l24-Farmakotoksikologi Klinis Dasar

8/14/2019 l24-Farmakotoksikologi Klinis Dasar

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FARMAKOTOKSIKOLOGI KLINIKDASAR

Eman Sutrisna

Bagian Farmakologi dan TerapiFKIK Unsoed


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TUJUAN PEMBELAJARAN

Mahasiswa akan dapat menjelaskan

Gejala dan tanda keracunan umum dan

khusus sesuai dengan zat toksik

Penerapan prinsip-prinsip penatalaksanaan

awal kasus keracunan dan tindak lanjut


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GEJALA DAN TANDA UMUM

Kesadaran

Tanda vital

Respirasi

Tekanan Darah

Suhu

Nadi

Jantung

Mata

Ekstremitas

Bising usus


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KESADARAN

Petunjuk berat-ringan keracunan

Derajat kesadaran (DK)~kadar obat dalam darah~berat

keracunan

DK 1ngantuk, bicara mudah DK 2sopor, bangun dengan ransang minimal

DK 3soporokoma, bereaksi thd rangsang maksimal

(menggosok sternum)

DK 4koma, tidak bereaksi dengan rangsangan


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RESPIRASI

Gangguan pusat pernafasan

Penghambatan jalan nafasbronkokonstriksi, sumbatan mukus

Penyebab kematiangagal nafasorganonfosfat dan karbamat

Pemeriksaanspirometer

Volume semenit < 4 liter/menitperlu O2 ataurespirator mekanis


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TEKANAN DARAH

Turunsyok Kerusakan pusat vasomotorsyok

beratkematian


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JANTUNG

Aritmia sampai gagal jantung

Contoh obat :

Digitalis

Antidepresan trisiklik

Beta blocker


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USUS

Perubahan bising usus ~ perubahan kesadaran

DK 3-4bising usus negatif

Bisa untuk konfirmasi kesadaran penderitayang pura-pura pingsan/koma


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KEJANG

Akibat perangsangan SSPamfetamin

Perangsangan medula spinalisstriknin,

toksin tetanus

Obat perangsang SSP lain


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DIAGNOSIS STANDAR

Pemeriksaan darah, urin atau muntahan

Cukup sulitkarena dalam tubuh obatmenalami perubahan molekul akibat

biotransformasi Metode lainkromatografi gas dan

kromatografi cair kinerja tinggi

menentukan zat aktif penyebab keracunan


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KEADAAN DARURAT

Gagal nafas

Syok


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PENATALAKSANAAN

Pencegahan absorbsi obat

Pemberian antidotum dan obat simptomatik

Tranfusi dan dialisis peritoneal Diuresis paksa

Hemodialisis dan hemoperfusi


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PENCEGAHAN ABSORBSI OBAT

Tergantung paparan

Perkutaneusdicuci dengan air dan sabun (jangan

menggunakan pelarut organik/lemak)

Perinhalasipindahkan ke tempat yang bebas paparan

Per-ingesti

Muntahkan : mengorek posterior faring, apomorfin 5-8 mg sc

Bilas lambung : air hangat, tiosulfat, KMnO4

Pencahar

Absorben : karbon aktiffenobarbital, karbamazepin,

fenilbutazon, digoksin, satolol, teofilin


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DIALISIS PERITONEAL

Peritoneum berfungsi sebagai membran semipermeabel

Cukup aman, efektivitas ~ diuresis paksa

Persyaratan : fraksi obat bebas >>>, zat aktif banyakdikeluarkan

Contoh : alkohol, metilalkohol, amfetamin, barbiturat,asam borat, karbon tetraklorida, bromida, salisilat,metilsalisilat, sulfonamid, primidon, natrium klorat

Bahan : cairan dialisis + 3 ml KCl, heparin 1000 U, 2 mlprokain 1%, bila dehidrasi 50 ml glukosa 50%

Cairan (Dewasa : 2 L, anak-anak : 200 ml)masukanmelalui trokar ke rongga peritoneum (10 mnt)tgg 30dikeluarkan


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DIURESIS PAKSA

Memberikan cairan parenteral dalam jumlah banyak0,5-1,5 L/jam

Persyaratan Keracunan berat

Obat larut dalam air

Berat molekul kecil

Obat tidak diikat protein/lemak

Tidak terakumulasi dalam organ

Obat tidak diekskresi lebih cepat dengan jalan lain (paru, feses)

Contoh : alkohol, metilalkohol, amfetamin, barbiturat, asamborat,, bromida, salisilat, metilsalisilat, sulfonamid,primidon, kina, kuinidin, litium

NaCl 0,9%, laevulosa 5%

Pada Asam+ NaCO3 1,25% + KCL 1,5%


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Tidak Over-treatment

Pengobatan simptomatik bisa > atau sama

baik

Menjaga fungsi organ vitalsampai obat

dimetabolisme dan dieliminasi secara alamiah


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CONTOH PENGOBATAN

KERACUNAN


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ALKOHOL (ETIL)

Gejalamuntah, depresi SSP

Terapi

Simptomatik

Kopi tubruk

Emetikmustrad 1 sendok makan dalam air

secukupnya


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ASAM BASA KUAT

HCl, H2SO4, KOH, NaOH

Gejala : korosif

Terapi Jangan bilas lambung

Simptomatik

Susumemperlambat absorbsi


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BENSIN

Gejala : mual, muntah, sakit kepala, penglihatan terganggu,depresi SSP, depresi nafas, koma

Terapi

Simptomatik

Jangan memberikan efineprin dan norepinefrinbahaya fibrilasiventrikel

1 g CaNa2 EDTA dalam 500 ml glukosa 5% 2 kali sehari selama 3hari

Ca glukonas 2 g iv

Laksan : MgSO4

Luminal 100-200mg bila kejang atau diazepam 5-10 mg iv


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ASPIRIN

Gejala : hiperventilasi, keringatan, muntah,

delirium, kejang, koma, depresi nafas

Terapi

Simptomatis

Susu

Bilas lambung : NaCO3 5%

Vit K bila perdarahan

Jangan memberikan antikonvulsandepresi SSP


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INSEKTISIDA ORGANON FOSFAT

Diazinon, malation, paration

Gejala : muntah, diare, hipersalivasi,

bronkokontriksi, keringat >>, miosis,bradikardi, hipotensi, kejang, depresi nafas

Terapi

Atropin sulfat 2 mg iv diulang tiap 10-15 sampai

atropinisasi positifmuka merah, gejalamenghilang

Observasi ketat

Sama dengan Karbamat

Baygon


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Insektisida Organonklorin

Aktrin, DDT, aldrin, endrin, klordan, tiodan,

toksafen

Gejala : kejan, tremor, komaparalisis

Terapi

Simptomatik

Bilas lambungtinggalkan MgSO4 30 g

Fenobarbital 100-200 mg iv atau diazepam 5-10

mg iv


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JAMUR

TOKSIN muskarinik

Terapi

Simptomatik

Atropin sulfat 2 mg sc


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JENGKOL

Gejala : kolik ureter, oligouri, hematuri, anuria

(berbahaya)

Terapi

NaCO3 4 x 2 g peroral

Jika anuriastandar pengobatan pasien uremia


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MINYAK TANAH

Iritasi saluran cerna, aspirasi (pneumonitis),

depresi SS, muntah (aspirasi), kejang

Terapi

Simptomatik

O2 under pressure

Antibiotik profilaktik (aspirasi)

Jangan Bilas lambung


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KARBON MONOKSIDA

Sakit kepala, depresi nafas, koma, syok

Terapi : bantuan nafas dengan O2


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SIANIDA

MUAL, MUNTAH, NAFAS CEPAT, SIANOSIS,

DELIRIUM, KOMA

TERAPI

Na tiosulfat 25%, 50 ml iv


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Reaksi Obat

Anafilaktik

Terapi

0,3 ml adrenalin 1% sctiap 5-10 sampai

perbaikan

Antihistamin

Deksametason 2 x 1 mg oral selama 4 hari

Bronkodilatorbila sesak nafas


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INTOKSIKASI LOGAM BERAT DAN

ANTINYA


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HM vs Anti-HM

Heavy metals (HM) exert their toxic effects bycombining with one or more reactive groups (ligands)essential for normal physiological functions.

Heavy metal antagonists (HMA) - chelating agents aredesigned specifically to compete with these groups forthe metals, and thereby prevent or reverse toxic

effects and enhance excretion of metals.


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HMORGAN

Nearly all organ systems are involved in heavy metaltoxicity;

The most commonly involved organ systems include the

CNS, PNS, GI, hematopoietic, renal, and cardiovascular(CV).

To a lesser extent, lead toxicity involves themusculoskeletal and reproductive systems.

The organ systems affected and the severity of thetoxicity vary with the particular heavy metal involved, theage of the individual, and the level of toxicity.


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chelation Treatment of Metal Poisoning

Chelaters (Greek = claw) bind directly with metalions to form stable complexes that remove the metalfrom competition with the body's cells.

Because a chelated metal is water soluble, it can beexcreted readily by the kidney.


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Ideal chelating agents

Water soluble

Resistant to biotransformation

Able to reach sites of metal storage

Capable of forming nontoxic complexes with

toxic metals

Be excreted from the body

Have a low affinity for essential metals


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Chelating Agents

An agent frequently used in chelation therapy isdimercaprol (also known as BAL or British Anti-Lewisite).Oral chelating agents used as alternatives to BAL are 2,3-demercaptosuccinic acid (DMSA),dimercaptopropanesulfonate (DMPS),

D-penicillamine Deferoxamine, is often used to chelate iron.

Ethylenediamintetraacetic acid (ETDA) also has an affinityfor lead and was one of the first chelators developed.


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The following table summarizes chelating agents,

the heavy metals they are used to treat, their route of administration,

and their brand name.

Chelating

Agent

Toxin Route** Drug

Dimercaprol (BAL)

Arsenic

Lead

Mercury (inorganic)*

i.m.

Dimercaptol

Injection B.P.

BAL in Oil

Dimercaptosiccinic acid(DMSA, Succimer)

ArsenicLead

Mercury

p.o. Chemet

Dimercaptopropane-

sulfonate (DMPS)Arsenic

p.o.

i.m.

Bulk form

(for compounding by

pharmacists)

D-pencillamine

Arsenic

MercuryLead

p.o.

Metalcaptase

PencillamineCuprimine

Depen

Ethylenediamintetra-

acetic acid (EDTA)

(Edetate disodium)

Lead IV Chealamide Versenate

*Not methylmercury poisoning. **Under supervision of a physician: i.m., intramuscular; p.o., peroral or by mouth; IV, intravenous.

Source: Data from Beers et al. 1999; Micromedex 1999; Roberts 1999; Wentz 2000; Anon. 2001; Ferner 2001; Marcus 2001; USNML/NIHDrug Information 2001a; 2001b; 2001c; 2001d.


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Dimercaprol - BAL (British Antilewisite)

BAL clinically useful for treating acute and chronicpoisoning by organic or inorganic arsenals and forprotecting against mercury-induced renal damage.

Not effective in treating mercury-induced neurologicalconditions or CNS damage.

Not useful to chelate cadmium because it can partiallydissociate in urine and enhance renal damage. Also truefor iron and selenium.


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Calcium Disodium Edetate

CaNa2 - EDTA

will chelate any metal that has a higher binding affinity than Ca(lead, iron, zinc, manganese, beryllium and copper)

CaNa2EDTA does not enter host cells but relies on excretion oflead into blood from bone. Lead chelates with EDTA to form acomplex that is much greater than that of the Ca complex.

Toxicity to EDTA partly restricts its usage. After IVadministration, severe proximal nephron degeneration may

occur. Other symptoms include fever, nasal congestion, anddermatitis.


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Penicillamine

Penicillamine is formed from hydrolysis of penicillin. It formstight chelates with copper, lead, mercury, and zinc.

An advantage of this chelator is that it is well absorbed from

the GI tract after oral administration. Penicillamine is oftengiven for long-term treatment of chronic metal poisoning,after the patient has been removed from immediate danger.(i.e. CaNa2EDTA - lead; BAL - mercury).* Pen is not universally recognized as the first-choice

antidote.


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Succimer,Dimercaptosiccinic acid (DMSA)

Succimer is chemically similar to dimercaprol (BAL)but is more water soluble, has a high therapeuticindex, and is absorbed well from the GI tract.

It is given orally.

It produces a lead diuresis comparable to that ofCaNa2-EDTA

reverses the biochemical toxicity of lead, as indicatedby normalization of circulatory delta-aminolevulinicacid dehydratase (an enzyme necessary for heme

synthesis. The most common adverse effects include nausea,

vomiting, diarrhea and anorexia.


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Deferoxamine

Deferoxamine possesses high affinity forboth ferrous and ferric iron;

especially in acute iron poisoning in small

children. It is also used to chelate aluminum.

It is given parenterally(IV), since less

than 15% is absorbed from the GI tract


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l24-Farmakotoksikologi Klinis Dasar