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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/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)
9
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 cholinesterase
Increase influx calcium
Neuromuscular transmission
muscle Agonist GABA
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 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)
Fasciola hepatica (pada hati domba) Bitionol Pra / emetin
Fasciolopsis buski (pada usus besar) Pra / niklosmid Tetrakloretilen
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)
Tugas:
Benzimidazoles cari struktur molekul

1. Thiabendazole
2. Mebendazole
3. Albendazole

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 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
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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

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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 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
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

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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 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)
Fasciola hepatica (pada hati domba) Bitionol Pra / emetin
Fasciolopsis buski (pada usus besar) Pra / niklosmid Tetrakloretilen
Cacing pita (cestoda)
T. Saginata ( pada sapi) Nik / Pra Alb/Meb
T. Solium ( pada babi) Nik / Pra
Diphyllobothrium latum ( pada Nik / Pra
ikan) Pra Nik
Hymenolepis nana (cacing pipih
kecil)
No Obat MK Penggunaan
1 Thiabendazole Penghambatan produksi Nematoda : strongyloidiasis
energi (penghambatan dan trichinosis
enzim fumarat reduktase)
2 Mebendazole Penghambatan produksi Nematoda : Cacing kremi,
energi (mengganggu ambilan gelang, tambang, pita,
glukosa ) cambuk
3 Albendazole Penghambatan produksi askaris, kremi, tambang dan
energi (menghambat trikuriasis , Strongiloidiasis,
ambilan glukosa , Neurosistiserkosis
menurunkan pembentukan
ATP)
4 Pirantel activation worm nicotinic Nematoda : Kremi, gelang,
Pamoat cholinergic receptors cambuk
persistent
depolarization spastic
paralysis
5 Piperazin blocks neuromuscular Nematoda : Gelang, kremi
transmission
hyperpolarization
flaccid paralysis
No Obat MK Penggunaan
6 Dietilkarbamazin Penurunan kegiatan otot dan Nematoda : Filariasis,
(DEC) kemudian melumpuhkan loa-loa, O. volvulus
mikrofilaria.
7 Ivermectin GABAergic transmission in Nematoda :
the worm tonic paralysis Onchocerciasis and
strongyloidiasis

Trematoda dan
cestoda tdk efektif
8 Praziquantel Increases membrane Schistosomiasis &
permeability to calcium Taenia.
paralysis
Fasciola hepatica tdk
efektif
9 Niklosamid act by inhibiting oxidative cestodes: Taenia
phosphorylation ATP tape saginata, T. solium,
worm decrease Diphyllobothrium
latum and
Hymenenolepis nana
and thread worm
Terimakasih