Flagellates.pptx TYJHJGUIOIYUTRDGFHJOIUY

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1. FLAGELLATES BY AGEN MOSES OLANYA DEPARTMENT OF PHARMACY GULU COLLEGE OF HEALTH SCIENCES [email protected] [phone]

2. FLAGELLATES Use flagella for movement Include: Trypanosomes: Trypanosomiasis Leishmaniasis Trichomonas vaginalis: Trichomoniasis STI Gardia Lamblia: Dysentery

3. 1. ANTI-TRYPANOSOMIASIS Trypanosomiasis Caused by Trypanosome Brucei species. African trypanosomiasis . Transmitted by Tsetse flies (Glossina palpalis). The species include : T. brucei Gambiensie (W. African) – Chronic , T. brucei Rhodensie (E.Africa)- Acute, T.brucei brucei. Trypanosoma brucei gambiense and T. brucei rhodesiense cause trypanosomiasis m ore commonly known as African sleeping sickness The disease is an arthropod (insect)-borne infections and is spread by the bite of the tsetse fly in which part of the trypanosome life cycle is completed.

4. South. American trypanosomiasis (chagas' disease) Transmitted by Ruduvid bugs ( Kissing bugs)- Trypanosoma cruzi The intermediate host in this case are triatomid bugs that feed off the blood of man Infection results from the inoculation of the bug's faeces that contains the organism into the bite wound Individuals who survive the acute stage of the disease are frequently left with chronic and progressive neuronal and smooth muscle lesions in the heart and gastrointestinal tract. T. cruzi has an extensive reservoir in wild and domestic mammals and therefore chagas ' disease is a zoonosis Has two phases: Acute & Chronic Phase Drugs are only useful in acute phase Chronic phase is controlled by surgery Causes: cardiomegally, megacolon, megaoesophagas

5. X-tics of trypanosomiasis Ulceration I nvasion of the lymph nodes followed by fever, anorexia, night sweats, enlarged nodes , CNS Meningoencephalitis, fatigue , confusion and somnolence, edematous face, etc.

6. Drugs used in A frican trypanosomiasis T rypasamide. CNS stage E nfornithine. CNS stage M elasoprol. Both CNS & Blood P entamidine isetionate. Blood Stage S uramin. Blood Stage

7. Suramin Sulphonated Naphthalene amine First line drug for early Haemolymphatic African Trypanosomiasis. Synergistic when used with pentamidine PK Given by Slow I.V Not absorbed Orally Highly bound to plasma proteins Small proportions cross BBB Metabolized in the Liver Excreted slowly through the Urine MOA Unknown. Forms a protein complex which is taken up by trypanosomes by phagocytosis Adverse effects Fatigue, nausea ,and Vomiting, seizures, shock and death

8. Pentamidine Isetionate An aromatic diamine Alternative to Suramin in early stages PK Given Only parenteral I.M in trypanosomiasis and aerosol in PCP Not absorbed Orally Extensively bound to Albumin Metabolized in the Liver Excreted 50% slowly through the Urine MOA Unknown Adverse Effects Cardio toxicity: Hypotension Nephrotoxicity Hepatoxicity

9. Melarsoprol Trivalent arsenical compound First line for advanced CNS AT Extremely toxic and only used when there are no alternatives PK Administered o nly parenteral I.V. Not absorbed Orally Actively concentrated in the parasite Extensively bound to Albumin, crosses BBB Metabolized in the l iver to non toxic substance Excreted 50% slowly through the Urine MOA . Oxidizes sulfhydryl group of pyruvate Kinase Adverse effects F ever , vomiting, abdominal pain and arthralgias. Most importantly encephalopathy including cerebral edema, seizures, coma and death.

10. Enflornithine Ornithine analogue ( synthetic amino acid) Second line for CNS late stage PK Administered orally or Parenteral I.V, well absorbed Extensively bound to Albumin, crosses BBB Metabolized in Liver Excreted slowly through the Urine MOA Unknown Adverse Effects Less toxic than Melarsoprol GIT disturbances Impaired hearing & convulsions Hematological disorders: Agranulocytosis, anaemia, thrombocytopenia

11. Trypasamide Pentavalent Pro drug Converted to Melarsoprol in the body More toxic than Melarsoprol but less active Originally used Withdrawn due to toxicity Has antitumor activity Causes Visual disturbances

12. Drugs used in south. American trypanosomiasis Nitrofuran Derivative Nifurtimox Primaquine + Puromycin Benzmidazole : Useful but not widely used

13. Nifurtimox A Nitrofuran derivative Orally absorbed Reduced to toxic oxides like Hydrogen peroxide , super oxides and hydroxyl radicals in the parasite Trypanosomes have low levels of glutathione & lack: catalase & glutathione peroxidase. Hence are selective susceptibility to toxicity Side effects : Gastric abscess, weight loss, Hypersensitivity

14. 2 . ANTILEISHMANIASIS Leishmaniasis The leishmaniasis protozoan was first described in 1903 by Leishman and Donovan, working separately Transmitted by the sand-fly - Phlebotomus genus Visceral leishmaniasis A lso known as kala-azar, black fever or Dumdum fever - caused by L. donovani in India and E.Africa, and by L. chagasi in Latin America. Affects the Reticuloendothelial system causes splenomegaly Cutaneous leishmaniasis caused by L. tropica and L. major in E.Africa and India, and by L. leishmania in Latin America. concentrates in the macrophages

15. Cutaneous Leishmaniasis

16. Drugs for Leishmaniasis Visceral Leishmaniasis S odium Stibogluconate ( 1 st line Drug ) P entamidine isetionate ( Second Line Drug ) A llopurinol: Inhibits Hypothanthine Oxidase Antimetabolite Leads to lethal synthesis in non flagellates A mphotericin B & Azole antifungals ( inhibits ergosterol ) Paramomycin M etronidazole Others: Meglumine antimoniate, Mitefosine

17. Antimonial compounds Sodium Stibogluconate Meglumine antimoniate Useful in ALL forms

18. Sodium Stibogluconate Pentavalent antimoniate Pk Administered Parenterally I.M & I.V. IM very painful, IV is preferred Poor oral absorption Metabolized in the liver 90% Rapidly excreted in Urine MOA Inhibit glycolytic enzymes Phosphofructokinase Adverse Effects GIT disturbances Fever & skin rashes Hematological disorders Organ toxicity: Liver, Kidney, Heart

19. Cutaneous Leishmaniasis Pentamidine Isetionate & Hydroxy Pentamidine As for Visceral Leishmaniasis

20. 3. Anti-Trichomoniasis Trichomoniasis It is an STD caused by Trichomonas vaginalis Common cause of vaginitis (with copious offensive frothy discharge) and urethritis in the males Drugs : Metronidazole (oral or pessaries) Tinidazole

21. 4. ANTI-GIARDIASIS Giardiasis Caused by Gardia Lamblia leading to Dysentery Treatment Nitroimidazoles: Metronidazole, Tinidazole, Secnidazole Albendazole