DR.ABDUL LATIF MAHESAR Department of Medical Pharmacology KSU ANTHELMINTIC DRUGS
INTRODUCTION • Humans are the primary hosts for the most of helminthic infections. • Most worms produce in human sexually by producing eggs and larvae • These pass out of body and infect the secondary host • Imature forms invade humans via skin or GIT and mature to adult worms with characterstic tissue distribution.
Types (clinical) 1. Worms live in hosts alimentary canal. 2. Worms or larvae live in other tissues of host body like muscles , viscera , menninges , lungs, subcutaneous tissues.
INTESTINAL WORMS CON’D A) INTESTINAL ROUND WORMS (NEMATODES) • Ascaris lmubricods (common round worm) • Enterobius vermicularis (pin worm) • Trichuris trichuria ( whip worm) • Strongyloids stercoralis ( thread worm) • Ankylostoma dudenale (hook worm)
1. Alimentary canal(intestinal tape worms) B) TAPE WORMS (CESTODES) • Taenia saginata(Beaf) , • Taenia solium(Pork),Hymenolepis nana(Dwarf) ,diphylobothrium latum(Fish) • Humans become infected by eating raw or under cooked meat containing larvae of infected cattle or pig which has encysted in the animal muscle tissue.
Cestodes con’d • In some conditions this larvae may develop in humans resulting cysticercosis (i.e. larvae gets encysted in the muscle and viscera or more seriously in the brain or eye.) • In case of H.nana both adult worm and larvae can be present in the same host. • In case of D.latum infections occurs by eating raw or undercooked fish
2. TISSUE WORMSA.TREMATODES(Schisotomes)OR FLUKES(leaf like) • Schistosoma haematobium • Schistosoma Japonicum • Schistosoma mansoni (These cause SCHISTASOMIASIS) also called (BILHARZIA) means disease of blood vessels. Adult worms of both sex live and mate in veins or venules of the gut wall or the bladder, eggs pass into the bladder or gutand produce inflammation of these organs , resulting in haematuria or loss of blood in feces.
Tremtodes (flukes) con’d • Eggs hatch in water and develop in to miracidia(1st stage of larva of trematode and further develop in the body of snail), which enter to 2ndry host a particular species of snail ,where it develops to free swimming cercarae (final free-swimming stage of a trematode),These infect humans by penetrating to skin
Paragonimus westermani (lung fluke) disease is caused by eating raw crab or fish , larvae move from intestine to blood and settle in lungs • Clonorchis sinensis(liver fluke) disease is caused by eating raw fish and worm settle in the biliary tract
Tissue worms cont’d • B. TISSUE ROUND WORMS Trichnella spiralis. Dracunulus medinensis (guinea worm)larva migrate from intestine to tissue of leg or foot and protrude out by making ulcer
FILARIAE includes Wuchereria bancrofti Loa loa Onchocerera volvulus Brugia malayi
Wuchereria or Brugia obstructs lymphatic vessels producing elephantiasis elephantiasis
Filariae: Wucheria bancrofti ,loa loa , onchocera volvulus and Brugia malayi • Adult filariae live in the lymphatics,and cause lymphadenitis and swelling of limb. connective tissue or mesentery of host and produce live embryos or microfilariae, which goes to blood stream. • They are ingested by mosquitoes or similar insects, they develop to larvae in 2ndry host and pass to mouth parts of insect and re-injected to humans
C. Hydatid tape worm • Echinococcus species . • These are cestodes ,primary in canines (dogs) and sheep as intermediate host. • humans can act intermediate host in which larvae develop to hydatid cyst with in tissue.
Helminths commonly infecting man Nematodes( round worm) Tissue worms wuchereria bancrofti Filariasis Brugia malayi Filariasis Loa loa loiasis Onchocerca River blindness Dracunculus medinensis Dracunculiaiss Intestinal human nematodes Enterobius vermicularis Threadworm Ascaris lumbricoides Roundworm Trichuris trichiura Whipworm Nector americanus Hookworm Ancylostoma duodenale Hookworm Strongyloides stercoralis Strongyloidosis Trematodes(flukes) Blood flukes Schistosoma species Schistosomiasis Lung flukes Paragonimus speies Paragonimiasis Intestinal / hepatic flukes Fasciolopsis buski Fasciola hepatica Clonorchis sinensis
Helminths commonly infecting man cont’d Cestodes(tapeworms) Intestinal adult worms Taenia saginata Beef tapeworm Taenia solium Porktaperworm Diphyllobothrium latum Fishetapeworm Hymenolepis nana Dwarftapeworm Larval tissue cysts Taenia solium cysticercosis Echinococcus granulosus Hydatid disease Echinococcus multilocularis Hydatid disease Spirometra mansoni Sparganosis
Diseases caused by filarial worms Organism adult worm Microfilariae C.signs W. bancrofti Lymphatics Blood Fever lymphangitis Elephantiasis B.Malayi lymphatics Blood Fever lymphangitis Elephantiasis Loa loa Subcutaneous Blood Urticaria Onchocerca Subcutaneous skin,eye subcut nodules Eye disease Mansonella perstans Retroperitoneal Blood Allergic eosinophilia
ANTHELMINTIC DRUGS BENZIMIDAZOLES 1.ALBENDAZOLE: • It is abroad spectrum • It is a drug of choice (primary therapeutic application) for treatmentofhydatid diseaseandcystecercosis, it is also used for the treatment of (intestinal nematodes) ascariasis ,tricurasis and strongyloidiasis , pinworm, hookworm
Albendazole con;d • Mechanism of action:It inhibits microtubule synthesis in nematodes(intestinal round worms) that irreversibly impairs glucose uptake, intestinal parasites are immobilized and die slowly. • It is larvicidal in hydatid ,cysticercosis , ascariasis and hook worm infection. • Also ovicidal in ascariasis , ancyclostomiasis(hookworm) , tricurasis
Pharmacokinetics (Albendazole) • It is benzimidazole carbamate • it is adminstered orally , and absorbed erratically (unpredictable) , absorption can beincreased with fatty meal • It ismetabolized in the liverrapidly to active metabolite albendazole sulphoxide
Pharmacokinetics (Albendazole) • It has a plasma half life of 8-12 hours • Sulphoxide is mostly protein bound , distributes well to tissues and enters bile, csf, hydated cyst • Metabolites are excreted in urine
Clinical uses (albendazole) • used on empty stomach when used against intraluminal parasites but with fatty meal when against tissue parasites. • Inascariasis ,tricurasis ,hookworm, pin worm infection : children under 2 years 400 mg orally as a single dose repeated for 2-3 days in heavy ascariasis ,repeated after 2-3 wks for pin worm 2. Hydated diseases: drug of choice ,400 mg twice with meals for 1 month or longer.
Albendazole con’d • Neurocysticercosis:It is controversial as it has not proved superior to corticosteroid alone. It is used along with cotricosteroid to decrease the inflammation caused by dying organism and it also reduces the duration of course i.e. 400 mg twice daily for 21 days 4. Other infections:Drug of choice in cutaneous and visceral larvea migrans , intestinal cappillariasis and others
Albendazole con’d Adverse effects: • In short term: use no significant adverse effects. • In long term use : as used in hydatid cyst and cysticercosis, abdominal distress, headache ,fever , fatigue, alopecia , increased liver enzymes , pancytopenia. Blood counts and LFT should be followed. • Not given during pregnancy and in hypersensitive people.
MEBENDAZOLE(Vermox) • it is a synthetic benzimidazole • it has wider spectrum and is more safer than albendazole Mechanism of action: It inhibits microtubule synthesis in nematodes that irreversibly impairs glucose uptake.Intestinal parasites are immobilized and die slowy. It kills hook worm, pin worm , ascariasis and trichuris eggs.
Mebendazole con’t Pharmacokinetics: • less than 10% of orally administered drug is absorbed • Absorption increases with fatty meal. • 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 urine.
Mebendazole con’t Clinical uses: • It is taken orally before or after meal tablets should be chewed before swallowing. • Pinworm infection: 100 mg as a single dose, to be repeated after 2-3 weeks. • Ascaris lumricoides , trichuris trichura , hookworm and trichstrongtlus; 100 mg /twice daily for 3 days to repeated in 2-3 weeks • in adults and children over 2 years cure rate is 90-100 % except hook worm but there occurs markedreduction
Mebendazole con’d • Intestinal cappilliaris: 400 mg /day in divided doses for 21 day or more. • Trichinosis :it has limited efficacy against adult worm.200-300 mg for 3 days ,then 400-500 mg for 10 days with fatty meal and co-administration with corticosteroids in sever infection
Mebendazole con’d Adverse effects and precautions: • No adverse effects in short term therapy.Mild GI disturbance. • With high dose Hypersensitivity reactions,agranulocytosis , alopecia ,elevation of liver enzymes . • used with caution under 2ys of age may cause convulsion in this group. • enzyme inducers and inhibitors affect plasma level of the drug. • hepatic parenchymal disease
Thiabendazole • it is benzimidazole • it is chelating agent and form stable complexes with metals including iron, but does not bind with calcium. • it is rapidly absorbed • 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 skin
Thiabendazole con’d: • mechanism of action: similar to other benzimidazoles.It is ovicidal for some paracites • clinical uses: • should be given after meals .and tablets should be chewed • for strongyloides(thread worms) infections: 25 mg /kg ( not more than 1.5 grams) twice daily for 2 days ,can be repeated after 2 week. In hyper infection syndrome drug is continued twice daily for 5-7 days. • for cutaneous larval migrans thiabendazole cream is applied topically or drug can be given orally for 2 days.
Thiabendazole con’d • adverse reactions and contraindications: • It is more toxic than other benzamidazoles • GI disturbances • Pruritus ,headache, drowsiness , psychoneurotic symptoms. • Irreversible live failure. • Fatal Steven –Johnson syndrome(inflammation of skin) • Not used in children below 15 kg weight. pregnancy, hepatic and renal diseases.
PYRANTEL PAMOATE • It is a broad specturm anthelmintic • but it is not effective against tricuriasis(whip worms), and trichostrongylus orientalis infections. Oxalate pamoate is effective • Pharmacokinetics: • It is poorly absorbed orally , • Half of the drug is excreted unchanged in the feces. • Mechanism of action: • It is a depolrazing neuromuscular blocking agent that causes release of acetylcholine and inhibition of cholinestrase leads to paralizes of worms.
Pyrantel pamoate con’d Efficacy and clinical uses: • it is very effective against luminal organisms. • It is not effective against migratory stages in the tissues or against ova • Entrobius vermicularis(pin worm) 11 mg /kg as a single dose to be repeated in 2 wks. • Ascariasis lumbricoids (common round worm).single dose to be repeated after 2wks • Ankylostoma dudenale (hook worm) single dose for light infection but a 3 days course is necessary for heavy infection.especially N amerianus.
Pyrental pamoate con’d • Adverse Effects . • Infrequent mild transient GI disturbance • drowsiness , headache ,insomnia. • Rash ,fever Contraindciations • Should not be used in liver diseases. • Pregnancy • and child under 2 years of age
PIPERAZINE • Only recommended 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 myoneural junction ,expelling the live worm by normal peristalsis. Not recommended for other helminth infections