Anthelmintics: Classification of Anthelmintics, Chemistry, Mechanism of action, Side effects and clinical use

1. Anthelmintics
• Mr. Hitesh Vishwanath Shahare
• Assistant Professor
• Dept. Ph.’ Chem.
• SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad

2. Introduction1
Classification, Structure & MOA2
Side effects3
Marketed Preparations4

3. Helminth
Helminths are macroscopic, multicellular organism, having their own digestive excretory
and reproductive system
Nematodes
Trematodes
Cestodes
They harm the host by depriving for food causing blood loss, injury to organs, intestinal
or lymphatic obstruction & by secreting toxins
Round worms
Fluke worms
Tape worms

4. Nematode
Infection
Helminth Infections
ENTROBIASIS
(Pin Worm)
ASCARIASIS
(Round worm)
Trematode
Infections SCHISTOSOMIASIS
(Fluke worm)
Cestode
Infections
HYDATID DISEASE
(Tape worm)

5. Anthelmintics
Any curative drug used to eradicate or reduce the
number of worms in GIT or Tissue is called Anthelmintics
Helminth: Worm

6. Classification
❑ Based on Mechanism of Action:
1. Inhibitors of Fumarate reductase and glucose uptake,
binding of tubulin in mitochondria
2. Inhibitors of mitochondrial phosphorylation
3. Inhibitors of glycolysis
Drugs affecting
energy production
Drugs causing
paralysis
1. Cholinergic agents
2. GABA agonist
3. Muscle Hyperpolarization
4. Acetyl cholinesterase inhibitors
5. Acetylcholine mimic

7. Classification
❑ Based on Type of Action:
Vermifuge
Vermicidal
Drug that expel infesting Helminth
Drug that kill infesting Helminth

8. Classification
❑ Based on Chemical Class:
No. Chemical Class Example
1. Phenols Dichlorophen
2. Chlorinated
Hydrocarbons
Tetraqchloroethylene
3 Antimonial Compounds Stibophen
4 Dye Suramin Na
No. Chemical Class Example
5 Heterocyclic Compounds
5.1 Benzimidazole derivatives Mebendazole, Albendazole
5.2 Piperazine derivatives Diethylcarbamazepine
5.3 Nitrothiazole derivatives Niridazole
No. Chemical Class Example
6. Miscellaneous
6.1 Salicylanilide Niclosamide
6.2 Organophosphate Metrifonate
6.3 Pyrimidine Pyrantel
6.4 Imidazothiazole Levamisol

9. Phenols
Used a Urinary Antiseptics
4-Chloro-2-[(5-chloro-2-hydroxyphenyl)methyl]phenol
Dichlorophen
2,2'-sulfanediylbis(4,6-dichlorophenol)
Bithionol
• Used in tapeworm infections
• Eliminate the worm from bowel
• Cause tissue irritation-so not used in patients with peptic ulcer

10. Chlorinated Hydrocarbons:
Tetrachloroethylene
• Against fluke worm, but now it is not used
• Antimonial Compound:
Stibophen
• Rarely used, High Toxicity and difficulty in administration
• Inhibit Phosphofructokinase which convert Fructose 6-
phosphate to Fructose 1,6-Diphosphate: Lack in energy source

11. Dye
• Mainly for treatment of sleeping sickness (Trypanosomiasis)
• SE: Diarrhea, Abdominal pain, Discomfort
Suramin Sodium
Lucanthone
• Yellow dye: Orally active
• Act by inhibiting Helminth ova production and its release
• Gives active Hydroxy metabolite: Hycanthone

12. Benzimidazole Derivatives
Mebendazole: Broad -spectrum oral anthelmintic drug-1972
Effective against various nematodes infestations including whipworm, pinworm,
roundworm & hookworm
Mechanism of Action:
•Selectively inhibiting the synthesis of microtubules via binding to colchicine binding site of β-tubulin,
thereby blocking polymerisation of tubulin dimers in intestinal cells of parasites.
•Disruption of cytoplasmic microtubules leads to blocking the uptake of glucose and other nutrients,
resulting in the gradual immobilization and eventual death of the helminths.
•It also blocks glucose uptake in parasite & deplets its glycogen stores.
Adverse Effect : Mild nausea, vomiting, diarrhoea and abdominal distress
Methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate

13. Benzimidazole
Albendazole: Broad -spectrum oral anthelmintic drug
Mechanism of Action: Similar to Mebendazole
Adverse Effect : Mild nausea, vomiting, diarrhoea and abdominal distress, insomnia
Thiabendazole: Broad -spectrum oral anthelmintic drug
Mechanism of Action: Inhibits the helminth-specific mitochondrial enzyme fumarate
reductase, thereby inhibiting the citric acid cycle, mitochondrial respiration and subsequent
production of ATP - leading to helminth's death
Adverse Effect : Loss of appetite Nausea, vomiting, diarrhoea
Methyl [5-(propylthio)-1H-benzoimidazol-2-yl]carbamate 4-(1H-1,3-Benzodiazol-2-yl)-1,3-thiazole

14. Piperazine
Diethylcarbamazine: Highly soluble crystalline compound , selective anthelmentic activity
Mechanism of Action: Sensitizing the microfilariae to get phagocytocize itself.
Clinical uses :
-In treatment of filariasis including lymphatic filariasis, tropical pulmonary eosinophilia
Adverse effects: Fever, GI disturbances
N,N-diethyl-4-methylpiperazine-1-carboxamide

15. Nitro-thiazole
Niridazole
Orally active
Anthelmentics, Antibacterial
MOA: Inhibit the oogenesis and spermatogenesis.
Inhibt the enzyme Phosphofructokinase : leading to glycogen depletion
Used to treat schistosomiasis
1-(5-Nitro-1,3-thiazol-2-yl)imidazolidin-2-one
SE: CNS toxicity and can cause dangerous side effects, such as Hallucinations

16. Quinoline
MOA: Inhibits glucose uptake, oxidative phosphorylation, and anaerobic
metabolism in the tapeworm
SE: Allergic-type reactions, including urticaria, pruritic skin rashes, and fever
Oxamniquine
1,2,3,4-Tetrahydro-2-isopropylaminomethyl
-7-nitro-6-quinolylmethanolTreatment of Schistosomiasis

17. MOA: Increases the permeability of the membranes of schistosome cells towards calcium
ions. The drug thereby induces contraction of the parasites' muscle, resulting in paralysis
Is often the preferred treatment
Quinoline
Praziquantel
2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-
pyrazino[2,1-a]isoquinolin-4-one
Adverse Effect: Headache, dizziness, stomach pain, nausea, tiredness, weakness,
joint/muscle pain, loss of appetite, vomiting, and sweating may occur

18. Salicylanilide
Niclosamide
Mechanism of Action : Inhibits glucose uptake, oxidative phosphorylation and anaerobic
metabolism in tapeworm.
5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
Used to treat tapeworm infections
SE: Abdominal pain, Constipation, and itchiness

19. Organophosphates
MOA: Irreversible organophosphate acetylcholinesterase inhibitor
Clinical Uses: Used to treat schistosomiasis, but not available commercially
Used as Insecticide
Metrifonate
Prodrug
Dimethyl (2,2,2-trichloro-1-hydroxyethyl)phosphonate

20. Ivermectin
Broad spectrum
Mechanism of Action: Causes an influx of Cl- ions through the cell membrane of
invertebrates by activation of specific Ivermectin-sensitive ion channels. The resultant
hyperpolarization leads to muscle paralysis.
Clinical Uses: Used to treat certain parasitic roundworm infections.
Adverse Effect: Headache, muscle pain, nausea, diarrhea, joint pain, weakness, red eye,
dry skin
Can be taken by mouth or applied to the skin for external infestations

21. Ivermectin

22. Pyrimidines
Mechanism of Action: Depolarizing Neuromuscular blocker, Release of Ach and inhibition
of cholinesterase, cause paralysis of worms
Clinical Uses : used to treat intestinal worm infections such as pinworm, roundworm, and
hookworm
Pyrantel:
Adverse Effect : Decreased Appetite, diarrhea, Difficulty sleeping, Dizziness, drowsiness,
Headache, nausea ,stomach cramps
1-Methyl-2-[(E)-2-(2-thienyl)vinyl]-5,6-dihydro-4H-pyrimidine

23. Imidazothiazol
Mechanism of Action : Agnositic activity towards the L-subtype nicotinic acetylcholine
receptors in nematode muscles. This agonistic action reduces the capacity of the males to
control their reproductive muscles and limits their ability to copulate..
Clinical Uses : For ascariasis and hookworm infections.
Adverse Effect : Nausea, vomiting, diarrhea, mouth sores, loss of appetite, stomach pain,
change in taste and smell, muscle aches, fatigue, dizziness.
Levamisole
6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole

24. Marketed Preparations

25. 16 September 2020 SNJB's SSDJ College of Pharmacy, Chandwad (Nasik) 25
shahare.hvcop@snjb.org
Thank You!
SNJBs Shriman Sureshdada Jain Coll. Ph. Chandwad