1. SCHISTOSOMIASIS By: Dr.Abdul latif Mahesar Dept. of Medical pharmacology King Saud university

2. Schistosomiasis is a group of diseases which is caused by trematodes and affects millions of people around the world. The middle east area is still suffering from this disease. The tremetodes which cause this disease are: 1.S. haematobium 2.S. mansoni 3.S. japonicum

3. Antischistosomal drugs 1.Praziquantel 2.Metrifonate 3.Oxamniquine

4. Praziquantel It is a broad-spectrum anthelminthic drug It is effective in the treatment of schistosomal infections of all species and most other trematodes and cestodes. Nematodes are an important exception. It is a synthetic isoquinoline-pyrazine derivative

5. Pharmacokinetics: It is rapidly absorbed after oral administration Carbohydrate diet and cimetidine increases its bioavailability Corticosteroids and antiepileptics (phenytoin and carbamazepine) reduce its bioavailability. Bioavailabilty is 80% It has large distribution volume It can cross BBB but its conc. reach 14-20% of the drug’s plasma conc.

6. Cont’d 80% bound to plasma proteins Metabolized extensively in liver to inactive metabolites T 1/2 = 0.8 – 3 hours (which is increased in liver diseases) 60% excreted in urine 10-20 % of drug is also found in bile, breast milk and feces.

7. Anthelminthic action: The drug increases cell membrane permeability to calcium resulting in paralysis, dislodgement, and death. At lowest effective concentration it causes increase in muscular activity followed by contraction and paralysis At higher doses it damages the capsule of the worm by influx of calcium across tegument غلاف. It is effective against adult worms and also against immature stages. It also possesses prophylactic effect against cercarial infection.

8. Clinical uses It is taken after meals with liquids & without chewing (b/c of praziquantel’s bitter taste which might cause vomiting). doses interval is 4 – 6 hours. Schistosomiasis: For S. Japonicum infections, 20 mg/kg at intervals 4-6 hours for a total of 3 doses. For S.mansoni and S.hamatobium 20 mg /kg in two divided doses.

9. Cont’d The drug is effective in children and in adults and is well tolerated. It is not clear whether the drug can safely be used during acute stage of disease (Katayama fever),because release of antigens from dying of immature worm may exacerbate the symptoms. Effectiveness of the drug for chemoprophylaxis has not been established.

10. 2. Use in other infestation 1. Clonorchiasis*, opisthorchiasis* and paragonimiasis*. 2. Taeniasis and diphyllobothriasis. 3. Neurocysticercosis ( albendazole is preferred) 4. Hymenolepis nana (drug of choice) 5. Hydatid cyst and others (fasciolopsiasis, metagonimiasis, and heterophyiasis). It is not effective against fasciola hepatica and hydatid disease.

11. PARAGONIMIASIS This disease is caused by Paragonimus Westermani (lung fluke) The disease is treated by praziquantel. CLONORCHIASIS The disease is caused by clonorchis sinenis (oriental liver fluke) It is treated by praziquantel.

12. Extra Clonorchiasis is an infectious disease caused by the Chinese liver fluke, Clonorchis sinensis. Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary tree.infectious diseaseliver flukeClonorchis sinensischolangiocarcinomaneoplasm Opisthorchiasis, disease caused by many genus of Opisthorchis, the disease charactrized by liver infection Paragonimiasis is a food-borne parasitic infection caused by the lung fluke, the disease outcome are, abdominal pain, fever…parasitic infection lung fluke Fasciolopsiasis results from an infection by the trematode Fasciolopsis buskiinfectiontrematode Fasciolopsis buski Metagonimiasis disease of intestine

13. Adverse reactions: Are mainly minor and transient and include: 1.Headache, dizziness, drowsiness, and lassitude كسل. 2.GIT disturbances (nausea, vomiting, diarrhea…) 3.Pruritus, urticaria,arthralgia, myalgia, low grade fever 4.Minimal to mild transient elevation of liver enzymes. 5. Skin rashes, augmented eosinophilia may appear several days after starting the medication due to the release of foreign protein from dying worm. Adverse effects may be more severe, especially in S.mansoni infections.

14. Contraindications and precautions Mainly in ocular cysticercosis for fear of destruction of the parasite in the eye. The drug can be used in liver impairment, but the dose should be reduced. Driving or in particular activities which require alertness and physical coordination. Patient should be informed regarding chewing, bitter taste, and drug regurgitation.

15. Cont’d It should not be used during pregnancy. In case of nursing mothers, feeding should be stopped for 3 days.

16. METRIFONATE (TRICHLORFON) It is safe, low-cost alternative for treatment of S. haematobium infections. Not active against S. mansoni or S. japonicum Pharmacokinetics: It is an organophosphate. It is rapidly absorbed after oral administration T 1/2 = 1.5 hours Metabolized to an active metabolite which is widely distributed to tissues similar to metrifonate.

17. Anthelmintic action It is effective against both the mature and immature stages of S. hematobium. Mechanism of action: inhibition of cholinestrase. It temporarily paralysis the adult worm which leads to their shift from the bladder venous plexus to the small arterioles of the lungs, where they are trapped by the immune system and killed. It is not effective against S. hematobium eggs, live eggs continue to pass in the urine for several months after all adult worms have been killed.

18. Clinical uses A single dose of 7.5-10 mg/Kg is given orally three times at a 14-day interval. It is also effective when used prophylactically when given once monthly to children in a highly endemic area. In mixed infection with S. mansoni & S. hematobium, metrifonate is successfully combined with oxamniquine.

19. Adverse Reactions Mild and transient cholinergic symptoms including, nausea, vomiting, diarrhea, abdominal pain, bronchospasm, headache, sweating, fatigue, weakness, dizziness, and vertigo, that may start after 30 min and persist up to 12 hours. The drug is tolerated by patients in the advanced hepatosplenic stage.

20. Contraindications and cautions It should not be used after recent exposure to insecticides or drugs that potentiate cholinestrase inhibition. The use of muscle relaxants should be avoided for 48 hours after administring the drug It is contraindicated in pregnancy.

21. OXAMNIQUINE It can be used as an alternative to praziquantel for treatment of S. mansoni. Pharmacokinetics: It is administered orally It has a half life of 2.5 hours It is extensively metabolized. It is excreted in urine

22. Anthelminthic actions: It is effective against mature and immature stages of S. mansoni, yet is not considered cercaricidal. Its mechanism of action is unknown. It causes contraction and paralysis of worms which leads to its detachment from the terminal venules in the mesentery and shift to the liver where worms may die, surviving females may return to the mesenteric vessels but cease to lay eggs.

23. Clinical uses Safe and effective in all stages of disease. Disappearance of symptoms of (Katayama fever) with the use of this drug. It is less effective in children It is better tolerated if given with food and at the end of the day and in divided doses separated by 6-8 hours. 15 mg /kg twice daily for 2 days

24. Adverse Effects Dizziness, headache, drowsiness  most common GIT disturbance Pruritus,urticaria,low grade fever. Orange to red discoloration of the urine Proteinuria Microscopic hematuria

25. Decrease in leukocytes Convulsion and seizures Increase in liver enzymes Eosinophilia, urticaria (allergic manifestation due to the death of parasites and release of antigen.

26. Contraindications CNS disturbances Epilepsy Pregnancy