terapi antidot

7/14/2019 Terapi Antidot

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TERAPI ANTIDOT



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



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 pengakhiranracun

– Ketepatan penanganan

•

Pemilihan strategi terapi berdasarkan informasi racun,saat pemejanan, penyebaran racun, serta berbagai faktor

intrinsik racun maupun penderita



Asas Umum Terapi Antidot

Sasaran

Strategi Dasar

Cara Pilihan



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



Tujuan Terapi Antidot

Sasaran terapi ant idot :in tens i tas e fek toks ik racun

Mencegahtimbullnya efek

berbahayaselanjutnya

Membatasi

intensitas efektoksik racun



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



(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 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



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




– 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




– 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



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)



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



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

theconcentration of toxic metabolites is also diminished.

– Caution ! : both agents are depressant drugs



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)



Hemodialisis



Dialisis peritonial

Pergeseran kurva fase eliminasi ke kiri



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



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





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



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 tricyclicantidepressants).



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 YOU ANY QUESTION?

terapi antidot

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