Anthelmintic drugs

Anthelmintic drugs are an important topic for the undergraduate students.

1. Anthelmintic Drugs Dr Bikash Meher Dr Bikash Ranjan Meher Assistant Professor AIIMS, Bhubaneswar

2. Case Study A 34-year-old female, who immigrated to US few years ago, presented to your clinic, complaining of dizziness and mild seizures that have been going on for the past 12 years. Her family noticed an increase in the frequency of her intermittent atypical near-syncopal attacks within the past two months and decided to seek medical attention. She also suffers from dyspepsia, nausea with scanty non bilious vomiting. During the initial conversation with the patient for obtaining her medical history, the patient started complaining of dizziness, which eventually led to generalized convulsions that lasted for about one minute. The patient was urgently transported to a near by hospital in the emergency department. At the hospital, computed tomography (CT) of the brain showed multilobulated cystic mass in the posteromedial left temporal/occipital region with surrounding oedema. Furthermore, the magnetic resonance imaging (MRI) of the head without contrast revealed a nodular focus of enhancement within the multilobulated cystic mass in the brain.

3. Introduction Individual drugs M.O.A Therapeutic Uses Adverse Effects Outline of lecture

4. Helminthiasis is infestation with one or more intestinal parasitic worms(helminth) Infected people excrete helminth eggs in their faeces, which then contaminate the soil in areas with inadequate sanitation. Other people can then be infected by ingesting eggs or larvae in contaminated food, or through penetration of the skin by infective larvae in the soil Lead to chronic illness,malnutrition,anemia Introduction

5. Helminths Nematodes Trematodes Cestodes

6. Prevalence of Worm infestations

7. Drug treatment Health education Improved sanitation

8. Goals of drug therapy

9. Albendazole Benzimidazoles Share common mechanism of action Mebendazole ,Thiabendazole, Triclabendazole

10. Mechanism of action

11. Pharmacokinetics Variable Oral absorption Increased with a fatty meal Metabolized Albendazole sulfoxide Wide distribution Elimination T1/2 8-12hrs

12. Clinical Uses

13. Other Uses Visceral larva migrans ( 400mg BD for 30days) Cutaneous larva migrans ( 400mg daily for 3 days) Microsporidiasis (400mg BD for 2wks) Intestinal capiliariasis(400mg daily for 10days) Strongyloidiasis(400mg OD for 3days) Clonorchis sinensis (400mg BD for 7days) Lymphatic filariasis

14. Adverse effects Epigastric distress, Diarrhea, Dizziness, Insomnia Headache ,Alopecia, Fatigue ↑ Aminotransferase enzyme

15. Precaution No prior preparation, no fasting after the drug and no laxatives required Administered on an empty stomach for intra luminal worms but with fatty meals for tissue parasites CI Pregnancy, Children< 2yrs Drug Interaction Glucocorticoids and Praziquantel ↑albendazole sulfoxide

16. Points to remember Albendazole is the drug of choice for neurocysticercosis and all nematodes EXCEPT Trichuriasis Strongyloidiasis Filariasis Dracunculiasis

17. Mebendazole Synthetic benzimidazole Wide spectrum Mechanism of action Same as albendazole

18. Pharmacokinetics Very less oral absorption(10%) but ↑ with fatty meal 90 % protein bound Converted to inactive metabolites Half- life of 2-6 hours

19. Clinical Uses

20. Adverse effects Short term(1-3 days) No significant adverse effects GI upset Long term use (3 months) Fever ,fatigue, alopecia ,Rash, Urticaria Increased liver enzymes ,Pancytopenia Not use In pregnancy Hypersensitive peoples Children under 2 years

21. Q. Albendazole is the drug of choice for following EXCEPT. A. Ascaris lumbricoides B. Necator americanus C. Visceral larva migrans D. Strongyloides

22. Thiabendazole First benzimidazole to be used Mechanism of action– Similar to other benzimidazole Inhibits tubulin polymerization

23. Pharmacokinetics Rapidly absorbed Chelate with iron but not with calcium Half- life of 1-2 hrs Completely metabolized in liver 90% is excreted in urine( Glucuronide conjugate) Can also absorbed through skin

24. Therapeutic Uses Strongyloides infections Cutaneous larva migrans ( topical) Trichinosis Dose 25mg/kg BD for 2 days

25. More toxic than other benzimidazoles GI disturbances Pruritus ,Headache, Drowsiness Psychoneurotic symptoms Irreversible liver failure Stevens –Johnson syndrome Not used In young children , pregnancy Hepatic and renal diseases Adverse effects

26. Triclabendazole Narrow spectrum benzimidazole DOC for fascioliasis ( 10mg /kg single dose) Paragonimus skrjasbini (10mg/kg orally daily for 3 days) No significant side effects

27. Piperazine Alternative drug for ascariasis Cure rate 90% for 2 days treatment Readily absorbed orally Excreted mostly unchanged in urine

28. Mechanism of action

29. Therapeutic Uses Ascariasis 4gm OD for 2 days Enterobiasis 2gm OD for 7days

30. Adverse Effects GI disturbance CNS effect- Vertigo, Ataxia Safe in pregnancy

31. Pyrantel Pamoate Pharmacokinetics Poorly absorbed from gut Half of the drug is excreted unchanged in the feces

32. Mechanism of action

33. Therapeutic Uses Ascariasis and Enterobiasis Dose -11mg/kg single dose Ankylostomiasis Dose 11mg/kg /day for 3 days Not effective against Trichuriasis and Strongyloidiasis

34. GI disturbances Drowsiness , Headache ,Insomnia, Rash ,Fever ↑ aminotransferase level Contraindications Pregnancy Children under 2 years of age Adverse Effects

35. Bithionol M.O.A Uncouple oxidative phosphorylation Alternative to triclabendazole for Fascioliasis Paragonimiasis Dose 30mg/kg in two divided doses on alternate day ( 10 doses) A/E Nausea, Vomiting ,diarrhea, Abdominal pain,Skin rash

36. Q. Why thiabendazole is not preferred at present for the treatment of ascariasis?

37. Filariasis is a disease group affecting humans and animals Filarial worms are nematodes which dwells in subcutaneous tissue and lymphatics Eight filarial species infect humans Affects approximately 170 million persons world wide W.bancrofti , B.malayi,O.volovolus,L loa Filariasis

38. Lymphatic filariais Elephantiasis Painful and profoundly disfiguring disease Caused by – W. bancrofti , B. malayi  and B. timori 110 million people are affected Annual loss of 1 billion  dollar

39. Dieth ) lcarbamazine (DEC )

40. Anthelminthic action Kills MFs form of W.bancrofti,B.malayi,L.loa Kills adult form of W.bancrofti,B.malayi,L.loa MF form of W.bancrofti are not killed in hydrocele fluid Kill the MF form of O.volvulus Doesn’t kill the adult form of O.volvulus MF forms of O. volovulus are not killed in nodules

41. Rapid oral absorption Peak plasma conc. in 2 hrs Half- life is 2-10 hours Rapid metabolism It is excreted in urine as unchanged or metabolite Dosage is reduced in renal impairment Pharmacokinetics

42. Mechanism of action

43. Clinical Uses

44. Adverse Effects

45. Ivermectin Semi-synthetic macrocyclic lactone Mixture of avermectin B1a and B1b Rapidly absorbed on oral administration High apparent volume of distribution Excreted in feces

46. Mechanism of action

47. Anthelminthic action In O. volvulus , ivermectin causes a marked decrease in MF counts in the skin and ocular tissues but has little effect on adult parasites, even at doses as high as 800 mg/kg Ivermectin is effective against microfilaria but not against adult worms of W. bancrofti , B. malayi , L. loa , and M. ozzardi

48. Clinical Uses

49. Adverse Effects Fatigue ,dizziness, GI disturbance Fever, headache, dizziness, somnolence Hypotension , tachycardia, peripheral edema Mazzoti like reaction Corneal opacities

50. Q. Which of following about DEC is NOT true? A. It kills microfilaria and adult form of W.bancrofti B. It is used in Mazzotti test C. It causes Mazzoti reaction D. It doesn’t kill the MF of Onchocerca volvulus

51. Praziquantel Pyrazino Isoquinoline derivative 80% bioavailability 80% protein bound Widely distributed Bioavailability ↑ with carbohydrate meals, Cimetidine ↓with concomitant Phenytoin, CBZ,Corticosteroids not against Nematodes

52. Mechanism of action

53. Therapeutic Uses

54. Adverse Effects Headache, Dizziness, Drowsiness Skin rash,Pruritus,Urticaria,Arthralgia,Myalgia Headache,Meningismus,Seizure,Mental abnormalities Contraindicated in ocular cysticercosis Safe in pregnancy

55. Niclosamide Salicylamide derivative Second-line drug for treatment of tape worm infections Poorly absorbed from gut & excreted in urine Acts by inhibiting oxidative phosphorylation Kills scoleces but no effect on ova

56. Clinical Uses T. saginata,T. solium,D.latum Purgative is necessary to purge all dead segments& prevent liberation of ova Dose 2gm 2 tab of 500mg in morning on empty stomach and 2 more after 1 hr Purgative should be given 2hrs after second and last dose

57. Adverse effects No significant side effects GI disturbance Not indicated in children under 2 years of age Safe in pregnancy

58. Metrifonate Organophosphorous compound Alternative for S.hematobium Not effective against S.mansoni,S.japonicum Dose 7.5-10 mg TDS at intervals of 2 weeks A/E Cholinergic side effects C/I Pregnancy, Recent insecticides exposure, with Succinyl choline

59. Oxamniquine S.Mansoni Not effective against S.hematobium,S.japonicum A/E Drwosiness,Dizziness,Seizures Pruritus , Urticaria Dose 15-20mg/kg single dose C/I Pregnancy,Epilepsy

60. Niridazole Alternative for guinea worm Schistosoma hematobium Intestinal and extra intestinal amoebiasis Dose 25mg/kg

61. Q.A patient Ram present with  fever, urticaria, swollen and tender lymph nodes tachycardia, hypotension, arthralgias,  oedema, and abdominal pain within seven days of treatment of onchocerciasis with DEC. A. What is this known as ? B. Why this has happened and how would you manage this patient .

62. Q. An anti helminthic drug that is effective against blood fluke,liver fluke,lung fluke and cystecercus is. A.Albendazole B.Praziquantal C.Ivermectin D.Thiabendazole

63. Infecting organism Drug of choice Nematodes Ascaris ( round worm) Albendazole Ankylostoma (hookworm) Albendazole T. Trichura (whipworm) Albendazole Enterobius ( pinworm) Mebendazole Strongyloides( thread worm) Ivermectin Trchinella Albendazole Mebendazole Dracunculus MTZ Onchocerca Ivermectin Cutaneous larva migrans Al/ Ivermectin Visceral larva migrans Al

64. Tape worm( cestode ) T.saginata ( beef tape worm) praziqunatel T.solium ( pork tape worm) praziqunatel D latum ( Fish tape worm) praziqunatel

65. Trematode (flukes) S hematobium Praziquantel C.Sinensis (liver fluke) Praziquantel P. Westermani (lung fluke) Praziquantel F.hepatica (Sheep liver fluke) Bithionol F.Buski ( intestinal fluke Praziqunatel

66. References Katzung Good man gilman Harrison

67. Q.Which of the following drug causes flaccid paralysis? A.Albendazole B.Pyrantel pamoate C.Piperazine D.Ivermectin .

68. Thank you