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ANTIHELMINTIC DRUGS
Indupalli Avinash & Paruchuri Aswini chand
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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 characteristic tissue distribution.
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Types (clinical)1. Worms live in hosts alimentary canal. 2. Worms or larvae live in other tissues
of host body like muscles , viscera ,
meninges , lungs, subcutaneous tissues.
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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)
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Ascaris lumbricoids ( common round worm)
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Hookworm
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Pinworm male ,female
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whipworm
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Tricuris tricura(whip worm)
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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 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
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Tapeworm
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cysticercosis
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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 gut and produce inflammation of these organs , resulting in haematuria or loss of blood in feces.
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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
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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
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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 manNematodes( round worm)Tissue worms wuchereria bancrofti Filariasis
Brugia malayi FilariasisLoa loa loiasisOnchocerca River blindnessDracunculus medinensis Dracunculiaiss
Intestinal human nematodes Enterobius vermicularis Threadworm
Ascaris lumbricoides RoundwormTrichuris trichiura WhipwormNector americanus HookwormAncylostoma duodenale Hookworm
Strongyloides stercoralis StrongyloidosisTrematodes(flukes)
Blood flukes Schistosoma species Schistosomiasis
Lung flukes Paragonimus speies Paragonimiasis
Intestinal / hepatic flukes Fasciolopsis buskiFasciola hepaticaClonorchis sinensis
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Helminths commonly infecting man cont’dCestodes(tapeworms)Intestinal adult worms Taenia saginata Beef tapeworm
Taenia soliumPorktaperworm
Diphyllobothrium latumFishetapeworm
Hymenolepis nanaDwarftapeworm
Larval tissue cysts Taenia solium cysticercosisEchinococcus granulosus Hydatid
diseaseEchinococcus multilocularis Hydatid
disease
Spirometra mansoni Sparganosis
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Diseases caused by filarial worms
Organism adult worm Microfilariae C.signsW. 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
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Dircrocoelium dendriticum
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Fasiola hepatica
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ANTHELMINTIC DRUGS
BENZIMIDAZOLES1.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) 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.
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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.
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 hookworm, pin worm infection : children under 2 years 400 mg orally as a single dose 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 con’d
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
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Albendazole con’d
Adverse effects: In short term: use no significant adverse
effects.
In long term use : as used in 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 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.
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Mebendazole con’tClinical 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.
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 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
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Mebendazole con’dAdverse 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 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 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.
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Thiabendazole con’d
adverse reactions and contraindications: It is more toxic than other benzamidazoles GI disturbances Pruritus ,headache, drowsiness , psychoneurotic
symptoms. Irreversible liver 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 con’dEfficacy and clinical uses: it is very effective against luminal organisms. It is not effective against migratory stages in the tissues or
against ova
pin worm: 11 mg /kg as a single dose to be repeated in 2 wks.
common round worm: single dose to be repeated after 2wks
hook worm: single dose for light infection but a 3 days course is necessary for heavy infection.especially N amerianus.
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Pyrental pamoate con’d Adverse Effects . Infrequent mild transient GI disturbance drowsiness , headache ,insomnia. Rash ,feverContraindciations 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 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 con’d
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 con’d
Adverse effects: GI disturbance Neurotoxicity ,allergic reactions serum sickness like
syndrome Contraindications Epilepsy Impaired liver or kidney functions pregnancy Malnutrition
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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 con’d
Clinical uses: Beef tape worm, pork tape worm, 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 con’d
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 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 con’d
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 con’d 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.
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DIETHYLCARBAMAZINE con’d 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 loiasis.
50 mg monthly for bancrofitan and malayan filariasis
Tropical eosinophilia 2 mg /kg tree time daily for 7 days
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DIETHYLCARBAMAZINE con’d
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 con’d
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 con’d
Mechanism of action:61
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 con’d
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 con’d
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 con’d 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 con’d
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 disturbanceDizziness,headachePruriuts ,urticaria,Leucopenia
Contraindications and precautions:hepatitis ,leucopeniaUsed with caution under 8 years of age.
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