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Drug Toxicology: Agung Nova Mahendra Department of Pharmacology & Therapy Faculty of Medicine, Udayana University

This document discusses drug toxicology and poison management. It defines poisons as substances that can cause harm when taken incorrectly. Poisons are classified based on their source as animal, vegetable, mineral or gaseous. Toxicity is measured using LD50 values. The most susceptible populations to poisons are children, the elderly, and those with organ impairments. Factors like route of administration and individual health status affect drug toxicity. Initial patient evaluation focuses on vital signs and identifying toxidromes. Therapeutic intervention includes decontamination through gastric lavage or activated charcoal, enhancing toxin elimination, and administering antidotes.

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132 views27 pages

Drug Toxicology: Agung Nova Mahendra Department of Pharmacology & Therapy Faculty of Medicine, Udayana University

This document discusses drug toxicology and poison management. It defines poisons as substances that can cause harm when taken incorrectly. Poisons are classified based on their source as animal, vegetable, mineral or gaseous. Toxicity is measured using LD50 values. The most susceptible populations to poisons are children, the elderly, and those with organ impairments. Factors like route of administration and individual health status affect drug toxicity. Initial patient evaluation focuses on vital signs and identifying toxidromes. Therapeutic intervention includes decontamination through gastric lavage or activated charcoal, enhancing toxin elimination, and administering antidotes.

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wayan lentara
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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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

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