Antiparasitic Drugs Overview: Classification, Mechanism, and Side Effects

1. Anti-aembic and anti-malarial drugs By Dr.Mohamed Abd AlMoneim Attia

3. Classifications • 1-Tissue amoebicidial: • Metronidazole(Flagyl) • Chloroquine • Emetine and Dihydroemetine • 2-Luminal amebicidal; • Diloxinade & etofamide • Iodoquinol & clioquinol • Paromomycin & Tetracycline

4. metronidazole

5. Mechanism of action: 5-nitroimidazole Ferrodoxine oxidoreductase enzyme Free radical Electron ransfer Multiple DNA breaks No transcription No replication No repair

6. Metronidazole • Indications: • Tissue amoebicidal: ( intestinal,hepatic,pulmonary) • Giardiasis • Trichominasis

7. Anaerobic infection:e.g - serious infection caused by bacteroid fragilis -enterocolitis cause by cl.difficil -acute ulcerative vaginitis -decubitus lesion -to reduce postoperativeinfection following abdominal surgery

8. Side effects: • GIT: bad taste in mouth,angular stomatitis,dry mouth • Dark red urine • CNS: headache,insomnia,parathesia • Blood:leucopenia & thrombocytopenia • Disulfiram like reaction in alcoholism • Phlebitis if given IV • Mutagenesis and carcinogenesis in mammalian cell culture

9. Contraindication & Cautions • Be caution if prescribe drugs to: Patients with hepatic,brain,or blood disorders. • Don't give it to pregnant , lactating or young age. • It increases the effects of oral anticoagulant by decreasing its metabolism.

10. Chloroquine • Reach high concentration in liver so it is effective in hepatic amoebiasis with little or no effect on intestinal or lumenal one. • Indication: • Prevention of amoebic liver abscess during ttt of intestinal amoebiasis • treatment of amoebic liver abscess in case of failure or contraindication to flagyl • Following metronidazole for ttt of amoebic hepatitis • Side effects:see antimalarial

11. Emetine & dihydroemetine: • They inhibit protein synthesis by preventing translocation • Indication: • Alternate therapy to metronidazole in treatment of intestinal or hepatic amoebiasis • Side effects: • Cardiotoxic: hypotension and ECG changes • Pain at site of injection • Muscular ache, tenderness,stiffness & weakness

12. Diloxanide Furoate • -luminal amoebicidial • -not absorbed from GIT • -used to eradicate amoebae present in intestinal lumen • -flatulence, dryness of mouth and vomiting are infrequent side effects • -the drug is contraindicated in pregnancy and in children below 2years of age

13. Iodoquinol • -luminal amoebicidial • -used to eradicate amoebae present in intestinal lumen • -Side effects: • Thyroid enlargement due to high iodine content of the drug • N/V and diarrhea • -Contraindication: • Thyroid, renal or hepatic disease • Shouldn't be used for prophylaxis or ttt of travelers or non specific diarrhea • Stop it if persistent diarrhea or iodine reaction occur

14. Anti Malaria PATHOPHYSIOLOGY and life cycle: • Anopheles mosquito inoculates sporozoites to human . • Sporozoites invade liver cells ( primary tissue phase). • Merozoites released from liver & invade erythrocytes . • Merozoites multiply, red cell enlarges ( blood schizont). • blood schizont ruptures, merozoites invade more RBCs. • Repeated cycles cause clinical illness, fever, etc. • In P. vivax & P. ovale some merozoite invade liver cells ( secondary tissue phase) & become dormant( hypnozoites ) hypnozoites may develop again and cause relapse. • In P. falciparum & P. malariaeno second liver phase. Some merozoite -- gametocytes-- mosquito -- sporozoites

15. Life cycle of malaria

16. Anti- malarial drugs • Classifications; • 1-clinical cure: drugs used to treat the acute attack of malaria by acting on the erythrocyte stage of the parasite • 1-chloroquine-sensitivemalaria:chloroquine • 2-chloroquine-resistancemalaria: • -Quinie • -mefloquine • -pyremethamine & proguanil • -sulphadoxine • -combination: • Fansidar = sulphadoxine + pyremethamine • Fansimaf = sulphadoxine + pyremethamine + mefloquine

17. II-chemoprophylaxis: 1-clinical prophylaxis: suppress the clinical manifestation of malaria by killing parasite as soon as they reach the RBCs .chloroquine, proguanil, fansidar 2-antirelapse therapy in P.vivax and ovale only by killing the dormant stage in liver. Primaquine 3-prevent transmission by killing the gametocytes: primaquine ,progunail ,pyremethamine

18. Chloroquine, hydroxy-chloroquine, amodiaquine. CHLOROQUINE: Mechanism and anti-malarial action: • Chloroquine ,accumulates in acid pH of RBCs & food vacuoles of plasmodia, ↓ polymerization of heme to hemozoin (food of malarial parasites). • Heme accumulates & cuases death of plasmodia. • Blood schizonticidal of all types of plasmodium. • Not effective against liver stages.

19. Uses: • Treatment : Drug of choice for acute attack of P. vivax, ovale, malariae, & non-resistant falciparum. • (P. falciparum is becoming resistant) • Prophylaxis: Effective in P. vivax & ovale regions. Also for P. falciparum in non-resistant regions. • Other uses: Hepatic amoebiasis & some autoimmune diseases ( like, rheumatoid arthritis & SLE ).

20. Adverse effects: • Neurological: headache, anorexia, malaise, optic neuritis & rarely seizures. • CVS: Cardiac depression, vasodilation & fall of blood pressure. • Give slow IV infusion & monitor cardiac functions. • Heamatologic: Heamatolysis in G6PD deficiency. Cautions/ Contraindications: ☻Visual defects, epilepsy, heart failure.

21. HYDROXY-CHLOROQUINE: - Less likely to cause optic neuritis. • Used in rheumatoid artharitis. AMODIAQUINE: - Can cause agranulocytosis. - Recommended for chloroquine resistant malaria.

22. Quinine • Therapeutic uses: • Treatment of acute attack of chloroquine resistant P.falciparum • Side effects: • Cinnchonism : sweeting,nausea,vomiting,diarrhea,ringing in ear,blurring of vision • Hypoglycemia • Hypotension and arrhythmias • Black water fever due to excessive haemolysis of RBCs in the form of fever, acute renal failure and jaundice

23. Mefloquine: • Therapeutic uses: • Treatment of acute attack of chloroquine resistant P.falciparum especially mild and moderate cases • chemoprophylaxis • side effects: • headache vertigo and visual disturbance • psychosis ,hallucination and confusion

24. Antifolate;(pyremethamine,progunail,sulphonamides): • Therapeutic uses: • Treatment of acute attack of chloroquine resistant P.falciparum in combination with Quinine • Chemoprophylaxis in chloroquine resistant P.falciparum • Side effects: see antimicrobials

25. Primaquine: • Therapeutic uses: • The only drug that used in prevention of relapse in P.vivax and ovale because it affects the dormant liver stage • It has no effect on erythrocytic stage (not used in acute attack) • Prevent transmission of infection from human to mosquito by killing the gametocytes • Side effects: • Haemolysis in G6PD deficiency • Purities • methaemoglobinemia manifested by cyanosis

26. بسم الله الرحمن الرحيم • (لايكلف الله نفسا إلا وسعها لها ما كسبت و عليها ما اكتسبت ربنا لا تؤاخذنا إن نسينا أو أخطأنا ربنا و لا تحمل علينا إصرا كما حملته على اللذين من قبلنا ربنا و لا تحملنا ما لا طاقة لنا به و اعف عنا واغفر لنا و ارحمنا أنت مولانا فانصرنا على القوم الكافرين) • صدق الله العظيم

27. هذا و ما كان من توفيق فمن الله و ما كان من خطا أو سهو أو نسيان فمني و من الشيطان.

28. سبحانك اللهم و بحمدك نستغفرك و نتوب اليك URTI:Throat infections