Anthelmintic Drugs ( antihelminthics) .pptx

Classification of Drugs which are used in the treatment of Helminthiasis.

1. DRUGS USED IN HELMINTHIASIS Presented By – Dhananjay S. Patil M. Pharm- First Year ( II sem ) MPL -09 R.C.PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION & RESEARCH, SHIRPUR 1

2. Introduction Classification of Helminths Classification of Anthelmintics Drugs Mebendazole Albendazole Thiabendazole Pyrantel pamoate Diethylcarbamazine Ivermectin Praziquantel Niclosamide References CONTENT 2

3. INTRODUCTION 3 Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. The helminths worms are macroscopic, multicellular organisms having their own digestive, excretory, reproductive and nervous system. The helminths could be nemathelminths (round bodied worms) or platyhelminths (flat bodied worms).

4. 4 Classification of Helminths

5. NEMATODES (ROUND WORMS) 5 . Nematodes (round worms) are long, round bodied segmented worms that are tapered at both ends In festation occurs if the embryonated eggs or tissues of infested host contain larva of the nematode. Most of the nematodes round worms, hook worms, whip worms, pin worms and thread worms. These are found primarily in intestine where they attach to the mucosa and feed on host blood and tissues fluid. Fig. Nematodes (Round worms)

6. Nematoids Infection: https://twitter.com/ManualOMedicine/status/1503797695802232837 6

7. TREMATODES (FLUKES) 7 Trematodes flukes are hermaphroditic, non segmented flattened helminths. The larvae are acquired either through ingestion of food as vegetable or fish or through skin penetration. After ingestion, those trematodes which mature in the intestinal tract are called intestinal flukes; some may migrate through the abdominal cavity to the lungs. Intestinal flukes cause diarrhoea, abdominal pain and anorexia. Liver flukes produce bile duct obstruction, jaundice, liver enlargement and diarrhoea. Ex-schistosomiasis Trematodes (Flukes)

8. 8 CESTODES ( TAPE WORMS ) Cestodes (tape worms) are ribbon-shaped parasitic worms of the genus Taenia. These are mainly intestinal parasites, though a few invade other tissues in the larval stage. The diseases arises from the tapeworm are N eurocysticercosis, Cysticercosis Tape worm

9. ANTIHELMINTHS DRUGS Anthelmintic are drugs used in the treatment of infection with helminths in the intestinal track or tissue of the body Anthelmintics that kill worms called vermicides and those that help to expel the worm are called vermifuges 9

10. CLASSIFICATION OF ANTIHELMINTHS DRUGS 10 Round worm disease Hookworm Pinworm Mebendazole Albendazole Pyrantel pamoate Levamisole Piperazine Whipworm Trichinella spiralis Albendazole Mebendazole Filariasis Diethylcarbamazine Ivermectin Albendazole Tape worms Praziquantel Niclosamide Albendazole Threadworms Ivermectin Albendazole Hydatin Albendazole Mebendazole

11. Mebendazole Mebendazole is a Benzimidazole compound. It is a Benzimidazole introduced in 1972, This congener of thiabendazole became very popular because it retained the broad-spectrum anthelmintic activity. Pharmacokinetics - Mebendazole is administered orally. Poorly absorbed from the GI tract. Highly bound to plasma proteins. Metabolized in liver. Absorption of mebendazole from intestines is minimal. Adverse effects- Adverse effects Mebendazole is well tolerated even by patients in poor health and rarely causes GIT side effects anorexia, nausea, vomiting, diarrhea, and abdominal Pain But occasionally it may cause skin rashes, itching, drug fever, etc. Dose:- 100mg chewable tablet. 11

12. Mechanism of action of Benzimidazole 12 (Mebendazole, Albendazole, Thiabendazole) Benzimidazole causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of B-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the B-tubulin of parasites than that of mammals). Consequently, glucose uptake and the digestive and reproductive capacities of parasites are interrupted, resulting in immobilization, hindrance of egg production, and death of the helminth. https://www.ncbi.nlm.nih.gov/books/NBK557705/#:~:text=Mebendazole%20is%20a%20medication%20used%20in%20the%20treatment%20of%20parasitic%20infection.

13. Mechanism of action of Benzimidazole 13 (Mebendazole, Albendazole , Thiabendazole)

14. Mebendazole Clinical uses:- Ascaris lumricoides , trichuris trichura , and hookworm; It is useful drug in case of mixed infection by these parasites. Contraindication:- Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy. It should be used with caution in children younger than 2 years of age because of limited experience and rare reports of convulsions in this age group. 14

15. Albendazole Albendazole is a Benzimidazole compound It is benzimidazole and has broad spectrum of anthelmintic activity. It is the drug of choice for treatment of hydatid disease and cysticercosis. It is also used in the treatment of pinworm and hookworm, round worm, whip worm, and thread worm infections. Pharmacokinetics :- Absorption of albendazole after oral administration is significant, but inconsistent. It is enhanced when the drug is taken with fatty meal (this may help in treating neurocysticercosis and hydatid disease). Metabolised in liver and primarily excreated in urine T½ approx. 8.5 hours. Side effects :- Albendazole is well tolerated; only gastrointestinal side effects have been noted. Few patients have felt dizziness. Headache, fever, alopecia, nausea, vomiting, epigastric pain. 15

16. Albendazole Dose and administration- Single oral dose of 400mg for adults and childrens >2 years of age, 200mg of single dose for children between 1-2 yrs of age. Clinical uses:- Trichinosis, Cutaneous larva migrans , Hydatid disease, Filariasis. Hydatid Disease:- Dosing is 400 mg twice daily with meals for 1 month or longer. Daily therapy for up to 6 months has been well tolerated. Neurocysticercosis:- Corticosteroids are given with the anthelmintic drug to decrease inflammation caused by dying organism. Albendazole is given in a dosage of 400 mg twice a day for up to 21 day. 16

17. Thiabendazole 17 A Benzimidazole, thiabendazole has broad spectrum of anthelmintic activity and effective against most of the nematodes. Thiabendazole is an alternative to ivermectin or albendazole for the treatment of cutaneous larva migrans . The drug is almost completely metabolized in the liver to the 5-hydroxy form; 90% is excreted in the urine in 48 hours, largely as the glucuronide or sulfonate conjugate. Clinical Uses- A course can be repeated in 1 week if indicated. In patients with hyperinfection syndrome, the standard dose is continued twice daily for 5-7 days. For cutaneous larva migrans , thiabendazole cream can be applied topically, or the oral drug can be given for 2 days (although albendazole is less toxic and therefore preferred).

18. Thiabendazole Adverse effects:- Dizziness, anorexia, nausea, and vomiting, epigastric pain, abdominal cramps, diarrhea , headache and drowsiness Symptoms:- Irreversible liver failure and fatal Stevens-Johnson syndrome have been reported Experience with thiabendazole is limited in children weighing less than 15kg. The drug should not be used in pregnancy or in the presence of hepatic or renal disease. The Mechanism of action is same as Mebendazole and albendazole Rarely used because of toxicity 18

19. Pyrantel Pamoate Pyrantel pamoate first was introduced into veterinary practice as a broad-spectrum anthelmintic directed against pinworm, roundworm, and hookworm infections. Its effectiveness and lack of toxicity led to its trial against related intestinal helminths in humans. Pharmacokinetics :- Pyrantel pamote is given orally but absorbed poorly(10-15% ), about 80-90% of oral dose is excreted in faeces . T½ approx. 1.36 hours. Side effects:- Occasional G.I symptoms, headache and dizziness. Abnormal migration of worms is not provoked, nausea, diarrhea, skin rashes, fever. 19

20. Mechanism Of Action Pyrantel pamoate Inhibit cholinesterases in worms Stimulates nicotinic receptors in the worm Ach Concentration Persistent depolarisation slowly developing contracture. Spastic paralysis Worms are expelled(vermifuge) 20

21. Mechanism Of Action By stimulating the release of acetylcholine, inhibiting cholinesterase, and stimulating ganglionic neurons, pyrantel acts as a depolarizing neuromuscular blocking agent in helminthes. These actions cause extensive depolarization of the helminth muscle membrane, producing tension of the helminth's muscles, which causes paralysis and release of their hold to the intestinal wall. This action is unlike piperazine , which is a hyperpolarizing neuromuscular blocking agent that relaxes helminth muscles, causing a subsequent detachment from the intestinal wall. (flaccid paralysis) Expulsion of the parasites from the GI tract occurs by normal peristalsis. 21

22. Pyrantel Pamoate 22 Clinical Uses: Use and administration For Ascaris and Ancylostoma : a single dose of 10 mg/kg is recommended. A 3 day course for Necator and for Strongyloides has been suggested, No fasting, purging or other preparation of the patient is needed. Contraindications:- Its safety in pregnant women but in children below 2 years has not been established

23. Diethylcarbamazine Citrate (DEC) 23 DEC developed in 1948, and its is the first drug for filariasis . Mechanism of action- Microfilaricidal Activity : DEC is primarily effective against the microfilarial stage of filarial worms. It impairs the mobility and viability of the microfilariae, preventing them from further development and reproduction. The exact mechanism by which DEC exerts its microfilaricidal effects is not fully understood. Immune Modulation: DEC has immunomodulatory effects, particularly on the host immune system's response to the filarial worms. It enhances the host immune response by promoting the release of certain cytokines, such as interleukin-5 (IL-5), which leads to increased activation of eosinophils. Eosinophils are a type of white blood cell involved in the immune response against parasites.

24. Diethylcarbamazine Citrate (DEC) 24 Pharmacokinetics- • Diethylcarbamazine is well absorbed oral administration with peak plasma concentrations reached within 1-2 hours. • The elimination half life ranges from 10-12 hours, Metabolized in urine and excreated in urine Adverse drug reaction: ADR is common but not serious. Nausea loss of Appetite weakness and dizziness.

25. Diethylcarbamazine Citrate (DEC) 24 Clinical Uses : Used for the treatment of O. volvulus(but less effective). Filariasis - DEC 2mg/kg TDS is the first line drug as used. Tropical pulmonary eosinophilia- DEC (2-4 mg/kg TDS) for 2-3 weeks produce dramatic improvement in the sign and symptoms of eosinophilic lung.

26. Ivermectin It is an extremely potent semisynthetic derivative of the antinematodal principle obtained from Streptomyces avermitilis . It is the drug of choice in onchocerciasis (O volvulus) It is effective against microfilaria of W.bacrofti and B.malayi . It acts through a special type of glutamate gated chloride channel found only in invertebrates Such channels are not involved in the motor control of flukes and tapeworms which are unaffected by ivermectin 25

27. Ivermectin Mechanism of action:- Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell https://go.drugbank.com/drugs/DB00602 That leads to paralysis and death of the parasite. 26

28. Ivermectin 27

29. Ivermectin Pharmacokinetics:- It is absorbed from GIT following oral administration. It is 93% plasma protein bound and has a plasma half life of 12 hrs. It is excreted mainly in the feces. The drug has a wide distribution in the body. Clinical uses:- Ivermectin has a wide spectrum of activity as it is active not only against filarial nematodes but against other nematodes and some parasites also. A single dose of 150 mg/kg orally, for patients over 5 yrs of age, is given every 6 months on empty stomach for treatment of onchocerciasis. 28

30. Ivermectin Adverse Effects:- These include fever, pruritus, arthralgia, postural hypotension, tachycardia, oedema, lymphadenopathy, sore throat, cough and headache. Contraindications:- Ivermectin should not be used in pregnancy and should be avoided in children below 5 yrs of age. 29

31. Praziquantel This anthelmintic has wide ranging activity against Schistosomiasis, other trematodes, cestodes and their larval forms but not nematodes. The selectivity of action of praziquntel on tapeworms and flukes may be dependent on the presence of a specific variant of Ca+ channel sensitive to praziquantel Mechanism of action:- Calcium Ion Influx : Praziquantel increases the permeability of the parasite's cell membrane to calcium ions. This leads to a rapid influx of calcium into the parasite's cells. The drug thereby induces contraction of the parasites' muscle, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). 30

32. Praziquantel Pharmacokinetics- It is readily absorbed after oral administration undergoes extensive first-pass metabolism in liver, highly bound to plasma protein, crosses the BBB and excreted mainly in urine. The plasma half life is short 1.5 hrs. Clinical Uses:- Tapeworm: Praziquantel administered as a single dose has achieved 90-100% cure rate in a all human tapeworms. This level of efficacy is similar to or better than that of Niclosamide Neurocysticercosis :- Praziquantel was first drug found to be effective in neurocysticercosis : 50mg/kg daily in 3 divided doses for 15- 30 days kills the larvae lodged in brain and tissues. 31

33. Praziquantel Adverse effects Praziquantel has exhibited no systemic toxicity. It can produce nausea and abdominal pain Other side effects are headache, dizziness When used for Schistosomes and visceral flukes, symptoms like itching, urticaria , rashes, fever and body ache occur as a reaction to the destroyed parasites. No interaction with food, alcohol or tobacco has been noted. 32 Hepatosplenomegaly

34. Niclosamide Niclosamide is a chlorinated salicylamide , and is used for the treatment of most cestodes (tape worm) infection. It is not absorbed from the GIT; hence high concentrations can be achieved in the lumen Mechanism of action:- 33 Niclosamide Bind to mitochondria of Worm Inhibit Oxidative phosphorylation Interfering in the anaerobic ATP generation No energy, Worm death

35. Niclosamide 33 Clinical Uses:- Niclosamide is a highly effective drug against Cestodes infesting man- Taenia saginata . Diphyllobothrium latum, as well as pin worm but is infrequently used now due to availability of Praziquantel. The recommended adult dose of should Niclosamide is 2 g OD orally in morning on an empty having stomach. The tablet is to be chewed thoroughly, and then swallowed with water. Niclosamide is not effective avoid against cysticercosis and hydatid disease. Adverse effect:- Niclosamide is tasteless and nonirritating. • Malaise, pruritus and light headedness are rare. Niclosamide is safe during pregnancy and in poor health patients.

36. References 33 Essential medical pharamcology 8th edition by KD Tripathi page no906-914. Goodman & Gilman's The pharmacological basis of therapeutics page no;1443-1451. Rang and Dale's Pharmacology 6th edition pageno;712-717. https://go.drugbank.com/drugs/DB00602 https://www.ncbi.nlm.nih.gov/books/NBK557705/#:~:text=Mebendazole%20is%20a%20medication%20used%20in%20the%20treatment%20of%20parasitic%20infection.

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