antihelminthic.ppt
- 1. By- Saud Aslam Ansari M. Pharm (Pharmacology) SPER, Jamia Hamdard Anthelmintic
- 2. Presentation Outline:- 1) Introduction 2) Anthelmintics 3) Types of worms 4) GLOBAL SCENERIO 5) INDIAN SCENERIO 6) Classification of Drugs 7) Drug of Choice 8) References 2
- 3. Introduction • Helminthiasis also known as worm infection is any macro parasitic 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. • They often live in the gastrointestinal tract of their hosts but they may also burrow into other organs where they induce physiological damage. • Helminthiasis is prevalent globally about 1/3rd of world’s population harbours them but is more common in developing countries with poorer personal and environmental hygiene. 3
- 4. Anthelmintics • Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting helminths. • The choice of drug for each worm infestation is based not only on efficacy but also on lack of side effects/toxicity ease of administration (preferably single dose) and low cost. • Development of resistance has not been a problem in the clinical use of anthelmintics. 4
- 5. Pathogenesis • Intestinal worms cause a variety of pathologic changes in the mucosa, some reflecting physical and chemical damage to the tissues, others resulting from immunopathologic responses. Hookworms (Ancylostoma and Necator) actively suck blood from mucosal capillaries. • The anticoagulants secreted by the worms cause the wounds to bleed for prolonged periods, resulting in considerable blood loss. Heavy infections in malnourished hosts are associated with anemia and protein loss. • Diversion of host nutrients by competition from worms is probably unimportant, but interference with normal digestion and absorption may well aggravate undernutrition. 5
- 6. Cont. • The tapeworm Diphyllobothrium latum can cause vitamin B12 deficiency through direct absorption of this factor. • Many helminths undertake extensive migrations through body tissues, which both damage tissues directly and initiate hypersensitivity reactions. The skin, lungs, liver, and intestines are the organs most affected. • Feeding by worms upon host tissues is an important cause of pathology, particularly when it induces hyperplastic and metaplastic changes in epithelia. For example, liver fluke infections lead to hyperplasia of the bile duct epithelium. 6
- 7. Types of worms Nemathelminthes (Roundworms) • The migration of the larval forms and eggs transmission through skin contact in moist soil and in tropical areas causes migraine ,eosinophilia and pulmonary related problems. • The common infections occurring with intestinal worms include Ascaris lumbricoides, Trichuris trichiura, Necator americanus and Ancylostoma duodenal with the household aggregation of infection. • The eggs are deposited on perianal area that is due to self infection. • These infections also occur due to the contaminated surfaces like carpets, curtains etc. 7
- 8. Cont. Trematoda (Flukes) • Flukes are the parasitic trematodes of Schistosoma species which are transmitted through direct contact with fresh water. • They penetrate into the intact human skin and enter the capillaries and then migrate to the central and portal system where they mature. • Acute schistosomiasis also known as Katayama fever, which is a form of visceral larval migraines. • The adult male and female pairs ultimately migrate to the superior mesenteric veins and ureteric vesicles. • The eggs are then shed in the faeces and urine. 8
- 9. Cont. Cestoda (Tapeworms) • Humans are the intermediate host for the Taenia solium with the development of the tissue cysts. • After the ingestion of the uncooked beef (T. saginata} or pork it develops the cysts and it causes the mild abdominal symptoms. • The infestations of the central nervous systems caused due to the pork tapeworm or flukes are known as neurocysticercosis which is treated through albendazole and praziquantel. 9
- 10. GLOBAL SCENERIO: • An estimated 120 million people in tropical and sub tropical areas of the world are infected with lympathic filariasis of these, 25 million men have genital disease (most commonly hydrocoele) and almost 15 million; mostly women, have lymphoedema or elephantiasis of the leg. • A recent study suggests that during the past 13 years >96.71million cases were prevented or cured with MDA(Methylenedioxyamphetamine) treatment, yet, as many as36 million cases of hydrocoele and lymphoedema remain. • One of the leading causes of global disability LF(Lympathic Filariasis) accounts for 2.8 million DALYs(Disability Adjacent Life Year) 10
- 11. INDIAN SCENERIO • A district-level endemicity map created in India in the year2000, shows that of the 289 districts as many as 257 were found to be endemic. • About 553 million people are exposed to risk of infection and of them about 146 million live in urban and the remaining in rural areas. • About 31 millions are estimated to be carriers and over 23million suffer from filarial disease menifestations in India. • B. Malayi is prevalent in the states of Kerela, Tamil Nadu, Andhra Pradesh, Madhya pradesh, Orissa, Assam, West Bengal. • Bihar has highest endemicity (over17%) followed by kerela (15.7%) and UttarPradesh(14.6%). • Andhra Pradesh and Tamil Nadu Has About 10%endemicity. • Goa showed the lowest endemicity(>1%), followed by Lakshwadeep(1.8%), Madhya Pradesh(above 3%)and Assam (5%). 11
- 12. TAPEWORM INFECTION(CESTODIASIS): GLOBAL SCENERIO: • Greatest infection is found in the temperate zones including several parts of Eurasia Australia, some parts of America and Northeast Africa. • Worldwide distribution of the zoonotic strains of Echinococcus granulosus and geographical endemicity. INDIAN SCENERIO: • The disease is endemic in India. • High prevalence is reported from Kashmir, Andhra Pradesh, Tamil Nadu and Central India. 12
- 14. 1. Mebendazole • It is a benzimidazole introduced in 1972. • This congener of thiabendazole became very popular because it retained the broad-spectrum anthelmintic activity but not the toxicity of its predecessor. • It has produced nearly 100% cure rate/reduction in egg count in roundworm, hook worm (both species). • The immobilizing and lethal action of Mebendazole on worms is rather slow takes 2-3 days to develop. 14
- 15. Mechanism of action- • The site of action of Mebendazole is the microtubular protein ‘B-tubulin’ of the parasite. • It binds to B-tubulin of susceptible worms with high affinity and inhibits its polymerization. • Intracellular microtubules in the cells of the worm are gradually lost • In addition, it probably blocks glucose uptake in the parasite and depletes its glycogen stores. 15
- 16. Cont. Pharmacokinetics- • Absorption of Mebendazole from intestines is minimal 75- 90% of an oral dose is passed in the faeces. • The fraction absorbed is excreted mainly as inactive metabolites in urine/faeces. Adverse effects- • Diarrhoea, nausea & abdominal pain have attend edits use in heavy infestation. • Allergic reactions, loss of hair & granulocytopenia have been reported with high doses. 16
- 17. 2. Albendazole • It is a subsequently introduced congener of Mebendazole. • Retains the broad-spectrum activity and excellent tolerability of its predecessor, and has the advantage of single dose administration in many infestations. • One dose treatment has produced cure rates in ascariasis, hookworm (both species) & enterobiasis which are comparable to 3 day treatment with Mebendazole. MOA- • The mechanism of action of Albendazole is similar to that of Mebendazole. 17
- 18. Cont. Pharmacokinetics- • Absorption of Albendazole after oral administration is significant, but inconsistent. • It is enhanced when the drug is taken with fatty meal. • The fraction absorbed is converted by first pass metabolism to its sulfoxide metabolite which has potent anthelmintic action. • Albendazole sulfoxide is widely distributed in the body, enters brain and is excreted in urine & exert anthelmintic activity in tissues as well. Adverse effects- • Gastrointestinal side effects, dizziness. • Prolonged use has caused headache, fever, alopecia, jaundice. 18
- 19. 3. Thiabendazole • It was the first benzimidazole poly antihelmintic introduced in 1961, which covered practically all species of nematodes infesting the g.i.t— roundworm, hookworm, pin worm. MOA- • It also inhibits development of the eggs of worms & kills larvae. Pharmacokinetics- • Since thiabendazole is well absorbed from g.i.t systemic adverse effects are common. • Adverse effects- • nausea, vomiting, abdominal pain, diarrhoea, giddiness, impairment of alertness, itching, etc. 19
- 20. 4. Pyrantel Pamoate • It was introduced in 1969 for pin worm infestation in children use soon extended to roundworm and hookworm as well. • Efficacy against Ascaris, Enterobius and Ancylostoma is high and comparable to that of mebendazole. MOA- • Pyrantel causes activation of nicotinic cholinergic receptors in the worms resulting in persistent depolarization slowly developing contracture and spastic paralysis. • Worms are then expelled. Pharmacokinetics- • Only 10-15% of an oral dose of Pyrantel Pamoate is absorbed this is partly metabolized and excreted in urine. 20
- 21. 5. Piperazine • Introduced in 1950, it is a highly active drug against Ascaris and Enterobius achieves 90-100% cure rates. • However, because of the availability at more convenient and better tolerated Albendazole/mebendazole it is now considered a second choice drug. Mechanism of action- • Piperazine causes hyperpolarization of Ascaris muscle by a GABA agonistic action. • Opening of Cl channels causes relaxation and depresses responsiveness to contractile action of ACh. • Flaccid paralysis occurs and worms are expelled alive. 21
- 22. Cont. Pharmacokinetics- • A considerable fraction of the oral dose of Piperazine is absorbed. • It is partly metabolized in liver and excreted in urine. Adverse Effect- • Piperazine is safe, but nausea, vomiting, abdominal discomfort and urticaria may be felt. • Dizziness and excitement occur at high doses toxic doses produce convulsions death is due to respiratory failure. 22
- 23. 6. Diethyl Carbamazine Citrate • Developed in 1948, it is the first drug for filariasis caused by the nematodes Wuchereria bancrofti (90% cases) & Brugiamalayi. MOA- • Diethylcarbamazine is microfilaricidal. • It has a highly selective effect on microfilariae (Mf). • A dose of 2 mg/kg TDS clears Mf of W. bancrofti and B. malayi from peripheral blood in 7 days. • The most important action of DEC appears to be alteration of organelle membranes of the Mf promoting cell death. 23
- 24. Cont. Pharmacokinetics- • DEC is absorbed after oral ingestion distributed all over the body metabolized in liver and excreted in urine. • Excretion is faster in acidic urine. • Plasma t'z of usual clinical doses is 4—12 hours depending on urinary pH. Adverse Effects- • Side effects are common but generally not serious. • Nausea, loss of appetite, headache, weakness & dizziness are the usual complaints 24
- 25. 7. Ivermectin • It is an extremely potent semisynthetic derivative of the antinematodal principle obtained from Streptomyces avermitilis. • It is the drug of choice in onchocerciasis and strongyloidiasis. • It is effective against microfilaria of W.bacrofti and B.malayi. 25
- 26. MECHANISM OF ACTION Ivermectin Activates glutamate-gated chloride channels increase Gaba (gama-aminobutyric acid) transmission in worms Hyperpolarisation and paralysis of worms Deaths/phagocytises of worms 26
- 27. Cont. Pharmacokinetics • It is given orally rapidly absorbed widely distributed to various tissues metabolized in the liver and excreted mainly in faeces Side effects • Itching, skin rashes, oedema, headache, fever, muscle and joint pain. Clinical uses • Onchoerciasis -Treatment is with a single oral dose of ivermectin,150 mg/kg, with water on an empty stomach. • Strongyloidiasis - Two daily of 200 mg/kg. 27
- 28. 8. Niclosamide • Niclosamide is a highly effective drug against cestodes infesting man—Taenia saginata, T. solium, Diphyllobothrium latum andHymenolepis nana, as well as pin worm. Mechanism of action • Niclosamide act by inhibiting oxidative phosphorylation in mitochondria and interfering with anaerobic generation of ATP by the tapeworm. 28
- 29. Cont. Adverse effects • Niclosamide is tasteless and non irritating. • It is minimally absorbed from g.i.t.—no systemic toxicity occurs. • It is well tolerated minor abdominal symptoms are produced occasionally. • Malaise (discomfort,illness), pruritus (severe itching of skin) and light headedness are rare. • Niclosamide is safe during pregnancy and in patients with poor health 29
- 30. It is effective in the treatment of trematodes and cestodes but not for Nematodes. Mechanism of action Praziquante Influx of calcium ion into the tegument Increased muscular contraction and spastic paralysis At higher concentration Damage tegument Death of the parasite 9. Praziquantel 30
- 31. Cont. 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. Adverse effects- • Dizziness, nausea, vomiting, abdominal discomfort,headache, drowsiness, skin rashes, itching, muscle and joint pain. 31
- 32. Drug of Choice
- 33. worm First choice of drugs Alternative drugs ROUND WORM (NEMATODES) Ascaris lumbricoides MEBENDAZOLE, ALBENDAZOLE, PYRANTEL PIPERAZINE, LEVANISOLE, IVERMECTIN HOOK WORM Accylostoma duodnale Necator americanus Pyrantel, Mebendazole Albendazole, Mebendazole, Albendazole Levamisole Pyrantel PIN WORM Enterobius vermicularis Pyrantel, Albendazole, Mebendazole piperazine Thread worm Strongyloides stercoralis Ivermectin Albendazole Whip worm Trichuris trichura Trichinella spiralis Albendazole, Mebendazole Albendazole, Mebendazole 33
- 34. Guineaworm Dracunculas medinesis Metronidazole Mebendazole Tapeworm (cestodes) Taenia saginata Taenia solium Hymenolepis nana Neurocysticercosis Praziquantel Praziquantel Praziquantel Albendazole Niclosamide Niclosamide Niclosamide Praziquental Hydatid disease Echinococcus granulosus E.multilocularis Albendazole Albendazole Mebendazole Cont. 34
- 35. References • Goodman and Gilman's The Pharmacological Basis of Therapeutics, by Bjorn Knollmann (Author), Laurence Brunton (Author) ,14th Edition, Section VII: Chemotherapy of Infectious Diseases, Chapter 68: Chemotherapy of Helminth Infections. • Essentials of Medical Pharmacology by K. D. Tripath, Edition-Eighth, Publisher- Jaypee Brothers Medical Publishers. • Rang & Dale's Pharmacology, 9th Edition, Authors: James M. Ritter, Rod J. Flower, Graeme Henderson, Yoon Kong Loke, David MacEwan, Humphrey Rang. • https://www.ncbi.nlm.nih.gov/books/NBK8191/#:~:text=Pathogenesis%3A %20direct%20damage%20caused%20by,suck%20blood%20from%20muc osal%20capillaries. 35
- 36. Thank You