The all the content in this profile is completed by the teachers, students as well as other health care peoples. thank you, all the respected peoples, for giving the information to complete this presentation. this information is free to use by anyone.

1. Antihelminthics
Ravish Yadav

2. Anthelmintics. (Anti = against, helminthes = worms)
Anthelmintics are drugs that have the capability of ridding the body of
parasitic worms or helminths. The prevalence of human helminthic
infestations is widespread throughout the globe and represents a major
world health problem
Vermicides : Drugs that kill worms
Vermifuges :Drugs that expel the worms from the body by
1)Peristaltic movement of intestine, or
2)cathartic and purgative action.
Characters of ideal anthelmintics:
1) Orally active.
2) Effective in single dose.
3) Inexpensive.
4) Wide safety margin between toxicity to worm and toxicity to host

3. Classification of Helminthes: they are two phyla
A]Phylum: Nemathelminthes. Class: Nematodes (true round worms)
I) Intestinal Nematodes: 1) Round worms as Ascaris. 2) Hookworms as
Ancylostoma. 3) Pinworms as Oxyuris. 4) Whipworms as Trichuris.
5) Thread worms as Strongyloids. 6) Enterobius Vermicularis.
II) Tissue Nematodes:Filaria.
B] Phylum: Platyhelminthes ( flatworms)
Class: Termatodes ( Flukes )
1) Liver flukes: Fasciola Hepatica. Fasciola Gigantica
.2) Blood flukes: Schistosoma haematobium. Schistosoma mansoni.
3) Intestinal flukes: Heterophyes heterophyes.
Class: Cestodes ( Tapeworms )
Beef tapeworm:Taenia saginata.
Pork tapeworm:Taenia solium.
Dwarf tapeworm:Hymenolepis nana.

4. A] Drugs active on Nematodes:
I] Piperazine derivatives: Diethylcarbamazine,
praziquantel.
II] Benzimidazole derivatives: Thiabendazole,
Mebendazole, Flubendazole, and Albendazole.
III] Vinylpyrimidine derivatives: Pyrantel pamoate.
VI] Ivermectins: Ivermectin

5. DiethylCarbamazine
N,N-Diethyl-4-methyl-1-piperazinecarboxamide
MOA:- diethylcarbamazine cause alterations in the microfilarial
surface membranes, thereby rendering them recognized as foreign
bodies by the host and destroyed by its defense mechanism
1) drug of choice in treatment of filariasis.
2) active against ascariasis.

6. Praziquantel
2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-
pyrazino[ 2,1-a] isoquinolin-4-one
Praziquantel 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.
It is a broadspectrum 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).

7. II] Benzimidazole derivatives:
H
N
N
S
N
Thiabendazole
2-(thiazol-4-yl)1H-benzimidazole
1
2
3
1
2
3 4
H
N
N
N
H
H3CO
O
O
Mebendazole
methyl-N-(5-benzoyl-1H-
benzimidazol-2-yl) carbamate
1
2
3 4 5
Flubendazole
H
N
N
N
H
H3CO
O
O
F
methyl-N-(5-(4-fluorobenzoyl)-1H-
benzimidazol-2-yl) carbamate
1
2
3 4 5
H
N
N
H
NH3CO
O
S
CH3
methyl-N-(5-propylthio-1H-
benzimidazol-2-yl) carbamate
Albendazole
1
2
3 4
5

8. SAR of benzimidazole derivatives
1) Substitition at C5 do not necessary increase potency but prevent
the metabolic inactivation of drug and thus enhances
amthelmintic activity.
2) Substitution at C2 with methyl carbamate (--NHCOCH3 ) or an
aromatic ring give active compounds , but those with aromatic or
heterocyclic ring are more toxic than those with carbamate. (
thiabendazole is the most toxic one).

9. Mode of action:
1) inhibition of certain enzyme: which is fumarate reductase
system of the worm thereby interfering with an important
energy source.
2)-inhibition of the cell division: inhibit nematode cell
division in the metaphase by interfering with the
microtubule assembly
3)-They have high affinity for tubulin, the precursor protein,
necessary for microtubule synthesis.
4)-they make irreversible blockade of glucose uptake by
susceptible helminthes, so depletion of glycogen stored
within the parasite leads to decrease in ATP, which is
responsible for survival and reproduction in helminthes.

10. No need for purgative use after oral administration
all of them have broad spectrum anthelmintic activity
mainly against intestinal nematodes, but,
1) thiabendazole also used in treatment of cutaneous
larva migrans.
2)mebendazole , flubendazole and albendazole
effective in some cestode worms.
• side effects of mebendazole and albendazole:
GIT side effects in normal doses.
Liver impairment, bone marrow depression in high
doses.
Should not given in pregnancy as teratogenic can
cross the placenta

11. 3) mebendazole, flubendazole, albendazole are less toxic
than thiabendazole due to:
a- they don not have heterocyclic ring in 2 position.
b- they are less absorbed from the GIT after oral
administration than in case of thiabendazole that is readily
absorbed from the GIT.

12. MOA:-
Depolarizing neuromuscular blocking agent that produce spastic paralysis in
susceptible helminthes followed by their expulsion from host. ( as pyrivinium
pamoate and piperazine derivatives ).*
* used in most intestinal nematode infection like pinworms and roundworms
(except whipworms).** piperazine may antagonize the effect of pyrantel so they
must not be used together.
Vinylpyrimidine derivatives: Pyrantel .

13. Ivermectin
Avermectins are members of a family of structurally complex antibiotics
produced by fermentation with a strain of Streptomyces avermitilis.
contain pentacyclic 16-membered–ring aglycones glycosidically linked at
the 3-position to a disaccharide that comprises two oleandrose sugar
residues.
The side chain at the 25-position of the aglycone is sec-butyl in
avermectin B1a, whereas in avermectin B1b, it is isopropyl.
Ivermectin contains at least 80% of 22,23-dihydroavermectin B1a and no
more than 20% 22,23-dihydroavermectin B1b.

14. Ivermectin has achieved widespread use in veterinary
Practice 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,
Ivermectin destroys the microfilariae, immature forms of the
nematode, which create the skin and tissue nodules that are
characteristic of the infestation and can lead to blindness.
Italso inhibits the release of microfilariae by the adult worms
living in the host.
MOA:- it blocks interneuron– motor neuron transmission in
nematodes by stimulating the release of the inhibitory
neurotransmitter GABA.

15. Drug active on cestodes
Niclosamide
OH
Cl
O
N
H
Cl
NO2
5-Chloro-N-(2-chloro-
4-nitrophenyl)-2-hydroxybenzamide
12
3
4
5
1 2
3
4
( 2-hydroxybenzamide = salicylamide )
2-
,5-dichloro-4-
-nitro salicylanilide

16. Niclosamide.1) interfere with helminthes metabolism where it inhibits
mitochondrial oxidative phosphorylation, inhibit respiration, block glucose
uptake by the cestode.2)after initial attack of the drug,helminthes ( taenia
solium ) become highly sensitive to the proteolytic enzymes of the host
intestine, undergo partial digestion.
** the drug of choice in treatment of most tapeworm infestations. (cestodes)
such as Taenia saginata, Taenia solium, Hymenolepis nana.
** the drug of choice in treatment of most tapeworm infestations.
(cestodes)** no systemic absorption of the drug occurs
.** the digestive juice of the host facilitates the drug penetration into various
cestodes.
** very important note:in case of Taenia solium, ( pork tapeworm):laxative
should be given within 1-2 hours after drug use to expel the dead worms and
to avoid cysticercosis [ as the drug is not active against the larval form
(cystcerci)].This cysticerci results from release of live ova from worm
segments damaged by the drug and migrate to the stomach.( now praziquantil
is the drug of choice in case of Taenia solium to avoid such limitation)

17. Worms (helminths) Drug of choice
Tapeworms (cestodes) Niclosamide or Praziquantel or
Albendazole
Roundworms (nematodes)
•Enterobius vermicularis (pinworm)
•Ascaris lumbricoides
•Trichuris trichiura (whipworm)
•Trichinella spiralis (trichinellosis)
•Strongyloides stercoralis
•Necator americanus (hookworm)
•Ancylostoma duodenale
•Onchocerca volvulus (Onchocercosis)
•Wuchereria bancrofti (Elephantiasis)
Mebendazole or Pyrantel
Mebendazole or Pyrantel
Mebendazole or Albendazole
Mebendazole
and Thiabendazole
Thiabendazole
Mebendazole or Pyrantel
Mebendazole, Pyrantel, or
Albendazole
Ivermectin
Diethylcarbamazine
Flukes (trematodes)
•Schistzoma (Schistozomes) Praziquantel

18. Synthesis of Mebendazole:-
Nitration of 4-chlorobenzophenone with nitric acid at a temperature lower than 5°C
gives 4-chloro-3-nitrobenzophenone, in which the chlorine atom is replaced with
an amino group by heating it to 125°C in a solution of ammonia in methanol to
make 4-amino-3-nitrobenzophenone. Reducing the nitro groups in this compound
with hydrogen using a palladium on carbon catalyst gives 3,4-
diaminobenzophenone . Mebebndazole is made by reacting 3,4-
diaminobenzophenone with N-methoxycarbonyl-S-methylthiourea.
4-chlorobenzophenone 4-chloro-3-nitrobenzophenone
3,4-diaminobenzophenone
N-methoxycarbonyl-S-methylthiourea
Mebendazole