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Anthelmintics are drugs that either kill (vermicide) or expel (vermifuge) infesting heminths high affinity to the parasite, but lowest toxicity to the host
by secreting toxins
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Group of Helminth
3 Groups of Helminth
Helminth
Nematodes (roundworms)
Trematodes (flukes)
Intestinal nematodes
Blood fluke
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)
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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)
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Obat alternatif
Pip, alb, atau Lev Alb atau Pir Alb atau Lev Alb atau Meb Alb Alb Ivr DEC + Suramin
Obat alternatif
Meb
Nik
Anthelmintics Target
Neuromuscular transmission Agonist GABA muscle Nerve Work on chloride ion Neurotransmitter palsu channel Contoh: Piratel, piperazin, befenium, Energy Production Enzymes involved Substrate Contoh: Mebendazol, niclosamide, dll
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 keuntukan
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
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)
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. 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
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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,
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
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
lymph nodes and fall of BP may occurs due to mass destruction of Mf and adult worms mild to severe.
may be fatal
IVERMECTIN
Is an extremely potent semisynthetic derivative of the antinematodal
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
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.
Selective toxicity.
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PRAZIQUANTEL
Pharmacokinetics
Rapidly absorbed from git and undergo first pass
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)
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 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
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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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.
NICLOSAMIDE
1960 highly effective against cestodes: Taenia saginata, T.
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
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.
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