terapi antidot

TERAPI ANTIDOTTERAPI ANTIDOT

Terapi AntidotKeberadaan racun dalam tubuh bergantung :– Waktu– Keefektifan translokasi

Terapi keracunan ditujukan u/ :– Memperbaiki kondisi penderita– Membatasi penyebaran racun dalam

tubuh– Peningkatan pengakhiran aksi racun

Treat the patient, not the poison

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

Asas Umum Terapi AntidotPenanganan 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

Tujuan Terapi Antidot

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

(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

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

Cara pelaksanaan strategi dasar terapi antidotMetode tak khas– Metode umum yang dapt diterapkan pada sebagian

besar racunMetode khas– Digunakan bila sudah diketahui secara spesifik senyawa

penyebab keracunan– Zat antidot

Pemilihan berdasar rentang waktu keberadaan racun dalam tubuh

Tata Cara Terapi Anti dot IPergeseran 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

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

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

Pergeseran kurva absorpsi ke arah kanan– Metode khas

• Pembentukan kompleks yang kurang toksik

Zat Antidot Produk Besi Sodium biokarbonat Ferokarbonat Besi Deferoksamina Besi kelatPerak nitrat Sodium klorida Perak kloridaNikotina Potasium

permanganatProduk oksidasi

Fluroida Kalsium laktat Kalsium fluorida

Tata Cara Terapi Anti dot IPergeseran kurva fase distribusi ke kanan– Metode tak khas

• Penjerat ion dengan cara mengubah pH darah (perbaikan keseimbangan asam-basa)

• Penggantian tempat ikatan racun (infusi albumin)

Pergeseran kurva fase distribusi ke kanan

Metode khasZat Antidot Produk atau

efekSianida Methemogoblin Sianmethemogobli

n Sianida Tiosulfat Tiosianat Metanol Etanol Hambatan

bersaingFluoroasetat

Asetat atau monoasetin

Penggantian bersaing

Heparin Protamina Pembentukan kompleks

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

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

Tata Cara Terapi Anti dot IIPergeseran 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)

Hemodialisis

Dialisis peritonial

Pergeseran kurva fase eliminasi ke kiriMetode 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

ginjalTimah, 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

Tata Cara Terapi Anti dot IIIPenaikan Ambang Toksik Metode tak khas – Pernapasan buatan mekanis untuk memelihara

oksigenasi darah– Pemeliharaan sirkulasi darah– Pemeliharaan keseimbangan elektrolit– Pemeliharaan fungsi ginjal

Penaikan Ambang Toksik Metode khas – Penggunaan anatgonis farmakologi atau jalur

penggantiZat Antidot Mekanisme Dikumarol, warfarin Vitamin K Antagonisme Insektisida organofosfat

Atropina Antagonisme

Morfin Naloksan Antagonisme Karbon monoksida Oksigen Antagonisme 5-Flurourasil Timidin Jalur penggantiMetotreksat Asam folat Jalur pengganti6-Merkaptopurin Purin Jalur pengganti Lysergic acid diethylamide

Phenothiazin 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)

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)

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).

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).

THANK YOUANY QUESTION?

terapi antidot

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