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ANTHELMINTIC DRUGS
BY
REVATHI SATYA SREE V
HELMINTHS
• Helminths (worms) are macroscopic, multicellular
organisms having their own digestive, excretory,
reproductive and nervous system.
• Helminths have a complex life cycle often
involving several host species.
• Infection by helminths may occur in many ways,
with poor hygiene a major contributory factor.
• Many enter by the mouth in unpurified drinking
water or in undercooked flesh from infected
animals or fish.
• However, other types can enter through the skin
following a cut.
• An insect bite or even after swimming or walking
on infected soil.
• Humans are generally the primary (or
definitive) host for helminth infections, in the
sense that they harbour the sexually mature
form that reproduces.
• Eggs or larvae then pass out of the body and
infect the secondary (intermediate) host.
• In some cases eggs or larvae may persist in the
human host and become encysted, covered
with granulation tissue, giving rise to
cysticercosis.
• Encysted larvae may lodge in the muscles and
viscera or more seriously in the eye or the
brain.
The helminths could be nemathelminths (round
bodied worms) or platyhelminths (flat bodied
worms).
• Nemathelminths include nematodes such as
intestinal round worms such as common round
worm (Ascaris lumbricoides), hook worms
(Necator americanus or Ancylostoma
duodenale), whip worms (Trichuris trichiura),
thread worms (Strongyloides stercoralis), pin
worms (Enterobius vermicularis).
• Tissue round worms such as filarias
(Wuchereria bancrofti or Brugia malayi),
onchocerciasis (Onchocerca volvulus) and
guinea worms (Dracunculus medinensis).
• Undercooked meat or contaminated food is an
important cause of infection by roundworm,
threadworm and whipworm, whereas hookworm
is generally acquired when their larvae penetrate
the skin. Blood loss caused by intestinal
hookworms is a common cause of anaemia in
regions where hookworm is endemic.
• In case of tissue roundworms adult filariae live in
the lymphatics, connective tissues or mesentery
of the host and produce live embryos or
microfilaria, which find their way into the
bloodstream.
• Platyhelminths are of two types:
TREMATODES (flukes) and CESTODES (tape
worms).
• Trematodes include blood flukes
(schistosomiasis or bilharziasis), liver flukes
(clonorchiasis), intestinal flukes
(fasciolopsiasis) and lung flukes
(paragonimiasis).
• The adult worms of both sexes live and mate in the
veins or venules of the bladder or the gut wall.
• The female lays eggs that pass into the bladder or
gut and produce inflammation of these organs,
resulting in haematuria in the former case and
occasionally, loss of blood in the faeces in the latter.
• The eggs hatch in water after discharge from the
body and thus enter the secondary host – a
particular species of snail.
• After a period of development in this host, free-
swimming cercariae emerge.
• These are capable of infecting humans by
penetration of the skin.
• Cestodes include beef tape worm (Taenia saginata),
pork tape worm (Taenia solium), fish tape worm
(Diphyllobothrium latum) and dwarf tape worm
(Hymenolepis nana).
• The usual intermediate hosts of the two common
tapeworms (T.saginata and T.solium) are cattle and
pigs respectively.
• Humans become infected by eating raw or
undercooked meat containing the larvae, which have
encysted in the animals’ muscle tissue.
• The infection is usually asymptomatic.
• . Humans become infected by eating raw or
incompletely cooked fish containing the larvae.
Anthelminthic drugs act either by paralysing the
parasite (e.g. by preventing muscular
contraction), or by damaging the worm such
that the immune system can eliminate it, or by
altering its metabolism (e.g. by affecting
microtubule function).
• The metabolic requirements of these parasites
vary greatly from one species to another,
drugs that are effective against one type of
worm may be ineffective against others.
• To be effective, a drug must able to penetrate
the tough exterior cuticle of the worm or gain
access to its alimentary tract.
• This may present difficulties because some
worms are exclusively haemophagous, while
others are described as tissue grazers
• The route of administration and dose of
anthelmintic drugs is very important.
• . A complication is that helminths also possess
active drug efflux pumps that reduce the
concentration of the drug in the parasite.
• Antihelminths attack the parasite cells but not
the mammalian cells and hence have selective
toxicity to the helminths only.
• Most available anthelmintic drugs exert their
antiparasitic effects by interfering with a)
neuromuscular functions, b) microtubular
functions, c) Ca+2 permeability and d) energy
metabolism.
Benzimidazoles
• Examples include Mebendazole,
tiabendazole and Albendazole.
• They are thought to act by inhibiting the
polymerisation of helminth β-tubulin, thus
interfering with microtubule-dependant
functions such as glucose uptake.
• They have a selective inhibitory action, being
250-400 times more effective in producing this
effect in helminth than in mammalian tissue.
• However, the effect takes time to develop and
the worms may not be expelled for several
days.
• Cure rates are generally between 60% and
100% with most parasites.
• Only 10% of Mebendazole is absorbed after
oral administration, but a fatty meal increase
absorption.
• It is rapidly metabolised, the products being
excreted in the urine and the bile within 24-48
hrs.
• It is generally given as a single dose for
threadworm, and twice daily for 3 days for
hookworm and roundworm infestations.
• Tiabendazole is rapidly absorbed from GIT,
very rapidly metabolised and excreted in the
urine in conjugated form.
• It is given twice daily for 3 days for guinea
worm and Strongyloides infestations, and for
up to 5 days for hookworm and roundworm
infestations.
• Albendazole is also poorly absorbed but, like
Mebendazole, this may be increased by food,
especially fats.
• It is metabolised extensively by first-pass
metabolism to the sulfoxide and sulfone
metabolites.
• Unwanted effects are few with Albendazole or
Mebendazole, although gastrointestinal
disturbances can occasionally occur.
• Unwanted effects with tiabendazole are more
frequent but usually transient, the
commonest being gastrointestinal
disturbances, although headache, dizziness
and drowsiness and allergic reactions may also
occur.
• Mebendazole is unsuitable for pregnant
women or children less than 2 years old.
PRAZIQUANTEL
• It is a highly effective broad-spectrum
anthelmintic drug that was introduced over 20
years ago.
• It is the drug of choice for all forms of
schistosomiasis and is the agent generally
used in large-scale schistosome eradication
programmes.
• It is also effective in cysticercosis.
• The drug effects not only the adult
schistosomes but also the immature forms
and the cercariae – the form of the parasite
that infects humans by penetrating the skin.
• The drug apparently disrupts Ca+2 homeostasis
in the parasite by binding to consensus
protein kinase C-binding sites in a subunit of
schistosome voltage-gated calcium channels.
• This induces the influx of the ion, a rapid and
prolonged contraction of the musculature,
and eventual paralysis and death of the worm.
• Praziquantel also disrupts the tegument of
the parasite, unmasking novel antigens, and
as a result it may become more susceptible to
the hosts normal immune responses.
• Given orally Praziquantel is well absorbed
much of the drug is rapidly metabolised to
inactive metabolites on first passage through
the liver, and the metabolites are excreted in
the urine.
• The plasma half-life of the parent compound
is 60-90 min.
• Praziquantel is considered to be a very safe
drug with minimal side effects in the
therapeutic dosage.
• Such unwanted effects as do occur are usually
transitory and rarely of clinical importance.
• Effects may be more marked in patients with
a heavy worm load because of products
released from the dead worms.
• Praziquantel is considered safe for pregnant
and lactating women.
PIPERAZINE
• Piperazine can be used to treat infections with
the common roundworm (A.lumbricoides) and
the threadworm (E.vermicularis).
• It reversibly inhibits neuromuscular
transmission in the worm, probably by
mimicking GABA at GABA-gated chloride
channels in nematode muscle.
• The paralysed worms are expelled alive by
normal intestinal peristaltic movements.
• It is administered with a stimulant laxative
such as senna to facilitate the expulsion of the
worms.
• Piperazine is given orally and some but not all
is absorbed.
• It is partly metabolised and the remainder is
eliminated, unchanged, via the kidney.
• The drug has little pharmacological action in
the host.
• When used to treat round worm, Piperazine is
active in a single dose.
• For thread worm, a longer course (7days) at
lower dosage is necessary.
• Unwanted effects may include gastrointestinal
disturbances, utricaria and bronchospasm.
• Some patients experience dizziness,
paraesthisias, vertigo and incoordination.
• The drug should not be given to pregnant
patients or to those with compromised renal
or hepatic function.
NICLOSAMIDE
• Niclosamide is widely used for the treatment
of tapeworm infections together with
Praziquantel.
• The scolex of the worm that attaches to the
host intestine and the proximal segment are
irreversibly damaged by the drug, such that
the worm separates from the intestinal wall
and is expelled.
• For T.solium, the drug is given in a single dose
after a light meal, usually followed by a
purgative.
• There is negligible absorption of the drug
from the GIT.
• Unwanted effects: nausea, vomiting, pruritus
etc,.
• May occur but generally such effects are few,
infrequent and transient.
DIETHYLCARBAMAZINE
• It is a Piperazine derivative that is active in
filarial infections caused by B.malayi,
W.bancrofti and L.loa.
• Diethylcarbamazine rapidly removes the
microfilariae from the blood circulation and
has a limited effect on the adult worms in the
lymphatics, but it has a little action on the
microfilariae in vitro.
• It may act by changing the parasite such that it
becomes susceptible to the hosts normal immune
responses.
• It may also interfere with helminth arachidonate
metabolism.
• The drug is absorbed following oral
administration and is distributed throughout the
cells and tissues of the body, excepting adipose
tissue.
• It is partly metabolised and both the parent drug
and its metabolites are excreted in the urine,
being cleared from the body within about 48 hrs.
• Unwanted effects are common but transient,
subsiding within a day or so even if the drug is
continued.
• Side effects from the drug itself include
gastrointestinal disturbances, arthralgias,
headache and a general feeling of weakness.
Allergic side effects referable to the products
of the dying filariae are common and vary
with the species of worm.
• In general, these start during the first days
treatment and last 3-7 days; they include skin
reactions, enlargement of lymph glands,
dizziness, tachycardia and gastrointestinal and
respiratory disturbances.
• When these symptoms disappear, larger dose
of the drug can be given without further
problem.
• The drug is not used in patients with
onchocerciasis, in whom it can have serious
unwanted effects.
LEVAMISOLE
• It is effective in infections with the common
roundworm (A.lumbricoides).
• It has a nicotine-like action, stimulating and
subsequently blocking the neuromuscular
junctions.
• The paralysed worms are then expelled in the
faeces. Ova are not killed.
• The drug is given orally, is rapidly absorbed
and is widely distributed.
• It crosses the blood-brain barrier.
• It is metabolised in the liver to inactive
metabolites, which are excreted via the
kidney.
• Its plasma half-life is 4hrs.
• When single-dose therapy is used, unwanted
effects such as mild gastrointestinal
disturbances are generally few and soon
subside.
IVERMECTIN
• First introduced in 1981 as veterinary drug,
Ivermectin is a safe and highly effective broad-
spectrum antiparasitic in humans.
• It is frequently used in global public health
campaigns and is the first choice of drug for
the treatment of filarial infections.
• It has also given good results against
W.bancrofti, which causes elephantiasis.
• A single dose kills the immature microfilariae
of O.volvulus but not the adult worms.
• Ivermectin is the drug of choice for
onchocerciasis, which causes river blindness
and reduces the incidence of this by up to
80%.
• It is also active against some roundworms:
common roundworms, whipworms and
threadworms but not hookworms.
• Chemically Ivermectin is a semisynthetic agent
derived from a group of natural substances,
the avermectins, obtained from an
actinomycete organism.
• The drug is given orally and has a half-life of
11hrs.
• It is thought to kill the worm either by opening
glutamate-gated chloride channels (found only in
invertebrates) and increasing Cl- conductance; by
binding to a novel allosteric site on the
acetylcholine nicotintc receptor to cause an
increase in transmission, leading to motor
paralysis; or by binding to GABA receptors.
• Unwanted effects include skin rashes and itching
but in general the drug is very well tolerated.
Anthelminthic drugs

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Anthelminthic drugs

  • 3. • Helminths (worms) are macroscopic, multicellular organisms having their own digestive, excretory, reproductive and nervous system. • Helminths have a complex life cycle often involving several host species. • Infection by helminths may occur in many ways, with poor hygiene a major contributory factor. • Many enter by the mouth in unpurified drinking water or in undercooked flesh from infected animals or fish. • However, other types can enter through the skin following a cut. • An insect bite or even after swimming or walking on infected soil.
  • 4. • Humans are generally the primary (or definitive) host for helminth infections, in the sense that they harbour the sexually mature form that reproduces. • Eggs or larvae then pass out of the body and infect the secondary (intermediate) host. • In some cases eggs or larvae may persist in the human host and become encysted, covered with granulation tissue, giving rise to cysticercosis. • Encysted larvae may lodge in the muscles and viscera or more seriously in the eye or the brain.
  • 5. The helminths could be nemathelminths (round bodied worms) or platyhelminths (flat bodied worms).
  • 6. • Nemathelminths include nematodes such as intestinal round worms such as common round worm (Ascaris lumbricoides), hook worms (Necator americanus or Ancylostoma duodenale), whip worms (Trichuris trichiura), thread worms (Strongyloides stercoralis), pin worms (Enterobius vermicularis).
  • 7. • Tissue round worms such as filarias (Wuchereria bancrofti or Brugia malayi), onchocerciasis (Onchocerca volvulus) and guinea worms (Dracunculus medinensis).
  • 8. • Undercooked meat or contaminated food is an important cause of infection by roundworm, threadworm and whipworm, whereas hookworm is generally acquired when their larvae penetrate the skin. Blood loss caused by intestinal hookworms is a common cause of anaemia in regions where hookworm is endemic. • In case of tissue roundworms adult filariae live in the lymphatics, connective tissues or mesentery of the host and produce live embryos or microfilaria, which find their way into the bloodstream.
  • 9. • Platyhelminths are of two types: TREMATODES (flukes) and CESTODES (tape worms).
  • 10. • Trematodes include blood flukes (schistosomiasis or bilharziasis), liver flukes (clonorchiasis), intestinal flukes (fasciolopsiasis) and lung flukes (paragonimiasis).
  • 11. • The adult worms of both sexes live and mate in the veins or venules of the bladder or the gut wall. • The female lays eggs that pass into the bladder or gut and produce inflammation of these organs, resulting in haematuria in the former case and occasionally, loss of blood in the faeces in the latter. • The eggs hatch in water after discharge from the body and thus enter the secondary host – a particular species of snail. • After a period of development in this host, free- swimming cercariae emerge. • These are capable of infecting humans by penetration of the skin.
  • 12. • Cestodes include beef tape worm (Taenia saginata), pork tape worm (Taenia solium), fish tape worm (Diphyllobothrium latum) and dwarf tape worm (Hymenolepis nana). • The usual intermediate hosts of the two common tapeworms (T.saginata and T.solium) are cattle and pigs respectively. • Humans become infected by eating raw or undercooked meat containing the larvae, which have encysted in the animals’ muscle tissue. • The infection is usually asymptomatic. • . Humans become infected by eating raw or incompletely cooked fish containing the larvae.
  • 13.
  • 14. Anthelminthic drugs act either by paralysing the parasite (e.g. by preventing muscular contraction), or by damaging the worm such that the immune system can eliminate it, or by altering its metabolism (e.g. by affecting microtubule function).
  • 15. • The metabolic requirements of these parasites vary greatly from one species to another, drugs that are effective against one type of worm may be ineffective against others. • To be effective, a drug must able to penetrate the tough exterior cuticle of the worm or gain access to its alimentary tract. • This may present difficulties because some worms are exclusively haemophagous, while others are described as tissue grazers
  • 16. • The route of administration and dose of anthelmintic drugs is very important. • . A complication is that helminths also possess active drug efflux pumps that reduce the concentration of the drug in the parasite. • Antihelminths attack the parasite cells but not the mammalian cells and hence have selective toxicity to the helminths only. • Most available anthelmintic drugs exert their antiparasitic effects by interfering with a) neuromuscular functions, b) microtubular functions, c) Ca+2 permeability and d) energy metabolism.
  • 17.
  • 18. Benzimidazoles • Examples include Mebendazole, tiabendazole and Albendazole. • They are thought to act by inhibiting the polymerisation of helminth β-tubulin, thus interfering with microtubule-dependant functions such as glucose uptake.
  • 19. • They have a selective inhibitory action, being 250-400 times more effective in producing this effect in helminth than in mammalian tissue. • However, the effect takes time to develop and the worms may not be expelled for several days. • Cure rates are generally between 60% and 100% with most parasites. • Only 10% of Mebendazole is absorbed after oral administration, but a fatty meal increase absorption.
  • 20. • It is rapidly metabolised, the products being excreted in the urine and the bile within 24-48 hrs. • It is generally given as a single dose for threadworm, and twice daily for 3 days for hookworm and roundworm infestations. • Tiabendazole is rapidly absorbed from GIT, very rapidly metabolised and excreted in the urine in conjugated form.
  • 21. • It is given twice daily for 3 days for guinea worm and Strongyloides infestations, and for up to 5 days for hookworm and roundworm infestations. • Albendazole is also poorly absorbed but, like Mebendazole, this may be increased by food, especially fats. • It is metabolised extensively by first-pass metabolism to the sulfoxide and sulfone metabolites.
  • 22. • Unwanted effects are few with Albendazole or Mebendazole, although gastrointestinal disturbances can occasionally occur. • Unwanted effects with tiabendazole are more frequent but usually transient, the commonest being gastrointestinal disturbances, although headache, dizziness and drowsiness and allergic reactions may also occur. • Mebendazole is unsuitable for pregnant women or children less than 2 years old.
  • 23. PRAZIQUANTEL • It is a highly effective broad-spectrum anthelmintic drug that was introduced over 20 years ago. • It is the drug of choice for all forms of schistosomiasis and is the agent generally used in large-scale schistosome eradication programmes. • It is also effective in cysticercosis.
  • 24. • The drug effects not only the adult schistosomes but also the immature forms and the cercariae – the form of the parasite that infects humans by penetrating the skin. • The drug apparently disrupts Ca+2 homeostasis in the parasite by binding to consensus protein kinase C-binding sites in a subunit of schistosome voltage-gated calcium channels. • This induces the influx of the ion, a rapid and prolonged contraction of the musculature, and eventual paralysis and death of the worm.
  • 25. • Praziquantel also disrupts the tegument of the parasite, unmasking novel antigens, and as a result it may become more susceptible to the hosts normal immune responses. • Given orally Praziquantel is well absorbed much of the drug is rapidly metabolised to inactive metabolites on first passage through the liver, and the metabolites are excreted in the urine. • The plasma half-life of the parent compound is 60-90 min.
  • 26. • Praziquantel is considered to be a very safe drug with minimal side effects in the therapeutic dosage. • Such unwanted effects as do occur are usually transitory and rarely of clinical importance. • Effects may be more marked in patients with a heavy worm load because of products released from the dead worms. • Praziquantel is considered safe for pregnant and lactating women.
  • 27. PIPERAZINE • Piperazine can be used to treat infections with the common roundworm (A.lumbricoides) and the threadworm (E.vermicularis). • It reversibly inhibits neuromuscular transmission in the worm, probably by mimicking GABA at GABA-gated chloride channels in nematode muscle.
  • 28. • The paralysed worms are expelled alive by normal intestinal peristaltic movements. • It is administered with a stimulant laxative such as senna to facilitate the expulsion of the worms. • Piperazine is given orally and some but not all is absorbed. • It is partly metabolised and the remainder is eliminated, unchanged, via the kidney. • The drug has little pharmacological action in the host.
  • 29. • When used to treat round worm, Piperazine is active in a single dose. • For thread worm, a longer course (7days) at lower dosage is necessary. • Unwanted effects may include gastrointestinal disturbances, utricaria and bronchospasm. • Some patients experience dizziness, paraesthisias, vertigo and incoordination. • The drug should not be given to pregnant patients or to those with compromised renal or hepatic function.
  • 30. NICLOSAMIDE • Niclosamide is widely used for the treatment of tapeworm infections together with Praziquantel. • The scolex of the worm that attaches to the host intestine and the proximal segment are irreversibly damaged by the drug, such that the worm separates from the intestinal wall and is expelled.
  • 31. • For T.solium, the drug is given in a single dose after a light meal, usually followed by a purgative. • There is negligible absorption of the drug from the GIT. • Unwanted effects: nausea, vomiting, pruritus etc,. • May occur but generally such effects are few, infrequent and transient.
  • 32. DIETHYLCARBAMAZINE • It is a Piperazine derivative that is active in filarial infections caused by B.malayi, W.bancrofti and L.loa. • Diethylcarbamazine rapidly removes the microfilariae from the blood circulation and has a limited effect on the adult worms in the lymphatics, but it has a little action on the microfilariae in vitro.
  • 33. • It may act by changing the parasite such that it becomes susceptible to the hosts normal immune responses. • It may also interfere with helminth arachidonate metabolism. • The drug is absorbed following oral administration and is distributed throughout the cells and tissues of the body, excepting adipose tissue. • It is partly metabolised and both the parent drug and its metabolites are excreted in the urine, being cleared from the body within about 48 hrs.
  • 34. • Unwanted effects are common but transient, subsiding within a day or so even if the drug is continued. • Side effects from the drug itself include gastrointestinal disturbances, arthralgias, headache and a general feeling of weakness. Allergic side effects referable to the products of the dying filariae are common and vary with the species of worm.
  • 35. • In general, these start during the first days treatment and last 3-7 days; they include skin reactions, enlargement of lymph glands, dizziness, tachycardia and gastrointestinal and respiratory disturbances. • When these symptoms disappear, larger dose of the drug can be given without further problem. • The drug is not used in patients with onchocerciasis, in whom it can have serious unwanted effects.
  • 36. LEVAMISOLE • It is effective in infections with the common roundworm (A.lumbricoides). • It has a nicotine-like action, stimulating and subsequently blocking the neuromuscular junctions. • The paralysed worms are then expelled in the faeces. Ova are not killed.
  • 37. • The drug is given orally, is rapidly absorbed and is widely distributed. • It crosses the blood-brain barrier. • It is metabolised in the liver to inactive metabolites, which are excreted via the kidney. • Its plasma half-life is 4hrs. • When single-dose therapy is used, unwanted effects such as mild gastrointestinal disturbances are generally few and soon subside.
  • 38. IVERMECTIN • First introduced in 1981 as veterinary drug, Ivermectin is a safe and highly effective broad- spectrum antiparasitic in humans. • It is frequently used in global public health campaigns and is the first choice of drug for the treatment of filarial infections. • It has also given good results against W.bancrofti, which causes elephantiasis.
  • 39. • A single dose kills the immature microfilariae of O.volvulus but not the adult worms. • Ivermectin is the drug of choice for onchocerciasis, which causes river blindness and reduces the incidence of this by up to 80%. • It is also active against some roundworms: common roundworms, whipworms and threadworms but not hookworms. • Chemically Ivermectin is a semisynthetic agent derived from a group of natural substances, the avermectins, obtained from an actinomycete organism.
  • 40. • The drug is given orally and has a half-life of 11hrs. • It is thought to kill the worm either by opening glutamate-gated chloride channels (found only in invertebrates) and increasing Cl- conductance; by binding to a novel allosteric site on the acetylcholine nicotintc receptor to cause an increase in transmission, leading to motor paralysis; or by binding to GABA receptors. • Unwanted effects include skin rashes and itching but in general the drug is very well tolerated.