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
4
Group of Helminth
3 Groups of Helminth
Helminth

Cestodes
Nematodes Trematodes
(flatworms and
(roundworms) (flukes)
tapeworms)

Intestinal Blood and tissue Lung and liver

Blood fluke
nematodes nematodes flukes
Nematodes (round worms)
 Nematode usus
– Enterobius vermicularis (pinworm)
– Ascaris lumbricoides (C.Gelang)
– Trichuris trichiuria (C. Cambuk)
– Hookworms
• Ancylostoma duodenale
• Necator americanus
– Strongyloides stercoralis (C.Kremi/benang)
– Trichinella spiralis (cacing 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)
9
Cestodes (tape worms)
 Taenia saginata
(beef tapeworm)
• Taenia solium
(pig tapeworm)
• Hymenolepis nana
(dwarf tapeworm)
• Diphyllobothrium latum
(fish tapeworm)

10
Pengobatan infeksi cacing
Obat-Obat Untuk Pengobatan
Infeksi Cacing
Organisme yang menginfeksi Obat pilihan Obat
alternatif
Cacing gelang (nematoda)
Ascaris (gelang) Pir / Meb Pip, alb, atau Lev
Trichuris (cambuk) Meb Alb atau Pir
Necator (tambang) Pir / Meb Alb atau Lev
Strongyloides (benang) Tib / Ivr Alb atau Meb
E. Vermicularis (peniti/kremi) Meb / Pir Alb
Kombinasi infeksi ascaris, tricuris
dan cacing tambang Meb / Alb Alb
W. Brancofti (filariasis); B. Malayi
(filariasis); Loa loa DEC Ivr
Onchocerca volvulus Ivr DEC + Suramin
(onkosersiasis)
Obat-Obat Untuk Pengobatan
Infeksi Cacing
Organisme yang menginfeksi Obat pilihan Obat
alternatif
Cacing pipih (trematoda)
Schistosoma Pra Metrifonat
Clonorchis sinensis (pada hati) Pra Oksamnikuin
Paragonimus westermani (pada Pra Meb / Alb
paru) Bitionol Pra / emetin
Fasciola hepatica (pada hati domba) Pra / niklosmid Tetrakloretilen
Fasciolopsis buski (pada usus besar)
Cacing pita (cestoda)
T. Saginata ( pada sapi) Nik / Pra Meb
T. Solium ( pada babi) Nik / Pra
Diphyllobothrium latum ( pada Nik / Pra
ikan) Pra Nik
Hymenolepis nana (cacing pipih
kecil)

Anthelmintics Target
 Neuromuscular transmission
 muscle
 Nerve
 Neurotransmitter  ”palsu”
 Contoh: Piratel, piperazin, befenium,
 Agonist acetylcholine
 Inhibitor cholinesterase
 Increase influx calcium
 Agonist GABA
 Work on chloride ion
channel

 Energy Production
 Enzymes involved
 Flacid paralisis
 Substrate

 Contoh: Mebendazol, niclosamide, dll
Spastic paralisis
 Tugas:
 Benzimidazoles cari struktur molekul

1. Thiabendazole
2. Mebendazole
3. Albendazole

 Broad spectrum agents.

 Bind to beta-tubulin—inhibit 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 keuntungan
karena penggunaannya single 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; now, second choice drug
even for these worms
 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
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 Cl- channel
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 its inability
to penetrate the blood-brain barrier
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
 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

 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 blood-brain barrier.
 Selective toxicity.
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 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, uncorrected hydrocephalus,
cysticerci near cerebral vessels, or ocular disease
11. PRAZIQUANTEL
Interactions
 Significant first-pass metabolism when co-
administered 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

40
 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