anti-helminthics.by dr fahad ...............

Helmith

1. ANTIHELMENTHICS By Dr Ayesha Jamil

2. TYPES OF HELMINTIHCS There are three major types of helminthics Nematodes Trematodes Cestodes Antihelminthics aim the metabolic processes of the worms ;processes that are not present in the host or have different characteristics than those in the host.

3. DRUGS EFFECTIVE AGAINST THE NEMATODES MEBENDAZOLE PYRANTAL PAMOATE THI- ABENDAZOLE IVERMECTIN DI-ETHYL-CARBAMAZPINE.

4. MEBENDAZOLE Synthetic drug belonging to benzimidazole compound,effective against broad spectrum of nematodes; Whip worm( trichuris trichiuria ). Pin worms( enterobius vermicularis ) Hook worms( necator americanus,ancylostoma duodenale ) Roundworms( ascariasis lumbricoides )

5. PHARMACODYNAMICS OF MEBENDOZOLE It binds to the microtubules and inhibit there aggregation and also reduce the glucose uptake by the parasite.

6. PHARMACOKINETICS OF MEBENDAZOLE Insoluble in water. Little of the dose is absorbed, unless taken along with fatty meals Has extensive first pass metabolism and changed mainly to inactive forms Affected parasites are expelled in the feces

7. TOXIC EFFECTS Relatively free of toxic effects. Some patients complain of mild abdominal pain and diarrhea. CONTRAINDICATED IN PREGNANCY (TERATOGENIC EMBRYO TOXIC) Drug interactions;cimetadine phenytoin and carbamazapine .

8. PYRANTEL PAMOATE Pyrantel pamoate along with mebendazole is effective against PIN WORMS,HOOK WORMS and ROUND WORMS.

9. PHARMACODYNAMICS It is a neuro muscular blocking agent Causes persistant depolarization due to release of acetylcholine and inhibition cholinesterase;i -e; there is activation of nicotinic receptors of the parasite. Effective against the mature and immature parasites but not the ova stage.

10. PHARMACOKINETICS Poorly absorbed Main site of action is the intestinal tract. The paralyzed parasite is expelled in the feces. TOXIC EFFECTS; Mild nausea ,vomiting and diarrhea.

11. THIABENDAZOLE It is synthetic drug belonging to benzimidazole group. Effective against ; 1) STRONGYLOIDIASIS caused STRONGYLOIDES STERCORALIS (THREAD WORM) 2);CUTANEOUS LARVA MIGRANS 3);TRICHINOSIS by TRICHINELLA SPIRALIS

12. Mechanism of action is the same as that of all benzimidazole i -e; the inhibition of microtubular aggregation. It is very well absorbed after oral administration , hydroxylated by the liver,excreted in the urine. Sometimes associated with CNS effects.

13. ADVERSE EFFECTS 1);ERYTHEMA MULTIFOFME 2);STEVEN JOHNSON SYNDROME Sometimes even associated with fatlities . Should not be used in pregnancy.

14. IVERMECTIN It is the drug of choice against by ONCHOCERCIASIS(RIVER BLINDNESS) By ONCHOCERCA VOLVULUS. Also effective against CUTANEOUS LARVA MIGRANSand STRONGYLOIDIASIS.

15. PHARMACODYNAMIS Intensifies GABA-mediated signaling to the peripheral nerve endings,opens the glutamate- gated cloride channels,so influx of Cl is enhansed leading to the hyperpolarization and ultimately paralysis of the parasite.

16. PHARMACOKINETICS After oral administration it is very well absorbed . Doesnot cross the blood brain barrier but should not be given in menengitis as the permeabilty of the meninges increases and CNS effects may be menifested . CONTRA- INDICATION Should not be given in pregnancy

17. SIDE EFFECTS The killing of micro filaria can cause Mazoti like reaction( fever,headache,dizzyness,somnolence and hypotension.)

18. DIETHYLCARBAMAZAPINE It is used to treat FILARIASIS caused by Wucheria bancrofti and Brugia malayi . MECHANISM OF ACTION Immobilize the microfilaria and render susceptible to the host defence mechanism ADVERSE EFFECTS;Due to host reaction to the immobilized parasites;the greater the load the greater the adverse effects like Arthalgia,myalgia ; fever , headache,malaise and rash. I nsevere cases anti histamines or corticosteroids should be given.

19. ONCHOCERCHIASIS Caused by onchocerca volvulus Characterized b cutaneous nodules,pruritic rashand ocular leisions often causing blindness Drug of choice IVERMECTIN

20. ENTEROBIASIS ( PIN WORM DISEASE) Caused by Enterobius vermicularis Characterized by perianal itching ,white coloured worms are seen at the perianal region and in the stools. Drugs of choice are Mebendazole and Pyrantel Pamoate .

21. PIN WORMS

22. ASCARIASIS ROUND WORM DISEASE Caused by the Ascaris Lumbricoidesow in the i Larvae grow in the intestine,causing abdominal symptoms and even obstruction,may pass into the blood and infect the Lungs. Drugs of choice are Mebendazole and Pyrantel Pamoate .

23. FILARIASIS Caused by the WucheriaBancrofti and Brugia Malayi . Obstructs the lymph flow,causing local inflamation and fibrosis of lymphtics occur. After years of infection , the arms, legs and the scrotum gets filled with fluid ;causing Elephantiasis. Drugs of choice are Di-ethyl- carbamazapine and albendazole .

24. WUCHERIABANCROFTI

25. ELEPHANTIASIS

26. TRICHURIASIS (whip worm disease) Caused by the Trichuris Trichuria Infection is usually asymptomatic, but sometimes there is abdominal pain , diarrhia and flatulance . Drugs of choice is Mebendazole .

27. HOOK WORM DISEASE Ancylostoma Duodenale (old world hook worm) NecatorAmericanus (new world hook worm) Worms attach to the intestinal mucosa causing anorexia and intestinal ulcers ,which when become chronic lead to intestinal bleeding and thus causing anemia. Drugs of choice are Mebendazole and Pyrantel Pamoate .

28. HOOK WORM

29. STRONGYLOIDIASIS (THREAD WORM DISEASE) Caused by the Strongyloides stercoralis . Relatively uncommon,benign in healthy but can be fatal in immuno compromised. Drugs of choice are Thiabendazole and Ivermectin .

30. strongyloides

31. TRICHINOSIS Caused by Trichinella Spirallis Source is insufficiently cooked meat,especially Pork Drug of choice is Thiaendazole .

32. Trichinella spirallis

33. TREMATODES (FLUKES) These are leaf shaped flat worms, generally by the characterized tissue they invade. Tissue that are effected are Lungs (fluke) liver (fluke) GI TRACT (fluke) Blood.(fluke)

34. PRAZIQUANTEL Trematode infections are usually treated by Praziquantel . It is the drug of choice of all Schistosomiasis , all trematodes and also Cestodes infections like cysticerciosis .

35. Mechanism of action Praziquantel increases the permeability of the cell memberanes to calcium;so increased Ca++ influx;leading to contracture and paralysis of the parasite.

36. PHARMACOKINETICS After oral administration rapidly absorbed and well distributed to the whole body ,high conc. are achieved in the bile it is also well distributed to the CSF. Metabolized by oxidation, to inactive metabolites; so has a shorter half life. Removed from the body in bile and urine.

37. CONTRA-INDICATIONS DRUG INTERACTIONS Praziquantel is contra indicated in pregnancy and nursing mothers . It is also contra indicated in occular cystecercosis because along with damaging the parasite it may also damage the eye. DRUG INTERACTIONS It interacts due its extensive metabolism with Dexamethsone,Carbamazapine and phenytoin . Cimetadide inhibitsCYP450 so decreases the metabolism of Praziquantel and increases the plasma conc. of the drug.

38. PARAGONIMIASIS (LUNG FLUKE) Caused by Paragonimus Westemani From the intestine through the blood accumalates in the lungs leading to cough blood stained sputum. Source is raw crab meat. Therapy; PRAZIQUANTEL

39. CLONORCHIASIS (LIVER FLUKE) Caused by clonorchis Sinensis Infects the billiary tract Damage occurs by hosts immune inflammatory response causing fibrosis and hyperplasia. Source is raw water fish. Therapy ; PRAZIQUANTEL

40. SCHISTOSOMIOSIS (NEW WORLD ) SCHISTOSOMA MANSONI SCHISTOSOMA JAPONICUM Deposit eggs on the intestinal wall, in response to this host inflammatory response is triggered there by damaging the intestines, also the eggs release proteolytic enzymes which further causes damage. This leads to GI bleeding ,diarrhea and liver damage. SOURCE;directly from the skin. Therapy ; PRAZIQUANTEL

41. SCHISTOSOMIOSIS (OLD WORLD) Schistosoma Haematobium Infects the bladder & veins leading inflammatory host response which causes Fibrosis Granulomas Heamaturia Therapy; PRARQUANTEL

42. CESTODES Cestodes are also called true tape worms ; They typically have a flat, segmented body and attach to the host`s intestine. Like nematodes they do not have a mouth and a digestive tract through out their life cycle .

43. Types of cestodes ECHINOCOCCUS GRANULOSIS TENIA SOLIUM {PORK TAPE WORM}. TENIA SAGINATA {BEEF TAPE WORM}. DIPHYLLOBOTHRIUMLATUM {FISH TAPE WORM}.

44. Identification Echinococcus granulosus

45. A cestode , a parasitic tapeworm

46. NICLOSAMIDE Drug of choice for cestodes MECHANISM OF ACTION It inhibits the phosphorylation of ADP to ATP ---so inhibition of energy source. It also inhibits the anaerobic metabolism. {prior to the drug administration laxative should be given}

47. INDICATIONS Drug is lethal against cestodes scolex Also against segments of cestodes. (not effective against ova stage) (alcohol should not be taken along with it)

48. Niclosamide and alcohol Drug Interactions Niclosamide is soluble in alcohol which enhances its absorption raising the possibility of dose related adverse effects. Alcohol intake is therefore restricted during treatment with niclosamide

49. Safety profile of niclosamide Safety in children and pregnancy According to Martindale, The Extra Pharmacopoeia, there is no contra-indication for the use of niclosamide in both small children and pregnant women. Pregnancy FDA Pregnancy Category B. According to Martindale, The Extra Pharmacopoeia, there is no contra-indication for the use of niclosamide in pregnant women. Breast Feeding No data on distribution into milk. No effects in humans documented

50. Conclusions The current review supports the continuous use of niclosamide as no major safety concerns have been raised. Its safety in children and pregnant women and efficacy and safety in treating T. solium carriers even in the presence of ( neuro ) cysticercosis has an advantage over praziquantel

51. Brand Name Manufacturer/Mnf. Representative MESAN SHAIGAN PHARMACEUTICALS (PVT) LTD. YOMESAN BAYER PAKISTAN PRIVATE LIMITED. YOSAN ADAMJEE PHARMACEUTICALS (PVT) LTD. Page 1

52. ALBENDAZOLE Albendazole is a benzimidazole . PHARMACOKINETICS Absorbed after oral administration. (fatty meals enhanse absorption) Has extensive first pass metabolism,its metabolite sulfoxide , is also active. Route of excretion is urine

53. PHARMACODYNAMICS Inhibits the synthesis of microtubules Inhibits the uptake of glucose by the nematodes. The primary mode of action of albendazole in susceptible parasites has been described as binding to β- tubulin and leading to inhibition of microtubule polymerization

54. ADVERSE EFFECTS Short term treatment; headache nausea. Long term treatment; hepatotoxicty rarely agranulcytosis and pancytopenia . Severe inflammatory response to dying parasites due to treatment of neurocystecercosis leading to headache, vomiting, hyperthermia, convulsions and mental changes.

55. Contraindications Should not be given in pregnancy Should not be given to children under two years of age .

56. Role of albendazole as an anticancer benzimidazole carbamates and in particular albendazole is a highly potent inhibitor of cell proliferation. Albendazole proved to be quite a potent inhibitor of a wide variety of cancer cell lines, including a range of hepatocellular cancer cells , colorectal, pancreatic, ovarian, and a number of other human cancer cells

57. ECHINOCOCCSIS Also called Hydatid disease. Caused by echinococcus granulosis (dog tape worm) Hydatid cyst are seen in the brain, liver and lungs. Rupure of cysts can lead to anaphylactic shock in some patients .

58. contd Occurs due to ingestion of eggs in the dogs feaces . Sheep acts as an intermediate host Diagnosed by CT scan or biopsy of infected tissue Treated by surgical excision Therapy : albendazole

59. The macroscopic appearance of the hydatid cyst in the lung.

60. Ultrasonographic appearance of echinococcal cysts

61. diphyllobothriasis Caused by diphyllobothrium latum (fish tape worm) Transmitted by raw fish diagnosed by eggs in the stool Treatment; niclosamide

62. Cysticercosis ( teania solium larvea ) Disease is caused by teania solium larvea Produces cystecerci in the brain and the eyes. Causes seizures, headache and vomitng . Transmmitted by ingestion of eggs in the human feaces . Therapy : praziquantel , albendazole ,\ surgery.

63. CNS images of cysticercosis

64. Teaniasis ( teania saginata adult) (beef tape worms) Infects the intestine but does not form cysts. Most of the pts are asymptomatic. Larvea transmitted by uncooked beef. Proglottides found in the stools Therapy : niclosamide .

65. Teania solium adult form(pork tape worm) Instestines are the primary site of action. Usually there is diarrhea but the pt can be asymptomatic . Disease transmitted by larvea in uncooked pork or by ingestion of eggs. Daignosed by the detction proglottids in the stool. Therapy = niclosamide .

66. Mature proglottid of T. saginata , stained with carmine. Note the number of primary uterine branches (>12). B:   Taenia saginata adult worms.  The adult in Figure A is approximately 4 meters in length.