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TOKSIKOLOGI :

mempelajari sifat-sifat racun zat kimia


serta keamanannya terhadap mahluk
hidup dan lingkungan
What is a Poison?
All substances are poisons;
there is none that is not a poison.
The right dose differentiates a poison and a
remedy.
Paracelsus (1493-1541)

TOKSIKOLOGI KLINIK
Fokus kajian pada penyakit yang disebabkan atau secara unik
berhubungan dengan substansi toksik
Keracunan menurut cara terjadi :
Self poisoning
Attempted poisoning
Accidental poisoning
Homicidal poisoning

Keracunan menurut mula waktu terjadi :


Akut
Kronis

Keracunan menurut alat tubuh yang terkena


Keracunan menurut jenis bahan kimia

PENYEBAB KERACUNAN
Anak balita

minyak tanah, obat berlapis gula

Dewasa

obat hipnotik sedatif, opiat, insektisida

Keracunan makanan Enterotoksin stafilokokus


Keracunan logam berat Arsen, Hg, dll

GEJALA DAN DIAGNOSIS


Anamnesis
Gejala spesifik sesuai jenis obat atau bahan kimia lihat tabel
Laboratorium pemeriksaan spesimen biologik
- kualitatif
- kuantitatif KLT
Kromatografi gas
HPLC kromatografi cair kinerja
tinggi

TERAPI KERACUNAN
Untuk kepentingan klinik, semua agen toksik dibagi 2 klas :
1. Agen toksik yang memerlukan terapi spesifik atau ada
antidotnya
2. Agen toksik yang tidak memerlukan terapi spesifik
Tx simtomatik memperbaiki fungsi vital
Tx supportive
Prinsip penting dalam toksikologi klinik :

Treat the patient, not the poison

Terapi keracunan akut :


1.Mempertahankan fungsi vital
2.Mengusahakan konsentrasi racun di jaringan
yang penting serendah mungkin dg cara mencegah
absorbsi dan meningkatkan eliminasi
Mencegah absorbsi racun selanjutnya dengan :
Emesis -merangsang pharynx di bag.posterior
-Ipecac
-Apomorphine
Gastric lavage
Chemical adsorbtion activated charcoal

Inaktivasi bahan kimia


-antidote
-netralisasi asam atau basa
Purgation
- Katartik
- WBI : whole bowel irrigation
Bila keracunan melalui inhalasi atau kulit :
-pindahkan pasien dari sumber racun
-bersihkan kulit yang terkena dg air
-pakaian yg terkena racun dilepas

-Bila kena mata secepatnya irigasi dg air selama 15


menit
MENINGKATKAN ELIMINASI RACUN
diuresis paksa
dialisis

Assessment and Management


The primary goal of physical assessment of
poisoned patients is to identify the poisons
effects on the three vital organ systems most
likely to produce immediate morbidity and
mortality:
Respiratory system
Cardiovascular system
Central nervous system

Five Signs of Major Toxicity


Coma
Cardiac dysrhythmias
GI disturbances
Respiratory depression
Hypotension or hypertension

HISTORY
What was ingested? (obtain samples of substance,
vomitus)
Route of intoxication?
When was the substance ingested?
How much of the substance was ingested?
Use of alcohol or other possibly potentiating
substances?
Was an attempt made to induce vomiting?
Has an antidote or activated charcoal been
administered?
Patterns of drug habituation or abuse?
Does the patient have a psychiatric history
pertinent to suicide attempts or recent episodes of
depression?

Physical Exam
Pay special attention to:
Skin condition (cyanosis, pallor, wasting, needle
marks, staining)
Pupil responses, impaired vision
Signs of caustic ingestion, burning
Amount of salivation, breath odor, presence of
vomitus
Breath sounds for evidence of aspiration,
atelectasis, pulmonary secretions
Cardiac dysrhythmias
Abdominal pain

General Principles of Management


Prevent aspiration, consider intubation
Reduce or prevent absorption
DO NOT induce vomiting in most cases
Use of gastric lavage and/or activated charcoal
may be preferred
Maintain airway, breathing and circulation

Gastric Lavage
A method of GI decontamination that may be superior to

ipecac-induces emesis
Advantages:
Immediate recovery of a portion of the gastric contents (if
performed within 1 hour of ingestion)
Control of lavage duration
Direct access for administration of activated charcoal

Tehnik gastric lavage


Use large bore (36-40 French) orogastric tube, smaller 2428 French NG tube may be too small to remove gastric
contents
Place the patient in left lateral Trendelenburg to minimize
chance of aspiration
Insert tube through mouth into esophagus and advance until
tip is placed in the stomach
Check tube placement by insufflation of air into stomach with
syringe while auscultating
Infuse 150-200 mL aliquots of tap water or NS in adults,
50-100 mL >5 years
Drain stomach contents after each infusion, return volume
should be approximately equal to what was infused
Continue until return fluid comes back clear
Follow with activated charcoal

Potential complications gastric lavage:


Patient agitation
Inadvertent tracheal intubation
Esophageal perforation
Aspiration pneumonitis
Fluid and electrolyte imbalances in pediatric patients

Activated charcoal:
A medication that works by
binding to certain poisons,
preventing them from being
absorbed into the body.
Used only for ingested
toxins.

Activated Charcoal Trade Names

InstaChar

Actidose

LiquiChar

SuperChar

Two Types
of
Activated

Contraindications to Charcoal

Altered mental status

Ingestion of an acid or alkali

Inability to swallow

History of recent seizures

Administration of Activated
Charcoal

Shake container
thoroughly.

Activated Charcoal

Pour liquid into


container.

continued

Activated Charcoal
continued

Have patient drink full


dose.

CHEMICAL ADSORPTION
Activated charcoal adsorbs drugs and chemicals
on the surfaces of the charcoal particles, thereby
preventing absorption and toxicity
chemicals are adsorbed by charcoal :theophylline,
phenobarbital carbamazepine, dapsone and quinine .
Chemical are not well adsorbed by activated
charcoal : alcohols, hydrocarbons, metals, and
corrosives
should not be used simultaneously with ipecac
because charcoal can adsorb the emetic agent in
ipecac and thus reduce the drug's emetic effect.

Charcoal also may adsorb and decrease the effectiveness of


specific antidotes
an adsorbent (charcoal) in the intestine may interrupt
enterohepatic circulation of a toxicant, thus enhancing its
excretion tricyclic antidepressants and glutethimide

CHEMICAL INACTIVATION
need more time than charcoal and gastric lavage
Antidotes can change the chemical nature of a
poison by rendering it less toxic or preventing its
absorption
Exp :
Formaldehyde + ammonia
hexamethylenetetramine
Sodium formaldehyde sulfoxylate can convert
mercuric ion to the less soluble metallic mercury
Sodium bicarbonate converts ferrous iron to ferrous
carbonate, which is poorly absorbed

PURGATION
to minimize absorption by hastening the passage of
the toxicant through the gastrointestinal tract
cathartic

indicated after the ingestion of enteric-coated tablets

when the time after ingestion is greater than 1 hour

Exp. Sorbitol
sodium sulfate avoided in patients with
congestive heart failure.
magnesium sulfate should be used cautiously in
patients with renal failure

Whole-bowel irrigation (WBI)


polyethylene glycol
is a technique that not only promotes defecation but
also eliminates the entire contents of the intestines
WBI may be considered in cases of acute poisoning
by sustained-release or enteric-coated drugs and
possibly toxic ingestions of iron, lead, zinc.

INHALATION AND DERMAL EXPOSURE TO POISONS

When a poison has been inhaled remove the patient


from the source of exposure
Skin has had contact with a poison washed thoroughly
with water
Contaminated clothing should be removed
chemical injuries to the eye thorough irrigation of the
eye with water for 15 minutes should be performed
immediately.

Carbon
monoxide
poisoning...

can be a
serious
possibility with
fire victims.

Common toxins that can


be absorbed.

Enhanced Elimination of the Poison


BIOTRANSFORMATION
Many chemicals are toxic because they are
biotransformed into more toxic chemicals
Exp : methanol formic acid (highly toxic metabolite),
by alcohol dehydrogenase ethanol is used to inhibit the
conversion

Acetaminophen is converted by the CYP system to an


electrophilic metabolite that is detoxified by glutathione, a
cellular nucleophile
Acetaminophen does not cause
hepatotoxicity until glutathione
is depleted, whereupon the
reactive metabolite binds to
essential macromolecular
constituents of the hepatocyte,
resulting in cell death. The liver
can be protected by
maintenance of the
concentration of glutathione,
and this can be accomplished
by the administration of Nacetylcysteine

Renal excretion of basic drugs such as amphetamine theoretically


can be enhanced by acidification of the urine
Acidification can be accomplished by the administration of
ammonium chloride or ascorbic acid.
Urinary excretion of an acidic compound is particularly sensitive to
changes in urinary pH if its pKa is within the range of 3.0 to 7.5; for
bases, the corresponding range is 7.5 to 10.5.

DIALYSIS
Hemodialysis and peritoneal dialysis
Hemodialysis is much more effective than peritoneal
dialysis and may be essential in a few life-threatening
intoxications, such as with methanol, ethylene glycol,
and salicylates

ANTAGONISM OR CHEMICAL INACTIVATION OF AN ABSORBED


POISON
Specific chemical antagonists of a toxicant, such as opioid
antagonists
Atropine as an antagonist of pesticide-induced acetylcholine
excess
fomepizole, an inhibitor of alcohol dehydrogenase, approved for
treatment for poisoning by ethylene glycol and methanol
Chelating agents with high selectivity for certain metal ions are
used more commonly
Antibodies offer the potential for the production of specific
antidotes for a host of common poisons and for drugs that
frequently are abused or misused
Exp purified digoxin-specific Fab fragments of antibodies in the
treatment of potentially fatal cases of poisoning with digoxin

Organophosphate Poisoning

MUSCARINIC
D-efacation
U-rination
M-iosis
B-bronchorrea
E-xcitation (muscular)
L-acrimation,
salivation

NICOTINIC
M-uscle weakness
T-achycardia
W-weakness
H-hypertension
F-fasiculations

Anticholinergic
Treatment
atropine
what physiologic effects would you expect to see
from atropine?

pralidoxime (2-PAM)
regenerates acetylcholinesterase
what is the function of acetylcholinesterase?
What physiologic response would you expect to
see?

The development of human monoclonal


antibodies directed against specific
toxins has significant potential
therapeutic value snake bite, marine
animal bite

Rattlesnake

Marine Animals
Stingray

Venom can destroy proteins, other


tissue components, red blood cells, and
affect clotting factor
Infarction and necrosis may develop at
the bite site
Severe bite can be fatal in 6-30 hours
(rarely in <30 minutes)

Snake bite

The development of human monoclonal


antibodies directed against specific toxins
has significant potential therapeutic value

snake bite

In Malang SABU = SERUM ANTI BISA


ULAR

Injection

Ingestion

Inhalation

Absorption