ANTELMINTIK

Oleh :
Faizal hermanto, S.Si., M.Si., Apt.

Out line Presentation

Pendahuluan
Pengelompokan Helmint
Pengobatan infeksi cacing

- target kerja Antelmintik

- obat antelmintik

introduction

Anthelmintics
are drugs that either kill (vermicide) or expel
(vermifuge) infesting heminths
high affinity to the parasite, but lowest
toxicity
to the host

In the human body they live in:

GIT,
Tissues or their larvae migrate into tissues

They harm the host by:

depriving him food,
causing blood loss,
injury to organs, intestinal or lymphatic

obstruction and

by secreting toxins

Group of Helminth

3 Groups of Helminth
Helminth

Nematodes
(roundworms
)

Intestinal
nematodes

Blood and
tissue
nematodes

Trematodes
(flukes)

Blood fluke

Cestodes
(flatworms
and
tapeworms)

Lung and liver

flukes

Nematodes (round worms)

Nematode usus

Enterobius vermicularis (pinworm/Kremi)

Ascaris lumbricoides (C.Gelang)
Trichuris trichiuria (C. Cambuk)
Hookworms
Ancylostoma duodenale
Necator americanus (C.Tambang)
Strongyloides stercoralis (C. benang)
Trichinella spiralis (c. otot)
7

Nematode darah dan jaringan

Filariae

Wuchereria bancrofti.
Obstruction of lymphatic vessels and
elephantiasis.
Filariasis.
Brugia malayi
Loa loa (inflammation of skin, eye)
Onchocerca volvulus
(ONCHOCERCIASIS or River blindness)
8

Trematodes (flukes)
Schistosoma species

(blood fluke)
S. mansoni
S. japonicum
S. haematobium
Fasciolopsis buski
(Intestinal fluke)

Fasciola hepatica (Sheep liver fluke)

Clonorchis sinensis (Chinese liver

fluke)
Paragonimus westermani (Lung fluke)

Cestodes (tape worms)

Taenia saginata
(beef tapeworm)
Taenia solium
(pig tapeworm)
Hymenolepis nana
(dwarf tapeworm)
Diphyllobothrium

latum

(fish tapeworm)

10

Pengobatan infeksi
cacing

 Agonist acetylcholine

Anthelmintics Target
Inhibitor cholinesteras

Increase influx calcium

Neuromuscular transmission
Agonist GABA
muscle

Nerve
Work on chloride ion
Neurotransmitter palsu
channel
Contoh: Piratel, piperazin, befenium,

Energy Production
Enzymes involved
Flacid paralisis
Substrate

Contoh: Mebendazol, niclosamide, Spastic paralisis

Obat-Obat Untuk Pengobatan

Infeksi Cacing
Organisme yang
menginfeksi
Cacing gelang (nematoda)
Ascaris (gelang)
Trichuris (cambuk)
Necator (tambang)
Strongyloides (benang)
E. Vermicularis (peniti/kremi)
Kombinasi infeksi ascaris,
tricuris dan cacing tambang
W. Brancofti (filariasis); B.
Malayi (filariasis); Loa loa
Onchocerca volvulus
(onkosersiasis)

Obat pilihan

Obat
alternatif

Pir / Meb
Meb
Pir / Meb
Tib / Ivr
Meb / Pir

Pip, alb, atau Lev

Alb atau Pir
Alb atau Lev
Alb atau Meb
Alb

Meb / Alb

Alb

DEC
Ivr

Ivr
DEC + Suramin

Obat-Obat Untuk Pengobatan

Infeksi Cacing
Organisme yang
menginfeksi
Cacing pipih (trematoda)
Schistosoma
Clonorchis sinensis (pada
hati)
Paragonimus westermani
(pada paru)
Fasciola hepatica (pada hati
domba)
Fasciolopsis buski (pada usus
besar)
Cacing pita (cestoda)
T. Saginata ( pada sapi)
T. Solium ( pada babi)
Diphyllobothrium latum ( pada
ikan)

Obat pilihan

Obat
alternatif

Pra
Pra
Pra

Metrifonat
Oksamnikuin
Meb / Alb

Bitionol
Pra / niklosmid

Pra / emetin
Tetrakloretilen

Nik / Pra
Nik / Pra
Nik / Pra
Pra

Meb
Nik

 Benzimidazoles
1. Thiabendazole
2. Mebendazole
3. Albendazole

Tugas:
cari struktur molekul

Broad spectrum agents.

Bind to beta-tubulininhibit
polymerization interfere with glucose
uptake by the worm.
Reduced ATP formation.

Mebendazol
Merupakan

benzimidazol
sintetik
yang
mempunyai aktivitas antelmintik spektrum
luas
MK : menghambat sintesis mikrotubulus
nematoda mengganggu ambilan glukosa
parasit mati atau diimobilisasi. Bekerja
vermicid, larvacid dan ovicid.
Farkin : penggunaan oral diabsorpsi sekitar 10
%, ekskresi lewat empedu dan urin.

Mebendazol
KI : wanita hamil embriotoksik & teratogenik.
ES : jarang terjadi dan berupa sakit perut & diare
Penggunaan klinik :

- infeksi cacing kremi: 1 x 100 mg diulangi

pada minggu ke 2 dan ke 4.
- infeksi cacing gelang, tambang, benang, pita
dan cambuk 2 dd 100 mg selama 3 hari bila
perlu diulang setelah 3 minggu.

Tiabendazol
Suatu benzimidazol sintetik
MK :mengganggu agregasi

mikrotubular
melalui
penghambatan
enzim
fumarat
reduktase. Bekerja larvacid dan ovicid.
Farkin : resopsi cepat diusus, sebagian besar
dikeluarkan melalui urin.
KI : wanita hamil
ES : mual, muntah, anoreksia, dan pising.

Tiabendazol
Penggunaan

klinis : nematoda khususnya

strongyloidiasis dan trichinosis serta larva
migran pada kulit. Dosis 15 mg/Kg BB,2 dd 1
PC. Selama 2-4 hari.

Albendazol
Antelmintik

spektrum
luas,
memiliki
karena penggunaannya single

keuntungan
dose
MK : menghambat ambilan glukosa oleh larva
dan parasit stadium dewasa, mengurangi
penyimpanan glikogen dan menurunkan
pembentukan ATP.
ES : gagngguan lambung-usus, alopesia,
demam.
KI : wanita hamil.

Albendazol
Penggunaan klinik :
Infeksi cacing askaris, kremi, tambang dan

trikuriasis dosis tunggal 400 mg.

Strongiloidiasis 1 dd 400 mg dc. Selama 7-14
hari.
Neurosistiserkosis : 15 mg/kg/hari selama 8 hari
plus steroid. Cysticercosis of other tissues (muscle,
subcutaneous area) also responds, but no drug should
be given for ocular cysticercosis-blindness can occur
due to the reaction.

Pirantel Pamoat
Derivat pirimidin yang merupakan antelmintik

spektrum luas dan efektif pada pengobatan

infeksi cacing kremi/peniti, askaris dan cacing
tambang.
Efektif terhadap cacing bentuk matur dan
imatur tetapi tidak efektif untuk stadium
migrasi dalam jaringan.

Pirantel Pamoat
MK :
Pyrantel activation worm nicotinic cholinergic receptors

persistent depolarization slow developing contracture and

spastic paralysis

It has high affinity to the worm cholinergic receptors

(selective tox.). It has low affinity to the

cholinergic receptors in mammalian skeletal muscle.
It has an anticholinesterase action
Antagonizes the action of piperazine

(piperazine hyperpolarization, flaccid

paralysis)

ES : gangguan saluran percernaan dan jarang

sakit kepala.
KI : wanita hamil
Pengguaan klinis :
Infeksi cacing kremi dan gelang : dosis
tunggal 2-3 tab @ 250 mg, anak-anak 10
mg/kgBB.
Infeksi cacing cambuk : dosis tunggal 2-3 tab
@ 250 mg selama 3 hari

Piperazine
Introduced 1950, highly active against ascariasis

and enterobiasis 100% cure rates;

second choice drug even for these worms

now,

Mechanism of action
It blocks neuromuscular transmission in round worm by

antagonizing ACh action and causing hyperpolarization

flaccid paralysis of the worm worms are expel alive
and recover if placed in piperazine free medium.

it does not affect neuromuscular transmission in man

lack of affinity for mammalian nicotinic cholinergic

receptors
selective tox.?

Pharmacokinetics
Oral absorbed, partially metabolized in liver and

excreted in urine.
It metabolites: mononitroso form is carcinogenic
25

Piperazine
Adverse effects
Safe and well tolerated
Nausea, vomiting, abdominal discomfort and
urticaria are occasional
Dizziness and excitement occur at high doses
Toxic doses: convulssion, death is due to
respiratory failure
Contraindicated in renal insufficiency and
epileptics, but it safe in the pregnant
Preparations
As its hexahydrate, or salts like citrate,

phosphate, adepate, all are water soluble and

tasteless
26

DEC
Uses

1. Filariasis:
2 mg/kg pc. produces rapid symptomatic relief; Mf disappear

from blood and patient become non infective to mosquitoes in

7 days; however, the adult worm survives in the lymphatics
and gives rise to intermittent microfilaria and symptoms.
Prolonged treatment with different schedules radical cure
A total dose of 72-126 mg/kg spread over 12 days to several
weeks satisfactory
> 1 courses are needed with a gap of 3-4 weeks

Elephantiasis (chronic lymphatic obstruction)

is not

affected by DEC
27

DEC
Uses
Loa loa and O. volvulus: small doses 25-50 mg initially

Preparations
50, 100 mg tab., 120mg/5mL syr., 50mg/5mL pediatric syr.;
inj. 200mg DEC + CPZ maleate 5 mg and lignocaine 20mg in
10 mL vial

DEC
Adverse effects
Nausea, loss of appetide, headache, weakness and

dizziness are common but generally not serious.

A febrile reaction with rash, pruritus, enlargement of

lymph nodes and fall of BP may occurs due to mass

destruction of Mf and adult worms mild to severe.

The reaction can be minimized by

starting

with a low doses (0.5 mg/kg)

Given an antihistaminics and/or Corticosteroids

Leukocytosis and mild albuminuria are also noted

The Mazzoti Reaction very common side

effect and may be fatal

The Mazzoti reaction an immune response to the

antigens that are released from dead or dying microfilariae:

papular rashes, severe itching, tachycardia and headache.

IVERMECTIN
Is an extremely potent semisynthetic derivative of the

antinematodal principle obtained from Streptomyces

avermitilis.

Drug of choice for Onchocerciasis and

strongyloidiasis

Alternative drug for single dose treatment of W. bancrofti, B.

malayi, Ascariasis, Enterobiasis, and trichuriasis.

Effective in visceral larva migrans

Mechanism of action
- nematodes tonic paralysis due to potentiation of
GABAergic
transmission in the worm
Action through a special type of glutamate gate Clchannel
in the susceptible worms.
* such channels are not involved in the motor control of
cestodes and trematodes, they are unaffected by
ivermectin
- It has low affinity to mammalian GABA receptors and

8. IVERMECTIN

A single 10-15 mg oral dose of ivermectin long

lasting reduction of Mf counts in onchocerciasis

without affecting the adult worm.
WHO:

ivermectin replaced DEC for onchocerciasis (river blindness)

control programmed

Side effects:
Mild: pruritus, giddiness and transients ECG

changes
Swelling of the face and lower limbs
More important are reactions due to degradation
product of the Mf

IVERMECTIN

Semisynthetic analog of avermectin.

Potent drug against human filaria infection,

Oncocerciasis (river blindness).

Could be used for W. bancrofti (elephantiasis).

Not effective against cestodes and trematodes.

Intensifies GABA-mediated neurotransmission and

causes tonic paralysis of the musculature.

Opens glutamate-gated chloride channels (found

only in invertebrates).

In humans, GABA is a neurotransmitter only in the

CNS, and Ivermectin does not cross the bloodbrain barrier.

Selective toxicity.
33

PRAZIQUANTEL

Uses
1. Tapeworms

- Single dose cure rate 90-100%

- T. saginata, T. solium: 10 mg/kg single dose in the morning
- H. nana, D. latum: 15-25 mg/kg single dose in the morning
in case of heavy infestation, re-treatment after 1 week

2. Neurocysticercosis

- 1st drug for neurocysticercosis: 50 mg/kg daily in 3 divided

doses for 15 days kills the larvae lodged in brain and
other
tissues.
Albendazole equally and more effective.
Praziquantel and Albendazole are being used as first line base
therapy
- also effective for dermal cysticercosis, but contraindicated in
ocular cycticercosis

3. Scistosomes
- all three species can be treated with 40-75 mg/kg given once
or in

divided dose in one day.

PRAZIQUANTEL
Broad spectrum drug.
Effective against schistosomes and
cysticercosis.
Human and animal trematodes,
cestodes, and nematodes.
Increases membrane permeability to

calcium, causing marked contraction

initially and then paralysis of trematode
muscles; followed by vacuolization and
parasite death.

PRAZIQUANTEL
Praziquantel (Biltricide) Increases cell membrane

permeability in susceptible worms, resulting in loss of

intracellular calcium, massive contractions, and
paralysis of musculature.
Also produces vacuolization and disintegration of
schistosome tegument. This is followed by
attachment of phagocytes to parasite and death.

Tabs should be swallowed whole with some liquid

during meals. Keeping tabs in mouth may release
bitter taste that can produce nausea or vomiting.

PRAZIQUANTEL

Pharmacokinetics
Rapidly absorbed from git and undergo first pass

metabolism in liver which limit its systemic

bioavailability

Phenytoin, Carbamazepin, and possibly

dexamethazone induce P metabolism reduce its

bioavailability

It crosses BBB conc. in the

brain and CSF

T1/2 is short (1.5 h)

Metabolites are excreted chiefly in urine

PRAZIQUANTEL

Adult Dose
- 50-100 mg/kg/d PO divided tid for 14 d (with
cimetidine at 300 mg PO qid if patient also taking
steroids or anticonvulsants)
- Longer courses (months) may be needed for
extraparenchymal infections
- Preliminary studies suggest alternative dosage
regimen of
75 mg/kg given in single day (25 mg/kg q2h for
total of 3 doses) may have similar efficacy
Pediatric Dose Administer as in adults

PRAZIQUANTEL

Adverse effects
despite systemic absorption no systemic

toxicity.

It tastes bitter can produce nausea

others: abdominal pain, headache, dizziness

and

sedation

when used for schistosomes and visceral flukes

destroyed parasite produce symptoms

like:
itching, urticaria, rashes, fever, and
bodyache

No interaction with food, alcohol, or with

tobacco

Contraindications
Documented hypersensitivity; ocular
cysticercosis; NCC resulting in cerebral edema,

11. PRAZIQUANTEL

Interactions

Significant first-pass metabolism when coadministered with corticosteroids,

carbamazepine, phenytoin, or, probably,
phenobarbital;
levels decrease by approximately one half
compared with praziquantel alone;
cimetidine co-administration significantly
inhibits metabolism and should be used to
counterbalance effect of concurrent
steroids or anticonvulsants
Pregnancy - Usually safe but benefits must

outweigh the risks.

PRAZIQUANTEL

Precautions

Destruction of parasite within eyes can

cause irreparable lesions (ocular
cysticercosis should not be treated with
praziquantel);
Caution while driving or performing other
tasks requiring alertness on day of and
following treatment;
Minimal increases in liver enzymes
reported;
When schistosomiasis or fluke infection
associated with cerebral cysticercosis,
hospitalize patient for duration of treatment
41

NICLOSAMIDE
1960 highly effective against cestodes: Taenia

saginata, T. solium, Diphyllobothrium latum and

Hymenenolepis nana and thread worm

Mechanism of action
- to act by inhibiting oxidative phosphorylation in
mitochondria and interfering with anaerobic
generation of ATP by the tape worm.
- Injured by niclosamide, the tape worm are partly
digested
in the intestine.
- In case of T. solium, digested of dead
segments can be hazardous, because the ova
released from them develop into larvae in
the intestine, penetrate its wall and cause
visceral cysticercosis

NICLOSAMIDE
Regimen for tape worm
Niclosamide (0.5 g tab.) after light breakfast, 2
tablets chewed, swallowed with water, followed
by another 2 tablets after 1h (total 2g);
Total dose for children 2-6 yrs is 1g
A saline purge is given 2h after the later dose to
wash off the worm
The scolex should be searched in the stools to be
sure that the worm will not grow again

NICLOSAMIDE
Regimen for tape worm
*

For H. nana, the 2g dose is repeated daily for 5

days needed because the cycticerci of H. nana
(which are not affected by niclosamide) develop in
jejunal villi of the same host and worm appear in
the intestinal lumen after 4 days.
However, no purgative is required.
Treatment may have to be repeated after
10 days

NICLOSAMIDE

Adverse effects
Niclosamide is tasteless and non irritating
Minimally absorbed from git no systemic tox.
occurs.
It is well tolerated minor abdominal symptoms
Malaise, pruritus and light headache are rare.
Safe during pregnancy and in patient with poor
health

Kesimpulan

Obat-Obat Untuk Pengobatan

Infeksi Cacing
Organisme yang
menginfeksi
Cacing gelang (nematoda)
Ascaris (gelang)
Trichuris (cambuk)
Necator (tambang)
Strongyloides (benang)
E. Vermicularis (peniti/kremi)
Kombinasi infeksi ascaris,
tricuris dan cacing tambang
W. Brancofti (filariasis); B.
Malayi (filariasis); Loa loa
Onchocerca volvulus
(onkosersiasis)

Obat pilihan

Obat
alternatif

Pir / Meb
Meb
Pir / Meb
Tib / Ivr
Meb / Pir

Pip, alb, atau Lev

Alb atau Pir
Alb atau Lev
Alb atau Meb
Alb

Meb / Alb

Alb

DEC
Ivr

Ivr
DEC + Suramin

Obat-Obat Untuk Pengobatan

Infeksi Cacing
Organisme yang
menginfeksi
Cacing pipih (trematoda)
Schistosoma
Clonorchis sinensis (pada
hati)
Paragonimus westermani
(pada paru)
Fasciola hepatica (pada hati
domba)
Fasciolopsis buski (pada usus
besar)
Cacing pita (cestoda)
T. Saginata ( pada sapi)
T. Solium ( pada babi)
Diphyllobothrium latum ( pada
ikan)

Obat pilihan

Obat
alternatif

Pra
Pra
Pra

Metrifonat
Oksamnikuin
Meb / Alb

Bitionol
Pra / niklosmid

Pra / emetin
Tetrakloretilen

Nik / Pra
Nik / Pra
Nik / Pra
Pra

Alb/Meb
Nik

N
o

Obat

MK

Penggunaan

Thiabendazo
le

Penghambatan produksi
energi (penghambatan
enzim fumarat
reduktase)

Nematoda :
strongyloidiasis dan
trichinosis

Mebendazole Penghambatan produksi

energi (mengganggu
ambilan glukosa )

Nematoda : Cacing
kremi, gelang, tambang,
pita, cambuk

Albendazole

Penghambatan produksi
energi
(menghambat
ambilan
glukosa
,
menurunkan
pembentukan ATP)

askaris, kremi, tambang

dan
trikuriasis
,
Strongiloidiasis,
Neurosistiserkosis

Pirantel
Pamoat

activation worm nicotinic Nematoda : Kremi,

cholinergic
receptors gelang, cambuk
persistent
depolarization

spastic paralysis

Piperazin

blocks neuromuscular
transmission
hyperpolarization
flaccid paralysis

Nematoda : Gelang,
kremi

N
o

Obat

MK

Penggunaan

Dietilkarbamazin
(DEC)

Penurunan kegiatan otot Nematoda :

dan
kemudian Filariasis, loa-loa,
melumpuhkan
O. volvulus
mikrofilaria.

Ivermectin

GABAergic transmission Nematoda :

in the worm tonic Onchocerciasis and
paralysis
strongyloidiasis
Trematoda dan
cestoda tdk
efektif

Praziquantel

Increases
membrane Schistosomiasis &
permeability to calcium Taenia.
paralysis
Fasciola hepatica
tdk efektif

Niklosamid

act by inhibiting
oxidative
phosphorylation ATP
tape worm decrease

cestodes: Taenia
saginata, T. solium,
Diphyllobothrium
latum and
Hymenenolepis

Terimakasih