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Anthelmintics SCHISTOSOMIASIS

Anthelmintics SCHISTOSOMIASIS. Alia Alshanawani Pharmacology Dep, Medical College; KSU. TREMATODES also called as flukes are leaf shaped flat worms characterized by ! tissues they infect as parasite: Lung / Liver / Intestinal / Blood FLUKES. Schistosomiasis

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Anthelmintics SCHISTOSOMIASIS

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  1. AnthelminticsSCHISTOSOMIASIS Alia Alshanawani Pharmacology Dep, Medical College; KSU.

  2. TREMATODES • also called as flukes • are leaf shaped flat worms • characterized by ! tissues they infect as parasite: • Lung / Liver / Intestinal / Blood FLUKES.

  3. Schistosomiasis Also known as bilharzia, bilharziosis/ snail fever: is a parasitic disease caused by several species of fluke of ! GenusShistosomiasis. Caused by trematodes: 1. Schistosomahaematobium 2. S. mansoni 3. S. japonicum.

  4. Although it has a low mortality rate, schistosomiasis often is a chronic illness that can damage internal organs &, in children, impair growth & cognitive development. • The urinary form of schistosomiasis is associated with increased risks for bladder cancer in adults. • Schistosomiasis is the 2nd most socioeconomically devastating parasitic disease after malaria.

  5. LIFE CYCLE

  6. Schistosomiasis (New world) • S. mansoni & S. Japonicum • Primary site of infection is GIT. • Damage to intestinal wall is caused by hosts inflammatory response to eggs deposited at that site. • The eggs also secrete proteolytic enzymes that further damage ! tissue. • Diagnosis: eggs in stools. • GIT bleeding, diarrhea, Liver damage.

  7. Schistosomiasis (old world) • S. Haematobium • ! primary sites of infection: veins of urinary bladder • eggs induce fibrosis , granulomas & haematuria. • transmitted by direct skin penetration. • Diagnosis: eggs in ! urine / bladder wall.

  8. Antischistosomal drugs • Praziquantel (all schistosomal diseases) • 2. Metrifonate (S. haematobium) • 3. Oxamniquine (S. mansoni).

  9. Praziquantel • a synthetic isoquinoline pyrazine derivative • PK: • rapid po absorption • maximum plasma conc: 1-3 hr. • Cross BBB. • bound to plasma proteins (80%). • undergoes 1st pass metabolism to inactive metabolite.

  10. T1/2 = 0.8 - 3 hr (increases in liver disease). • excreted in urine & bile. • Bioavailability: • Increased by carbohydrate meal & cimetidine. • Reduced by antiepileptics (phenytoin & carbamazepine).

  11. Mechanism of Action of praziquantel increases trematode cell membrane permeability to Ca2+: contraction, paralysis, dislodgement & death.

  12. Anthelminthic action; praziquantel • broad spectrum anthelminthic drug • effective in the Tr of schistosome infections of all species & most other trematodes + cestodes (tapeworms) but nematodes (round worms) are unaffected. • effective against mature & immature stages of worms. • Cure rate is up to 95%.

  13. Clinical uses; praziquantel • Schistosomiasis: Drug of choice for all forms For S.Japonicum infections, 20 mg/kg at intervals 4-6 hours for a total of 3 doses. For S.mansoni and S.hamatobium 40 mg /kg in two divided doses.

  14. taken after meals. • the interval between doses should not be < than 4 hr & not > than 6 hr. • effective in children & adults.

  15. 2- Other trematodesinfections: • Clonorchiasis (liver), & paragonimiasis (lung) 3- Cestodes infections: • Taeniasis & diphyllobothriasis (intestine) • Neurocysticercosis (albendazole is preferred) • Hymenolepis nana • Hydatid disease.

  16. Adverse reactions of praziquantel : • Headache, dizziness, drowsiness. • GIT disturbances. • Pruritus, urticaria, arthralgia, myalgia. • transient elevation of liver enz. • Fever, skin rashes , augmented eosinophilia may appear after several days;; release of foreign protein from dying worm.

  17. Adverse reactions of praziquantel • In neurocysticercosis: neurologic abnormalities (headache, mental changes, seizures) increases by inflammation around dying parasite. Rx: used with corticosteroids.

  18. Contraindication & precautions • Ocular cysticercosis for fear of destruction of parasite in eye. • Children < 4 years. • Pregnancy& nursing mothers. • Driving. • Activities require alertness & physical coordination (prohibited). • Reduce the dose in liver impairment. • Patient should be informed not chewing; bitter taste

  19. Metrifonate (TRICHLORFON) Organo-phosphate compound PK • Rapid po absorption. • t1/2 = 1.5 hr. • Nonenzymatic transformed to active metabolite. • widely distributed to tissues. • Excreted in urine.

  20. Pharmacodynamics; Metrifonate • produces its effect due to inhibition of cholinesterase, produces depolarizing block of S. haematobium • paralyzes the adult worm & their shift from bladder venous plexus to a small arterioles of the lungs, where they are trapped by ! immune system & killed. • NOT effective against S. haematobium eggs, only adult worms are killed.

  21. Clinical uses; Metrifonate • Safe, low cost alternative drug for S. hematobium infections ONLY . • A single dose of 7.5-10 mg /kg 3 times at 14 days intervals. • effective as prophylactic when given monthly to children in a highly endemic area. • In mixed infection with S. haematobium & S. mansoni: metrifonate + oxamniquine.

  22. Adverse reactions of Metrifonate : • Mild cholinergic symptoms: N , V, diarrhea, abdominal pain, B.spasm, headache, sweating, fatigue, weakness, dizziness, & vertigo these start after 30 min & persist up to 12 hr.

  23. Contraindications & cautions; Metrifonate • Pregnancy. • Recent exposure to insecticides / drugs that potentiate cholinesterase inhibition.

  24. Oxamniquine • Semisynthetic tetra-hydro-quinoline PK: • po • T1/2 = 2.5 hr • extensively metabolize into inactive metabolites. • excreted via kidney.

  25. Anthelmintic actions: • Effective against mature & immature stages of S. mansoni ONLY. • Its mechanism of action is unknown. • It may cause contraction & paralysis of worms; its detachment from the mesentery & shift to the liver where worm may die. • Surviving females may return to mesenteric vessels but cease to lay eggs.

  26. USES of Oxamniquine • Alternative to praziquantel for Tr of all stages of S. mansoni ONLY. • Effective in praziquantel resistance.

  27. Clinical uses • Less effective in children (higher doses) • better tolerated with food. • 15 -20 mg /kg twice for 1 day. • In mixed infection with S.H & S.M: metrifonate + oxamniquine.

  28. Adverse reactions; Oxamniquine • CNS: Dizziness , headache, & drowsiness • GIT disturbance • Pruritus, urticaria, fever • Discoloration of urine (orange-red) • Proteinuria • Transient elevation of liver enzymes • Seizures.

  29. Contraindications & Precautions; Oxamniquine • Epilepsy • Pregnancy • Activities require alertness.

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