TERAPI ANTIDOT

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Terapi Antidot
Keberadaan racun dalam tubuh bergantung : 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 pengakhiran racun

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

Sasara Strateg n i Dasar
Cara Pilihan

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Asas Umum Terapi Antidot

Penanganan keracunan : Terapi suportif Upaya pembatasan penyebaran racun Meningkatkan aksi pengakhiran racun

Pemilihan strategi terapi antidot bergantung pada informasi tentang rentang waktu kejadian dan pengetahuan kinetika absorpsi, distribusi & eliminasi racun

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Tujuan Terapi Antidot

Membatasi intensitas efek toksik racun

Mencegah timbullnya efek berbahaya selanjutnya

Sasaran terapi antidot : intensitas efek toksik racun

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Sasaran Terapi Antidot

Penghilangan atau penurunan intensitas efek toksik 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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Strategi dasar terapi antidot

(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

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Strategi dasar contnd

(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 terapi antidot

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 Besi Besi Perak nitrat Nikotina Fluroida

Antidot Sodium biokarbonat Deferoksamina Sodium klorida Potasium permanganat Kalsium laktat

Produk Ferokarbonat Besi kelat Perak klorida Produk oksidasi Kalsium fluorida

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Tata Cara Terapi Anti dot I

Pergeseran kurva fase distribusi ke kanan
Metode tak khas
Penjerat ion dengan cara mengubah pH darah (perbaikan keseimbangan asambasa) Penggantian tempat ikatan racun (infusi albumin)

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Pergeseran kurva fase distribusi ke kanan

Metode khas
Zat Sianida Antidot Methemogoblin Produk atau efek Sianmethemogoblin

Sianida
Metanol

Tiosulfat
Etanol

Tiosianat
Hambatan bersaing Penggantian bersaing Pembentukan kompleks

Fluoroasetat Asetat atau monoasetin Heparin Protamina

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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 the concentration 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 kiri
Metode 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

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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 Ion bromida Strontium, radium Timah, nikel, kobalt, kupri Toksin botulinnus Fosfat organik Asetaminofen
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Antidot Ion klorida Kalsium EDTA

Mekanisme Peningkatan ekskresi ginjal Peningkatan ekskresi ginjal Khelati Khelati Kompleksasi Reaktivasi enzim nukleofil Metabolit kurang toksik

Merkuri, arsenik, emas BAL (dimerkaprol) Antitoksik botulisme Pralidoksim N-Asetilsistein

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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

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Penaikan Ambang Toksik

Metode khas
Penggunaan anatgonis farmakologi atau jalur pengganti
Zat Dikumarol, warfarin Insektisida organofosfat Morfin Karbon monoksida 5-Flurourasil Antidot Vitamin K Atropina Naloksan Oksigen Timidin Mekanisme Antagonisme Antagonisme Antagonisme Antagonisme Jalur pengganti

Metotreksat 6-Merkaptopurin Lysergic acid diethylamide

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Asam folat Purin Phenothiazin

Jalur pengganti Jalur pengganti Antagonisme

 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 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 tricyclic antidepressants).

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Management contd
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?

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