ANTHELMINTIC DRUGS

DR.ABDUL LATIF MAHESAR Department of Medical Pharmacology KSU

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.
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Types (clinical)
1. 2. Worms live in hosts alimentary canal. Worms or larvae live in other tissues of host body like muscles , viscera , menninges , lungs, subcutaneous tissues.

INTESTINAL WORMS COND

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)
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Ascaris lumbricoids ( common round worm)

Hookworm

Pinworm male ,female

whipworm

Tricuris tricura(whip 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.
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Cestodes cond
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
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Tapeworm

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cysticercosis

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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.
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Tremtodes (flukes) cond

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

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 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
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Tissue worms contd

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

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FILARIAE includes
Wuchereria bancrofti Loa loa Onchocerera volvulus Brugia malayi

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Trichinela spiralis

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filariasis

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Wuchereria or Brugia obstructs lymphatic vessels producing elephantiasis

elephantiasis
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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

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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.
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Hydateid cyct

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Helminths commonly infecting man

Nematodes( round worm)
Tissue worms wuchereria bancrofti Brugia malayi Loa loa Onchocerca Dracunculus medinensis Enterobius vermicularis Ascaris lumbricoides Trichuris trichiura Nector americanus Ancylostoma duodenale Strongyloides stercoralis Schistosoma species Paragonimus speies Fasciolopsis buski Fasciola hepatica Clonorchis sinensis Filariasis Filariasis loiasis River blindness Dracunculiaiss Threadworm Roundworm Whipworm Hookworm Hookworm Strongyloidosis Schistosomiasis Paragonimiasis

Intestinal human nematodes

Trematodes(flukes) Blood flukes Lung flukes Intestinal / hepatic flukes

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Helminths commonly infecting man contd

Cestodes(tapeworms) Intestinal adult worms Taenia saginata Taenia solium Diphyllobothrium latum Hymenolepis nana Taenia solium Echinococcus granulosus Echinococcus multilocularis Spirometra mansoni Beef tapeworm Porktaperworm Fishetapeworm Dwarftapeworm cysticercosis Hydatid disease Hydatid disease Sparganosis

Larval tissue cysts

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Diseases caused by filarial worms

Organism
W. bancrofti

adult worm
Lymphatics

Microfilariae
Blood

C.signs
Fever lymphangitis Elephantiasis Fever lymphangitis Elephantiasis Urticaria subcut nodules Eye disease Allergic eosinophilia
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B.Malayi

lymphatics

Blood

Loa loa Onchocerca

Subcutaneous Subcutaneous

Blood skin,eye

Mansonella perstans

Retroperitoneal

Blood

Dircrocoelium dendriticum

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Fasiola hepatica

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ANTHELMINTIC DRUGS
BENZIMIDAZOLES
1.ALBENDAZOLE:

It is a broad spectrum It is a drug of choice (primary therapeutic application) for treatment of hydatid disease and cystecercosis, it is also used for the treatment of (intestinal nematodes) ascariasis ,tricurasis and strongyloidiasis , pinworm,
hookworm
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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

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Pharmacokinetics (Albendazole)

It is benzimidazole carbamate it is adminstered orally , and absorbed erratically (unpredictable) , absorption can be increased with fatty meal It is metabolized in the liver rapidly to active metabolite albendazole sulphoxide
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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
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Clinical uses (albendazole)

used on empty stomach when used against intraluminal parasites but with fatty meal when against tissue parasites.

In ascariasis ,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.
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Albendazole cond
3. 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
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Albendazole cond
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.
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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.
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Mebendazole cont
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.

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Mebendazole cont
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 marked reduction

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Mebendazole cond
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

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Mebendazole cond
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
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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
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Thiabendazole cond:
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 45 applied topically or drug can be given orally for 2 days.

Thiabendazole cond
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.
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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.

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Pyrantel pamoate cond

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 48 infection.especially N amerianus.

Pyrental pamoate cond

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
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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

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Piperazine cond
pharmacokinetics : it is readily absorbed orally and excreted unchanged in urine. 75 mg /kg/day for 2 days once daily treatment is continued for 3-4 days or repeated after one week in case of heavy infections.
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Piperazine cond
Adverse effects: GI disturbance Neurotoxicity ,allergic reactions serum sickness like syndrome Contraindications Epilepsy Impaired liver or kidney functions pregnancy Malnutrition
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Drugs used for treating human intestinal nematodes (single dose unless otherwise stated

Ascariasis

Hookworm

enterobius

tricuris

strongloides

Piperazzine
Pyrantal pamoate Albendazole Mebendazole Thiabendazole Ivermectin

++
++ ++ ++ n/a n/a

+
++ ++ ++ n/a n/a

++
++ ++ ++ n/a n/a

+ + n/a n/a

+ + ++ ++

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NICLOSAMIDE
It is a useful drug for treatment of tape worm (cestodes)infestation Mechanism of action: Adult worm is rapidly killed by inhibition of oxidative phosphorylation or stimulation of ATPase activity. Pharmacokinetics: It is poorly absorbed from gut Neither drug nor its metabolites are found in blood or urine
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Niclosamide cond
Clinical uses: T.Saginata( Beef tape worm),T.solium( pork tape worm), Diphyllobothrium latum (fish tape worm) 2 gram of single dose is given in the morning on the empty stomach. not effective against cysticercosis or hydatic disease. Hymenolepis nana: It is effective against adult parasite
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Niclosamide cond
Adverse effects: Mild ,infrequent and transitory GI disturbance Alcohol consumption should be avoided not indicated in children under 2 years of age.

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DIETHYLCARBAMAZINE
Is a drug of choice for the treatment of filariasis ,loiasis and tropical eosinophillia. Pharmacokinetics: It is synthetic peprazine derivative Rapidly absorbed from gut It has a half life of 2-3 hours which increases in alkaline urine to 10 hours. It is excreted in urine unchanged. dosage is reduced in urinary alkalosis and renal impairment.
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DIETHYLCARBAMAZINE cond
Mechanism of action: It immobilizes microfilariae and alters its surface structure ,making them susceptible to destruction by host defense mechanis

It is not teratogenic

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DIETHYLCARBAMAZINE cond
It is a drug of choice for the treatment of W.bancrofti, B.malayi,B.timori, loa loa Microfiliariae are rapidly killed .adult worms are killed slowly requiring several course of treatment

It is highly effective against L.loa. for these infections the dose is 2mg/kg three times a day for 2-3 weeks.
for W.bancrofti infections to reduce the incidence of allergic reactions to dying microfilariae a single dose is administered on the first day , two doses on the second day and three doses on the 3rd day. 59

DIETHYLCARBAMAZINE cond
For loa ( with risk of encephalopathy) or B.malayi infections ,individual doses should start at 1 mg /kg once on the first day and gradually increased over 5-6 days Anti histamines and corticosteroids are given in allergic manifestations.

Complete Cure may be require several courses of treatment over 1-2 years. The drug may be used in prohylaxis 300 mg weekly or 300 mg on 3 successive day each month for 60 loiasis.

DIETHYLCARBAMAZINE cond
Reactions induced by Dying parasites: Fever , mailase, papular rash, headache, GI disturbance,cough, chest,muscle,joint pain Leucocytosis Retinal haemorrhage Encephalopathy lymphangitis and lymphadenopathy.
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DIETHYLCARBAMAZINE cond
contraindications and precautions Hypertension Renal disease Patient suspected of malaria patient with lymphangitis

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IVERMECTIN
It is drug of choice for treatment of filaria and onchoceriais,elephantiasis it is a macrocyclic lactone It is used orally and is rapidly absorbed, posses wide volume of distribution. It has a half life of 16 hrs It is exclusively excreted in urine
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IVERMECTIN cond
Mechanism of action:64 it intensifies GABA mediated transmission of singals in peripheral neverse In onchoceriasis it is microfilaricidal It does not kill adult worm

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IVERMECTIN cond
Clinical uses: Onchoceriasis: a single dose of 150 mg/kg with water on empty stomach,repeated after every 3 months for one year,after this it is repeated yearly untill adult worm dies which may take a year or more

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IVERMECTIN cond
Strongyloidiasis: 200mg for 2 days in immunosuppresed patient ,repeated treatment is often needed. Bancrofti filaricidal: as it is mirofilaricidal It is also used for scabies and cutaneous larva migrains.

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IVERMECTIN cond
Adverse effects: Fatigue ,dizziness, GI disturbance In onchoceriasis: Mazotti reaction i.e. fever, headache, dizziness, somonlence, weekness, rash ,diarrhea, arthralagia, hypotension, lymphadenitis, peripheral edema due to killing of microfiliariae, for this steroids may be necessary for several days Swelling and abscess at site of adult worm Punctuate corneal opacities.
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IVERMECTIN cond
Contraindication: other drugs that enhance GABA e.g Barbiturates, bnezodiazepines, valproaic acid. pregnancy Imparied blood brain barrier Children under 5 years of age.

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BITHIONOL
it is drug of choice for the treatment of fasioliasis ( sheep liver fluke) It is also alternative drug for pulmonary paragonimiasis Pharmacokinetics: It is orally administered and excreted in urine.
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BITHIONOL
Clinical uses: 30-50 mg /kg in 2-3 divided doses administered orally after meals on alternate day for 10 15 days. Adverse effects: GI disturbance Dizziness,headache Pruriuts ,urticaria,Leucopenia Contraindications and precautions: hepatitis ,leucopenia Used with caution under 8 years of age.
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