DRUG TOXICOLOGY

Agung Nova Mahendra

Department of Pharmacology & Therapy

Faculty of Medicine, Udayana University
 Defining Poison
A substance may be harmful
or poisonous if taken the
wrong way, by the wrong
person or in the wrong
amount.

It may cause a mild reaction

to a serious illness or
possible death.

Synonyms:
-Toxin
- Toxicant
- Bane
 Classification of Poisons in
Materia Medica by Dioscorides

 Animal poisons: from snakes, toads,

salamanders, jellyfish, stingrays, sea hares,
etc
 Vegetable poisons: poison hemlock (Conium
maculatum), opium poppy (Papaver
somniferum)
 Classification of Poisons in
Materia Medica by Dioscorides

 Mineral poisons: antimony, arsenic, lead,

mercury
 Gaseous poisons: CO
Measuring Toxicity

 LD50
 Comparing LD50 to ED50  LD50/ED50 =
Therapeutic Index (TI)
Most Susceptible populations

 Children
 The elderly patients
 Patients with renal & hepatic failure
 Patients with mental disorders
 Factors Affecting Drug Toxicity
 Physicochemical properties of toxicant
(formulation, particle size, drug pH)
 Route of administration (PO, inhalation, skin
contact)
 Health status (renal & hepatic impairment, blood
pH, hypertension, traumatic brain injury)
 Dietary & nutritional status (Ca, Fe, lipid, protein,
tyramine, & vitamin)
 Genetics (atypical pseudocholinesterase, G6PD
deficiency)
 Sex (weight, blood volume, tissue mass in man >
woman)
 Others: environmental temperature & work
environment
Initial Patient Evaluation
 VS (BP, RR, HR, Temp) monitoring --> most
important
 Normal (Rectal) Temp Range: 35 – 38 0C
 Mofenson & Greensher: Toxidrome  groups
of signs & symptoms that consistently result
from particular toxins
 Toxidrome is best described by combination
of VS & clinically-obvious end organ
manifestations
Most clinically useful signs

 CNS: mental status

 Ophthalmic: pupil size
 GI: peristalsis
 Dermatology: skin dryness vs. diaphoresis
 Mucous membranse: dry vs. moist
 GU: urinary retention vs. incontinence
Normal VSs by Age
Age SBP DBP Pulse RR
(mmHg) (mmHg) (beats/mi (breaths/
n) min)
Adult 120 80 60-100 16-24
1 0 years 115 74 90 16-30
6 years 107 69 100 20-30
4 years 104 65 110 20-30
2 years 102 58 120 25-30
1 years 100 55 120 25-30
Newborn 65 50 145 35-40

Goldfrank (2005)
Toxidromes (example)
Anticholinergics Intoxication
 BP: -/increases
 Pulse: increases
 Respi: +
 Temp: increases
 Mental status: delirium
 Pupil: mydriasis
 Peristalsis: decreases
 Diaphoresis: decreases
 Other: dry mucous membranses, flushing,
urinary retention
Toxidromes (example)
Ethanol or Sedative-Hypnotic Intoxication
 BP: decreases
 Pulse: decreases
 Respi:decreases
 Temp: -/decreases
 Mental status: depressed
 Pupil: +
 Peristalsis: decreases
 Diaphoresis: -
 Other: ataxia, hyporeflexia
How to Deal with Intoxication

 ABCDE (Airway, Breathing, Circulation, Drug,

& Exposure)
 Quickly determine: CV, respiratory, & CNS
involvements
 Determine the identity of poison
 Decide whether the substance is toxic or not.
 If not toxic, observe for delayed effects
 If TOXIC, proceed with managements
Therapeutic Intervention

 Decontamination
 Toxin elimination
 Antidote use
Decontamination (1)
 Used to prevent toxin absorption from its port
d’entrée
 Inhalational toxin: evacuation & additional
oxygen
 Dermal toxin: removal of clothing, irrigation
(running water & light soap  green soap
tincture that contain 30% alcohol)
 Ophthmalmic exposure: irrigation using 1 L
saline or until sx improvement or using warm
water for 15-20 minutes
Decontamination (2)
 Oral exposure:
 Emesis
 Gastric lavage
 Activated charcoal
 Whole bowel irrigation
 Cathartics
Emesis

 Do not induce emesis if the toxin is:

convulsant, hydrocarbon, alkali, corrosive
acids
 Do not induce emesis if the px is in LOC or
commatose state, has severe cardiovascular
disease, emphysema, < 6 months-old
Emesis Induction

 Ipecac syrup is used in the induction

 Vomiting occurs within 30-60 min
 Dose:
 6-12 months  5-10 mL
 1-12 yrs  15 mL
 Adults  30 mL
 Gastric Lavage
 Gastric drainage using water, saline, sodium
bicarbonate, salt, or other agent
 Indications: immediate elimination of toxin or if
emesis is contraindicated
 Semiconscious
 Conscious but had been ingesting large amount of
substance
 Loss of swallowing reflex
 Uncooperative child/adult
 Ineffective ipecac therapy

 Contraindications:
 Corrosives, petroleum distillates, & seizures
Activated Charcoal

 Contraindications: GIT obstruction

 Side effects: nausea, obstipation
 Effective: especially if given within 30
minutes from the onset of toxin ingestion
 Chemical substances that is not sufficiently
adsorbed by activated charcoal: Alkali, boric
acid, cyanide, DDT, electrolytes, ferrous
sulphate, malathion, mercury, tolbutamide,
lithium salts, N-methyl carbamate
Whole Bowel Irrigation
(Cathartics)
 Also used to clean GIT before surgery
 Most commonly used solution: sodium
sulfate, PEG electrolyte solution 
nonabsorbable & do not lead to
fluid/electrolyte imbalance
 Indications: negative peristalsis, highly
corrosive substances, electrolyte disorders
 Cathartics that contains Mg: should NOT be
given to px with renal disorders 
hypermagnesemia  CNS depression
Enhancing Toxin Elimination

 MDAC
 Alkaline diuresis
 Haemodialysis
 Plasma exchange
This method is used to enhance removal of
toxins that have been absorbed & circulating
in the blood stream or have been distributed
to tissues
Antidotes (1)

Classification: chemical, receptor,

dispositional, & functional antidotes
 Chemical antidotes: reacts with toxins to
produce less toxic compounds & reduce their
absorption
 Ex: dimercaprol (BAL) & desferoxamine
(Desferal)  chelators of heavy metals 
water soluble  renal elimination
Antidotes (2)

 Receptor antagonist: competitive antagonist

of the toxin
 Ex:
 Naloxone (IV, IM, SC)  antagonist of morphine
 Physostigmine  reversible AChE inhibitors 
increase ACh level  competes with Atropine in
anticholinergic intoxication
Antidotes (3)

 Dispositional Antidotes: Modulators of ADME

of toxins  decrease toxin level
 Ex: N-acetylcystein  source of sulfhydryl
moiety  used in paracetamol intoxication
Antidotes (4)

 Functional antidotes: works at the system

that oppose the toxin-affected system
 Ex: Epinephrine (Adrenaline)  used in
anaphylaxis
 Epinephrine works via sympathetic nervous
system that oppose the effect of histamine &
other mediators on CV, respiratory, GI, & skin
system
THANK YOU