Helminths infect billions worldwide and effective drugs are available to treat most infections. However, drug costs are high. Mass treatment programs by WHO and governments have significantly reduced some infections. Anthelmintics expel or kill parasitic worms. They work by inhibiting worm metabolism or muscle paralysis. Common anthelmintic drugs include albendazole, mebendazole, pyrantel, and ivermectin. Praziquantel is effective against most flukes and schistosomes by increasing calcium permeability in the worm's tegument. While treatments are generally well tolerated, anthelmintic resistance has emerged as a threat to future control of parasitic worms.

1. DRUGS FOR INFECTIONS CAUSED
BY HELMINTHS
AMIR SOHAIL

2. Helminths

3. Helminths
• Helminths can be classified as
• nematodes (roundworms)
trematodes (flukes), and
cestodes (tapeworms)
• Responsible for infecting billions of people
throughout the world.
• Effective drugs are available to treat most
of
the helminthic infections, but the cost of
drug treatment is high.

4. • Fortunately, the World Health Organization
and government agencies have sponsored
mass treatment programs that appear to
have had a significant impact on some
helminthic infections, such as
schistosomiasis and onchocerciasis .

5. Anthelmintics
• Anthelmintics or antihelminthics are
drugs that expel parasitic worms
(helminths) from the body, by either
stunning or killing them. They may also be
called vermifuges (stunning) or
vermicides (killing).

6. Anthelmintics

7. Anthelmintic drugs
• Anthelmintic drugs usually act either by
inhibiting metabolism in the parasite (as
occurs when a benzimidazole drug is
used) or
• by causing muscle paralysis of the
parasite
(as occurs when praziquantel, or pyrantel
is used).

8. Anthelmintic drugs
• The anthelmintic drugs kill the parasites
without harming host cells, but the
molecular basis for their selective toxicity
is not entirely clear.
• In many cases, a single dose or a few
doses of the drug are curative.

9. Ideal Anthelmintic drugs
Broad spectrum
Effective against both mature and immuture
Parasite
Wide margin of safety
Not interfere with normal physiological funtions
of host
No or short residue period
Economical
Easy to administer

10. Drugs for Nematode Infections
• Albendazole
• Mebendazole
• Thiabendazole
• Pyrantel
• Ivermectin
• Diethylcarbamazine

11. Benzimidazole drugs
• albendazole
• fenbendazole
• oxfenbendazole
• thiabendazole
• mebendazole

12. MECHANISMS
• The benzimidazoles
(thiabendazole,mebendazole and
albendazole) bind to beta-tubulin and thereby
inhibit the polymerization of tubulin dimers to
form cytoplasmic microtubules in parasites.
This action impairs the uptake of glucose by
these organisms and leads to depletion of
glycogen stores and decreased production of
adenosine triphosphate (ATP). Eventually the
organisms are immobilized and die.

13. SPECTRUM AND INDICATIONS
• Albendazole and mebendazole are
primarily used to treat intestinal nematode
infections,
including ascariasis, hookworm infection,
pinworm infection, and whipworm
infection.
• For trichinosis, the anthelmintic drug is
usually given in combination with a
corticosteroid (e.g., prednisone) to relieve
the
inflammation.

14. PARASITIC RESISTANCE
• Resistance to the benzimidazoles is now a
worldwide problem in veterinary medicine,
but it is not yet a significant problem in
human medicine.

15. ADVERSE EFFECTS
• The adverse effects of thiabendazole include
anorexia, nausea, vomiting, paresthesias,
delirium, and hallucinations.
• Albendazole and mebendazole are well
tolerated and produce fewer adverse effects
than thiabendazole does. The most common
side effects of albendazole and mebendazole
are mild gastrointestinal discomfort. The high
doses of albendazole can cause hepatitis or
hematologic toxicity.

16. CONTRAINDICATIONS
• All of the benzimidazole drugs are
contraindicated during pregnancy because
of their potential to inhibit mitosis and
impair fetal development.

17. Pyrantel
• Pyrantel is a pyrimidine derivative. The
drug activates cholinergic nicotinic
receptors in the somatic muscles of
nematodes leading to persistent
depolarization and spastic
paralysis(depolarizing neuromuscular
blocker). The paralysed worms are
expelled.

18. Pyrantel

19. Pyrantel
• In contrast, pyrantel has no marked effect
on neuromuscular function in mammalian
species.
• This has led investigators to conclude that
the pharmacologic properties of nicotinic
receptors of nematode and mammalian
species are significantly different.

20. Pyrantel
• Pyrantel pamoate (ANTIMINTH) is
available as an oral suspension for
administration to children and adults who
have ascariasis, hookworm infection, or
pinworm infection.
• The drug is poorly absorbed from the gut
and
acts primarily within the intestinal tract. It is
usually well tolerated, but it can cause
abdominal cramps, anorexia, diarrhea,
and vomiting.

21. Ivermectin
• CHEMISTRY AND
PHARMACOKINETICS Ivermectin is a
semisynthetic derivative of avermectin, an
antibiotic obtained from
Streptomyces avermitilis.
• Ivermectin has a complex macrocytic
lactone structure. The drug is well
absorbed from the gut, undergoes hepatic
biotransformation, and is excreted in the
feces. Its elimination half-life is about 25
hours.

23. Ivermectin
• MECHANISMS. Ivermectin increases the
chloride permeability of invertebrate muscle
cells. This hyperpolarizes the cell membrane
and causes paralysis of the pharyngeal
muscles in helminths.
• Ivermectin is believed to activate the
glutamate- gated chloride channel in
invertebrate tissue, but it has no effect on
chloride ion permeability in mammalian
tissue.

24. Ivermectin
• SPECTRUM AND INDICATIONS.
Ivermectin is a broad-spectrum
anthelmintic drug that is active against a
wide range of nematodes. It has been
used to treat a number of intestinal
helminthic infections in domestic and
companion animals.
In humans, it is used to treat
strongyloidiasis, onchocerciasis, and
cutaneous larva migrans.

25. Ivermectin
• ADVERSE EFFECTS. Ivermectin is
usually well tolerated and produces few
adverse effects. Uncommonly; it causes
diarrhea, dizziness, or sedation.

26. Drugs for Trematode and
Cestode Infections
• MECHANISMS. Each schistosome is surrounded
by a tegument. Praziquantel acts to increase the
calcium permeability of the tegument and thereby
cause its depolarization. When the outer bilayer of
the tegument is damaged, Schistosoma antigens
that were previously hidden from host defenses
are exposed. This enables host immune cells to
move in and attack the schistosomes. Thus,
praziquantel acts to facilitate host immunity to
these flukes.
• The drug's mechanism of action in other flukes
and in tapeworms is unknown but is thought to be
similar to that in schistosomes.

28. Drugs for Trematode and
Cestode Infections
• SPECTRUM AND INDICATIONS.
Praziquantel is active against most tissue
flukes, including the Chinese liver fluke
(Clonorchis sinensis), the lung fluke
(Paragonimus wester-
mani), and the various Schistosoma
species that cause human infections.

29. Drugs for Trematode and
Cestode Infections
• ADVERSE EFFECTS. Adverse effects are
uncommon but include abdominal
discomfort, dizziness, drowsiness, and
headache.

30. Other Drugs
• Triclabendazole is the drug of choice for the treatment
of
sheep liver fluke infection (Fasciola hepatica infection).
Bithionol is an alternative drug for the treatment of
sheep
liver fluke and lung fluke infection (P. westermani
infection).
• Oxamniquine is used as an alternative to praziquantel
for
Schistosoma mansoni infections, but it is not useful in
treat-
ing infections caused by other Schistosoma species.
• Niclosamide an alternative to praziquantel for treating
cestode infections.

31. Anthelmintic resistance
• The ability of worms to survive treatments that are
generally effective at the recommended dose rate
is considered a major threat to the future control of
worm parasites. This is especially true of
nematodes and has contributed to the
development of aminoacetonitrile derivatives for
treatment against drug resistant nematodes.
• Treatment with an antihelminthic drug kills worms
whose phenotype renders them susceptible to the
drug. Worms that are resistant survive and pass
on their "resistance" genes. Resistant worms
accumulate and finally treatment failure occurs