Clinical Toxicology

The branch of toxicology that is

concerned with human poisoning
Drug overdose
1. Pharmaceuticals
2. Drugs of abuse (penyalahgunaan obat)
Toxic exposure
a) Environmental (lingkungan)
b) Occupational ( berhubungan dengan pekerjaan)
 Paracetamol overdose
Tanda-tanda klinis

Phase 1 (0.5-24 hrs): nausea, vomiting, no jaundice 1 hari

Phase 2 (24-72 hrs): Right Upper Quadrant pain, abnormal

liver enzyme & bilirubin 2-3 hari

Phase 3 (72-96 hrs): coagulation defect, hepatic

encephalopathy, death 3-4 hari

Phase 4 (4 days-2 wks): resolution of liver function

4 hari 2 mgg
Penanganan Keracunan Parasetamol
Penanganan keracunan MeOH
Basic Life support ---- oxigenasi
Hemodialysisu/ membuang MeOH yg
belum termetabolisme dan mengeliminasi
metabolit MeOH
Pemberian antidotum
--- EtOH sterile i.v for menghambat
metabolisme MeOH
--- 4-methylperazole-----inhibitor alcohol
dehydrogenase.
Metabolisme MeOH
MeOH-----1-----Formaldehide--2---asam
format

1. Alcohol dehydrogenase
2. Aldehyde dehydrogenase
Strategi Klinik untuk Pengobatan bagi
Pasien Keracunan

1. Stabilisasi pasien
2. Evaluasi Klinik ( sejarah, fisik, laboratorium,
radiologi)
3. Pencegahan lebih lanjut dari absorpsi toksin
4. Peningkatan eliminasi toksin
5. Pemberian antidotum
6. Supportive care and clinical follow-up
Stabilisasi klinis dari pasien
*Merupakan prioritas Utama
*Sering disebut ABCs (Airway, Breathing, Circulation)
of initial emergency treatment.
*Penilaian Tanda-tanda vital dan efektifitas dari respirasi
dan sirkulasi merupakan tujuan utama dari awal menghadapi
pasien keracunan

Contoh: Benzodiazepin: tanda-tanda klinis: awalnya sedatif

yang parah tetapi juga dapat yang sedang.

camphor, awalnya memperlihatkan efek klinis yg kecil

tetapi dapat berlanjut menjadi fatal
Beberapa senyawa kimia dapat menyebabkan kejang
Kontrol terhadap senyawa kimia yg menyebabkan
kejang menjadi komponen sangat penting dari
stabilisasi awal bagi penderita keracunan
Tingkat stabilisasi klinis awal dibutuhkan bagi
penderita keracunan
Prosedur klinis mampu menstabilkan penderita
keracunan yg kritis termasuk penilaian awal dan
berjalan dan jika ada indikasi , suport ventilasi ,
sirkulasi dan oksigenasi.

Once the poisoned patient is clinically stabilized, the

remainder of the assessment and treatment steps can
proceed. In critically ill patients, sometimes treatment
interventions must be initiated before a patient is
truly stable.
Sejarah Klinis dari Penderita
keracunan
Untuk menentukan:
Substansi ( bahan) penyebab
keracunan
Tingkat keracunan
Waktu keracunan ( kapan terjadinya)
Pengujian Fisik
Pengujian yang seksama diperlukan
1. untuk menilai kondisi pasien,
2. kategori status mental, jika berubah
3. untuk menentukan kemungkinan status mental abnormal
atau pengaruh di CNS

One very helpful tool for the clinical toxicologist is to categorize the
patients physical examination parameters into broad classes referred to
as toxic syndromes. These toxic syndromes have been called toxidromes
(Mofenson and Greensher, 1970). A toxidrome is a constellation of
clinical signs and symptoms that, when taken together, are likely
associated with exposure from certain toxicologic classes of chemicals.
The major toxic syndromes include narcotic, cholinergic,
sympathomimetic, and anticholinergic.
Periodic reexamination of the patient is a very important aspect
of clinical toxicology treatment procedures. Follow-up clinical
examinations can help gauge the progression of the clinical
course of poisoning as well as determine the effectiveness of
treatment interventions and gauge the need for additional
treatment procedures
Occasionally a characteristic odor can be detected on the poisoned
patients breath or clothing which may point toward exposure or
poisoning by a specific agent. Table 32-2 lists some of the better
recognized odors and the substance associated with the odor.
Detection of one of these odors may provide an important historical
clue as to the agent responsible for the poisoning.

odor potential poison

Bitter almonds ------------------Cyanide
Eggs----------------------------- --Hydrogen sulfide,
mercaptans
Garlic As,-------------------------organophosphates,
DMSO,Thallium
Mothballs ------------------------ Naphthalene,
camphor
Vinyl ------------------------------Ethchlorvynol
Wintergreen --------------------Methylsalicylate-
Radiographic Examination
Pengujian Radiographic digunakn untuk mendiagnosis \
racun yg spesifik dan jumlahnya relatif sedikit
Untuk memvisualisasikan overdosis obat atau racun dgn
kadar kecil

Radiopacity refers to the relative inability of electromagnetism to pass through a

particular material, particularly X-rays

Radiopaque: Anything that does not let X-rays or other types of radiation penetrate.
Radiopaque objects block radiation. They are opaque to radiation.
Generally, plain radiographs can detect a
significant amount of ingested oral medication
containing ferrous or potassium salts. However, a
study of the in vitro and in vivo visualization of
chewable oral formulations of iron supplements
showed that once the chewable iron was ingested
it was no longer detectable by plain abdominal
radiograph (Everson et al., 1989). However,
certain formulations that have an enteric
coating or certain types of sustained
release products are radiopaque and can be
visualized (Savitt et al., 1987; Nelson et al., 1993).
abdominal radiograph ===== bisa digunakan
untuk mendeteksi carbon tetrachloride or
chloroform

abdominal plain radiographs sangat berguna

untuk mengetahui posisi sesuatu yg benda
asing yang terdeteksi di saluran pencernaan.

Another example of the use of radiological imaging in clinical

toxicology is with computed tomography (CT) of the brain.
Significant exposure to carbon monoxide (CO) has been
associated with CT lesions of the brain consisting of low-density
areas in the cerebral white matter and in the basal ganglia,
especially the globus pallidus.
 Evaluasi klinis awal dari pasien keracunan
merupakan fase kritis yg penting dari
terapi untuk mengobati penderita
keracunan

Pengujian fisik, uji lab, umumnya digunakan

lebih pada diagnosis dan manajemen akut

Pengujian radiologi dimaksudkan untuk

membantu deteksi dan manajemen
patology yg diinduksi oleh toksikan.
Pencegahan absorpsi racun lebih lanjut
Selama fase awal penanganan atau tindakan bagi pemaparan
yg toksik melalui oral, inhalasi, atau rute topikal , team
penanganan mungkin mempunyai kesempatan untuk
mencegah absorpsi lebih lanjut dari racun untuk
meminimalisir jumlah total yang mencapai sirkulasi sistemik

Bagi senyawa kimia yg masuk ke tubuh lewat inhalasi,

intervensi yg utama adalah mencegah absorpsi lebih lanjut
dengan memindahkan dari lingkungan dimana senyawa kimia
ditemukan, serta menyediakan ventilasi yg cukup serta
oxigenasi bagi pasien
Untuk pemaparan topikal, pakaian
pasien yg mengandung toxin harus di
buang, dibungkus dengan benar agar
tidak terjadi pemaparan sekuder
(berlanjut)

Pemaparan lewat topikal kulit harus

dicuci dengan air dan sabun yg lembut
untuk mencegah terjadinya lecet
sehingga tidak terjadi peningkatan
absorpsi lewat kulit yg lecet
Peningkatan Eliminasi dari Racun
There are several methods available to enhance the
elimination of specific poisons or drugs once they
have been absorbed into the systemic circulation.

The primary methods employed for this use today

include:
alkalinization of the urine,
hemodialysis,
hemoperfusion,
hemofiltration,
plasma exchange or exchange transfusion,
and serial oral activated charcoal.
Alkalinization of the urine

renal clearance meningkat dari senyawa asam

lemah.
prinsip dasar adalah meningkatkan pH urin yang
terfiltrasi sampai level yang cukup untuk
mengionisasi asam lemah dan mencegah molekul
mengalami reabsorpsi renal tubular. Seperti
menjerat ion
Pertama kali toxin diionisasikan, kemudian
reabsorpsi renal tubuler di halangi, akibatnya sisa obat
banyak terdapat di filtrat urin dan diekskresikan di urin
Hemodialysis
Syarat :
1. rendah volume distribusi
2. rendah ikatannya dengan protein
3. relatif tinggi kelarutannya dengan
air dan kecil berat molekulnya
Use of hemodialysis to attempt to remove a
chemical with the later three characteristics but
with a high volume of distribution, such as
digoxin, would not be clinically beneficial because
the vast majority of the drug is not in the
physiologic compartment (blood) accessible to
the dialysis membrane.

Therefore, despite hemodialysis being able to

effectively clear the digoxin in plasma during the
dialysis run, most of the body burden of digoxin is
located outside of the blood compartment and is
not appreciably affected by the procedure.
 Hemoperfusion
The technique of hemoperfusion is similar to
hemodialysis except there is no dialysis membrane or
dialysate involved in the procedure.

The patients blood is pumped through a perfusion

cartridge where it is in direct contact with adsorptive
material (usually activated charcoal) that has a coating
of material such as cellulose or a heparin-containing gel to
prevent the adsorptive material from being carried back to
the patients circulation.

Prinsip metode ini untuk sukses membuang toxin atau obat

dengan charcoal aktif sehingga vol distribusi dan absorpsi
rendah
Untuk senyawa yg larut lemak, berat molekul besar

Protein binding does not significantly interfere with

removal by hemoperfusion. Because of the more direct
contact of the patients blood with the adsorptive
material, the medical risks of this procedure include
thrombocytopenia, hypocalcemia and leukopenia.

This technique is primarily used for the treatment of

serious theophylline overdose, and possibly
amanita toxin exposure, paraquat and
meprobamate poisoning.
The technique is seldom used currently and it is
possible that access to the sterile hemoperfusion
cartridge necessary for the procedure may be limited,
even at major medical centers.
The use of oral charcoal, now a mainstay in the
treatment of many human poisonings, can be dated to
early Greek and Roman civilizations when wood
charcoal was used for the treatment of maladies such
as anthrax and epilepsy (Cooney, 1995).

The antidotal properties of charcoal were

demonstrated in the 1800s by the French with
dramatic demonstrations of a reduction in lethality
when charcoal was ingested with potentially lethal
dosages of arsenic trioxide by Bertrand and strychnine
by Touery (Holt and Holz, 1963).
One of the earliest reported human studies
examining the efficacy of charcoal in poisoning
was in 1948 by the American physician Rand (Holt
and Holz, 1963). The use of superheated steam to
treat the charcoal to enhance its absorption
capacity was reported by Ostrejko, a Russian
scientist in 1900 (Greensher et al., 1987). By the
1960s, the use of activated charcoal was routinely
recommended for the treatment of patients
poisoned with substances thought to be adsorbed
to charcoal.