Transcript anthelmintic drugs

Anthelmintic Drugs
Helmintic infections
Helmintic infections
 Human is the primary host for most
helminthic infections.
 Most worms produce eggs and larva
 These pass out of human body and
infect secondary host
 Immature forms invade humans via
skin or GIT
Types of worms
 Worms live in host,s alimentary canal
 Worms or larvae live in muscles ,
viscera , menninges, lungs.
Subcutaneous tissues
Intestinal Worms
A) Round worms
( Nematodes )
 Ascaris lmubricods ( common )
 Enterobius vermicularis ( pin
worm)
 Trichris trichuria ( whip worm)
 Strongyloids stercoralis ( thread
 Ankylostoma dudenale ( hook
worm
B) Tape worms ( cestodes )
 Taenia saginata ( Beef)
 Taenia solium ( pork)
Humans become infected by eating
raw or unde cooked meat containing
larvae of infected cattle or pig
Continue ( cestodes )
 In some cases the larva gets
encysted in muscles , viscera , brain
, eye resulting in cysticercosis
Tissue worms
 Filariae ( bancrofti, loa loa )
Adult filariae live in the lymphatics ,
causing lymphadenitis , swelling of
limb. Microfilariae goes to blood
stream to be ingested by mosquitoes
 Trichnella spiralis : larva migrats
from intestine to tissues of leg or foot
producing ulcer
Anthelminthic Drugs
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.
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
 Drug of choice for treatment of hydatid
disease and cysticercosis.
 Used for the treatment of ( intestinal
nematodes ) e.g. ascariasis , tricurasis and
strongyloidiasis, pinworm, hookworm
Mechanism Of Action
 Inhibits microtubule synthesis that irreversibly impairs
glucose uptake , 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 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
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 & others
Adverse Effects
 In short term(1-3 days): No significant adverse
effects
 In long term use :
abdominal pain, headache ,fever ,fatigue, alopecia ,
increased liver enzymes , pancytopenia.
 Not given during pregnancy, hypersensitive peoples &
children under 2 years .
MEBENDAZOLE (Vermox)
 Synthetic benzimidazole
 Wide spectrum and safer than albendazole
Mechanism of action:
As albendazole
It kills hookworm, pin worm , ascariasis 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 in urine .
Clinical Uses
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.
.
Thiabendazole

Mechanism as other 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
Clinical uses
 Should be given after meals .and tablets should be
chewed
 Strongyloidal infections
 In 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 orally
 Half of the drug is excreted unchanged in the feces.
Mechanism of action:
 Neuromuscular blocking drug leads to paralizes of worms
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 GI disturbance
 drowsiness , headache ,insomnia.
 Rash ,fever
Contraindications
 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
 Impaired liver or kidney functions
 pregnancy
NICLOSAMIDE
 Second-line drug for treatment of tape worm
infections.
Mechanism of action:
 Adult worm 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
 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
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
Patients suspected of malaria
IVERMECTIN
 Drug of choice for treatment of filaria &
strongyloidiasis
 It is a macrocyclic lactone ring
 Given only orally
 Rapidly absorbed
 Does not cross BBB.
 Half- life is 16 hrs
 Excretion in urine & feces.
Mechanism Of Action

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 ( it is microfilaricidal ).
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
Dizziness, headache
Skin rashes , urticaria, Leucopenia
 Contraindications and precautions:
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Hepatitis , leucopenia

Used with caution in children under 8 years of
age.