ANTHELMINTIC DRUGS

1. DR.ABDUL LATIF MAHESAR Department of Medical Pharmacology KSU ANTHELMINTIC DRUGS Pharma Team

2. تنبيه • في هذه السلايدات قمنا بما يلي: • حذف المقدمة في كيفية انتقال العدوى واشكالها والاكتفاء فقط بأسماء الديدان وأصنافها • حذف الجرعات من ناحية الكمية وفترة استخدامها • يمكنكم العودة لسلايدات الدكتور للحصول على المعلومات السالفة الذكر

4. Nematodes A) INTESTINAL ROUND WORMS • Ascaris lmubricoides (common round worm) • Enterobius vermicularis (pinworm) • Trichuris trichuria (whipworm) • Strongyloids stercoralis (threadworm)  Strongyloidiasis • Ancylostoma duodenale & Necator americanus (hookworm) B) TISSUE ROUND WORMS Trichinella spiralis. (Trichinosis) Dracunculus medinensis (guineaworm)  Dracunculiasis

5. Other round worms FILARIAE, includes: • Wuchereriabancrofti (filariasis) • Loa loa (loiasis) • Onchocercavolvulus (onchocerciasis) River blindness. • Brugiamalayi and B. timori

6. Cestodes (tape worms) • Teniasaginata (Beef tapeworm) • Teniasolium (Pork tapeworm), • Cysticercosis (Pork tapeworm larval stage) • Hymenolepis nana (Dwarf tapeworm) • Diphyllobothriumlatum (Fish tapeworm)

7. Hydatid tape worm • Echinococcus species

8. TREMATODES/FLUKES (leaf-like) • Schistosomamansoni • Schistosomahematobium • SchistosomaJaponicum • Paragonimus species  Paragonimiasis • Fasciolopsisbuski • Fasciola hepatica • Clonorchissinensis

9. ANTIHELMINTIC DRUGS BENZIMIDAZOLEs 1.ALBENDAZOLE: • It possessbroad-spectrum activity . It is the drug of choice for treatmentof • Hydatid diseaseand • Neurocysticercosis. • It is also a major drug the treatment of (intestinal nematodes) : • Ascariasis, • Trichuriasis, • Strongyloidiasis, • Enterobiusvermicularis (pinworm), • Nectoramericanus, & Ancylostomaduodenale (Hookworms) infections.

10. Albendazole cont’d Mechanism of action: • Inhibits microtubule synthesis and glucose uptake • It has larvicidal effects on hydatid disease, cysticercosis, ascariasis, and hookworm infection. • Also, ovicidal in ascariasis , ancylostomiasis (hookworm), trichuriasis

11. Pharmacokinetics of Albendazole: • It is a benzimidazole carbamate • It is administered orally, and absorbed erratically (unpredictable), absorption can beincreased with fatty meal. • It ismetabolized in the liverrapidly to its active metabolite albendazole sulphoxide. (1st pass metabolism)

12. Contnued • It has a plasma half life of 8-12 hours • Sulphoxide is mostly (80%) protein bound , distributed to the tissues and enters the bile, cerebrospinal fluid, and the hydatid cyst. • urinary excretion

13. Clinical uses of albendazole: • It is administered on empty stomach when used against intraluminal parasites but with fatty meal when against tissue parasites. • Ascariasis, trichuriasis, hookworm, pin worm infection (intestinal): Acheives 100% cure in pinworm infection and high cure rates for others or marked reduction in eggs counts.

14. 2. Hydatid diseases: Drug of choice, with meals. Bone cyst may require treatment for 1 year. • If patients are to be treated surgically, both albendazole and praziquantel are used preoperatively for one month to reduce cyst fluid leakage. After surgery albandazole should be continued for a whole month.

15. Albendazole cont’d • Neurocysticercosis:It is the drug of choice. It is effective for symptomatic parenchymal and interventricular cysts. Less effective in arachnoid cyst. • It is superior to Praziquantel for neurocysticercosis for the following: • Shorter course of treatment. • It is cheaper • It is co-administeration with steroid increases its absorption • It is better in penetration arachnoid space.. • It is also effective for ocular cysts. • Other infections:Drug of choice in cutaneous and visceral larvea migrans , intestinal cappillariasis, microsporidial infections, gnathostomiasis, trichinosis, clonorchiasis, opisthorchiasis, toxocariasis, and loiasis.

16. It is used along with cotricosteroid to decrease the inflammation caused by dying organism, and it also reduces the duration of course • During the acute phase of cysticercotic encephalitis, albandazole is contraindicated and corticosteroid is indicated instead. N.B:In intestinal nematodes, treatment in days But in hydatid disease & Neurocysticercosis, the treatment take longer duration

17. Albendazole con’d Adverse effects: • In short termuse there is no significant adverse effects. • In long term use: abdominal distress, headache, fever, fatigue, alopecia , increased liver enzymes , pancytopenia. Blood counts and LFT should be carried out regularly. • Not given during pregnancy and in hypersensitive people. • Safety in children is not established in children below 2 years of age.

18. MEBENDAZOLE (Vermox) • it is a synthetic benzimidazole • it has wider spectrum and is safe Mechanism of action: Similar to albendazole Effecacy influenced by: GI transit time, intensity of infection, and strain of parasite. It is also used to kill hook worm, pin worm , ascaris and trichuris eggs.

19. Mebendazolecon’t Pharmacokinetics: • Less than 10% of orally administered drug is absorbed • Absorption increases with fatty meals • Absorbed drug is 90% protein bound • It is converted to inactive metabolites rapidly in liver. • It has half life of 2-6 hours • It is primarily excreted in bile.

20. Mebendazolecon’t Clinical uses: • It is taken orally before or after meal, tablets should be chewed before swallowing. • Ascaris lumricoides , trichuris trichura , hookworm and trichstrongylus; It is useful drug in case of mixed infection by these parasites. • in adults and children over 2 years cure rate is 90-100 % except hookworm but a marked reduction in worm burden occurs

21. Mebendazole cont’d • Intestinal cappilliaris • Trichinosis: It has limited efficacy against adult worm. • Corticosteroids coadministered in sever infection.

22. Mebendazole con’d Adverse effects and precautions: • No adverse effects in short term therapy except for mild GI disturbances. • With high dose hypersensitivity reactions, agranulocytosis , alopecia, elevation of liver enzymes. • Contraindicated in pregnancy. • Used with caution under 2 years of age may cause convulsion in this group. • carbamazepine or phneytoin ↓ conc. Cimetidine  ↑ conc. • used with caution in cirrhosis

23. Thiabendazole • It is benzimidazole. It is tasteless and insoluble in water. • It is a chelating agent and forms stable complexes with metals including iron but does not bind with calcium. • It is rapidly absorbed orally • It has half life of 1.2 hrs • It is completely metabolized in liver and 90% is excreted in urine • It can also get absorbed through the skin. Thus, could be applied in creams.

24. Thiabendazole con’d: • Mechanism of action: similar to other benzimidazoles. • It is ovicidal for some parasites. • It also possesses immunosuppressive, antipyretic, and mild antifungal and scabicidal (destroying the itch mite causing scabies ) effects.

25. Clinical uses: • Should be given after meals and tablets should be chewed • For strongyloides (threadworms) infections:cure rate is 93% • For cutaneous larval migrans thiabendazole cream is effective and applied topically or given orally • Also effective for intestinal capillariasis and scabiasis.

26. Thiabendazole cont’d • Adverse reactions and contraindications: • It is more toxic than other benzamidazoles • GI disturbances • Pruritus, headache, drowsiness, neuropsychiatric symptoms rarely may cause tinnitus, bradycardia, hypotension, hyperglycemia, convulsions, neutropenia and other adverse effects may occur. • Irreversible live failure. • Fatal Stevens–Johnson syndrome (inflammation of the skin) • Not used in children below the weight of 15 kg, during pregnancy, hepatic and renal diseases.

27. PYRANTEL PAMOATE • It is a broad-specturm antihelminthic • It is not effective against trichuriasis (whipworms) and trichostrongylus orientalis infections, yet oxantel pamoate is considered effective against trichuriasis. Both drugs can be combined for their synergistic effect. • Pharmacokinetics: • It is poorly absorbed orally. Active mainly against luminal organisms. • Half of the drug is excreted unchanged in the feces. • Mechanism of action: • It is a depolarizing neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinesterase leading to the paralysis of worms followed by their expulsion from the GIT.

28. Pyrantelpamoate (cont’d) Efficacy and clinical uses: • it is very effective against mature and immature luminal organisms, but not effective against migratory stages in the tissues or against ova • Enterobius vermicularis(pinworm). • Ascaris lumbricoids (common roundworm) • Ancylostoma duodenale (hookworm) single dose for light infection but a 3-day course is necessary for heavy infection especially N americanus infection.

29. Pyrantelpamoatecont’d: • Adverse effects are infrequent and mild. • GI disturbance • Drowsiness, headache ,insomnia. • Rash, fever • Contraindications: • Should not be used in liver diseases. • Pregnancy • In children under 2 years of age

30. PIPERAZINE • Only used for the treatment of ascariasis. • It is readily absorbed orally and excreted in urine • Mechanism of action: It causes paralysis of ascaris by blocking acetylcholine at the myoneural junction, expelling the live worm by normal peristalsis.

31. Piperazine cont’d • Treatment is continued for 3-4 days or repeated after one week in case of heavy infections.

32. Piperazine cont’d • Adverse effects: • GI disturbances • Neurotoxicity, allergic reactions serum sickness like syndrome • Contraindications • Epilepsy or chronic neurologic disease • Impaired liver or kidney functions • Pregnancy • Malnutrition

33. Drugs used for treating human intestinal nematodes (single dose unless otherwise stated Ascariasis Hookworm enterobiustricurisstrongyloides Piperazine ++ + ++ - - Pyrantel pa ++ ++ ++ - - Albendazole ++ ++ ++ + + Mebendazole ++ ++ ++ + + Thiabendazole n/a n/an/an/a ++ Ivermectin n/a n/an/an/a ++

34. Drug treatment for tape worm(cestodes) infection • Niclosamide • Praziquantel • Albendazole

35. NICLOSAMIDE • It is useful for the treatment of adult tape worm (cestodes) infestation • Mechanism of action: • Adult worm is rapidly killed by inhibition of the oxidative phosphorylation or stimulation of ATPase activity. • has no effect on ova • Pharmacokinetics: • It is not absorbed from the gut • Neither drug nor its metabolites are found in the blood or urine.

36. Niclosamide cont’d • Clinical uses: • T. Saginata (Beef tape worm),T. solium (pork tapeworm), Diphyllobothriumlatum (fish tapeworm) • In case of T. solium after 2 hrs of treatment, purge of magnesium sulphate should be given to eliminate all mature segments. • Not effective against cysticercosis or hydatid disease. b/c it’s not absorbed from the gut • Hymenolepis nana • H diminuta and Dipylidiumcaninum • Alternative for Fasciolopsisbuski, Heterophyesheterophyes, Metagonimusyokogawi.

37. Niclosamide cont’d • Adverse effects: • Mild, infrequent and transitory GI disturbances • Alcohol consumption should be avoided • Not indicated in children under 2 years of age or pregnancy.

38. Diethylcarbamazine • The drug of choice for the treatment of filariasis, loiasis and tropical eosinophilia. • Pharmacokinetics: • It is a synthetic derivative of piperazine • Rapidly absorbed from the gut • It has a half life of 2-3 hours which increases in alkaline urine up to 10 hours. • Equilibrates with all tissues except fat • It is excreted in urine unchanged. • Dosage is reduced in urinary alkalosis and renal impairment.

39. DIETHYLCARBAMAZINE con’d • Mechanism of action: • It immobilizes microfilariae in tissues and alters its surface structure, making them more susceptible to destruction by host defense mechanism • Unknown mechanism against adult worms • It also possesses an immunosuppressive effects • It has no teratogenic effects on experiment animals

40. DIETHYLCARBAMAZINE con’d • It is a drug of choice for the treatment tissue cestodes, W. bancrofti, B. malayi, B. timori, and Loa loa. • Microfiliariae are rapidly killed. Adult worms are killed slowly requiring several courses of treatment. Adult worms are either killed or sterilized. • It is highly effective against L. loa.

41. DIETHYLCARBAMAZINE con’d • Anti histamines and corticosteroids are given in allergic manifestations. • Complete Cure may be require several courses of treatment over 1-2 years. • The drug may be used in prophylaxis for loiasis, bancroftian, and Malayan filariasis • Tropical (pulmonary) eosinophilia • Mansonellastreptocerca

42. DIETHYLCARBAMAZINE con’d • Drug induced/ Reactions induced by Dying parasites: • Fever , malaise, papular rash, headache, GI disturbance, cough, chest, muscle, joint pain • Leukocytosis, proteinurea, ↑ eosinophilia • Retinal hemorrhage • Encephalopathy • Lymphangitis and lymphadenopathy.

43. DIETHYLCARBAMAZINE con’d • Contraindications and cautions • Hypertension • Renal disease • Patient suspected of having malaria • Patients with lymphangitis

44. IVERMECTIN • It is the drug of choice for treatment of strongyloidasis and onchocerciasis • It is a macrocyclic lactone • It is used orally and is rapidly absrobed, possesses wide volume of distribution about 50 L. • It has a half-life of 16 hrs • It is exclusively excreted in feces

45. IVERMECTIN cont’d • Mechanism of action: • It intensifies GABA –mediated transmission of signals in peripheral nerves  paralyzing the worm. • In onchocerciasis it is microfilaricidal. It does not kill the adult worm

46. IVERMECTIN cont’d • Clinical uses: • Onchocerciasis: with the 1st treatment, patients with microfilariae in the cornea or anterior chamber may be treated with corticosteroid.

47. IVERMECTIN cont’d • Strongyloidiasis: in immunosuppresed patient, repeated treatment is often needed. • Bancrofti filaricidal: as it is mirofilaricidal • It is also used for scabies, lice, and cutaneous larva migrans. • Eliminates adcarid worms • Reduces microfilariae in Brugia malayi and M ozzardi.

48. IVERMECTIN cont’d • Adverse effects: • Fatigue • dizziness, • GI disturbance • In Onchocerciasis: • Mazotti reaction: fever, headache, dizziness, somnolence(state of being drowsy), weekness, rash ,diarrhea, arthralagia, hypotension, lymphadenitis, peripheral edema due to killing of microfiliariae, for this steroids may be necessary for several days • Swelling and abscess at site of adult worm • Punctuate corneal opacities.

49. IVERMECTIN con’d • Contraindication: • other drugs that enhance GABA activity e.g Barbiturates, bnezodiazepines, valproic acid. • pregnancy • Impaired blood brain barrier • Children under 5 years of age.

50. BITHIONOL • It is the drug of choice for the treatment of fascioliasis (sheep liver fluke) • It is also used as an alternative for praziquantel in treating pulmonary paragonimiasis • Repeat doses in case of cerebral paragonimiasis. • Pharmacokinetics: • It is orally administered and excreted in urine.