Transcript Anthelminthics

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Content
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 Introduction
 Treatment of infection caused by nematodes
 Treatment of infection caused by cestodes
 Treatment of infection caused by trematodes
 References
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Antihelminthics
 Helminthic infections are the major health
problem in tropical countries and many people
suffering from worm infections, worm can cause
g.i.t and general symptoms.
 They are also causes blood loss, nutritional
deficiencies, urticaria, allergic manifestation and
even intestinal obstruction.
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 Pathogenic helminths can be divided into the
following major groups:
 cestodes (flatworms),
 nematodes (roundworms),
 trematodes (flukes)
 Acanthocephala (thorny-headed worms).
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HELMINTH INFECTIONS
 Examples of worms that live in the host's alimentary
canal are as follow.
 Tapeworms:
Taenia
saginata,
Taenia
solium,
Hymenolepis nana and Diphyllobothrium latum..
 Intestinal
roundworms:
Ascaris
lumbricoides
(roundworm), Enterobius vermicularis (threadworm),
Trichuris trichiura (whipworm), Necator americanus and
Ankylostoma duodenale (hookworms).
Tricuris tricura
Hookworm
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The main examples of worms that live
in the tissues of the host are as follow:
 Flukes: Schistosoma haematobium, Schistosoma
mansoni, and Schistosoma japonicum. These cause
schistosomiasis (bilharzia). The adult worms of both
sexes live and mate in the veins or venules of the gut
wall or the bladder.
 Tissue roundworms: Trichinella spiralis, Dracunculus
medinensis (guinea worm) and the filariae, which
include Wuchereria bancrofti, Loa loa, Onchocerca
volvulus and Brugia malayi. They live in lymphatic
connective tissueor mycentry of host.
 Hydatid tapeworm: These are cestodes of the
Echinococcus species for which canines are the
primary hosts, and sheep the intermediate hosts.
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 Most available anthelmintic drugs exert their
antiparasitic effects by interference with body
function like:1.
energy metabolism,
2.
neuromuscular coordination,
3.
microtubular function,
4.
cellular permeability.
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TREATMENT FOR INFECTIONS CAUSED
BY NEMATODES
 Nematodes are long, cylindrical unsegmented
worms that are tapered at both ends. Because of
their shape, they are commonly referred to as
roundworms.
 They produce abdominal pains, diarrhea and, if
many worms are present, anemia ,pneumonia in
lung.
Ascaris lumbricoids
Piperazine
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 MA
o It acts on the musculature of the helminthes to cause
reversible paralysis mediated by chloride-dependent
hyperpolarization of the muscle membrane.
o This results in expulsion of the worm.
o Piperazine acts as an agonist at GABA- gated chloride
channels on the parasite muscle.
o Piperazine is administered orally and is readily absorbed
from the intestinal tract. Most of the drug is excreted in
the urine within 24 hours.
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o It is used to treat infection of round worm (ascaris
lumbricoides) and thread worm
(enterobius
vermicularis )
o Side effects
 gastrointestinal distress,
 urticaria, and dizziness. Neurological symptoms of
 ataxia, hypotonia, visual disturbances
 It should not be used in pregnant women because of
the formation of a potentially carcinogenic and
teratogenic nitrosamine metabolite. And renal ,
hepatic insufficiency.
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levamisole
 It is immunomodulating agent in cancer , auto
immune disease and chronic bacterial infection.
 It is a nicotinic like action stimulating and block NM
junction to paralysis and death.
 It is given orally is rapidly absorbed , it cross BBB . It is
metabolized in liver and excreted via kidney.
 Plasma half life is 4 hr.
 It is used infection of round warm like ascarsis
lumbricoides
Diethylcarbamazine
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 MA
o It interferes with the metabolism of arachidonic acid
and blocks the production of prostaglandins, resulting
in capillary vasoconstriction and impairment of the
passage of the microfilaria.
o Diethylcarbamazine
is
absorbed
from
the
gastrointestinal tract, and peak blood levels are
obtained in 4 hours; the drug disappears from the
blood within 48 hours. The intact drug and its
metabolites are excreted in the urine
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It is used infection caused by wuchereria bancrofti
and loa loa.
o Side effect
o fever,
lymphadenopathy,
cutaneous
swelling,
leukocytosis, and intensification of any preexisting
eosinophilia,
o
edema, rashes, tachycardia, and headache.
o If microfilariae are present in the eye, further ocular
damage may result
Ivermectin
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o Ivermectin
acts
on
parasite-specific
inhibitory
glutamate-gated chloride channels that are related to
GABA-gated chloride channels.
o
Ivermectin
causes
increase
cl
conductance,
hyperpolarization of the parasite cell membrane and
muscle paralysis.
o At higher doses it can potentiate GABA-gated chloride
channels.
o It does not cross the blood-brain barrier and therefore
has no paralytic action in mammals,
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o Ivermectin is administered
subcutaneous routes.
by
the
oral
and
o It is rapidly absorbed. Most of the drug is excreted
unaltered in the feces.
o The half-life is approximately 12 hours.
o
it is active against roundworm, tapeworm but not hook
warm.
o The side effects are minimal, with purities, fever, and
tender lymph nodes occasionally seen
Pyrantel Pamoate
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 MA
o Pyrantel pamoate
is a agonist at the nicotinic
acetylcholine receptor, and its actions result in
depolarization and paralysis of the helminthes muscle.
o Its selective toxicity occurs primarily because the
neuromuscular junction of helminthes muscle is more
sensitive to the drug than is mammalian muscle.
o This drug is administered orally, and because very little
is absorbed, high levels are achieved in the intestinal
tract. Less than 15% of the drug and its metabolites
are excreted in urine.
o Side effect
o headache, dizziness, and drowsiness.
BENZIMIDAZOLES
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 Three benzimidazoles are in use for the treatment of
helminthic infections.
A.
Thiabendazole
B.
Mebendazole
C.
Albendazole
A. Thiabendazole
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o Thiabendazole
inhibits fumarate reductase and
electron
transport–associated
phosphorylation
in
helminths.
o Interference with ATP generation decreases glucose
uptake and affects the energy available for
metabolism.
o Benzimidazole
anthelmintics
as
a
class
(e.g.thiabendazole, mebendazole, and albendazole),
bind selectively to -tubulin of nematodes (roundworms),
cestodes (tapeworms), and trematodes (flukes).
o This inhibits microtubule assembly, which is important in
a number of helminth cellular processes, such as mitosis,
transport, and motility.
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o Thiabendazole is administered orally and is rapidly
absorbed from the intestinal tract, with peak plasma
levels achieved in 1 to 2 hours. The drug is metabolized
in the liver and excreted in urine within 24 to 48 hours
o Side effect
o Anorexia, nausea, vomiting, drowsiness, and vertigo
o occur in up to one-third of patients. Diarrhea, pruritus
,rash, hallucinations, crystalluria, and leukopenia
o shock, hyperglycemia, lymphadenopathy, StevensJohnson syndrome
B. Mebendazole
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o MA
o mebendazole does not inhibit fumarate reductase.
o The selective binding to nematode tubulin may inhibit
glucose absorption, leading to glycogen consumption
and ATP depletion.
o Mebendazole is given orally; it is poorly soluble, and
very little is absorbed from the intestinal tract. About 5
to 10%, principally the decarboxylated derivatives, is
recovered in the urine
o Abdominal discomfort and diarrhea may occur when
the worm load is heavy.
o It is contraindicated during pregnancy.
C. Albendazole
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 MA
 Albendazole
appears
to
cause
cytoplasmic
microtubular degeneration, which in turn impairs vital
cellular processes and leads to parasite death.
 There is some evidence that the drug also inhibits
helminth-specific ATP generation by fumarate
reductase.
 Albendazole is given orally and is poorly and variably
absorbed (5%) because of its poor water solubility. The
drug is rapidly metabolized in the liver
 The half life of the metabolites is 8 to 12 hours.
 It is use in ascariasis, trichuriasis, enterobiasis and
capallariasis.
 side effects
 Epigastric distress, nasea, dizziness, hepatotoxicity and
bon marrow dipression.
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TREATMENT FOR INFECTIONS CAUSE
BY CESTODES
 Cestodes, or tapeworms, are flattened dorsoventrally
and are segmented. The tapeworm has a head with
round suckers or sucking grooves.
 Some tapeworms have a projection that bears hooks.
This head, or scolex is used by the worm to attach to
tissues.
Tapeworm
Niclosamide
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 Mechanism of Action
 Niclosamide is a chlorinated salicylamide that inhibits
the production of energy derived from anaerobic
metabolism and inhibition of oxidative phosphorylation.
 Niclosamide is not absorbed from the intestinal tract,
high concentrations can be achieved in the intestinal
lumen.
 Adverse Effects
 No serious side effects are associated with niclosamide
use
 some patients report abdominal discomfort and loose
stools.
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TREATMENT FOR INFECTIONS
CAUSED BY TREMATODES
 Trematodes (flukes) are nonsegmented
helminths that are often leaflike in shape.
flattened
 Most have two suckers, one found around the mouth
(oral sucker) and the other on the ventral surface. Most
are hermaphroditic
 Diarrhea, abdominal pain, and anorexia are common
symptoms associated with trematode infestation. Liver
flukes may cause bile duct blockage, liver enlargement,
upper right quadrant pain, and diarrhea.
Praziquantel
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The neuromuscular effects of praziquantel appear to
increase parasite motility leading to paralysis.
 The drug increases calcium permeability through parasitespecific ion channels by protein kinase C- binding site in b
sub unit of schistosome voltage gated channel, so that
muscle cells of the parasite accumulate calcium leads to
paralysis and death.
 Praziquantel is readily absorbed (80% in 24 hours) after oral
administration, with serum concentrations being maximal
in 1 to 3 hours; the drug has a half-life of 0.8 to 1.5 hours.
Praziquantel is excreted by the kidneys.
 Side effect
 gastrointestinal intolerance with nausea, vomiting, and
abdominal discomfort.
 This may be due to the liberation of helminth proteins from
dead worms rather than any direct effect of the drug
Oxamniquine
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 MA
 The drug may act by esterification and binding of DNA,
leading to the death by interruption of its nucleic acid
and protein synthesis.
 The fluke may esterify oxamniquine to produce a
reactive metabolite that alkylates parasite DNA.
 Oxamniquine is given orally and is readily absorbed
from the intestinal tract. Peak concentrations in plasma
are obtained in about 3 hours. The drug is excreted in
urine mostly as a 6-carboxyl derivative
 Side effect
 CNS toxicity with unsteadiness and occasionally seizures,
especially in patients with a history of seizures.
 It is contraindicated in pregnancy.
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Bithionol
 MA
 Bithionol is a phenolic derivative whose mode of action
is related to uncoupling of parasite specific fumarate
reductase–mediated oxidative phosphorylation leads to
death of parasites.
 The drug is administered orally and is absorbed from the
intestinal tract. Peak blood levels are achieved in 4 to 8
hours. Excretion is mainly by the kidneys.
 Side effects
 nausea, vomiting, diarrhea,
urticaria, and other skin rashes
headache,
dizziness,
Choice of drugs for helminthiasis
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no
worm
1st choise
2nd choise
1
Round worm
Ascaris lumbricoides
Mebendazole Piperazine,
,
livamisole,iver
albendazole, mictim.
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Hook worm
Ancylostoma
Necator americanus
Mebendazole levamisole
, albendazole
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Thread worm
Mebendazole piperazine
Enterobius vermicularis , albendazole
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Filaria
Wuchereria bancrofti,
Brugia malayi
Diethyl
carbamazepi
ne, ivermictin
albendazole
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Tape worm
T.Saginata
T.Solium
Hymenolepsis nana
Praziquantel,
miclosamide
albendazole
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References
1. Goodman LS, Hardman JG, Limbird LE, Gilman AG.
Goodman and Gilman's the pharmacological basis of therapeutics:
McGraw-Hill; 2001.
2. Rang HP, Dale M. Pharmacology: Churchill Livingstone,
Elsevier; 2007. page no:712-716
3. Tripathi KD. Essentials Of Medical Pharmacology: Jaypee
Brothers Medical Publishers; 2008.page no:808-815
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