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Anthelmintics - drdhriti

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A power point presentation on “Anthelmintics” suitable for undergraduate level MBBS students

A power point presentation on “Anthelmintics” suitable for undergraduate level MBBS students

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  • 1. Anthelmintics Dr. D. K. Brahma Department of Pharmacology NEIGRIHMS, Shillong
  • 2. Introduction• Anti – against and helminths – worms• May be  Vermicide – Drugs that kill worms  Vermifuge – expel infesting helminths  Peristaltic movement of Intestine  Cathartic and purgative action Ideal anthelmintics:  Orally effective  Effective in single dose  Inexpensive  Wide safety of margin with highest toxicity to worms, but lesser toxic to the host
  • 3. Common Helminths• Roundworm: Ascaris lumbricoides• Hookworm: Ancylostoma duodenale and Necater americanus• Threadworm: Enterobius vermicularis and Strongyloides stercoralis• Whipworm: Trichuris trichiuria and Trichinella spiralis• Filaria: W. Bancrofti, Brugia malayi• Tapeworms: T. saginata, T. solium, H. nana• Hydatid disease: E granulosus and E multilocuralis• Guniea worm: Dracunculus medinensis
  • 4. Available Drugs1) Mebendazole2) Albendazole3) Pyrantel pamoate4) Piperazine5) Levamisole and tetramisole6) Diethyl carbamazine citrate (DEC)7) Ivermectin8) Niclosamide9) Praziquantel
  • 5. Mebendazole• Synthetic benzimidazole derivative• Action: o 100% cure rate for round worm, hook worm, enterobius (less for Strongyloides) and trichuris (not for tissue Trichinella spiralis) o 75% effective for tape worms but not for H. nana o Hadatid cyst: prolonged treatment o Hatching of nematode eggs and larva inhibited and Ascaris eggs are killed• MOA: o Slow in action, takes 2-3 days to develop o Blocks glucose uptake in the parasite and depletion of glycogen store o Site of action: microtubular protein “ß-tubulin” – inhibits polymerization o Intracellular mictotubules are grdually lost
  • 6. Mebendazole – contd.• Pharmacokinetics: Minimal absorption, 75-90% is passed unabsorbed in the faeces. Excreted mainly in urine as inactive metabolite• Adverse effects: o No adverse effects with short term therapy, mild GIT disturbanes- nausea, diarrhoea and abdominal pain o Allergic reactions, granulocytopenia, loss of hair and elevation of liver enzymes o Enzyme inducers and inhibitors o Pregnancy - ????• Uses: Available as 100 mg chewable tablet and 100mg/ml suspension o Common indications: 100 mg twice daily for 3 days o Enterobius 100 mg single dose + repeat after 2-3 weeks o Trichinella spiralis – 200 mg twice daily for 4 days Albendazole o Hydatid cyst: 200-400 mg twice daily for 3-4 weeks preferred
  • 7. Albendazole• Congener of Mebendazole• Action: comparable efficacy with mebendazole for round worm, hook worm and enterobius o Less effective against trichuris o But, more effective against strongyloides o Trichinella effectiveness is almost same o More effective in tape worm (including H. nana) and hydatid larvae and ova of ascaris and hook worm o Weak microfilarial action and cutaneous larva migrans• Pharmacokinetics: Moderate and inconsistent oral absorption o Fatty meals enhance absorption o Fraction absorbed is converted to “sulfoxide” metabolite – active o Its active and penetrates brain with t1/2 of 8-9 Hrs – BASIS of TISSUE Anthelmintic action o For intesinal worm given in empty stomach and for tissue action – with fatty meals
  • 8. Albendazole – contd.• Uses and dosage: Available as 400 mg tablet and 200 mg/5ml susp. o Normal dosing: Single dose of 400 mg (200 mg below 2 years) o Tape worm: 400 mg for 3 days o Cutaneous larva migrans: treatment of choice - 400 mg for 3 days o Neurocysticercosis: treatment of choice – 400 mg twice daily for 1-2 weeks o Hydatid disease: 400 mg BD for 4 weeks, repeat after 2 weeks upto 3 courses. Treatment of choice before and after urgery o Filariasis: with DEC or Ivermectin – in lymphatic filariasis o Used in mass programmes – yearly dose for microfilaraemia transmission o Contraindicated in pregnancy
  • 9. Pyrantel pamoate• Originally for thread worm but extended to hook worm and round worms• Less active against necater, strongyoides and trichuris• MOA: o Activation of nicotininic cholinergic receptors o Persistent depolarization leding to contracture and spastic paralysis – expelling of worms o Piperazine causes flaccid paralysis – antagonizing action• Pharmacokinetics: Only 10-15% is absorbed• ADRs: free from ADRs – mild GIT symptoms, tasteless, non- irritant and abnormal migration to tissues is not provoked o Safety in pregnancy and children below 2 years not established• Dose and Uses: 250 mg tabs and 50 mg/ml susp. o Used in Ascaris, entarobius and ancylostoma – single dose o 3 days course for necater and strongyloides
  • 10. Piperazine• Highly active drug against Ascaris and Enterobius – but 2nd choice drug• Less/not active against hook worms• MOA: o Hyperpolarization of Ascaris muscles GABA agonistic action of Cl- channel opening o Decreased responsiveness to ACh contractile response – flaccid paralysis o Recover – purgation required o Does not excite Ascaris for abnormal migration• ADRs: usually well tolerated - nausea, vomiting o Dizziness and convulsion in high doses o Contraindicated in renal insufficiency and epileptics• Uses: Round worm infestation – 4 gm. once a day for 2 days o Safe in pregnants o Used in Intestinal obstruction
  • 11. Levamisole and Tetramisole• Effective against any nematodes, but restricted to Ascriasis and ancylostomiasis• MOA: 2 mechanisms o Tonic paralysis of worms and expulsion of live worms - by stimulating ganglia of worms o Inhibition of fumerate reductase enzyme: carbohydrate metabolism interfered• Dose: 50/100/150 mg single dose o Ascariasis and A. duodenale o Immunomodulator o Safe and well tolerated – mass treatment of round worms
  • 12. Diethyl carbamazine citrate (DEC)• Drug of choice for the treatment of filariasis, loiasis and tropical eosinophillia• Pharmacokinetics: o It is synthetic piprazine derivative o Rapidly absorbed from gut o It has a half life of 2-3 hours which increases in alkaline urine to 10 hours o It is excreted in urine unchanged o Dosage is reduced in urinary alkalosis and renal impairment• MOA: 2 mechanisms o Alteration of Mf membrane – to be readily phagocytosed by tissue monocytes o Since piperazine derivative – hyperpolarization and muscular weakness• Uses: 50 mg, 100 mg tabs and susp available o Filariasis: 2 mg/kg tds X 7 days – improved • Intermittent microfilaria is problem (100 mg/kg for 3 weeks) – more than 1 course of therapy in a gap of 3-4 weeks • Elephantiasis not affected o Tropical eosinophilia (2-4 mg/kg tds for 2-3 weeks)• ADRs: Nausea, vomiting, loss of appetite etc. o Febrile condition – rash, pruritus, enlargement of lymph nodes – withdraw the drug and start antihistamines and corticosteroids o Can be minimized by starting low dose
  • 13. Ivermectin• Obtained from Streptomyces avermitilis• Action: o Drug of choice for Onchocercosis volvulus and Strongyloides and equal to DEC in Filaria o Also efective against cutaneous larva migrans and ascariasis – also scabies and head lice• MOA: o Acts via special type of glutamate gated Cl- channel found only in invertebrates o Such channels are absent in man, flukes and tape worms – not effective o Potentiation of GABA activity – paralysis of muscles of worms• Pharmacokinetics: absorbed well orally, widely distributed but not in CNS, long half-life – 48 to 60 Hrs• Uses: 3/6 mg tablets o Filaria: single dose 0.2 mg per kg with 400 mg Albendazole annually for 5-6 years o Strongyloides: 0.2 mg/kg single dose o Replaced DEC in O. volvulous by WHO• ADRs: Pruritus, giddiness, nausea, abdominal pain and sudden ECG changes
  • 14. Niclosamide• Against tape worms – saginata, solium, latum and nana• MOA: Inhibition of oxidative phosphorylation in mitochondria and interference of anaerobic generation of ATP o Injured worms are digested or expelled (purgation) o But, problem with T. solium – dangerous visceral cysticercosis• Regimen: available as 0.5 gm tabs. 1. 2 gm stat – repeat after 1 Hr and saline purgation 2. 2 gm daily for 5 days in H. nana infestation• ADRs: well tolerated, no systemic toxicity and can be given in pregnancy
  • 15. Praziquantel• Novel anthelmintic with wide range of action• Action: Mainly on Schisosomiasis and other Trematodes, cestodes but not nematodes• MOA: o Rapidly taken up by worms o Leakage of intracellular Ca++ causing paralysis o Worms lose grip on intestinal wall including tissues and veins o Acts against all stages of worms including larvae o Other MOA – vacuolization of membrane and release of contents of tap worms• Pharmacokinetics: Rapidly absorbed and enhanced by food o High first pass metabolism o Crosses BBB and attains therapeutic conc. In CSF o Phenytoin, carbamazepine and steroids induce metabolism – failure of therapy
  • 16. Praziquantel – contd.• ADRs: Bitter in taste, produce nausea and vomiting and abdominal pain o Headache, dizziness and sedation o Urticaria, rash, fever etc- destroyred flukes• Uses: available as 500 mg/600 mg tabs o First line of drug in all tape worms except Neurocysticercosis (10-25 mg/kg per day single dose) o Neurocysticercosis (50-100mg/kg/day for 2 weeks) o First line of drug in all schistosome infestations and flikes except Fasciola hepatica (50-75 mg/kg/day)
  • 17. NLEM (INDIA) – 2011• Deleted from 2003: Pyrantel pamoate, Niclosamide, Mebendazole• Present 2011: Albendazole, Piperazine and Praziquintel
  • 18. Important to learn• Albendazole• Piperazine• DEC in Filariasis• Ivermectin• Praziquantel
  • 19. THANKYOU- for the Hygienic atmosphere