Novel anthelmintics

1. Chemotherapy Of
Helminthiasis
Presented by
Nyira shafi
Research scholar, Pharmacology
Deptt. Of Pharmaceutical sciences.
University of Kashmir.

2. ANTHELMINTIC DRUGS
•Anthelmintics are drugs that are used to treat infestation with
different species of parasitic helminths (worms) including both
flat worms, e.g., flukes and tapeworms and round worms, i.e.,
nematodes.
•WHO estimation - two billion people are suffering from
helminthiasis globally.
• Human is the primary host.
• In the human body GIT is the main harbor of many Helminths,
but some also reside in tissues or their larvae migrate into tissues.

3. ANTHELMINTIC DRUGS
•Helminthiasis generally occurs in low-income countries
including inhabitants of tropical and subtropical regions where
there is lack of proper sanitation and hygiene.
•Helminthiasis is rarely fatal, but is a major cause of ill health.
•They harm the host by depriving him of food, causing blood
loss, injury to organs, intestinal or lymphatic obstruction .

4. HELMINTIC INFESTATIONS
• Approximately 20 Helminth species are considered to be
clinically significant.
• Commonest among them are:
 ROUNDWORM INFESTATIONS( NEMATODES)
• Ascariasis
( Ascaris lumbricoid)
• Enterobiasis
( Enterobius vermicularis

5. HELMINTH INFESTATIONS
• Ancyclostomiasis
( Ancyclostoma duodenale)
• Cutaneous larva migrans
( Ancyclostoma duodenale
Larvae)
• Trichuriasis
( Trichuris trichiura)
• Elephantiasis
( Wuchereria bancrofti)

6. HELMINTH INFESTATIONS
• Onchocerciasis
(Onchocerca volvulus)
 FLUKE INFESTATIONS (TREMATODES)
• Fascioliasis
( Fasciola hepatica

7. HELMINTH INFESTATIONS
TAPEWORM INFESTATIONS( CESTODES)
Taeniasis/ Cystecerciasis
( Taenia solium)
• Hydatid disease
( Echinococcus granulosus)

8. ANTHELMINTICS
ANTHELMINTICS
VERMICIDAL
(KILLS PARASITE)
Examples: Benzimidazoles,
Praziquantel
VERMIFUGE
( EXPELS WORM)
Examples: Piperazine,
Ivermectin

9. CLASSIFICATION OF ANTHELMINTICS BASED ON
THEIR CHEMICAL STRUCTURE
•Benzimidazoles: Albendazole, Mebendazole, Thiabendazole.
•Piperazines: Diethylcarbamazine citrate (DEC), Piperazine .
•Heterocyclics: Oxamniquine, Praziquantel.
•Natural products: Ivermectin, Avermectin, Milbemycin
•Vinyl Pyrimidines: Pyrantel, Oxantel.
•Amide: Niclosamide.
•Nitro derivatives: Niridazole
•Imidazo thiazole: Levamizole.

10. NEWER ANTHELMINTIC DRUGS
 Aminophenylamidines: Tribendimidine
 Benzimidazole: Triclabendazole
 Macrocyclic Lactone: Moxidectin
 Diaminothienopyrimidines/ DATP

11. ALBENDAZOLE
•Albendazole is a benzimidazole carbamate, used worldwide
against a variety of parasites.
• Introduced in 1982 as an anthelmintic for human use.
• It is the gold standard to treat infections with soil-transmitted
helminths (STH) due its good safety and efficacy profile.
•MOA : Its vermicidal activity is due to
inhibition of Glucose uptake and depletion of glycogen stores
that is critical for parasite growth.
 Drug binds to intracellular β – tubulin of parasite and
preventing their polymerization to form microtubules, ultimately
leads to death of the parasite due to collapse of parasitic
cytoskeleton .
 Binding to β – tubulin also inhibits cell division.

12. ALBENDAZOLE
•Pharmacikinetics:
 relatively water insoluble and is poorly absorbed in the
intestine.
 Eating fatty meals enhances absorption.
Metabolised in liver and primarily excreted in urine.
T Half = 8.5 hrs.

13. ALBENDAZOLE
•Clinical uses
• Ascaris, hookworm, Enterobius and Trichuris: a single dose of
400 mg (for adults and children above 2 yrs), 200 mg for 1–2 yr
age. Three day treatment may be needed in heavy trichuriasis.
• Neurocysticercosis: ADZ crosses blood brain barrier so it is the
anthelmintic drug of choice for the treatment of
neurocysticercosis; 400 mg BD for 8- 15 days
• Hydatid disease: 400 mg BD for 4 weeks (repeat after 2 weeks if
required up to 3 courses).
• Cutaneous larva migrans: 400 mg daily for 3 days.

14. ALBENDAZOLE
• contraindications:
Liver diseases and Pregnancy.
• Interactions: The plasma concentration and half life of ADZ
increase when it interacts with cimetidine.
• Cimetidine inhibit the breakdown of ADZ sulfoxide by
interfering with CYP3A4
• Adverse Effects: Elevated liver enzymes, abdominal pain,
nausea, vomiting, fever.
• Major serious side effect : myelosuppression ( including
leucopenia, anemia, thrombocytopenia, and pancytopenia)

15. MEBENDAZOLE
• Mebendazole (MEB) is a typical broad spectrum benzimidazole
used for more than 20 years in human and veterinary medicine
to treat a variety of parasitic infestations.
• MOA : Same as that of Albendazole.
• Pharmacokinetics:
Poor oral bioavailability.
Clearance is predominantly as metabolites in bile and feces.

16. MEBENDAZOLE
•Clinical uses:
 100 mg tablet / 5ml suspension
 MBZ is one of the preferred drugs for the treatment of
Ascaridosis, Cerebral Echinococcosis and Trichuriasis.
 More effective than Albendazole in Trichuriasis.
MBZ shows other pharmacological actions like Tubulin
depolymerization, Apoptosis and cytoxicity and inhibition of
Angiogenesis , kinases and Signal transduction pathways
involved cancer progression due to these facts MBZ is under
evaluation for anticancer activity and was tested first time for
same in 2002.

17. MEBENDAZOLE
• Contraindications:
 in first trimester as it has shown some teratogenic influence in
Rats.
Interactions:
 Stevens–Johnson syndrome and the more severe toxic
epidermal necrolysis can occur when mebendazole is
combined with high doses of metronidazole.
• ADRS:
 same as that of albendazole.

18. THIABENDAZOLE
• It is the first benzimidazole poly-anthelmintic introduced in
1961.
• MOA: Same as that of other Benzimidazoles.
• PK:
Rapidly absorbed orally
 Plasma half life is 1.2 hrs .
Excreted via urine.
C/I:
 Pregnancy
Hepatic and Renal Dysfunction
•ADRS:
Same as that of others benzimidazoles.

19. THIABENDAZOLE
• Clinical uses:
25mg/kg/day is given in a two day course for:
Stronglyloidosis
 CLM
Trichinosis
Shows some antipyretic, analgesic and anti-inflammatory
actions hence produce symptomatic effect in:
Cutaneous Larva Migrans
 Inflammation in tissues due to Larva and Worms

20. PIPERAZINE / PIPERAZINE CITRATE
• Piperazine was first used as an anthelmintic in 1950.
• MOA:
•PK: Orally active and partly metabolized in liver and
Excreted in urine.
shows GABA mimetic action opening Cl- channels leads to
hyperpolarization of worm muscle
Relaxation and inhibits contractile action of Ach.
Flaccid paralysis of worm muscles and worm is expelled out
by normal peristalsis

21. PIPERAZINE / PIPERAZINE CITRATE
• Uses:
 Ascaridosis: 4 g OD for 2 days
 Enterobiosis: 50 mg/kg (max. 2 g) OD for 7 days.
 Safe in pregnancy.
•C/I: Renal dysfunction and Epilepsy
•ADRs: Blurring of vision, hypersensitivity and convulsions.

22. Diethylcarbamazine (DEC)
• DEC (piperazine derivative) was first developed in 1948, and
is first antifilariasis drug.
• MOA:
DEC alters MF membranes so that they are readily
phagocytosed by tissue fixed monocytes and also
piperazine moiety of DEC causes hyperpolarization
affects the activity of MF and adult worms.
• PK:
 Absorbed after oral ingestion.
 Metabolised in liver and excreted in urine ( faster in
acidic urine).
 Plasma half life 4-12 hrs.

23. Diethylcarbamazine (DEC)
•USES:
 Filariasis: 2 mg /kg TDS for 7 days.
 Tropical eosinophilia: 2-4 mg/ kg TDS for 2-3 weeks.
 Loa Loa and O. volvulus: DEC if produces allergic
reactions on test dosing then Ivermectin is preferred for
initial treatment.
• The Dec produces synergistic effects in combination with
Emodepside( a semi synthetic anthelmintic drug ) and led to the
development of resistance-busting regimen for helmintic infection
in case of animals .
• ADRs: Nausea, hypotension, enlargement of lymph nodes and
pruritus .

24. PRAZIQUANTEL
• Pyrazin isoquinoline derivative.
• Developed after its discovery as an anthelmintic compound in
1972.
• Effective in animals and humans against Cestodes and
Trematodes.
• Not effective against Nematodes.

25. PRAZIQUANTEL
Increase in membrane permeability to Ca ions
Contraction
Spastic paralysis
Worm expelled out
• MOA:

26. PRAZIQUANTEL
• PK:
 Rapidly absorbed with 80% oral bioavailability.
Excretion via kidneys and bile
• USES:
 Liver fluke : 25mg/kg TID
 Blood fluke: 20mg/kg TID
 Intestinal fluke: 25mg/kg TID

27. PRAZIQUANTEL
C/I:
 Children below age 4 yrs.
 Contraindicated for the treatment of ocular
cystecercosis because destruction of parasite in the eye
may damage the organ.

28. OXAMNIQUINE
• Semisynthetic tetrahydroquinoline derivative.
• MOA: Acts by DNA binding, resulting in contraction and
paralysis of the worms and eventual detachment from the
mesentery, leads to the death.
•PK:
 Plasma half life is 1-2.5 hrs
 Excreted in urine.
• USES:
 Effective against Schistosoma mansoni.
Dose: 15-20mg/ kg single dose.
• C/I: Pregnancy and Epilepsy

29. IVERMECTIN
•Ivermectin is a semisynthetic derivative of Avemectin B
(was first isolated by fermentation of a soil microorganism,
the actinomycete Streptomyces avermitilis ).
• Belongs to class Macrocyclic lactones.
• In 1996 FDA its use for Onchocerciasis and Strongyloidiasis.
• PK :
 Absorption is rapid when given orally on an empty
stomach
 half-life of 36 hrs

30. IVERMECTIN
• MOA:
Binds to glutamate activated Cl channel in nerve and muscle
Hyperpolarization by increasing permeability of Cl channel
Causes paralysis of worm and ultimately death

31. IVERMECTIN
Clinical uses:
Strongyloidiasis 200 mcg/kg/day for 2 days
Onchocerciasis
Lymphatic filariasis 400mcg/kg/yr
Loa loa 8-10mg/kg/day for 3 weeks
Tropical Pulmonary
Eosinophilia 6-10mg/kg/day for 3 weeks
150mcg/kg single dose

32. IVERMECTIN
• C/I : PREGNANCY
• ADRs:
 Fatigue, dizziness, GI disturbance
 Hypotension, Tachycardia
 Corneal opacities
 Mazzoti Like Reaction:
Life threatening & chracterized by fever, urticaria,
swollen lymph nodes, tachycardia and abdominal pain
that occurs within seven days of treatment of
microfilariasis.

33. IVERMECTIN
Recently FDA has
approved
IVERMECTIN to
inhibit the replication
of SARS-CoV-2 in
Vitro, therefore
IVERMECTIN
warrants further
investigations for
possible benefits in
humans.

34. PYRANTEL POMATE
• Pyrantel pomate is a tetrahydopyrimidine derivative.
• MOA:
Depolarizing neuromuscular blocking agents
Causes release of Ach & inhibition of cholinesterase
Contraction , paralysis & expulsion of worm
• PK:
 Poor oral absorption
 Peak plasma conc. 1-3hrs
 Excreted in urine

35. PYRANTEL POMATE
• Clinical uses:
• Pyrantel pomate is an alternative to Mebendazole
 Ascaris: 11 mg/kg
 Enterobiasis: 200 mcg /kg BD once a month
 Hookworm Infestations: 200 mcg/kg oral dose
•C/I
 Pregnancy and Children

36. NICLOSAMIDE
• Amide derivative.
• Introduced in 1960s for human use as a taeniacide.
•Clinical uses:
 Taenea saginata ( beef worm) – A single 2g dose
 T. solium ( Pork tapeworm) – A single 2g dose

37. NICLOSAMIDE
• MOA:
Inhibits the parasite’s mitochondrial phosphorylation of
ADP
Disrupts formation of ATPs & also Anaerobic
metabolism
Ultimately death of the parasite

38. NICLOSAMIDE
• Poorly absorbed from GIT.
• ADRs: Nausea, vomiting and abdominal discomfort.
RESEARCH
 In 2016 a Drug repurpose screening study suggested that
niclosamide may inhibit zika virus replication in vitro.

39. LEVAMISOLE
• Imidazothiazole derivative
• Anthelmintic and Immunomodulator
• MOA:
 Acts as a nAchR agonist resulting in spastic paralysis and
ultimately death of the organism.
 Interference with carbohydrate metabolism (inhibition of
fumarate reductase) may also be contributing .
• Clinical uses:
 Used for treatment of Ascaridosis and Ancylostomiasis.
 Levamisole is listed as an anthelmintic for human use
(WHO Model List of Essential Medicines, 2013) but is rarely
used in practice due to its low therapeutic index.

40. NIRIDAZOLE
• Nitro Derivative
• Alternative for the treatment of Dranacunculiasis
( guinea worm)
• Used for the treatment of Schistosomiasis (Schistosomo
hematobium blood fluke )
• Intestinal and extra intestinal amoebiasis
• DOSE: 25mg/kg

41. NEWER ANTHELMINTICS
TRIBENDIMIDINE
 Belongs to class Aminophenylamidine
 Developed in 1980s by China, as a broad spectrum
anthelmintic drug .
 In 2004, tribendimidine was approved by the Chinese Food
and Drug Administration for treatment of helminth infections
in humans.

42. NEWER ANTHELMINTICS
TRIBENDIMIDINE
• MOA: Acts as nAchR agonist causing spastic paralysis and
leads to death of the parasite.
• Efficacy And Uses
• Broad spectrum anthelmintic.
• Tribendimidine shows same efficacy as that of albendazole
in the depletion of helminths.
• Its efficacy is similar as that praziquantel against liver fluke
infestation.

43. NEWER ANTHELMINTICS
TRICLABENDAZOLE
 Triclabendazole, a benzimidazole derivastive, was developed
and marketed by Ciba to treat fascioliasis in livestock and has
been in veterinary use since the 1980s.
 FDA approved Triclabendazole for human use in 2019.
The development of triclabendazole for human use started
during the 1990s via a collaboration between Ciba and the
WHO.
 Triclabendazole has been used in fascioliasis control programs
by WHO through a donation program in endemic countries.

44. NEWER ANTHELMINTICS
TRICLABENDAZOLE
•MOA:
Triclabendazole and its active metabolites (sulfoxide and
sulfone )
inhibition of tubulin function
as well as protein and enzyme synthesis.
Clinical uses:
• Triclabendazole is effective against all stages of Fasciola
spp. in humans.

45. NEWER ANTHELMINTICS
MOXIDECTIN
• Moxidectin, a macrocyclic lactone obtained from Streptomyces
bacteria, was developed during the 1980s.
• In 2018, the FDA approved moxidectin for the treatment of
onchocerciasis (river blindness) in humans.
•MOA:
 Causes Hyperpolarization followed by muscle paralysis .
 It also inhibits intra-uterine embryogenesis and release of
microfilariae from the adult worms.

46. NEWER ANTHELMINTICS
MOXIDECTIN
• Uses and efficacy:
 Useful in the treatment of Onchocerciasis ; a single
dose of 8 mg
 Shows resistance busting effects over Ivermectin
 More potent than Ivermectin
More effective than standard regimens of Ivermectin

47. NEWER ANTHELMINTICS
DIAMINOTHIENOPYRIMIDINES OR DAPTS
• The (DATPs) is a new class of anthelmintic compounds.
• The DATPs, possesses activity against adult stages of
whipworm, and also block the development of the model
nematode C. elegans.
• DATP compounds reduce the ability of treated eggs to
successfully establish infection in a mouse model of human
whipworm.
• Importantly, as a chemical series the DATPS are notable,
since they are relatively facile to produce synthetically thereby
presenting considerable scope for structural modifications to
improve efficacy and deliver an optimized agent.

48. DRUG OF CHOICE FOR VARIOUS ANTHEL MINTIC
INFESTATIONS IN HUMANS
Source: wormbooks.org

49. FUTURE ANTHELMINTICS
• Here are some compounds showing anthelmintic activity and
may prove to be useful in the future for the treatment of in the
various helmintic infestations.
• These compounds are in pipeline for the development of novel
anthelmintics for both human and livestock use.
Paraherquamide
and Derquantel
Induce flaccid paralysis in parasitic
nematodes in vitro. Currently in veterinary use
Fluensulfone
Has proven effective against plant
parasitic nematode infections

50. FUTURE ANTHELMINTICS
Closantel (a salicylanilide)
Monepantel: Amino-
acetonitrile derivative
Filaricidal , effective against
onchocerciasis
Anhelmintic in sheeps
Active against Covid 19
Spiroindolines: SYN351
Anthelmintic activity studied in
Caenorhabditis elegans.
Emodepside:
(Cyclooctadepsipeptides)
Anthelmintic for cats and dogs ;
recently introduced in market

51. ANTHELMINTIC VACCINE
Cysvax
• First ever licensed Vaccine in India (2017)
• A novel recombinant porcine cysticercosis vaccine developed
by Indian Immunological Limited.
• Used in pigs to stop larva infection by Teania solium in them
,in turn protecting human from neurocysticercosis (
neurocysticercosis contributes 30% to world total epilepsy cases).
Formulation:
Each dose of 1 ml contains
T. Solium onchosphere antigen
(TSOL 18) 150µg.

52. ANTHELMINTICS FROM KASHMIR VALLEY
Artemesia absinthium
Allium sativum

53. Ajuga bracteosa
Nelumbo nucifera
Peganum harmala

54. Plant species with traditional anthelmintic activities reported in
humans & animals in Kashmir valley, India
Plant species Local name Part used
Acacia arabica Kekar Root and bark
Euphorbia royleana Guir sochel Aerial plant
Juglans regia Doon Bark and leaf
Achillea millifolium Pahel- ghass Whole herb
Ajuga bracteosa Jani-adam Whole herb
Allium sativam Rohun Bulb
Artemisia absinthium Tethwan Whole herb

55. Continued;
Plant species Local name Part used
Nelumbo nucifera Pamposh Whole plant
Nepata cataria Gand soi/ Barei ghass Whole plant
Cannabis sativa Bhangh Leaf
Ocimum basilicum Babire baeol seeds
Peganum harmala Issband seeds
Platanus orientalis Boin Bark, Seeds
Prunella vulgaris Kalaveuth Root and Bark
Urtica dioica Soi Leaf