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7/14/2019 Terapi Antidot
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TERAPI ANTIDOT
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Terapi Antidot
Keberadaan racun dalam tubuhbergantung :
– Waktu
– Keefektifan translokasi
Terapi keracunan ditujukan u/ :
– Memperbaiki kondisi penderita
– Membatasi penyebaran racun dalam
tubuh
– Peningkatan pengakhiran aksi racun
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Treat the patient, not the poison
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Penentu keberhasilan terapi antidot :
– Kecepatan penanganan
• selang waktu penanganan dg timbulnya gejala
• Mengatasi & mengurangi gejala keracunan
• Mencegah akibat yang fatal
• Membatasi penyebaran & meningkatkan pengakhiranracun
– Ketepatan penanganan
•
Pemilihan strategi terapi berdasarkan informasi racun,saat pemejanan, penyebaran racun, serta berbagai faktor
intrinsik racun maupun penderita
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Asas Umum Terapi Antidot
Sasaran
Strategi Dasar
Cara Pilihan
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Asas Umum Terapi Antidot
Penanganan keracunan :
– Terapi suportif
– Upaya pembatasan penyebaran racun
–
Meningkatkan aksi pengakhiran racunPemilihan strategi terapi antidot bergantung pada informasi
tentang rentang waktu kejadian dan pengetahuan kinetika
absorpsi, distribusi & eliminasi racun
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Tujuan Terapi Antidot
Sasaran terapi ant idot :in tens i tas e fek toks ik racun
Mencegahtimbullnya efek
berbahayaselanjutnya
Membatasi
intensitas efektoksik racun
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Sasaran Terapi Antidot
Penghilangan atau penurunan intensitas efektoksik racun
Intensitas efek racun ditunjukkan oleh tingginya
jarak antara nilai ambang toksik (KTM) dan kadar puncak racun dalam plasma atau tempat aksi
tertentu
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(1) decrease the slope of the rising portion of the curve
– Pergeseran absorpsi ke arah kanan memperlambat
kecepatan absorbsi racun mempercepat penurunan
intensitas efek toksik
– Pergeseran fase distribusi ke arah kanan mempercepat
penurunan intensitas efek toksik penyebaran racun
diperlambat
Strategi dasar terapi antidot
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Strategi dasar contn’d…
(2) increase the slope of the descending portion of the curve or displace the descending portion of the curve to the left
– Pergeseran fase eliminasi ke arah kiri mempercepat
penurunan intensitas efek toksik
(3) elevate the level or threshold at which the toxic range of
effect occurs.
– Penaikan ambang nilai toksik mempercepat penurunan
intensitas efek toksik krn ambang toksik sukar dicapai
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Cara pelaksanaan strategi dasar terapiantidot
Metode tak khas – Metode umum yang dapt diterapkan pada sebagian besar
racun
Metode khas
– Digunakan bila sudah diketahui secara spesifik senyawa
penyebab keracunan
– Zat antidot
Pemilihan berdasar rentang waktu keberadaan racun dalam
tubuh
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Tata Cara Terapi Anti dot I
Pergeseran kurva absorpsi ke arah kanan
– mechanical removal and the use of chemical
agents that will combine with and detoxify the
offending chemical – Removal of the chemical from the stomach
by gastric lavage or by the use of an emetic
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Pergeseran kurva absorpsi ke arah kanan
– Metode tak khas
• Emetika (apomorfina, sirup ipekak)
• Pemuntahan mekanis (sentuhan jari pada kerongkongan
bag atas)
• Pembilasan lambung (Gastric lavage)
• Penetralan kimia (penetral asam-basa)
• Penyerapan arang
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Gastric lavage
inserting a tube into the stomach and washing the
stomach with water or any suitable and relatively
harmless solvent for the agent involved Water is the lavage fluid preferred since it is the most
innocuous of fluids
In the case of lipid-soluble agents, liquid petrolatum would
be a suitable lavage agent
Emetic agents
In humans, emesis can be induced by parenteral
injection of apomorphine or by oral administration of
syrup of Ipecac
the sedative drug antagonizes the action of the emetic
drug
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Pergeseran kurva absorpsi ke arah kanan
– Metode khas
• Pembentukan kompleks yang kurang toksik
Zat Antidot Produk
Besi Sodium biokarbonat FerokarbonatBesi Deferoksamina Besi kelat
Perak nitrat Sodium klorida Perak klorida
Nikotina Potasium permanganat Produk oksidasi
Fluroida Kalsium laktat Kalsium fluorida
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Tata Cara Terapi Anti dot I
Pergeseran kurva fase distribusi kekanan
– Metode tak khas
• Penjerat ion dengan cara mengubah pHdarah (perbaikan keseimbangan asam-
basa)
• Penggantian tempat ikatan racun (infusi
albumin)
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Pergeseran kurva fase distribusi ke kanan
Metode khas
Zat Antidot Produk atau efek
Sianida Methemogoblin Sianmethemogoblin
Sianida Tiosulfat TiosianatMetanol Etanol Hambatan bersaing
Fluoroasetat Asetat atau monoasetin Penggantian
bersaing
Heparin Protamina Pembentukan
kompleks
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Cyanide
– cyanide reacts with a number of metal-containing enzym
toxicity primarily to its ability to react and form a stable
complex with the iron in ferric cytochrome oxidase inhibited.
– Since aerobic metabolism is dependent on this enzyme
system, the tissues can no longer utilize oxygen and the
tissues suffer from hypoxia
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Methanol
– Methanol blindness in humans and other primates destruction of
the retina and degeneration of the optic nerve responsible : a
metabolite of methanol and not the unchanged methanol
– Ethanol and methanol oxidized by the same enzyme = alcohol
dehydrogenase (ADH).
– ADH is localized most abundantly in the liver and it converts ethanol to
acetaldehyde and methanol to formaldehyde with subsequent
conversion of the formaldehyde to formic acid the blindness
– Ethanol is the preferred substrate for the enzyme ADH and is
metabolized several times more rapidly than is methanol.
– Both alcohols are present at the same time compete for the enzyme
the rate of metabolism of methanol is suppressed
theconcentration of toxic metabolites is also diminished.
– Caution ! : both agents are depressant drugs
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Tata Cara Terapi Anti dot II
Pergeseran kurva fase eliminasi ke kiriMetode tak khas
– Hemodialisis
– Dialisis peritoneal
– Pertukaran tranfusi (Exchange transfusion)
– Penyesuaian pH dan diuresis (membasakan air kencing
untuk asam organik lemah dan mengasamkan air kencing
untuk basa organik lemah)
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Hemodialisis
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Dialisis peritonial
Pergeseran kurva fase eliminasi ke kiri
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Pergeseran kurva fase eliminasi ke kiri
Metode khas
– Peningkatan ekskresi atau pemebentukan produk kurang
toksik dengan cara khelati atau pemebentukan kompleksasi
Zat Antidot Mekanisme
Ion bromida Ion klorida Peningkatan ekskresi
ginjalStrontium, radium Kalsium Peningkatan ekskresi
ginjal
Timah, nikel, kobalt,
kupri
EDTA Khelati
Merkuri, arsenik, emas BAL (dimerkaprol) Khelati
Toksin botulinnus Antitoksik botulisme Kompleksasi
Fosfat organik Pralidoksim Reaktivasi enzim nukleofil
Asetaminofen N-Asetilsistein Metabolit kurang toksik
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Tata Cara Terapi Anti dot III
Penaikan Ambang Toksik
Metode tak khas
– Pernapasan buatan mekanis untuk memelihara oksigenasi
darah
– Pemeliharaan sirkulasi darah
– Pemeliharaan keseimbangan elektrolit
– Pemeliharaan fungsi ginjal
Penaikan Ambang Toksik
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Penaikan Ambang Toksik
Metode khas
– Penggunaan anatgonis farmakologi atau jalur pengganti
Zat Antidot Mekanisme
Dikumarol, warfarin Vitamin K Antagonisme
Insektisida
organofosfat
Atropina Antagonisme
Morfin Naloksan Antagonisme
Karbon monoksida Oksigen Antagonisme
5-Flurourasil Timidin Jalur pengganti
Metotreksat Asam folat Jalur pengganti
6-Merkaptopurin Purin Jalur pengganti
Lysergic acid
diethylamide
Phenothiazin Antagonisme
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Morfin
– morphine reacts with the receptor (respiratory center in the brain)
respiratory depression
– Naloxone also reacts with and displaces morphine from the same
receptor, but the product of this reaction has considerably less
respiratory depressant effect.
Dicumarol
– Dicumarol reacts with unidentified enzyme system (in the liver and for which vitamin K is the normal substrate) enzyme-substrate complex
fails to produce the proteins necessary for the coagulation of blood
hemorrhage
– Vit K will compete with and displace Dicumarol from the enzyme
complex and reestablish normal formation of the coagulation factors of the blood antagonistic on the receptor (enzyme)
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Aplikasi
Faktor penting : waktu
Hala yg fundamental dalam penatalaksanann terapi antidot :
rentang waktu pemejanan sampai timbulnya gejala toksik
Pemilihan strategi antidot
Contoh :
Sesorang terpapar racun yg diabsorpsi relatif kurang cepat
(t(Cpmaks)=15 menit) terapi 20 jam stlh gejala nampak
tidak diperlukan penghambatan absorpsi & distribusi
mungkin diperluakan peningkatan eliminasi atau mungkin
terapi supotif saja (tergantung t ½ eliminasi racun)
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Management
How can you reduce the absorption of the drug
Can you increase the elimination of the drug?
– Is the drug excreted by the kidney or liver?
– Elimination by the kidney can be increased by increasing urine flow (e.g.
salicylate poisoning).
What are the supportive treatments?
– Begin with the ABC (airway, breathing, and circulation).
– Hypoglycaemia and altered potassium handling are common in severe
poisoning.
–
Cardiac monitoring may be required (e.g. poisoning by tricyclicantidepressants).
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Management cont’d
Is there a specific antidote? – For example, acetylcysteine for paracetamol.
What are the most likely complications and how can you treat them?
– Respiratory depression and cardiac arrhythmias are the most likely to
kill the patient in the short term. What can you do to reduce the risk of repeat overdose?
– Psychiatric/psychological assessment of intent.
– Is there a safer alternative drug (e.g. SSRIs are safer in overdose than
tricyclic antidepressants).
– Issue short-term prescriptions (12 weeks rather than 3 months).
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THANK YOU ANY QUESTION?