly concentrated in liver. Therefore it is only used in hepatic amoebiasis.

13. AMIDE : EXAMPLE : Diloxanide furoate , Nitroimidazole . MOA: Is directly amoebicidal . Highly effective luminal amoebicide , which directly kills trophozoites. It split in the intestine to diloxanide and furoic acid, it act on the parasite intestines but not in the tissue. Diloxamide furoate Diloxanide + Furoic acid ( exert antiamoebic activity )

14. Clinical uses and Adverse effect : Clinical uses Is used along with nitroimidazole for the cure of amoebiasis. Eradication of cysts. Adverse effect : Flatulence Nausea and occasionally abdominal cramps and rashes can occur.

15. 8- hydroxyquinolines : EXAMPLES : Iodoquinol Quiniodochlor These 8- hydroxquinolines are directly acting luminal amoebicide . Exact mechanism is not known . They kill the cysts forming amoebic trophozoites in the intestine . Is an inexpensive these drug widely and injudiciously used for prophylaxis and treatment of nonspecific diarrhoea , traveller’s diarrhoea , dietary indiscretion. Active against Entamoeba , Giardia , Trichomonas.

16. Clinical uses and Adverse effect : Clinical uses :  Antibacterial A ntifungal Anticancer Antiviral Side effect : Nausea , transient loose and green stools , pruritus. Iodism (furunculosis, inflammation of mucous membrane) and goiter- prolonged intake .

17. ANTIBIOTICS : Paromomycin : Aminoglycoside antibiotic given orally . Is an intestinal amoebicide ( luminal amoebicide ) . ADR : mild diarrhoea and abdominal discomfort . Tetracyclines: Older tetracyclines, like chlortetracycline are not well absorbed and large amount reach colon – These are useful intestinal amoebiasis . They inhibit the intestinal flora and break symbiosis between them and amoebea . Tetracyclin used as adjuvant in chronic cases.

18. Treatment of different forms of amoebiasis : Acute intestinal amoebiasis : Metronidazole 400-800 mg TDS for 5-7 days or 2.4 g OD for 3 days. Trinidazole 2g OD for 3 days. Secnidazole 2g single dose. Chronic amoebiasis and asymptomatic cysts passers : Diloxanide furoate 500mg TDS for 10 days or tetracyclin 250mg qid for 10 days. Alternative iodoquinol (650mg TDS for 21 days).

19. Hepatic amoebiasis : Requires intensive treatment for complete eradication of the parasite from the liver in order to avoid relapse. Metronidzole 600-800mg TDS for 10 days + chloroquine given to ensure complete destruction of liver forms. Diloxanide furoate 500mg TDS for 10 days eradicate the cysts .

20. GIARDIASIS : Giardia lamblia – flagellate protozoa . It infect children and adult by oro-faecal contamination and mostly lives as a commensal in intestine. It invade the mucosa and cause acute watery diarrhoea with foul smelling stool, gas and abdominal cramps.

21. Drugs for Giardiasis : Metronidazol : 400mg TDS (children 15mg/kg/day) for 5-7 days or 2g daily for 3 days . Trinidazole : 0.6 g daily for 7days or 2g single dose . Secnidazole : 2g single dose. Nitazoxamide : prodrug PFOR enzyme inhibitor for treatment of diarrehea and dysentery caused by GIARDEIAN , E.HISTOLYTICA. Quiniodochlor Furazolidone nitrofuran compound against salmonella, shigella and giardia . Dose 100mg TDS for 5-7 days.

22. TRICHOMONIASIS : Trichomonas Vaginalis – microaerophilic flagellate protozoon causes vulvovaginitis. Sexually transmitted disease effecting 10% sexually active women. Several drugs are partly effective , but may not entirely clear the infection.

23. Drug used orally: Metronidazole : 400mg TDS for 7 days or 2g single dose . Tinidazole : 600mg daily for 7 days or 2g single dose . Secnidazole : 2g single dose are the drug of choice. Vaginitis due to nitroimidazole resistant t.vaginalis is being reported. Additionally intravaginal treatment required only in refractory cases. Repeate course can be given after six weeks. In some cases recurrences are due to relinfection from male partner who harbours the parasite in the seminal vesicales but remain asymptomatic, such cases both partner should be treated concurrently.

24. Drug used intravaginally: Dilodohydroxyquin : 200mg inserted intravaginally at bed time 1 to 2 weeks. Quiniodochlor : 200mg inserted intravaginal every night for 1 to 3 weeks . Povidone –iodine : 400mg inserted in the vagina daily at night for 2 weeks.