Module 4

Toxicology
Mr. Merrene Bright D. Judan, BSIP, RPh

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Lecturer Background

● BS Industrial Pharmacy in UP Manila (2020), Cum Laude (Top 3)

● PhLE June 2021 Boards Passer (90.83%)
● Works under the health regulations team of the Department of Health
● Violinist at UP Symphony Orchestra
● Contact details
○ Facebook
○ mdjudan@up.edu.ph

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MODULE 4 (15%)

PRACTICE OF PHARMACY WEIGHT

Pharmacology 58%
Pharmacokinetics 21%
Toxicology, Incompatibilities, and 21%
ADR
100%

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Lecture Outline

Live Lecture
I. General Principles
II. The Poisoned Patient
III. Clinical Toxicology

Recorded Lecture
IV. Environmental and Occupational Toxicology

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General Principles

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Toxicology

● Branch of pharmacology that deals with the undesirable effects of

chemicals on living systems, from individual cells to humans to complex
ecosystems

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“The dose makes
the poison.”

Paracelsus
Father of Modern Toxicology

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Mathieu Orfila Modern father of toxicology
(quantification)
Traite des poisons, also called
Toxicologie generale
Lex Cornelia First book regarding poisoning

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Poisons

● Corpus delecti (body of

evidence)
● any agent which may
cause serious body
injury, disease or death
when applied,
introduced into, or
developed within the
body

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Effects of Poison
POISON EFFECT SITE OF ACTION EXAMPLES
LOCAL ON the site of CORROSSIVES
contact
REMOTE OTHER than the ATROPINE taken
site of contact orally
SYSTEMIC WHOLE BODY
COMBINATION BOTH PHOSPHORUS
CANTHARIDIN

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Related Terms
TERM KEY WORDS
Intoxication Toxicity associated with any chemical substance
Poisoning A clinical toxicity secondary to accidental exposure
Overdose An intentional exposure with the intent of causing
self-injury or death
Hazard Likelihood that injury will occur in a given situation or
setting
Risk Expected frequency of the occurrence of an undesirable
effect arising from exposure to a chemical or physical
agent

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Branches of Toxicology

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Analytical Toxicology

Descriptive Toxicology

Forensic Toxicology

Environmental Toxicology

Occupational Toxicology

Industrial Toxicology

Forensic Toxicology

Regulatory Toxicology

Mechanistic Toxicology

Chemical Toxicology

Clinical Toxicology

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The Poisoned Patient

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Evidence of Poisoning

Circumstantial Deduced from various events or facts

Not a strong evidence
Post-mortem Gathered after an autopsy is performed
Experimental Administering the suspected substance to some living
animal and noting the effect of samples of body fluids
collected
Chemical Detection of suspected substance via analysis
Symptomatic Poisoning signs or effects are observed

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Types of Poisoning

● Acute

● Chronic

● Combined

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Management of the Poisoned Patient

1. Initial Assessment
2. History and Physical Exam
3. Laboratory Tests
4. Toxicology Screening Tests
5. Decontamination
6. Specific Antidotes
7. Elimination of Toxins

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1. Initial Assessment

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2. History and Physical Examination

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Symptomatic Evidences
Ocular Olfactory Dermal

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Symptomatic Evidences
Blood Changes Urinary Gastrointestinal

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3. Laboratory and Imaging Procedures

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4. Toxicology Screening Tests

● Toxidrome
○ A group of signs, symptoms,
and laboratory findings that
suggest a specific ingestion

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4. Toxicology Screening Tests
Toxic Syndrome Causes
Anticholinergic
syndrome

Cholinergic
syndrome

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4. Toxicology Screening Tests
Toxic Syndrome Causes
Sympathomimetic
syndrome

Sedative syndrome

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5. Decontamination
● Involves removing toxins from the skin or gastrointestinal tract.
● Surface
○ Skin
○ Eye
○ Inhalation
● GI Tract
○ Emesis
○ Gastric lavage
○ Activated charcoal
○ Cathartics

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 Emesis
● MOA
○ Local: gastric irritation
○ Systemic: (+) CTZ Age Dose (mL)
● Ipecac syrup
<6 months Not
● Others (not recommended) recommended
○ Stimulation of pharynx 6-12 months 5-10
○ Salt water
1-12 years 15
○ Tepid water
>12 years 30
○ Apomorphine
● Not indicated for Drink water after
administration
○ Corrosive agent
○ Petroleum distillate
○ Rapid-acting convulsant

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 Gastric Lavage
● Indications
○ w/in 1 hour of oral intake
○ Fully-awake and cooperative patients
○ Patients with protected airway (i.e.,
NGT)
● Contraindications
○ Corrosives
○ Volatile substances
○ Significant risk of GI bleeding
○ Unconscious (unless intubated)
○ Uncooperative patient
● Activated charcoal is usually administered

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 Activated Charcoal

● Primary means of GI decontamination

● MOA: Adsorption (high SA)
● Dose: 10:1 charcoal-to-poison by
weight or 1 g/kg body weight
● Component of universal antidote
○ Activated charcoal
○ Tannic acid
○ Magnesium oxide

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 Cathartics

Class Examples
Bulk-Forming Psyllium, methylcellulose

Stool Softeners Mineral oil, docusate

Osmotic Mannitol, sorbitol, MOM, Mg

citrate, Na3PO4, PEG

Stimulant Aloe, senna, cascara, bisacodyl

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Whole Bowel Irrigation
● Use of nonabsorbable PEG
(GoLYTELY, CoLyte)
● Usually administered via NGT
● Used with antiemetic (ex.
Metoclopramide)
● Dose: Adults (2 L/hr), children
(35 mL/kg/hr)
● Indications
○ Agents that do not bind to
charcoal (ex. heavy metals,
lithium)
○ SR or enteric-coated drugs
○ Packets of illicit drugs
● Contraindicated in patients
with
○ Bowel perforation
○ GI hemorrhage or
obstruction
○ Compromised airways
○ Intractable vomiting
○ Hemodynamic instability
● Endpoint: Effluent is clear (~6
hrs)
● SE: N/V, abdominal cramping,
bloating
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6. Specific Antidotes

Antidote Poison/s Antidote Poison/s

N-Acetylcysteine Flumazenil
Atropine Fomepizole
NaHCO3 Glucagon
Calcium Hydroxocobalamin
Deferoxamine Naloxone
Digoxin antibodies Oxygen
Esmolol Physostigmine
Ethanol Pralidoxime

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7. Elimination of Toxins

● Dialysis
○ Peritoneal dialysis
○ Hemodialysis
○ Hemoperfusion
● Forced Diuresis and Urinary pH Manipulation

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Hemodialysis vs Peritoneal Dialysis
Hemodialysis Peritoneal Dialysis
Filters are outside Uses the peritoneal
the body (artificial membrane inside
machine) the abdomen as
filter (natural)
Hemodynamic Fewer
complication hemodynamic
complications
More efficient Less efficient

Complex Simple

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Hemodialysis vs Hemoperfusion

Hemodialysis Hemoperfusion
Effective for water-soluble drugs Effective for protein-bound and
and small molecules lipid-soluble drugs
Can correct for fluid and electrolyte Cannot correct for fluid and
imbalance electrolyte imbalance
Slower Faster

Via diffusion Via activated charcoal or resin

ex. Ethylene glycol, methanol, ex. Phenobarbital, phenytoin,

ethanol, lithium, aspirin carbamazepine, methotrexate,
theophylline

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Clinical Toxicology

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Clinical Toxicology

● Aka Medical Toxicology

● Diagnosis and treatment of poisoning
● Concerned with the toxic effect of therapeutic and non-therapeutic
substances (i.e., household products, alcohol, drugs of abuse, industrial
chemicals)

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Toxidromes

● A group of signs, symptoms, and

laboratory findings that suggest a
specific ingestion

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General Types of Toxins
TYPES EFFECT EXAMPLES
Irritants cause tissue necrosis on contact Acids and Alkali
Neurotics affect the CNS Hallucinogens
Carcinogenics stimulate growth of Industrial Poisons
cancer cells
Asphyxiants cause dyspnea CO, Methane
Lacrimators stimulate flow of Organophosphates
tears
Sternutator cause excessive Veratrine
sneezing
Asthenics produce muscular weakness Neuromuscular Blockers
Narcotics mental weakness / depression Sedative Hypnotics

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Toxicology of Selected Drugs

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Acetaminophen

● MOA: weak inhibitor of COX-1 and COX-2

● Toxic dose: > 4g/day (adult)
● Presentation
○ N/V
○ Liver necrosis and hepatic failure
○ Encephalopathy
○ Metabolic acidosis
● Toxic form: NAPQI
● Antidote: NAC (within 8 hours)
● CI: alcoholics and P450 enzyme inducers

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Aspirin (Salicylates)

● MOA: only irrev inhibitor of COX-1 and COX-2

● Presentation
○ Tinnitus and vertigo
○ Hyperventilation
○ Respiratory alkalosis
○ Metabolic acidosis
○ Hyperthermia
○ Seizures and coma
○ Reye’s syndrome*
● Antidote: NaHCO3, hemodialysis (severe)

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Stimulants
● Methamphetamine
● MDMA/ecstasy
● Cocaine
● Pseudoephedrine
● Ephedrine (in Ma huang)
● Caffeine
● Presentation
○ Euphoria and wakefulness
○ Restlessness and agitation, acute psychosis
○ HTN, Tachycardia
○ Seizures, hyperthermia

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Antidepressants

● Tricyclic antidepressants
● MAOI
● SSRI

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Antipsychotics

● 1st gen (Typical) – blocks D2 and HAM

● 2nd gen (Atypical) – blocks D4 and 5HT

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Anticholinergics

● Effect: Opposite of DUMBELLS

● Antidote
○ For agitation: _________
○ For peripheral and central anticholinergic syndrome: ___________

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Beta Blockers

● Effect:
● Antidote: Glucagon

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Drugs of Abuse

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Drugs of Abuse

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Drugs of Abuse

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Sedative-Hypnotics

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Opioids

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Cyanide

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Digoxin

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Others

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 Environmental and
Occupational Toxicology

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Toxicology of Selected Substances

● Air Pollutants
● Heavy Metals
● Industrial and Household Chemicals
● Agricultural Chemicals
● Toxins
● Others

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Air Pollutants

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Carbon monoxide
● Most common cause of air pollution
● MOT: combines with Hb to form carboxyHb
(210x affinity than oxygen)
● Presentation
○ Cherry red color of blood
○ Headaches, dizziness, and nausea
○ Breathing difficulties
○ Blurring of vision
○ CNS effects
● Management
○ 100% O2
○ Hyperbaric O2
○ Artificial air (___% helium, ___%
oxygen)

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Sulfur oxides

● Main component of acid rain (along

with NxOy)

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Nitrogen oxides

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Ozone

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Heavy Metals

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Lead

● MOT: combines with –SH (thiol group)

→ inactivation of enzymes
● Plumbism
o Milky vomitus
o Black stool
o Wrist Drop/ Foot Drop
o Black Line gums
● Antidote: BAL and EDTA

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Cadmium

● Component of stink bombs,

antidandruff shampoo
● Itai –itai Disease
○ Osteomalacia
○ Fractures, Gaits and renal
abnormalities
● Antidote: BAL, EDTA

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Mercury

● MOT: Blockage of sulfhydryl group

● Presentation
○ Acrodynia
○ Pink palms and toes
○ Oliguria
○ Minamata’s disease
● Forms
○ Elemental
○ Inorganic
○ Organic
● Antidote: Na formaldehyde sulfoxinate
and EDTA

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Arsenic
● Aka Lewisite metal
● Choice of professional poisoners
● MOT: protoplasmic poison
● Presentation
○ Aldrich Mees’ Line
○ Garlic Odor Breath
○ Luminous Vomitus
○ Black Line Gums
● Antidote: BAL
● Test
○ Marsh: (+) mirror-like ppt
○ Reinsch: (+) dull black ppt

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Iron

● Presentation
○ I - nausea, vomiting, diarrhea, GI
bleeding, hypotension
○ II - clinical improvement seen 6-
24 hours post-ingestion
○ III - metabolic acidosis, renal &
hepatic failure, sepsis,
pulmonary edema, & death
● Antidote: DEFEROXAMINE

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Thallium
● MOT: Binds to –SH groups
● Presentation
○ Gastroenteritis
○ Paresthesia
○ Alopecia
● Treatment
○ Prussian blue

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Common Antidotes Summary

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Industrial and Household Chemicals

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Ethylene Glycol

● Antifreeze chemical
● MOT:
○ ETHYLENE GLYCOL → glycol aldehyde →
glycolic acid AND glyoxylic acid → ACIDOSIS
● Toxic metabolite: Oxalic Acid
● Treatment: Ethanol and Fomepizole (Antizol)

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Methanol

● Wood alcohol
● Denaturant
● Paint remover
● Presentation
○ Visual disturbances, metabolic acidosis
● MOT: Methanol → formaldehyde (blindness) →
Formic acid → Acidosis
● TEST: Lieben’s iodoform → yellow ↓
● Antidote: Ethanol, fomepizole

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Formaldehyde

● Aka formalin, formol

● Embalming agent
● Similar presentation with methanol toxicity
● Signs & symptoms
○ Local: mucosal irritation
○ Systemic: CNS depression, coma,
metabolic acidosis
● MOT: Formaldehyde (blindness) → formic
acid → acidosis

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Acetone

● Primary ingredient in fingernail polish

remover, airplane glues, varnish, &
rubber cement
● Signs & Symptoms
○ CNS depression → coma, respiratory
depression
● Treatment
○ Neutralization with milk or water
● Test
○ Benzoldt Gunning → (+)
indigotine

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Hydrocarbons
● Mostly derived from petroleum
distillation
● Gasoline, kerosene
● Signs and symptoms: Lung aspiration
● Treatment:
○ Aspiration & pneumonitis
○ Mineral oil
● MOT: Hydrocarbons cannot be
metabolized in the body → CNS
DEPRESSION

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Acids and Bases

● BASES: Liquefaction necrosis

● ACIDS: Coagulation necrosis
● TREATMENT: Dilutional therapy

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 HOUSEHOLD CHEMICAL ANTIDOTE
Ethylene Glycol Fomepizole
Methanol Ethanol and Fomepizole
Formaldehyde NH4 and NaHCO3
Acetone Neutralization with milk
Hydrocarbon Mineral Oil
Acids and Bases Dilutional Therapy

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Agricultural Chemicals

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Organophosphates

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Carbamates

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Rodenticides

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Botanical Insecticides

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Zootoxins

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 Poison Source

Tetrodotoxin Puffer fishes

Cantharidin Blister fly/ Spanish fly

Clupeotoxin Oyster, sardines (Venerupin) anchovies

Scromboid toxin Tuna (saurine) Mackerel (Gemblid)

Ciguatoxin Fish organs (liver)

Latrotoxin Black widow spider/ Hourglass spider (Latrodectus mactans)

5-HT Scorpion (Centuroides sculpturatus)

Bee venom Hymenoptera (bee, wasps, ants)

Hyaluronidase Snakes

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Phytotoxins

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 Poison Source
Abrin Jequirity bean
Aconite, monkshood aka DEVIL’S
Aconitine
HELMET
Atropine Belladonna or Deadly Nightshade

Digitalis glycosides Foxglove

Quinine BITTER BARK, CINCHONA

Nicotine TOBACCO

Amygdalin Aka LAETRILE. From prunus sp.

Ricin Castor bean

Sanguinarine Bloodroot

Taxines Japanese yew

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 Poison Source
Arecoline Betel nut
Brucine, strychnine Nux vomica
Fish berries
Picrotoxin Equimolar mixture of two compounds
(picrotoxinin and picrotin)
Myristicin Nutmeg
Cicutoxin water hemlock Cicuta douglasii
Colchicines Autumn crocus
Convallarin Lily of the valley Convallaria majalis
Coniine Poison hemlock Conium maculatum
Phenanthridine Daffodil, jonquil Narcissus pseudonarcissus
American mandrake, May apple,
Podophyllotoxin
Podophyllum peltatum

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 Poison Source
Pyrethrin Flower heads of Crysanthemum
Mycotoxin Claviceps purpurea
Solanine Potatoes
Mannihotoxin Cassava
Uroshiol Poison Ivy

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Mushroom Toxins

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 Poison Source
Saxitoxin Dinoflagellates

Aflatoxin Aspergillus flavus

Ptomaine Bacterial decay

Tyrotoxicon Bacterial decay

Ergot Claviceps purpurea

Exotoxins Mostly from Gram(+)

Botulinumtoxin C. botulinum

Tetanospasmin C. tetani

Cytotoxin C. perfringens

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Microbial Toxins

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Group Toxins Source
I Amanitotoxins, cyclopeptides Hepatotoxins

IA Orellanine, orelline Nephrotoxins

Hallucinogens, anticholinergic
II Muscimo, Iboteric acid
signs & symptoms
III Gyrometrin Hepatotoxin
Hydrolyzes to form
IV Muscarine
monomethylhydrazine
V Coprine Cholinergic overstimulation

VI Psilocin, psilocybin Disulfiram reaction

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