ANTHELMINTICS PHARMACOLOGY

Agung Nova Mahendra

Department of Pharmacology & Therapy,

Faculty of Medicine, UNUD
 Introduction
Anthelmintic Drugs: used against invasion of parasitic worms (helminthiasis)
roundworms, pinworms, whipworms, hookworms and tapeworms in animals &
human.

Broad spectrum anthelmintics are effective against parasitic flat worms

(trematodes) and nematodes.

However, the majority of drugs are more limited in their action, e.g., praziquantel
(PZQ)

Despite the prevalence of parasitic worms, anthelmintic drug discovery is the

poor relation of the pharmaceutical industry.
 Parasitic worms of Importance in the hygiene & sanitation field

• Nematodes: Ascaris spp., Onchocerca spp., Ancylostoma spp., Necator

americanus, Trichuris trichiura., Rhabditis spp., Enterobius spp.

• Trematodes: Schistosoma spp., Fasciola hepatica

• Cestodes: Taenia spp., Hymenolepis spp., Echinococcus granulosus,

Multiceps multiceps
Anthelmintics Classes
Class Members
BENZIMIDAZOLE (BZD) Thiabendazole, Mebendazole, Albendazole,
Flubendazole
IMIDAZOTHIAZOLE Levamisole, Butamisole
TETRAHYDROPYRIMIDINE Pyrantel, Morantel, Oxantel
QUARTERNARY Bephenium, Theniuna
AMMONIUM SALTS
TILE PYRIMIDINE Methyridine
MACROCYCLIC LACTONE Avermectin, Ivermectin,
ANTIBIOTICS
OTHERS AMINO ACETONITRILE DERIVATIVE & SPIROINDOLE:
Monepantel, Derquantel-Abamectin combination
Anthelmintics Classes
Class Members
OTHERS Niclosamide
OTHERS PIPERAZINE DERIVATIVE: Diethylcarbamazine (DEC)

OTHERS Oxamniquine
OTHERS Praziquantel (PZQ)

It is hard to eradicate helminthiases because of the close relationship

between these diseases & poverty

The demand for new and effective anthelmintic is immense, as:

• The chemically drugs currently employed in the control of helminth is expensive
• Most of them lose their efficacy in 20 years due to the problem of resistance
A. BENZIMIDAZOLES (BZ)
• PD:
• Inhibits microtubule formation  loss of transport of secretary vesicles,
• Impairs glucose uptake, promote glycogenolysis & ↓ ATP formation

• Other use: Mebendazole is also known as anti-melanoma agent, due

to cytoskeleton disrupting property  induces apoptosis
Albendazole
• Unique feature: able to cross BBB  used to treat CNS infection (neurocysticercosis)

• Broad spectrum: adult & larvae of most GI nematodes, cestodes, & trematodes;
suggested to be taken with fatty meals

• Effective as single dose treatment for:

• Ascaris lumbricoides (also ovicidal)
• Necator americanus (idem)
• Ancylostoma duodenale (idem)
• Trichuris trichiura (idem)
• Enterobius vermicularis
Thiabendazole
• Effective against: Strongyloidiasis (alternative drug is albendazole),
cutaneous larva migrans (CLM/creeping eruption), Trichinosis

• Up to date, there is little knowledge on the PD of this drug against

Echinococcosis
Potential candidate of novel BZ
Oxfendazole (OXF)
• Broad spectrum
• OXF has an excellent profile against a wide range of animal-infecting
gut nematodes  Good activity is therefore expected against the
similar human gut nematodes.
• Recent studies have shown that oxfendazole has excellent oral activity
which is comparable to flubendazole (currently known as the only BZ
with macrofilaricidal activity)

Gonzalez et al. Expert Rev Anti Infect Ther. 2019 January ; 17(1): 51–56
B. IMIDAZOTHIAZOLE
• Levamisole, Butamisole

• Pyrantel, Morantel, Oxantel Selective Agonists of Synaptic &

Extrasynaptic nAChRs
of body wall muscle
• Bephenium, Theniuna

• Methyridine SPASTIC PARALYSIS

Pyrantel Pamoate

• PD:
• promoting the release of acetylcholine
• inhibiting cholinesterase
• stimulating ganglionic neurons

• For the treatment of enterobiasis including:

• roundworm (ascariasis),
• pinworm (enterobiasis)
• hookworm (strongyloidiasis, ancylostomiasis)
Not recommended in pregnancy, lactation, & for those
who are < 2 yo, & with hepatic functional impairment
PHARMACOLOGICAL PEARLS
 ANTHELMINTICS
Antinematodes
• Active against Intestinal Nematodes: mebendazoles,
tiabendazoles, levamisole, piperazine, pyrantel
pamoate
• Active against Tissue Nematodes: ivermectin,
diethylcarbamazine (DEC)

Antiplatyhelminths:
• Active against Trematodes: praziquantel
• Active against Cestodes: praziquantel, niclosamide
 Antinematodal Pharmacodynamics
Mebendazole & Tiabendazole: benzimidazole derivative, bind to
beta tubulin  blocking organelles & secretory granules transport.

Levamizole: stimulates nicotinic ACh receptor of nematodal

neuromuscular junction (NMJ)  spasm & spastic paralysis

Piperazine: GABA agonist  flaccid paralysis

Pyrantel Pamoate: Cholinesterase inhibitor

Ivermectin: enhances GABA-mediated inhibition  flaccid

paralysis

Diethylcarbamazine (DEC): unknown PD (may modify parasite’s

tegument, thus it can be eradicated by host immune response)
 Creative
thinking…
Mnemonics on anthelmintics PDs:

Antinematodes
• Levamizole: Elevate muscle contractility  spasm
• -bendazoles: bind to beta tubulin (B-B-B)
• Piperazine: GABA channel looks like pipe  GABA receptor agonist
(GABA mimetic)
• Ivermectin: increases inhibition mediated by Glutamate-gated Cl-
channels (IG)

Antiplatyhelminthes
• Praziquantel: Platyhelminthes infections; prazite influx of qalcium
 Antinematodes Clinical Uses (DoC)

• Ascariasis: mebendazole & levamizole. Piperazine

is also effective (may cause diarrhea & vomiting)
• Hookworms inf: Mebendazole
• Strongyloidiasis: Tiabendazole, Albendazole, or
Ivermectin
• Threadworm/pinworm inf: Mebendazole
• Whipworm inf: Mebendazole
 Antinematodes Clinical Uses (DoC)

• Onchocerciasis: Ivermectin. DEC kills microfilaria

 exacerbates disease  ocular lesion

• Toxocariasis: DEC (kills organ- & ocular-migrating

larvae of Toxocara canis or T. cati
Antiplatyhelminths PD & Clinical Uses

Cestode inf : Praziquantel  increase Ca2+ influx

into parasite  flaccid paralysis  parasite
dislodgement
Trematode inf (Schistosomiasis/Bilharziasis):
Praziquantel

Note: praziquantel breaks tegmentum 

activation of host immune response & parasite
destruction
THANK YOU