Pharmacotherapy of helminthiasis....pptx

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1. Pharmacotherapy of helminthiasis Mentor:- Presenter:- Dr. Arbindra Chansoria Dr. Asmita Pandey Assistant Professor PG- I Year

2. Organisms Infestation Intestinal nematodes Ancylostoma duodenale(old world hookworm) Ancylostomiasis Necator americanus(new world hookworm) Necatoriasis Ascaris lumbricoides(round worm) Ascariasis Enterobius vermicularis(threadworm/pinworm) Enterobiasis Trichuris trichiura (whipworm) Strongyloides stercoralis Trichuriasis Strongyloidiasis Organisms Infestation Tissue dwelling human nematodes Wuchreria bancrofti (filarial worm) Filariasis Onchocerca volvulous Onchocerciasis Loa loa(eye worm) Loiasis Brugia malayi Lymphatic filariasis Dracunculus medinensis(guinea worm) Dracunculiasis

3. Zoonotic nematodes(incidental infestation) Toxocara sp Toxocariasis(visceral larva migrans ) Trichinella spiralis Trichinosis Ancylostoma brazilienze (cat hookworm) Cutaneous larva migrans (creeping eruption) Ancylostoma caninum(dog hookworm) Creeping eruption Cestodes(tapeworm) Taenia saginata (beef tapeworm) Taeniasis, cysticercosis(larval forms) Taenia solium (pork tapeworm) Taeniasis, cysticercosis(larval forms) Echinococcus granulosus (dog tapeworm) Echinococcosis(hydatid disease) Diphyllobothrium latum(broad fish tapeworm) Diphyllobothriasis Hymenolepis nana(dwarf tapeworm) Hymenolopiasis Trematodes(flukes) Fasciola hepatica(liver fluke) Fascioliasis Schistosoma mansoni (blood fluke) Schistosomiasis Schistosoma japonicum(blood fluke) Schistosomiasis Schistosoma haematobium(blood fluke) Schistosomiasis Paragonimus westermani (lung fluke) paragonimiasis

4. Either kill (vermicide) or expel (vermifuge) the worms

5. HELMINTHIASIS MACROPARASITIC DISEASE OF HIMANS AND ANIMALS INFESTATION MAY BE WITH PINWORM, ROUNDWORM OR TAPEWORM. WORMS RESIDE IN THE GI TRACT BUT MAY BURROW INTO OTHER ORGANS SUCH AS LIVER CAN HAVE IMMUNOMODULATORY EFFECTS ON THE HOST WITH IMPLICATIONS FOR COINFECTING PATHOGENS.

6. BENZIMIDAZOLE- MEBENDAZOLE, ALBENDAZOLE MECHANISM OF ACTION INHIBITS POLYMERISATION OF TUBULIN PROTEIN BY BINDING TO B-TUBULIN OF INTESTINAL AND TEGUMANTAL CELLS OF WORM INHIBITS ENZYME FUMARATE REDUCTASE Irreversibly decreases glucose uptake and depletes glycogen stores Parasites are immobilised and die slowly Gi clearance occurs in several days LOSS OF CYTOPLASMIC MICROTUBULES LEADS TO UPTAKE OF MICROTUBULE DEPENDENT GLUCOSE AND DEPLETION OF GLYCOGEN STORES, NO GLUCOSE, NO ATP, INHIBITED OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA Ovicidal action against hookworm, roundworm and whipworm

7. Mebendazole Spectrum of activity Effective against Intestinal nematodes Zoonotic nematodes- trichinella, toxocara High doses- echinococcus Guinea worm

8. Pharmacokinetics Poor GI absorption Absorption increased with fatty meals Undergoes high first pass metabolism T1/2 – 6-8hrs Adverse effects Transient abdominal pain , diarrhea , headache and dizziness High doses- alopecia, allergy, and bone marrow depression Heavy infestation can cause abnormal migration and expulsion through mouth and nose Indications Ascariasis and ancylostomiasis- 100mg BD for 3 days/ 500mg single dose- >2 years ½ the dose- <2 years No laxatives needed after the dose Enterobiasis - 100mg single dose. Repeat after 2-3 weeks

9. ALBENDAZOLE Basic Pharmacology Albendazole is a benzimidazole carbamate. After oral administration, it is erratically absorbed (increased with a fatty meal) and then rapidly undergoes first-pass metabolism in the liver to the active metabolite albendazole sulfoxide. It reaches variable maximum plasma concentrations about 3 hours after a 400-mg oral dose, and its plasma half-life is 8–12 hours. The sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts. Albendazole metabolites are excreted in the urine.

10. Spectrum of activity albendazole Superior aginst strongyloidiasis, neurocysticercosis, hydatid disease and ankylostomiasis than mebendazole Effective against t. vaginalis and giardia Mechanism of action Same as benzimidazole Additional larvicidal action against echinococcus, cysticerci , ascaris and ancylostoma

11. Pharmacokinetics- Absorption- 3-5 times increased after fatty meal Converted to active metabolite albendazole sulfoxide after rapid first pass metabolism. Active metabolite is responsible for therapeutic effect outside the gut Enters bile, csf , hydatid cysts T1/2- 8-12 hrs

12. Clinical Uses Albendazole is administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites. 1. Ascariasis, trichuriasis , and hookworm and pinworm infections—For adults and children older than 2 years with ascariasis and pinworm infections, the treatment for ascariasis is a single dose of 400 mg orally (repeated daily for 2–3 days for heavy infections and in 2 weeks for pinworm infections). These treatments typically achieve good cure rates and marked reduction in egg counts in those not cured. For hookworm infections and trichuriasis , albendazole at 400 mg orally once daily for 3 days is now recommended, with albendazole showing improved efficacy over mebendazole. For trichuriasis , combination of either mebend combination of albendazole with oxantel pamoate markedly improved treatment outcomes. 2. Hydatid disease—Albendazole is the treatment of choice for medical therapy and is a useful adjunct to surgical removal or aspiration of cysts. It is more active against Echinococcus granulosus than against Echinococcus multilocularis . Dosing is 400 mg twice daily with meals for 1 month or longer. Daily therapy for up to 6 months has been well tolerated. One reported therapeutic strategy is to treat with albendazole and praziquantel, to assess response after 1 month or more, and, depending on the response, to then manage the patient with continued chemotherapy or combined surgical and drug therapy. 3. Neurocysticercosis—Indications for medical therapy for neurocysticercosis are controversial, since antihelminthic therapy is not clearly superior to therapy with corticosteroids alone and may exacerbate neurologic disease. Therapy is probably most appropriate for symptomatic parenchymal or intraventricular cysts. Corticosteroids are usually given with the antihelminthic drug to decrease inflammation caused by dying organisms. Albendazole is now generally considered the drug of choice over praziquantel because of its shorter course, lower cost, improved penetration into the subarachnoid space, and increased drug levels (as opposed to decreased levels of praziquantel) when administered with corticosteroids. Albendazole is given in a dosage of 400 mg twice daily for up to 21 days. Albendazole combined with praziquantel improves efficacy in patients with multiple brain cysts.

13. Adverse effects Same as mebendazole Neurological effects may occur during treatment of neurocysticercosis Prior use of glucocorticoids prevent this. Indications Intestinal worm infestation- empty stomach administration- 1hr before dinner Intestinal nematode infestation- 400mg Single dose Strongyloidiasis- 400mg OD for 3 days Echinococcosis- 400mg B.D. with meals for 28 days Neurocysticercosis- drug of choice. Cheaper than praziquantel, crosses blood brain barrier effectively Coadministration of glucocorticoids to reduce inflammation increases its level Dose:- 400mg BD for 8-30 days on full stomach 6. Zoonotic infection- 400mg OD for 7 days 7. Lymphatic filariasis- 400mg Single dose with diethylcarbamazine citrate.

14. Triclabendazole Spectrum of activity Effective against Fasciola hepatica and Paragonimus sp. Little activity against nematodes, cestodes and other trematodes. Mechanism of action Converted to active sulfoxide metabolite which binds to fluke tubulin and disrupts the microtubule based processes. Pharmacokinetics Rapidly absorbed after oral administration Food increases bioavailability More than 99% is plasma protein bound Undergoes extensive first pass metabolism to form an active metabolite Adverse effects Abdominal cramps, diarrhoea, biliary colic and transient headache

15. Pyrantel pamoate Spectrum of activity Effective against Intestinal nematodes- Ascaris, Enterobius and hookworm Trichinella spiralis 2. No action against- Trichuris and strongyloides Migratory stages in tissues and against ova Mechanism of action Depolarising neuromuscular blocking agent Causes release of acetylcholine and decreases cholinesterase Stimulates ganglionic nicotinic receptors causing spastic paralysis of worms Expulsion with host’s faeces Pharmacokinetics Less absorbed orally More than 85% unaltered drug is passed in faeces Less than 4% is recovered in the urine

16. Adverse effects Mild and transient Adverse effects - nausea, vomiting, anorexia, abdominal pain, diarrhoea , headache, dizziness, drowsiness, insomnia Indications Ascariasis- 10mg/kg single dose Ancylostomiasis- 10mg/kg for 3 days Oxantel pamoate Effective against trichuris trichuria Dose - 10mg/kg single dose Piperazine citrate Spectrum of activity Effective aginst ascaris and Enterobius Mechanism of action Blocks acetylcholine at neuromuscular junction and produces neuromuscular block leading to flaccid paralysis in worms Paralysed worms get dislodged from their positons by gut movements Reversible paralysis Antagonistic action with pyrantel pamoate- irrational combination

17. Pharmacokinetics Rapid GI absorption Excreted in urine Adverse effects Nausea, vomiting, diarrhoea, abdominal pain, headache, skin rash, urticaria Cerebellar ataxia aka worm wobble Neurotoxic adverse effects- dizziness, nystagmus, muscular weakness, chorea, convulsions Indication Ascariasis- 5g Single dose. Repeat after 2 weeks Levamisole Effective against Intestinal nematodes Acts by paralysing worms Can cause disulfiram-like reaction with alchohol Dose(ascariasis)- 150mg Single dose

18. Diethylcarbamazine citrate Effective against Adult worm and microfilaria- W. bancrofti , B. malayi and L. loa Micrifilaria - O. volvulus Mechanism of action Complex action Affects cellular enzymes and transport systems of worms Decreases muscle activity and affects microfilarial motility Causes disruption of microtubulr formation Alters helminthic surface membrane; enhanced host immune response and killing of worms Pharmacokinetics Rapid GI, dermal and conjunctival absorption T1/2- 5-13 hrs Renal excretion Increased urinary acidity increases excretion Adverse effects Nausea, vomiting, abdominal pain Hypersensitivity reaction due to microfilarial death Onchocerciais - mazotti reaction- sight threatening ocular toxicity, tender lymphadenopathy, joint pain, muscle pain, tachycardia, hypotension No longer recommended

19. Indications Filariasis- 2mg/kg TDS after meals for 3 weeks Or 6mg/kg orally every 6-12 months + albendazole Tropical pulmonary eosinophilia Drug of choice- 8-10mg/kg/day- 3 divided doses- 2-3 weeks Dermal filariasis Dipetalonema streptocerca infestation Toxocariasis Ivermectin Spectrum of activity Causes opening of chloride channels causing its influx This leads to worm tonic paralysis, immobilization and death Pharmacokinetics Well absorbed orally Highly protein bound Accumulated in adipose tissue and liver T1/2- 16 hrs 100% fecal excretion

20. Adverse effects Less severe and fewer than DEC Fever, myalgia, malaise, lightheadedness Postural hypotension Severity of adverse effects is directly proportional to the intensity of infestation Eye edema , eye irritation- onchocerciaisis patients Indications Drug of choice- onchocerciasis Dose- 150mcg/kg single dose very 6-12 months for 9-10 doses Strongyloidiasis- 100mcg/kg Cutaneous larva migrans - 200mcg/kg single dose Filariasis 200mcg/kg single dose + albendazole 400mg single dose every 6-12 months 400mcg/kg single dose + DEC 6mg/kg single dose every 6-12 months Scabies, pediculosis- 200mcg/kg single dose

21. Niclosamide Spectrum of activity Effective against Adult tapeworms- T. saginata , T. solium , H. nana, D. latum Ineffective against larval forms Mechanism of action Inhibits mitochondrial oxidative phosphorylation, ATP synthesis, causes energy depletion and death of worms Scoleces and segments are killed nut ova survive Viable ova are released into the gut lumen Larval forms are released from the ova. Larvae penetrate the gut wall and cause cysticercosis in case of T. solium Pharmacokinetics Insignificant gi absorption Adverse effects Rare gi disturbances, light headedness, pruritus If incompletely eliminated- larval forms of T. solium cause cysticercosis

22. Indications Taeniasis Tablet must bethoroughly chewed to ensure mixing with intestinal contents and then swallowed and washed down with water. Drug is administered on an empty stomach in the morning after a liquid at night on the previous day Dose- 2gSD. Two 500mg tablets to be thoroughly chewed followed by two 500mg tablets after 1 hour Purge after 2 hours to eliminate killed worms and minimise larval migration Hymenolepiasis - 2g for 7 days

23. Praziquantel Spectrum of activity Effective against- cestodes, trematodes Kills protoscoleus of echinococcus but doesn’t affect germinal membrane No action against liver flukes Mechanism of action Increases calcium permeability of calcium in the worms, increasing contraction Worms get paralysed and detached Encysted larvae of T. solium are killed Doesn’t kill ova Interferes with glucose metabolism in schistosoma Pharmacokinetics Rapid gi absorption Food increases bioavailability Pronounced first pass effect T1/2- 1.5hours Crosses the blood brain barrier Adverse effects Nausea, vomiting, headache, drowsiness, dizziness, pruritus, urticaria, and seizures

24. Indications Taeniasis- 5-25mg/kg SD after a meal Cysticercosis(combined use with steroids decreases praziquantel levels) Fascioliasis, paragonimiasis, schistosomiasis Hymenolepiasis , diphyllobothriasis

25. National Deworming Day Soil Transmitted Helminths (STH) are a significant public health concern for India. 22 crore Indian children aged 1-14 are at risk of worm infections. Worms in children interfere with nutrient uptake, and can contribute to anaemia , malnourishment, and impaired mental and physical development. In 2015 the Government of India launched the fixed-day Anganwadi and school-based National Deworming Day to deworm all children aged 1-19 years. The National Deworming Day is conducted in all states/UTs in 2 rounds – 1st round on February 10 followed by 2nd round on 10 August every year The objective of National Deworming Day is to deworm all preschool and school-age children between the ages of 1-19 years through schools and Anganwadi Centers in order to improve their overall health, nutritional status, access to education and quality of life.

26. Adverse Event Management System ● In case of any reported adverse events, the child should be managed as per protocols and information provided in the Adverse Event Management Reporting form. ● Schools and Anganwadi must have emergency helpline numbers and contact numbers of nearest MO-PHC/ANM (List of contact numbers preferably stuck/fixed on the entrance door or wall). ● The Medical officer at PHC should ensure that the medicines that are mentioned in the Adverse Event Management Protocol should be available in the health center on Deworming Day and Mop Up Day. MO-PHC must ensure functional referral services ready with them for any prompt actions.