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.

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)

B)TAPE WORMS (CESTODES) Taenia saginata(Beaf) , Taenia solium(Pork) 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. 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.)

2. TISSUE WORMS A.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 gut and produce inflammation of these organs , resulting in haematuria or loss of blood in feces.

B. TISSUE ROUND WORMS Trichnella spiralis. 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 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

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.

Ascaris lumbricoids ( common round worm)

filariasis

Hookworm

Pinworm male ,female

Tapeworm

whipworm

Dircrocoelium dendriticum

Fasiola hepatica

Tricuris tricura

Trichinela spiralis

elephantiasis

Hydateid cyct

cysticercosis

Anthelminthic Drugs Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting helminths. May act by causing : paralysis of the worm. damaging the worm leading to partial digestion or rejection by immune mechanisms. interfere with the metabolism of the worm.

Mebendazole Benzimidazole introduced in 1972 broad-spectrum SPECTRUM: 100% cure rate in roundworm, hook worm (both species), Enterobius and Trichuris infestations, Upto 75% cure shown in tapeworms. It expels Trichinella spiralis from intestines and regression of hydatid cysts in the liver but is much less active on Strongyloides, H. nana efficacy in killing larvae from muscles is uncertain.

Mechanism Of Action action is slow: takes 2-3 days to develop. Inhibits microtubule synthesis that irreversibly impairs glucose uptake , intestinal parasites are immobilized and die slowly. It kills hookworm, pin worm , ascariasis and trichuris eggs. Hatching of nematode eggs and their larvae are also inhibited.

Pharmacokinetics less than 10% of orally administered drug is absorbed Absorption increases with fatty meal. Absorbed drug is 90 % protein bound Converted to inactive metabolites . Half- life of 2-6 hours Excreted in urine .

Adverse Effects & Precautions Short term therapy.Mild GI disturbance. High dose : hypersensitivity reactions, agranulocytosis , alopecia ,elevation of liver enzymes . Used with caution under 2ys of age may cause convulsion. Contraindicated in pregnancy. .

Clinical Uses Tablets should be chewed before swallowing. Pinworm trichuriasis hookworm ascaris infections. Whipworm Enterobius Trichinella spiralis Hydatid disease in adults and children over 2 years cure rate is 90-100 % except hookworm it is less.

Albendazole broad-spectrum activity excellent tolerability single dose administration Spectrum of action: ascariasis, hookworm (both species) and enterobiasis, trichuriasis, strongyloidosis, Tapeworms, hydatid disease and hookworm. kills cysticerci, hydatid larvae, ova of ascaris/hookworm and is also effective in cutaneous larva migrans. weak microfilaricidal action.

Mechanism Of Action as mebendazole larvicidal in : hydatid ,cysticercosis , ascariasis and hook worm infections. Ovicidal in ascariasis ,hookworm , trichuriasis

Pharmacokinetics Benzimidazole carbamate Administered orally , absorption increased with a fatty meal Metabolized in the liver to the active metabolite albendazole sulfoxide Plasma half life 8-12 hours sulfoxide is mostly protein bound distributes well to tissues and enters bile, CSF & hydatid cysts. Metabolites are excreted in urine

Plasma half life 8-12 hours Pharmacokinetics Plasma half life 8-12 hours sulfoxide is mostly protein bound distributes well to tissues and enters bile, CSF & hydatid cysts. Metabolites are excreted in urine

Adverse Effects In short term(1-3 days): No significant adverse effects. only gastrointestinal side effects. In long term use : abdominal pain, headache ,fever ,fatigue, alopecia , jaundice and neutropenia. Not given during pregnancy, hypersensitive peoples & children under 2 years .

USES Used on empty stomach when used against intestinal worms but with a fatty meal when used against cysticercosis, hydatid and cutaneous larva migrans . Ascaris, hookworm, Enterobius and Trichuris Tapeworms and strongyloidosis Trichinosis Neurocysticercosis Cutaneous larva migrans Hydatid disease Filariasis

Thiabendazole first benzimidazole polyanthelmintic Introduced in 1961, Spectrum: all species of nematodes infesting the g.i.t.-roundworm, hookworm, Enterobius, Trichuris, Strongyloides and Trichinella spiralis. inhibits the eggs of worms and kills larvae. symptomatic relief in cutaneous larva migrans, Trichinella spiralis larvae, guinea worm disease.

mechanism of action same as mebendazole. has antiinflammatory, analgesic and antipyretic actions. well absorbed from g.i.t.

Adverse effects are frequent often interfere with normal activity. Nausea, vomiting, loss of appetite, headache, giddiness are most common. It can impair alertness-driving and operation of machinery should be prohibited. Itching, abdominal pain, diarrhoea.

Clinical uses Because of frequent side effects and poor patient acceptability used only when other better tolerated drugs are ineffective. strongyloidosis Cutaneous larva migrans Trichinosis-intestinal infestation and larvae in muscles

PYRANTEL PAMOATE It is a broad specturm anthelmintic SPECTRUM: Threadworm, roundworm ,hookworm, Ascaris, Enterobius and Ancylostoma, Necator infestation. It is less active against Strongyloides and inactive against Trichuris and other worms. 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 activation of nicotinic cholinergic receptors in the worms resulting in persistent depolarization slowly developing contracture and spastic paralysis. Worms are then expelled.

Adverse Effects Infrequent mild GI disturbance drowsiness , headache ,insomnia. Rash ,fever Contraindications Pregnancy Children under 2 years of age

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) Ascariasis lumbricoids (common round worm Ankylostoma dudenale (hook worm) single dose for light infection but a 3 days course is necessary for heavy infection.especially N amerianus.

Piperazine Introduced in 1950 highly active drug against Ascaris and Enterobius Mechanism of action: causes hyperpolarization of Ascaris muscle by a GABA agonistic action opening Cl- channels that causes relaxation and depresses responsiveness to contractile action of ACh. Flaccid paralysis worms are expelled alive It does not affect neuromuscular transmission in man.

PHARMACOKINETICS fraction of the oral dose of piperazine is absorbed. partly metabolized in liver ; excreted in urine. ADVERSE EFFECTS safe and well tolerated. Nausea, vomiting, abdominal discomfort and urticaria Dizziness and excitement occur at high doses toxic doses produce convulsions; death is due to respiratory failure. CONTRAINDICATIONS: in renal insufficiency in epileptics CLINICAL USES: Only recommended for the treatment of ascariasis cure rate 90% for 2 days treatment.

LEVAMISOLE, TETRAMISOLE Tetramisole :- in the late 1960s. recemic; levo isomer (levamisole):- more active and is preferred. Both are active against many nematodes, but use is restricted to ascariasis and ancylostomiasis. Strongyloides larvae are killed, but adult worms are not sensitive. MECHANISM OF ACTION: The ganglia in worms are stimulated causing tonic paralysis and expulsion of live worms. Interference with carbohydrate metabolism (inhibition of fumarate reductase) may also be contributing.

Uses For Ascaris infestation Levamisole is a second line drug for A. duodenale It is less efficacious against Necator. ADVERSE EFFECTS nausea, abdominal pain, giddiness(an impulsive scatterbrained manner), fatigue, drowsiness or insomnia .

Diethyl carbamazine citrate (DEC) Developed in 1948 it is the first drug for filariasis. Pharmacokinetics: absorbed after oral ingestion distributed all over the body metabolized in liver and excreted in urine. Excretion is faster in acidic urine. Plasma t1/2 of usual clinical doses is 4-12 hours, depending on urinary pH.

SPECTRUM highly selective effect on microfilariae (Mf). active against Mf of W. bancrofti and B. malayi, Loa loa, onchocerca volvulus . Mechanism Of Action Immobilizes microfilariae alters their surface structure displacing them from tissues making them susceptible to destruction by host defense mechanism

USES Filariasis Tropical eosinophilia Loa loa and 0. volvulus infections ADVERSE EFFECTS Nausea, loss of appetite, headache,weakness and dizziness A febrile reaction with rash, pruritus, enlargement of lymph nodes and fall in BP Leukocytosis and mild albuminuria

lvermectin extremely potent semisynthetic derivative obtained from Streptomyces avermitilis, SPECTRUM: choice for single dose treatment of onchocerciasis and strongyloidosis. highly effective in bancroftian, brugian filaria,cutaneous larva migrans and ascariasis, while efficacy against Enterobius and Trichuris is moderate. Certain insects, notably scabies and head lice are killed by ivermectin.

MECHANISM OF ACTION Paralyze nematodes by intensifying GABA- mediated transmission of signals in peripheral nerves. PHARMACOKINETICS well absorbed orally, widely distributed in the body, but does not enter CNS, sequestrated in liver and fat, long terminal t1/2 of 48--60 hours. SIDE EFFECTS pruritus, giddiness, nausea, abdominal pain, constipation, lethargy and transient ECG changes

PHARMACOKINETICS well absorbed orally, widely distributed in the body, but does not enter CNS, sequestrated in liver and fat, long terminal t1/2 of 48--60 hours. SIDE EFFECTS pruritus, giddiness, nausea, abdominal pain, constipation, lethargy and transient ECG changes

USES Filariasis Strongyloidosis other intestinal nematodes scabies pediculosis

Niclosamide highly effective SPECTRUM: Against cestodes infesting man –Taenia saginata, T. solium, Diphyllobothrium latum and Hymenolepis nana, aswell as threadworm. MECHANISM OF ACTION: The drug appears to act by inhibiting oxidative phosphorylation in mitochondria interfering with anaerobic generation of ATP by the tapeworm.

PHARMACOKINETICS tasteless and nonirritating. minimally absorbed from g.i.t. no systemic toxicity occurs It is well tolerated Adverse effects minor abdominal symptoms Malaise, pruritus and light headedness are rare. safe during pregnancy and in patients with poor health.

Praziquantel novel anthelmintic wide ranging activity against Schistosomes, other trematodes, cestodes and their larval forms but not nematodes.

MECHANISM OF ACTION rapidly taken up by susceptible worms act by causing leakage of intracellular calcium from the membranes contracture and paralysis. tapeworms lose grip of the intestinal mucosa and are expelled. Flukes and schistosomes are also dislodged in tissues and veins. Praziquantel is active against adult as well as juvenile and larval stages of tapeworms. At relatively higher concentrations, it causes vacuolization of the tegument and release of the contents of tapeworms and flukes followed by their destruction by the host. This action appears to be more important in cases of schistosomes and flukes.

Pharmacokinetics rapidly absorbed from intestines absorption is enhanced by ingesting it with food. high first pass metabolism in liver which limits its systemic bioavailability. It crosses blood-brain barrier and attains therapeutic concentrations in the brain and CSF. The plasma t1/2 is short (1.5 hours). Metabolites are excreted chiefly in urine.

Adverse effects nausea and abdominal pain, headache, dizziness and sedation. When used for schistosomes and visceral flukes, symptoms like itching, urticaria, rashes, fever and bodyache occur as a reaction to the destroyed parasites. No interaction with food, alcohol or tobacco has been noted.

Clinical uses Tapeworms T. saginata, T. solium H. nana, O. latum Neurocysticercosis Schistosomes Other flukes

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