Transcript 06. ANTHELMINTIC DRUGS 2006(nov 25).

ANTHELMINTIC DRUGS
Helminth Infections
1-Tapeworms ( cestodes)
Beef tapeworm / fish tapeworm
2- Intestinal round worms ( nematodes)
Ascaris, pinworm ,whipworm, strongyloides,
ancylostoma ( hookworm ).
A skin infection is termed cutaneous larva
migrans
Visceral larva migrans .
Anthelminthic Drugs
 May act by causing :
 1- paralysis of the worm.
 2- damaging the worm leading to partial digestion
or rejection by immune mechanisms.
 3- interfere with the metabolism of the worm.
*Worms or larvae live in tissues of host
body like muscles , viscera , menninges ,
subcutaneous tissues.
 Adult filariae live in the lymphatics,
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
Ascaris lumbricoids ( common round worm)
filariasis
Hookworm
Pinworm male ,female
Tapeworm
whipworm
Dircrocoelium dendriticum
Fasiola hepatica
Tricuris tricura
Trichinela spiralis
elephantiasis
Hydateid cyct
cysticercosis
ANTHELMINTIC DRUGS
ALBENDAZOLE
 Broad spectrum oral anthelmintic
 Drug of choice for treatment of hydatid
disease and cysticercosis,it is also used for
the treatment of ascariasis ,tricurasis and
strongyloidiasis, pinworm, hookworm
Mechanism Of Action
 Inhibits microtubule synthesis by binding to β –
tubulin.
 Inhibits mitochondrial reductase causing reduced
glucose transport.. Intestinal parasites are immobilized
and die slowly.
 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
Pharmacokinetics
 Plasma half life is 8-12 hours
 sulfoxide is mostly protein bound
distributes well to tissues and enters
bile,CSF & hydatid cysts.
 Metabolites are excreted in urine
Clinical uses
 Used on empty stomach when used against
intraluminal parasites but with a fatty meal
when used against tissue parasites.
 In ascariasis ,trichuriasis ,hookworm, pin
worm infections : children over 2 years &
adults (single dose 400mg, repeated for 2-3 day
in heavy ascaris infection . For 2 wks for pin
worm infection
2. Hydatid diseases:
drug of choice for medical therapy& adjunctive
to surgical removal or aspiration of cysts.
Albendazole (con’)
3. Neurocysticercosis:
Used with corticosteroid to decrease the
inflammation caused by dying organism and it
also reduces the duration of course for 21 days
4.
Other infections: Drug of choice in cutaneous
and visceral larva migrans , intestinal
capillariasis, giardiasis & taeniasis.
Adverse Effects
 In short term(1-3 days): Mild epigastric
pain,diarrhea, nausea, headache & insomnia.
 In long term use : for hydatid cyst and cysticercosis :
abdominal pain, headache ,fever ,fatigue, alopecia ,
increased liver enzymes , pancytopenia. Blood counts
and liver enzymes should be followed.
 Not given during pregnancy, hypersensitive people to
benzimidazole drugs & children under 2 years .
MEBENDAZOLE (Vermox)
 Synthetic benzimidazole
 Wide spectrum and low incidence of adverse
effects
Mechanism of action:
Inhibits microtubule synthesis .
It kills hookworm, pin worm , ascaris and
trichuris eggs.
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 mostly in urine .
Clinical Uses
It is taken orally before or after meal ,
tablets should be chewed before
swallowing.
 Pinworm , trichuriasis, hookworm &
ascaris infections.
 in adults and children over 2 years cure
rate is 90-100 % except hookworm it is
less.
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.
 Enzyme inducers and inhibitors affect plasma level of the
drug.
Thiabendazole
 Benzimidazole
 Chelating agent and form stable complexes with metals
including iron, but does not bind with calcium.
 Rapidly absorbed

Half- life of 1-2 hrs
 Completely metabolized in liver and 90% is excreted in
urine
 Can also absorbed through skin
Mechanism Of Action
 Similar to other benzimidazoles. It is ovicidal for
some parasites
 Clinical uses:
 Should be given after meals .and tablets should be
chewed
 Strongyloidal infections & cutaneous larva
migrans .Thiabendazole cream is applied topically
or drug can be given orally for 2 days.
Adverse Effects & Contraindications
 More toxic than other benzamidazoles
 GI disturbances
 Pruritus ,headache, drowsiness , psychoneurotic
symptoms.
 Irreversible liver failure.
 Fatal Stevens –Johnson syndrome
 Not used in young children , pregnancy, hepatic
and renal diseases.
PYRANTEL PAMOATE
 Broad spectrum
 Pharmacokinetics:
 Poorly absorbed from GIT
 Half of the drug is excreted unchanged in the feces.
 Mechanism of action:
 result in paralysis of worms. It is a neuromuscular blocking
agent
Efficacy
 Very effective against luminal organisms( mature or
immature forms).
 Not effective against migratory stages in the tissues or
against ova
Clinical uses
Pin worm given orally with or without food.
 Ascariasis
 Hookworm
Adverse Effects
 Infrequent mild transient GI disturbance
 drowsiness , headache ,insomnia.
 Rash ,fever
Contraindications & Cautions
 Should be used with caution in liver dysfunction.
 Pregnancy
 Children under 2 years of age
PIPERAZINE
 Only recommended for the treatment
of ascariasis cure rate 90% for 2 days
treatment.
 Readily absorbed orally and excreted
mostly unchanged in urine
 Mechanism of action:
Causes paralysis of ascaris by blocking
acetylcholine at myoneural junction ,
the live worms expelled by normal
peristalsis.
 Treatment is continued for 3-4 days or
repeated after one week in case of heavy
infections.
Adverse Effects







GI disturbance
Neurotoxicity ,allergic reactions .
Contraindications
Epilepsy or a history of epilepsy
Impaired liver or kidney functions
pregnancy
Chronic neurologic disease
NICLOSAMIDE
 Second-line drug for treatment of most
tapeworm infections.
 Mechanism of action:
 Adult worm( not ova) is rapidly killed by
inhibition of oxidative phosphorylation .
 Pharmacokinetics:
 Poorly absorbed from gut & excreted in urine.
Clinical Uses
 Treatment of most forms of tapeworms.
 Not effective against cysticercosis or hydatic
disease.
 Given in the morning on empty stomach.
 Purgative is necessary to purge all dead segments&
prevent liberation of ova.
Adverse effects & Contraindications
 Mild ,infrequent and transitory GI
disturbance
 Alcohol consumption should be
avoided
 Not indicated in children under 2
years of age or in pregnancy.
DIETHYL CARBAMAZINE
 Drug of choice for the treatment of filariasis and
tropical eosinophilia.
 Pharmacokinetics:
 Rapidly absorbed from gut
 Half- life is 2-3 hours
 The drug should be given after meals
 It is excreted in urine as unchanged or metabolite.
 Dosage is reduced in urinary alkalosis and renal
impairment.
Mechanism Of Action
 Immobilizes microfilariae and alters their
surface structure ,displacing them from
tissues & making them susceptible to
destruction by host defense mechanism
 It has immunosuppressive effects
Adverse Effects
 Fever , malaise, papular rash, headache, GI
disturbance,cough. Chest,muscle,joint pain
 Leucocytosis
 Retinal hemorrhage
 Encephalopathy
 lymphangitis and lymphadenopathy.
 *It is not teratogenic
Contraindications & Cautions
 *
Hypertension
*
Renal disease
*patient with lymphangitis
IVERMECTIN
 Drug of choice for treatment of
strongyloidiasis
 Macrocyclic lactone ring
 Given only orally
 Rapidly absorbed
 Does not cross BBB.
 Half- life is 16 hrs
 Excretion is mainly in feces.
Mechanism Of Action
Acts on the parasitte,s glutamategated Cl- channel receptors . Chloride
influx increased , hyperpolarization
occurs , resulting in paralysis of the
worm. Or
 Paralyze nematodes by intensifying
GABA- mediated transmission of
signals in peripheral nerves.

Clinical uses
 Drug of choice for cutaneous larva
migrans & strongyloidiasis.
 Onchocerciasis
 It is also used for scabies , lice .
 Filariasis.
Adverse Effects
 Fatigue ,dizziness, GI disturbance
 Killing of microfilaria result in a Mazotti
reaction ( fever, headache, dizziness,
somnolence, hypotension , tachycardia,
peripheral edema……).
 Corneal opacities & other eye lesions.
Contraindications & Cautions
 Concomitant use with other drugs that enhance
GABA
e.g Barbiturates, bnzodiazepines, valproic acid.
 pregnancy
 Meningitis
 Children under 5 years of age.
BITHIONOL
 Drug of choice for the treatment of fascioliasis
( sheep liver fluke)
 Pharmacokinetics:
 It is orally administered and excreted in urine.
Adverse Effects

GI disturbance ( N., V., D., A.)
Dizziness, headache
Skin rashes , urticaria, Leucopenia
 Contraindications and precautions:
Hepatitis , leucopenia
Used with caution in children under 8 years of age.