ANT-HELMINTIC DRUGS
Introduction:
There are three major groups of helminthes ( or worms ) :
1- the nematodes.
2-the trematodes.
3-the cestodes.
As in all antibiotic regimes ,the antihelminthic drugs are aimed at
metabolic target that are present in the parasite but are either absent from
or have different characteristics than those of the host. so, antihelminthic
drugs are used to eradicate or reduce the number of helminthes parasites.
Classification of antihelminthic drugs :
We can classify it to 3 groups :
1- drugs used for treatment of nematodes.
2- drugs used for treatment of trematodes.
3- drugs used for treatment of cestodes.
1- drugs used for treatment of nematodes.
Q: what are the nematodes?
Answer :nematodes are elongated roundworms that posses a complete
digestive system., including both a mouth and an anus. They cause
infection s of the intestine as well as the blood and tissues.
Drugs :
1-MEBENDAZOLE:
mode of action :
it can act by two pathways:
1-It act by binding to and interfering with the synthesis of the parasites
micro-tubules .
2- also act by decreasing glucose uptake.
As a result of that ,the effected parasites are expelled with the feces.
Pharmacokinetics :
1-it is nearly insoluble in aqueous solution .
2- little of an oral dose ( which is chewed ) is absorbed by the body unless
taking with high fat meals.
3-the drug is relatively free from toxic effects ( because its little
absorption ).
Clinical uses :
It is used in treatment of :
1- infection by whipworms ( trichuris trichura).
2- infection by pinworms( enterobius vermicularis ).
3- infection by hookworms( nector americanus ).
4-infection with ancylostoma duodenale.
5-infection with roundworms ( ascariasis lumbricoides ).
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Side effects :
1-abdominal pain .
2- diarrhea.
Contraindication :
It is contraindicated in pregnant women because it has been shown to be
emberyotoxic and teratogenic in experimental animals.
2-ALBENDAZOLE.
Pharmacokinetics :
1- after oral administration ,it is erratically absorbed .
2-it is rapidly undergoes first –pass metabolism in the liver .
3- plasma half-life is 8-12 hours .
4- plasma level decrease with continuous treatment.
5- it is distributed to tissues including bile and cerebrospinal fluid and
enter hydatid cyst.
6- excretion through biliary tract.
Clinical uses :
1- ascariasis infection.
2-tichuriasis infection.
3-hook worms infection.
4-pnin- worm infection.
5-ganthostomiasis.
6- strongyloidiasis .
7- hydatid disease.
8-neurocysticercosis.
9- cutanous larva migrans.
10-intestinal capillariasis.
Side effects :
1- rash and pruritis.
2-leukopenia.
3- reversible low grade aminotransferase elevation..
4-alopecia.
5- jaundice.
All these side effects will become more clear when we use drug for long
periods ( months )
Contraindication :
1- pregnant females.
2-children under 2 years.
3-patient with cirrhosis.
4- patient with hyper-sensitivity to benzimidazole drugs ( because
albendazole is a benzimidazole carbamate).
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3-PYRANTEL PAMOATE.
Mode of action :
It act as a depolarizing neuro-muscular blocking agent causing persistent
activation of the parasites nicotinic receptors .the paralyzed worm is then
expelled from the hosts intestinal tract.
pharmacokinetics :
1- it is poorly absorbed orally.
2-it exert its effects in the intestinal tract.
Clinical uses :
1- infection with round worms.
2- infection with pin worms.
3- infection with hook worms.
In all these above clinical situation pyrantel pamoate used with
mebendazole give good results in treatment.
Side effects :
1-nausea and vomiting .
2- diarrhea.
4-THIABENDAZOLE OR TIABENDAZOLE.
Mode of action :
It inhibit cellular enzymes of susceptible helminthes.
Pharmacokinetics:
1-it is nearly insoluble in water.
2- it is readily absorbed on oral administration.
3-it is hydroxylated in the liver.
4-it is excreted in the urine.
Clinical uses :
1- treatment of strongyloidiasis( thread worms ).
2- treatment of cutanous larva migrans.
3-early stage of trichinosis.
Side effects :
1-erythema multiforme.
2- steven-johanson syndrome .some of cases are fatal.
3- liver damage.
4- crystalluria may be induced.
5- IVERMECTIN.
1- the drug is given orally .
2-it is not cross blood brain barrier.
Mode of action :
It attack GABA ) receptors leading to paralysis of the parasite.
Clinical uses :
1- river blindness ( onchocerciasis )( infection caused by onchocerca
volvulus ).
2- it is also effective against scabies.
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Contraindication :
1- patient with meningitis.
2- pregnancy.
3- patient taking benzodiazepine or barbiturates drugs.
2- drugs used for treatment of trematodes
Trematodes ( flukes) are leaf-shaped flatworms that are generally
characterized by the they infect ,for example they may be categorized as
liver ,lung , intestinal or blood flukes.
Drugs that used for treatment of trematodes :
1-PRAZIQUANTEL:
MODE OF ACTION :
it cause increase in permeability of cell membrane to calcium that will
cause contracture and paralysis of the parasite( both adult worms and
larvae) .
Pharmacokinetics :
1-it is rapidly absorbed after oral administration.
2-it distributed in the cerebrospinal fluid.
3-high level occur in the bile,.
4- the drug is extensively metabolized oxidatively resulting in a short
half-life .
5- the metabolite are inactive and are excreted through the urine and bile.
Clinical uses :
1-it is the drug of choice in treatment of all forms of schistosomiasis .
2- treatment of cestodes infection like cysticercosis.
Side effects :
1-drawsiness.
2-dizziness.
3-malaise.
4-anorexia.
Contra-indication :
The drug is not recommended for :
1- pregnant women.
2-nursing mothers.
3- contraindicated in treatment of ocular cysticercosis because the
distraction of organisms in the eye may damage the organ.
Drug interaction :
1-dexamethazone.
2-phenytoin.
3-carbamazepine.
4-cimetidine.
All these drugs will cause increase level of prazequantel by inhibition of
cytochrome P- 450.
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2-BITHIONOL:
1-it is the drug of choice in treatment of fascioliasis( sheep liver flukes ).
2-it reach to peak level in 4-8 hours.
3- given orally in divided doses .
4- excretion appear mainly through kidney.
5- side effects :
a-Diarrhea.
b-abdominal cramp.
Contraindication :
1- children below 8 years.
3- drugs used for treatment of cestodes.
The cestodes (true tapeworms )typically have a flat ,segmented ,body and
attach to the host intestine .
Like in trematodes the tapeworms lack a mouth and digestive tract
throughout their life cycle.
Drugs that used in treatment of cestodes:
1- NICLOSAMIDE.
Mode of action :
It act by inhibition of the parasites mitochondrial anaerobic
phosphorylation of ADP which produce usable energy in the form of
ATP.
Clinical uses :
1-t.saginata(beef tapeworm).
2-t.solium (pork tapeworm ).
3-hymenolepis nana (dwarf tapeworm ).
4-fish tapeworm.
5- intestinal flukes infection.
Side effects :
1-vomiting.
2-headache.
3-skin rash.
Contraindication :
1-consumption of alcohol.
2-children under 2 years.
3- pregnant women.
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