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BASIC
TOXICOLOGY
Department of Pharmacology and Therapy
Faculty of Medicine
Lambung Mangkurat University
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 Learning Outcomes
• Basic concept
• Classification
• Recognition
• Clinical Manifestation
• Management

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 Introduction
• Poison • Drug
– Substance that is toxic, – Substance that has a
no matter how it gets therapeutic effect
into the body or how when given in the
much is taken appropriate:
• Circumstances
• Dose

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 Obat
Peraturan Kepala Badan Pengawas Obat Dan Makanan
Republik Indonesia, Nomor 16 Tahun 2015 Tentang
Tata Laksana Dan Penilaian Obat Pengembangan Baru

Obat adalah obat jadi termasuk produk biologi yang merupakan

bahan atau paduan bahan yang digunakan untuk mempengaruhi
atau menyelidiki sistem fisiologi atau keadaan patologi dalam rangka
penetapan diagnosis, pencegahan, penyembuhan, pemulihan dan
peningkatan kesehatan, dan kontrasepsi untuk manusia.

Racun adalah zat atau senyawa yang dapat masuk ke dalam tubuh
dengan berbagai cara yang menghambat respons pada sistem biologis
sehingga dapat menyebabkan gangguan kesehatan, penyakit, bahkan
kematian.

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Toxicology is the study of the adverse effects of
chemical or physical agents on living organisms.
Factors: What is there that is not poison?
• Type All things are poison and nothing (is)
without poison.
• Route The right dose differentiates a poison
from a remedy
• Dose
• Frequency Paracelsus (1493–1541)

• Characteristic
• Individual response (condition)

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CLASSIFICATION

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 CLASSIFICATION
Source: Based on physical
• Organic characteristic:
• Environment • Solid
• Liquid
• Gas

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 CLASSIFICATION
Based on utilization
• Pesticide → substances or mixtures of substances
intended for preventing, destroying, repelling, or
mitigating any pest (insectiside, herbicide, fungicide
and rodenticide)
• Food additives
• Drugs
• Others

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 CLASSIFICATION
• Based on intention
– Self-poisoning → wrong dose, wrong direction of
use
– Attempted poisoning → suicide
– Accidental poisoning → unintentionally
– Homicidal poisoning → crime

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 CLASSIFICATION
• Based on Duration and Frequency of Exposure
– Acute: 1 exposure, <24 hours
– Subacute: <1 month
– Subchronic: 1 to 3 months
– Chronic: >3 months

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(Casarett, 2015)
Routes
• Oral
• Intranasal
• inhalation
• Parenteral (epidermal, intradermal,
transdermal, subcutaneous (sc), intramuscular
(im), and intravenous (iv))

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Chemical interaction
• Additive → 1+1=2, 1+5=6
e.g. iinsecticide+herbicide
• Synergism → 1+1=4, 1+5=10
e.g. asbes and smoking → lung
cancer
• Potentiation → 0+2=5, 0+1=3
e.g. Isopropanol and carbon
tetrachlorida → hepatotoxicity
• Antagonis → 4+6=7, 2+(-2)=0
e.g. cyanide → sodium
thiosulfate
Tolerance → a state of decreased
responsiveness to a toxic effect of
a chemical resulting from prior
exposure to that chemical or to a
structurally related chemical.
- decreased amount of toxicant
reaching the site
- reduced responsiveness of a
tissue to the chemical.
e.g. morphine tolerance
Resistance → reduction in
effectiveness of a drug in curing a
disease or condition
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GENERAL PRINCIPLES FOR

INTOXICATION
Department of Pharmacology and Therapy
Faculty of Medicine
Lambung Mangkurat University
 Part I: Approach to the poisoned patient.

• “Attempts to identify the poison should not delay

care.”
• Initial management of the poisoned patient begins
with basic life support.
• ACLS algorithms apply in toxicology with only a few
exceptions.
• Once these are stable, begin considering how to
minimize bioavailability. Then you may begin your
history and physical.

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History: find out all of this information:
The question words:
• Which drug(s) or substance (s) were taken?
• When was it taken?
• How much was taken?
• How was it taken?
• Why was it taken?
• Was anything else taken? (Consider co-ingestants:
other things which may be in this person’s medicine
cabinet.)

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Physical examination

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Key principles of BLS

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 THERAPEUTICAL PROCESS
Establish diagnosis of intoxication
(taking history, clinical and laboratory examinations)

Clinical intervention
(surgical, drug therapy, etc.)
what kind of drug (age, main and concomitant disease, genetic)
how much (the dose, frequency)
how to give (route of administration)

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 Diagnosis of acute intocication
Laboratory examination
- the rest toxin or suspect substance
- the rest of suspect material
- washing container
- vomiting material
- gastric lavage
- urine
- blood - serum
- etc. identify of suspected toxin
- medical aspect - therapy
- medico legal aspect

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 THERAPY OF ACUTE INTOXICATION
• Supportive / nonspecific measurements

• Specific measurements
– inhibits further absorption of toxic substances

– increase elimination process

– inhibit or antagonize of toxic effects

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 Therapy of acute intoxication
First aid • → assessment of basic life support
• (airway – breathing, brain, circulation,
disability)
• prevent the progression of intoxication
• → keep the victim away from source of poison
• → decontamination (wash the area of body contact,
• emesis, gastric lavage, laxant)

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 Supportive measurements
- Life saving → maintenance vital function (heart and lung)
- Remove mucus (from airway)
- Use appropriate suction pump (if necessary)
- Artificial respiration (→ respirator)
- Corticosteroids
(if pneumonitis is the most undesired complication)

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 Emesis
- An oral intoxication
- Consciousness
- Less than 1 – 4 hrs.
- The ingested thing was not a
corrosive material or distillated
petroleum oil

- an orally route intoxication 39

 Emesis
- Physical stimulation :
(stimulate uvula or pharynx wall)
- Pharmacological stimulation :
* apomorphine subcutaneous injection.
* ipecac (7 g in 100 ml syrup : 30 ml in 100 ml distilled water in adult).
* do not give any salt solution or any vegetable oil to
induce emesis.

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 Gastric lavage
- Oral intoxication
- Consciousness – unconsciousness :
* is not shock, delirium or convulsive patients

- 4 hours or less
- is not corrosive material ingestion
- Procedure (using a gastric tube)
→ give 150 - 300 ml saline or water or KMnO4, 37o C,
few minutes → aspirated using a syringe. Do again 5 - 10 times
the last aspirate leave 30 - 50 g activated charcoal in the stomach

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 Adsorbent
- Inhibit gastrointestinal absorption.
(by form a physicochemical bound with toxin)
- Orally
* activated charcoal → universal antidote
* resin (cholestyramine)
* kaolin.
* bentonite (for bipyridil intoxication)

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 Other acute intoxication
- Inhalation
(get into the body through respiratory tract)

- Injection
* morphine
* snake bite
* insect bite
* etc.

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 Forced diuresis
- Requirement : good heart and kidney function
- Drink water
- intravenous ringer / ringer dextrose :
* drops according to the needs.
* monitor the urine production.
* monitor the side effect occurred.

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 Forced diuresis
- Harmful and side effect :
lung and cerebral edema

- Contraindication :
* shock
* cardiac or / renal insufficiency
* edema, suspect cerebral edema, convulsion.

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 Dialysis
- Hemodialysis :
(machine dialysis)
- Peritoneal dialysis :
* dialysis fluid 100 - 250 ml (37o C, sterile,
isotonic, iso-pH), → intraperitoneal injection

* wait 1/2 -1 hrs → aspirate again.

* do again 8 - 12 times.

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 Hemodialysis
- Patient blood → dialysis machine
which is equipped with :

- membrane dialysis (semi permeable)

- dialysis fluid (→ counter direction to the blood)
- peristaltic pump (to draw the blood and
dialysis fluid)

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 Dialysis
- Indication :
- life-threatening poisoning (caused by ethanol,
methanol, ethylene glycol, isopropanol)
- substance with small volume distribution
- substance with small MW
- substance (water soluble)
- nonprotein binding (blood and tissue)

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 Hemodialysis
- Factors affecting the rate of dialysis :
- Toxin properties (protein binding, lipid solubility,
distribution volume, dissociation)

- Dialyzer properties (dialysis area, dialysis pressure)

- Flow rate of dialysis fluid
- Volume of dialysis fluid

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Antidotes
Substance used to counteract the effects of poison :

- Neutralizing the toxic substance (poison)

(antigen-antibody reaction, chelation, chemical binding)

- Antagonize the poison physiological effects

(activation of the opposing nerve system, competitiveness in
metabolism or receptors)

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 Antidotes
Counteract the effects of the poison by :
➢ Chemical reaction → chemical antidotes
➢ Physiological reaction → physiological antidotes
It can be → Specific antidotes

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 Chemical Antidotes
- Chelators :
EDTA and CaNa2EDTA (edatamil) for Pb, Au and Cd intoxication

BAL (dimercaprol) for As, Pb, Fe, Se, and U intoxication

diferoxamine (for Fe intoxication)

penicilamine (for Cu, Hg and Zn intoxication)

- KMnO4 (oxidize the alkaloids → for alkaloids intoxication)

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 DIMERCAPROL (BAL : British Anti Lewesite)
• Dithiol,2,3-dimercaptopropanol

• Metal chelator
for inorganic or elemental mercury, As (arsen) toxicity and Pb.
• As (arsen) bind to sulfhydryl – SH – group (→ cell
damage)
→ effective at lo concentration
→ administered up to 1 hrs after skin contaminatios.
• Dimercaprol
→ 3 mg / kg i.m. (every 4 hours for 2 days, then every 12
hours for 7 – 10 days)

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 Activated charcoal
• Fine black odorless powder
• To adsorb the toxic molecules
• Adsorptive capacity
• depends on its internal surface area and external pores →
diameter
• May decrease the absorption of drugs given in the same time
(aspirin, acetaminophen, barbiturates, phenytoin, theophyline,
cyclic antidepresants)
• Best administered as a water slurry
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 Physiological antidote
• anticonvulsants (for caffeine intoxication)
• atropine (for AChE inhibitor intoxication)
• antihistamines (for histamine intoxication)
• anticonvulsants (for chlorine intoxication)
• naloxone (for morphine intoxication)
• acetylcystein (for acetaminophen intoxication)

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 Physiological antidote
• atropine as antidote for
cholinergic drug poisoning
→ cholinergic drugs → stimulate r-M
(direct or indirectly by inhibit AChE)
→ atropine or atropinic drugs,
block r-M,
→ prevent the stimulation of r-M (by ACh or muscarinic durg).

→ competitive antagonism.

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 Physiological antidote
physostigmine as antidote for
anticholinergic poisoning
→ reverse coma, seizures, severe myoclonic and
choreoathetoid activities caused by anticholinergic drugs
→ reverse peripheral manifestation such as mydriasis,
hyperthermia, dry skin and mucosa, tachycardia,
constipation, urine retention etc.

→ transverse blood brain barrier.

→ inhibit AChE → ACh accumulation

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 References
• Hoffman RS, et al. Goldfrank’s Manual of Toxicologic
Emergencies. McGraw-Hill Companies, Inc 2007
• Katzung BG, et al. Basic and Clinical Pharmacology 13th
Ed. San Fransisco: McGraw Hill, 2015
• Klaassen CD, Watkins III JB. The Basic Science of Poison 8th
Ed. McGraw-Hill Companies, Inc, 2013
• KLaassen CD. Casarett & Doull’s Essentials of toxicology 3rd
Ed. McGraw-Hill Companies, Inc, 2015
• Ngatidjan. Specific Therapy of Acute Intoxication.
Department of Pharmacology and Therapy, Faculty of
Medicine, Univesitas Gadjah Mada

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Half of what we are going
to teach you is wrong, and
half of it is right. Our
problem is that we don't
know which half is which.
-Charles Sidney Burwell
(Dean of the Harvard Faculty of Medicine,
1935-1949)

Contact: hendranuramin@gmail.com
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