Transcript helminthic drugs final

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.
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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.
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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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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.)
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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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• 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
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FILARIAE includes
• Wuchereria bancrofti
• Loa loa
• Onchocerera volvulus
• Brugia malayi
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• 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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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.
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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
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.
•.
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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.
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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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-PHARMA STREET