Parasitic infections are caused by organisms that live and feed off another organism, known as the host, often causing harm in the process. These parasites can be single-celled organisms like protozoa or multicellular organisms like helminths (worms). Types of Parasitic Infections: 1. Protozoal Infections: Caused by single-celled organisms such as Plasmodium (malaria), Giardia lamblia (giardiasis), Entamoeba histolytica (amebiasis), and Trypanosoma (sleeping sickness, Chagas disease). 2. Helminthic Infections: Caused by parasitic worms including nematodes (roundworms), trematodes (flukes), and cestodes (tapeworms). Examples include Ascaris lumbricoides (roundworm), Schistosoma (schistosomiasis), and Taenia solium (tapeworm). 3. Ectoparasitic Infections: Caused by organisms that live on the external surface of the host's body, such as lice, fleas, ticks, and mites.

1. Medicinal Chemistry-III
Anthelmintics
Department of Pharmacy, Indira Gandhi National Tribal
University, Lalpur, Amarkantak (M.P.)
Dr. Akhilesh Tiwari
Assistant Professor
Department of Pharmacy,
IGNTU, Amarkantak
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2. Anthelmintics
Parasitic infections are caused by organisms that live and feed off another organism, known as the host,
often causing harm in the process. These parasites can be single-celled organisms like protozoa or
multicellular organisms like helminths (worms). Types of Parasitic Infections:
1. Protozoal Infections: Caused by single-celled organisms such as Plasmodium (malaria), Giardia lamblia
(giardiasis), Entamoeba histolytica (amebiasis), and Trypanosoma (sleeping sickness, Chagas disease).
2. Helminthic Infections: Caused by parasitic worms including nematodes (roundworms), trematodes
(flukes), and cestodes (tapeworms). Examples include Ascaris lumbricoides (roundworm), Schistosoma
(schistosomiasis), and Taenia solium (tapeworm).
3. Ectoparasitic Infections: Caused by organisms that live on the external surface of the host's body, such
as lice, fleas, ticks, and mites.
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3. Transmission:
- Parasites are often transmitted through contaminated food, water, soil, or vectors like mosquitoes,
flies, and ticks.
- Direct contact with infected individuals or animals can also lead to transmission.
- Some parasites have complex life cycles involving intermediate hosts or vectors before infecting
humans.
Symptoms:
- Symptoms of parasitic infections vary widely depending on the type of parasite and the affected
organ systems.
- Common symptoms include gastrointestinal disturbances (diarrhea, abdominal pain), fever,
fatigue, weight loss, anemia, skin rashes, and organ damage in severe cases.
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4. Diagnosis and Treatment:
- Diagnosis often involves laboratory tests such as stool examination, blood tests, or imaging studies.
- Treatment typically involves antiparasitic drugs, which may vary depending on the specific parasite and
the severity of the infection.
- Prevention measures include practicing good hygiene, avoiding contaminated food and water, insect
repellents, and vaccination where available.
- Parasitic infections remain a significant global health burden, particularly in tropical and subtropical
regions, where factors such as poor sanitation, limited access to clean water, and inadequate healthcare
infrastructure contribute to their prevalence. Efforts in research, prevention, and treatment are essential
to control and eliminate parasitic infections and improve public health worldwide.
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5. Antihelminthic drugs play a crucial role in combating parasitic infections caused by helminths, which are
multicellular worms that infect humans and animals. Here are several key reasons highlighting the
importance of antihelminthic drugs:
1. Control of Disease Burden: Helminthic infections affect millions of people worldwide, particularly in low-
resource settings where access to clean water, sanitation, and healthcare services is limited. These
infections can cause chronic diseases, malnutrition, anemia, and impaired growth and development,
especially in children. Antihelminthic drugs are essential for controlling the spread of these diseases and
reducing their impact on public health.
2. Prevention of Complications: Helminthic infections can lead to severe complications if left untreated.
For example, infections with intestinal worms like Ascaris lumbricoides and hookworms can cause
intestinal obstruction, malabsorption of nutrients, and anemia. Infections with tissue-invasive helminths
like Schistosoma spp. can lead to organ damage, including liver and bladder complications.
Antihelminthic drugs help prevent these complications by eliminating the parasites from the body.
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6. 3. Improvement of Quality of Life: Helminthic infections often cause debilitating symptoms such as
abdominal pain, diarrhea, fatigue, and skin rashes, which significantly impact the quality of life of
affected individuals. By effectively treating these infections with antihelminthic drugs, individuals
experience relief from symptoms, enabling them to lead healthier and more productive lives.
4. Prevention of Transmission: Many helminthic infections have complex life cycles involving
transmission between humans, animals, and intermediate hosts or vectors. By treating infected
individuals with antihelminthic drugs, the parasite burden is reduced, decreasing the likelihood of
transmission to others. Mass drug administration (MDA) programs, which involve treating entire
communities in endemic areas, have been successful in reducing transmission and controlling helminthic
infections such as lymphatic filariasis and onchocerciasis.
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7. Contribution to Global Health Initiatives: Addressing helminthic infections aligns with global health
goals such as the Sustainable Development Goals (SDGs), which aim to reduce the burden of
neglected tropical diseases (NTDs) and improve health equity worldwide. Antihelminthic drugs are an
essential component of integrated control programs targeting NTDs, contributing to the overall
improvement of public health and well-being.
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8. Types of Helminths
They are classified into three main groups based on their morphology and lifecycle: nematodes
(roundworms), trematodes (flukes), and cestodes (tapeworms).
1. Nematodes (Roundworms):
- Nematodes are cylindrical, unsegmented worms with a tough, flexible outer cuticle.
- Common examples include:
- Ascaris lumbricoides: Causes ascariasis, one of the most common helminthic infections worldwide,
transmitted through contaminated food and water.
- Enterobius vermicularis: Causes pinworm infection, predominantly affecting children, characterized by
itching around the anus.
- Trichuris trichiura: Causes trichuriasis (whipworm infection), transmitted through ingestion of soil
contaminated with feces.
- Hookworms (Ancylostoma duodenale and Necator americanus): Cause hookworm disease, transmitted
through skin penetration by larvae present in contaminated soil.
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9. 2. Trematodes (Flukes):
- Trematodes are flat, leaf-shaped worms with oral and ventral suckers for attachment.
- Common examples include:
-Schistosoma spp.: Causes schistosomiasis (bilharzia), a waterborne disease transmitted by freshwater snails. Schistosomiasis
affects millions of people in tropical and subtropical regions, leading to chronic complications such as liver and bladder
damage.
-3. Cestodes (Tapeworms):
- Cestodes are ribbon-like worms composed of a series of segments called proglottids.
- Common examples include:
- Taenia solium: Causes taeniasis (tapeworm infection), transmitted through ingestion of undercooked pork containing
cysticerci (larval stage).
- Taenia saginata: Causes taeniasis, transmitted through ingestion of undercooked beef containing cysticerci.
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10. How Helminths Infect Hosts
- Ingestion: Many helminths, especially nematodes and cestodes, infect hosts through the ingestion of
contaminated food, water, or soil. Eggs or larvae present in the environment are ingested and develop
into adult worms in the host's gastrointestinal tract.
- Penetration: Some helminths, particularly trematodes and a few nematodes, infect hosts by penetrating
the skin. Larvae in contaminated water or soil penetrate the skin barrier, enter the bloodstream, and
migrate to various organs or tissues where they develop into adult worms.
- Vector-Borne Transmission: Certain helminths, such as filarial nematodes, rely on vectors such as
mosquitoes or flies for transmission. Infective larvae are injected into the host's skin during a vector’s
blood-feeding activity, leading to infection.
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11. 2. Lifecycle of Common Helminths:
- Each helminth species has a distinct lifecycle involving multiple developmental stages and often
requiring intermediate hosts or vectors.
- For example:
- Nematodes typically have direct lifecycles, with eggs or larvae passed in the feces of infected hosts.
After environmental exposure, eggs hatch, and larvae develop into infective stages capable of infecting
new hosts.
- Trematodes often have complex lifecycles involving snail intermediate hosts. Eggs shed by adult worms
in the host's intestine release miracidia, which infect snails. Within the snail, the parasite undergoes
several developmental stages before releasing cercariae, which can infect vertebrate hosts.
- Cestodes have indirect lifecycles that involve intermediate hosts such as pigs, cattle, or fish. Ingestion
of intermediate hosts containing larval stages (cysticerci) leads to infection in the definitive host.
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12. 3. Sites of Infection in the Human Body:
- Gastrointestinal Tract: Many helminths, including roundworms and tapeworms, primarily infect the
gastrointestinal tract, where they attach to the intestinal mucosa and absorb nutrients from the host.
- Blood Vessels and Lymphatic System: Certain helminths, such as schistosomes and filarial nematodes,
inhabit the blood vessels or lymphatic system, where they cause damage and inflammation.
- Tissues and Organs: Helminths like tissue-invading nematodes (e.g., Trichinella spp.) and liver flukes
(e.g., Fasciola hepatica) can migrate to and infect various tissues and organs, leading to localized or
systemic disease.
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13. Source: Laudisi F, Marônek M, Di Grazia A, Monteleone G, Stolfi C. Repositioning of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System. International Journal of
Molecular Sciences. 2020; 21(14):4957. https://doi.org/10.3390/ijms21144957
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14. Classification of Antihelminthic Agents
1. Anthelmintic Agents:
- Anthelmintic agents are drugs used to treat infections caused by parasitic worms (helminths).
- They are classified based on their mechanism of action, target organism, and chemical structure.
2. Broad Categories of Anthelmintic Agents:
a. Benzimidazoles:
- Examples: Albendazole, Mebendazole, Thiabendazole.
- Mechanism of Action: Inhibit microtubule formation, leading to disruption of worm metabolism and
paralysis.
- Spectrum: Effective against a broad range of helminths, including nematodes and some cestodes.
b. Nicotinic Acetylcholine Receptor Agonists:
- Example: Pyrantel pamoate.
- Mechanism of Action: Stimulate nicotinic acetylcholine receptors in the nematode neuromuscular
junction, leading to paralysis and expulsion of the worm, Spectrum: Primarily effective against nematodes.
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15. c. Avermectins and Milbemycins:
- Examples: Ivermectin, Milbemycin.
- Mechanism of Action: Enhance chloride ion influx through glutamate-gated chloride channels in
nematode and arthropod nerve and muscle cells, leading to paralysis and death of the parasite.
- Spectrum: Broad-spectrum activity against nematodes and some ectoparasites.
d. Praziquantel:
- Mechanism of Action: Increases permeability of the parasite's cell membrane to calcium ions,
leading to muscle contraction, paralysis, and eventual death.
- Spectrum: Highly effective against cestodes and trematodes.
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16. 3. Other Anthelmintic Agents:
- Diethylcarbamazine (DEC): Used primarily for the treatment of lymphatic filariasis caused by filarial
nematodes, Nitazoxanide: Broad-spectrum anthelmintic with activity against protozoa and helminths.
- Tribendimidine: A synthetic anthelmintic agent effective against various nematodes.
4. Combination Therapies:
- Some anthelmintic drugs are combined to enhance efficacy, broaden the spectrum of activity, or delay
the development of drug resistance.
- Example: Albendazole combined with ivermectin for the treatment of lymphatic filariasis and
onchocerciasis.
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17. Diethylcarbamazine citrate
• Highly water-soluble crystalline compound that has selective anthelmintic activity
• It is effective against various forms of filariasis, including Bancroft, onchocerciasis, and
laviasis
• It is also active against ascariasis
• Mechanim- not clearly known
• Suggestion- inhibition of microtubule polymerization and disruption of preformed
microtubules
• Or interference with arachidonic acid metabolism
• Adverse reactions- anaphylactic reactions, intense pruritus, and ocular complications
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18. Thiabendazole
• White crystalline substance that is only slightly soluble in water but is soluble in strong
mineral acids.
• Thiabendazole is a basic compound with a pKa of 4.7 that forms complexes with metal ions
• Mechanism- inhibits the helminth-specific enzyme fumarate reductase (important enzyme in
helminthes that appears to be involved in oxidation of NADH to NAD for ATP production)
• Also arrest nematode cell division in metaphase by interfering with microtubule assembly
and exhibit a high affinity for tubulin, the precursor protein for microtubule synthesis
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19. Thiabendazole
• Has broad-spectrum anthelmintic activity
• It is used to treat enterobiasis, strongyloidiasis (threadworm infection), ascariasis,
uncinariasis (hookworm infection), and trichuriasis (whipworm infection)
• Also used to relieve symptoms associated with cutaneous larva migrans (creeping
eruption) and the invasive phase of trichinosis.
• Widely used in veterinary practice to control intestinal helminths in livestock
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20. Mebendazole
Broad-spectrum anthelmintic that is effective against various nematode infestations, including
whipworm, pinworm, roundworm, and hookworm
• Mechanism- irreversibly blocks glucose uptake in susceptible helminths, thereby depleting
glycogen stored in the parasite
• It apparently does not affect glucose metabolism in the host. It also inhibits cell division in
nematodes
• Poorly absorbed by the oral route
• Adverse reactions are uncommon and usually abdominal discomfort
• It is teratogenic in laboratory animals and should not be given during pregnancy
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21. Albendazole
• Broad-spectrum anthelmintic that is not currently marketed in North America
• Widely used throughout the world for the treatment of intestinal nematode infection
• It is effective as a single-dose treatment for ascariasis, New and Old World hookworm
infections, and trichuriasis
• Multiple-dose therapy with albendazole can eradicate pinworm, threadworm,
capillariasis, clonorchiasis, and hydatid disease
• Effectiveness of albendazole against tapeworms (cestodes) is generally more variable
and less impressive
• White crystalline powder that is virtually insoluble in water
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22. Albendazole
• Oral absorption of albendazole is enhanced by a fatty meal
• Drug undergoes rapid and extensive first-pass metabolism to the sulfoxide, which is the
active form in plasma
• Elimination half-life of the sulfoxide ranges from 10 to 15 hours
• High dose can result in adverse effects such as bone marrow depression, elevation of
hepatic enzymes, and alopecia
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23. Niclosamide
• Occurs as a yellowish white, water-insoluble powder
• Potent taeniacide that causes rapid disintegration of worm segments and the scolex
• Penetration of the drug into various cestodes appears to be facilitated by the digestive juices
of the host
• Niclosamide is well tolerated following oral administration, and little or no systemic
absorption of it occurs
• A saline purge 1 to 2 hours after ingestion of the taeniacide is recommended to remove the
damaged scolex and worm segments- mandatory
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24. Oxamniquine
• Antischistosomal agent that is indicated for the treatment of Schistosoma mansoni (intestinal schistosomiasis) infection
• Mechanism- Shown to inhibit DNA, RNA, and protein synthesis in schistosomes
• 6-hydroxymethyl group is critical for activity;
• metabolic activation of precursor 6-methyl derivatives is critical
• Free base occurs as a yellow crystalline solid that is slightly soluble in water but soluble in dilute aqueous mineral acids
and soluble in most organic solvents
• Dizziness and drowsiness are common, but transitory, side effects
• Serious reactions, such as epileptiform convulsions, are rare
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25. Praziquantel
• Broad-spectrum agent that is effective against various trematodes (flukes)
• It has become the agent of choice for the treatment of infections caused by
schistosomes (blood flukes)
• Effective treatment for fasciolopsiasis (intestinal fluke), clonorchiasis (Chinese liver
fluke), fascioliasis (sheep liver fluke), opisthorchosis (liver fluke), and paragonimiasis
(lung fluke)
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26. • Mechanism- increases cell membrane permeability of susceptible worms, resulting in the
loss of extracellular calcium. Massive contractions and ultimate paralysis of the fluke
musculature occurs, followed by phagocytosis of the parasite
• Oral administration, about 80% of the dose is absorbed
• Drug is rapidly metabolized in the liver in the first-pass
• White crystalline solid that is insoluble in water
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27. Ivermectin
• Is a mixture of 22,23-dihydro derivatives of avermectins B1a and B1b prepared by
catalytic hydrogenation
• Avermectins are members of a family of structurally complex antibiotics produced by
fermentation with a strain of Streptomyces avermitilis
• Ivermectin is active in low dosage against a wide variety of nematodes and
arthropods that parasitize animals
• Structure- pentacyclic 16-membered–ring aglycones glycosidically linked at the 3-
position to a disaccharide that comprises two oleandrose sugar residues
• Side chain at the 25-position of the aglycone is sec-butyl in avermectin B1a, whereas
in avermectin B1b, it is isopropyl
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28. avermectins B1a (-C2H5) and B1b (-CH3)
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29. Ivermectin
• Ivermectin contains at least 80% of 22,23-dihydroavermectin B1a and no more than
20% 22,23-dihydroavermectin B1b
• Widespread use in veterinary practice in the United States and many countries
throughout the world for the control of endoparasites and ectoparasites in domestic
animals
• It has been found effective for the treatment of onchocerciasis (“river blindness”) in
humans, an important disease caused by the roundworm Oncocerca volvulus
• Mechanism- It blocks interneuron–motor neuron transmission in nematodes by
stimulating the release of the inhibitory neurotransmitter GABA
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30. Diethylcarbamazine citrate- Synthesis
1-methylpiperazine
N, N-diethyl-4-methyl-1-piperazin
Carbonyl chloride
Citric acid
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31. Mebendazole- Synthesis
4-chlorobenzophenone
Nitration Reduction
methyl chloroformate
S-methylthiourea N-methoxycarbonyl-S-methylthiourea
3,4-diaminobenzophenone
3,4-diaminobenzophenone N-methoxycarbonyl-S-methylthiourea
Step 1
Step 2
Mebendazole
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