Anthelminthic Drugs

1. ANTHELMINTIC DRUGSHelminth Infections1-Tapeworms ( cestodes) Beef tapeworm / fish tapeworm2- Intestinal round worms ( nematodes)Ascaris, pinworm ,whipworm, strongyloides, ancylostoma ( hookworm ).A skin infection is termed cutaneous larva migrans Visceral larva migrans .

2. Anthelminthic Drugs • May act by causing : • 1- paralysis of the worm. • 2- damaging the worm leading to partial digestion or rejection by immune mechanisms. • 3- interfere with the metabolismof the worm. *Worms or larvae live in tissues of host body like muscles , viscera , menninges , subcutaneoustissues.

3. Adult filariae live in the lymphatics, connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream. • They are ingested by mosquitoes or similar insects, they develop to larvae in 2ndry host and pass to mouth parts of insect and re-injected to humans

4. Ascaris lumbricoids ( common round worm)

5. filariasis

6. Hookworm

7. Pinworm male ,female

8. Tapeworm

9. whipworm

10. Dircrocoelium dendriticum

11. Fasiola hepatica

12. Tricuris tricura

13. Trichinela spiralis

14. elephantiasis

15. Hydateid cyct

16. cysticercosis

17. ANTHELMINTIC DRUGS ALBENDAZOLE • Broad spectrum oral anthelmintic • Drug of choice for treatment of hydatid disease and cysticercosis,it is also used for the treatment of ascariasis ,tricurasis and strongyloidiasis, pinworm, hookworm

18. Mechanism Of Action • Inhibits microtubule synthesis by binding to β –tubulin. • Inhibits mitochondrial reductase causing reduced glucose transport.. Intestinal parasites are immobilized and die slowly. • larvicidal in hydatid ,cysticercosis , ascariasis and hook worm infections. • Ovicidal in ascariasis ,hookworm , trichuriasis

19. Pharmacokinetics • Benzimidazole carbamate • Administered orally , absorption increased with a fatty meal • Metabolized in the liver to the active metabolite albendazole sulfoxide

20. Pharmacokinetics • Plasma half life is 8-12 hours • sulfoxide is mostly protein bound distributes well to tissues and enters bile,CSF & hydatid cysts. • Metabolites are excreted in urine

21. Clinical uses • Used on empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites. • In ascariasis ,trichuriasis ,hookworm, pin worminfections : children over 2 years & adults (single dose 400mg, repeated for2-3 day in heavyascaris infection . For 2 wks for pin worm infection 2. Hydatid diseases: drug of choice for medical therapy& adjunctive to surgical removal or aspiration of cysts.

22. Albendazole (con’) • Neurocysticercosis: Used with corticosteroid todecrease theinflammation caused bydying organism andit also reduces the duration of course for 21 days 4. Other infections:Drug of choice in cutaneousand visceral larvamigrans , intestinal capillariasis, giardiasis & taeniasis.

23. Adverse Effects • In short term(1-3 days): Mild epigastric pain,diarrhea, nausea, headache & insomnia. • In long term use : for hydatid cyst and cysticercosis : abdominal pain, headache ,fever ,fatigue, alopecia , increased liver enzymes , pancytopenia. Blood counts and liver enzymes should be followed. • Not given during pregnancy, hypersensitive people to benzimidazole drugs & children under 2 years .

24. MEBENDAZOLE (Vermox) • Synthetic benzimidazole • Wide spectrum and low incidence of adverse effects Mechanism of action: Inhibits microtubule synthesis . It kills hookworm, pin worm , ascarisand trichuriseggs.

25. Pharmacokinetics less than 10% of orally administered drug is absorbed • Absorption increases with fatty meal. • Absorbed drug is 90 % protein bound • Converted to inactive metabolites . • Half- life of 2-6 hours • Excreted mostly in urine .

26. Clinical Uses It is taken orally before or after meal , tabletsshould be chewedbefore swallowing. • Pinworm , trichuriasis, hookworm & ascaris infections. • in adults and children over2 years curerate is90-100 % except hookworm it is less.

27. Adverse Effects & Precautions • Short term therapy.Mild GI disturbance. • High dose : hypersensitivityreactions, agranulocytosis , alopecia ,elevation ofliver enzymes . Used with caution under 2ys of age may cause convulsion. Contraindicated in pregnancy. • Enzyme inducersand inhibitorsaffect plasma level of the drug.

28. Thiabendazole • Benzimidazole • Chelating agent and form stable complexes with metalsincluding iron, but does not bind with calcium. • Rapidlyabsorbed • Half- life of 1-2 hrs • Completely metabolized in liver and 90% is excreted in urine • Can also absorbed throughskin

29. Mechanism Of Action • Similar to other benzimidazoles. It is ovicidal for some parasites • Clinical uses: • Should be given after meals .and tablets should be chewed • Strongyloidal infections & cutaneous larva migrans .Thiabendazole cream is applied topically or drug can be given orally for 2 days.

30. Adverse Effects & Contraindications • More toxic than other benzamidazoles • GI disturbances • Pruritus ,headache, drowsiness , psychoneurotic symptoms. • Irreversible liver failure. • Fatal Stevens –Johnsonsyndrome • Not used in young children , pregnancy, hepatic andrenal diseases.

31. PYRANTEL PAMOATE • Broad spectrum • Pharmacokinetics: • Poorly absorbed from GIT • Half of the drug is excreted unchanged in the feces. • Mechanism of action: • result in paralysis of worms. It is a neuromuscular blocking agent Efficacy • Very effective against luminal organisms( mature or immature forms). • Not effective against migratory stages in the tissues or against ova

32. Clinical uses Pin worm given orally with or without food. • Ascariasis • Hookworm

33. Adverse Effects • Infrequent mild transient GI disturbance • drowsiness , headache ,insomnia. • Rash ,fever Contraindications & Cautions • Should be used with caution in liver dysfunction. • Pregnancy • Children under 2 years of age

34. PIPERAZINE • Only recommended for the treatment of ascariasis cure rate 90% for 2 days treatment. • Readily absorbedorally and excreted mostly unchanged in urine • Mechanism ofaction: Causes paralysis of ascaris by blocking acetylcholineat myoneuraljunction , the live worms expelled by normal peristalsis.

35. Treatment is continued for 3-4 days or repeated after one week in case of heavy infections.

36. Adverse Effects • GI disturbance • Neurotoxicity ,allergicreactions . • Contraindications • Epilepsy or a history of epilepsy • Impaired liver or kidneyfunctions • pregnancy • Chronic neurologic disease

37. NICLOSAMIDE • Second-line drug for treatment of most tapeworm infections. • Mechanism of action: • Adult worm( not ova) is rapidly killed by inhibition of oxidative phosphorylation . • Pharmacokinetics: • Poorly absorbed from gut & excreted in urine.

38. Clinical Uses • Treatment of most forms of tapeworms. • Not effective against cysticercosis or hydatic disease. • Given in the morning on empty stomach. • Purgative is necessary to purge all dead segments& prevent liberation of ova.

39. Adverse effects & Contraindications • Mild ,infrequent and transitory GI disturbance • Alcohol consumption should be avoided • Not indicated in children under 2 years of age or in pregnancy.

40. DIETHYL CARBAMAZINE • Drug of choice for the treatment of filariasis and tropical eosinophilia. • Pharmacokinetics: • Rapidly absorbed fromgut • Half- life is 2-3 hours • The drug should be given after meals • It is excreted in urine as unchanged or metabolite. • Dosage is reduced in urinary alkalosisand renalimpairment.

41. Mechanism Of Action • Immobilizes microfilariaeand alters theirsurfacestructure ,displacing them from tissues & making them susceptibleto destruction byhost defense mechanism • It has immunosuppressiveeffects

42. Adverse Effects • Fever , malaise, papular rash, headache, GI disturbance,cough. Chest,muscle,joint pain • Leucocytosis • Retinal hemorrhage • Encephalopathy • lymphangitis and lymphadenopathy. • *It is not teratogenic

43. Contraindications & Cautions • *Hypertension • * Renal disease *patient with lymphangitis

44. IVERMECTIN • Drug of choice for treatment of strongyloidiasis • Macrocyclic lactone ring • Given only orally • Rapidly absorbed • Does not cross BBB. • Half- life is 16 hrs • Excretion is mainly in feces.

45. Mechanism Of Action • Acts on the parasitte,s glutamate-gated Cl- channel receptors . Chloride influx increased , hyperpolarization occurs , resulting in paralysis of the worm. Or • Paralyze nematodes by intensifying GABA- mediated transmission of signals in peripheral nerves.

46. Clinical uses • Drug of choice for cutaneous larva migrans & strongyloidiasis. • Onchocerciasis • It is also used for scabies , lice . • Filariasis.

47. Adverse Effects • Fatigue ,dizziness, GI disturbance • Killing of microfilaria result in a Mazotti reaction ( fever, headache, dizziness, somnolence, hypotension , tachycardia, peripheral edema……). • Corneal opacities & other eye lesions.

48. Contraindications & Cautions • Concomitant use with other drugs that enhance GABA e.g Barbiturates, bnzodiazepines, valproic acid. • pregnancy • Meningitis • Children under 5 years of age.

49. BITHIONOL • Drug of choice for the treatment of fascioliasis ( sheep liver fluke) • Pharmacokinetics: • It is orally administered and excreted in urine.

50. Adverse Effects • GI disturbance ( N., V., D., A.) Dizziness, headache Skin rashes , urticaria, Leucopenia • Contraindications and precautions: Hepatitis , leucopenia Used with caution in children under 8 years of age.