MODULE 4│PHARM CHEM 5
TOXICOLOGY
TOXICOLOGY sola dosis facit venenum – “the dose makes the poison”
• Branch of Pharmacology that deals with the study of poison, - a.k.a. deleterious/ toxic
mechanism of toxicity and its treatment., Side effects
Adverse 1. Hypersensitivity
Effects 2. Idiosyncrasy
I. INTRODUCTION TO TOXICOLOGY Effects
3. Tolerance/
- related to therapy Desensitization
Forensic Toxicology Clinical Toxicology 4. Teratogenicity
– medicolegal Mechanistic – diseases cause by
US FDA Pregnancy Risk Classification
aspects of poisoning Toxicology toxicants
(mechansim of Category Animal studies Human studies
action) A Safe Safe
B Safe None
Risk NOT SAFE Safe
Assessment C NOT SAFE None
Regulatory None None
Descriptive
Toxicology D NOT SAFE: benefits outweigh risk
Toxicology
(decides if a X Contraindicated in pregnancy = Teratogenic
(toxicity effects
substance
testing)
possess a risk
Teratogens Presentation
Thalidomide Amelia/ Phocomelia
Warfarin Hypoplastic nose
Tetracycline Tooth discoloration
Environmental Toxicology – Lithium Ebstein’s anomaly
harmful effects of chemicals to ACE inhibitors Renal dysgenesis
the environment/ organisms Methimazole Aplasia cutis
Carbamazepine, Valproic acid Neural tube defects (spina bifida)
Diethylstilbestrol (DES) Clear cell adenocarcinoma of the
RISK ASSESSMENT vagina/ cervix
Phenytoin Fetal hydantoin syndrome
• estimate of potential effects of poison to human health and Ethanol Fetal alcohol syndrome
environmental significance of various types of chemical • Facial anomalies
exposure • Growth retardation
• Hazard – ability of a chemical agent to cause injury in a • Neuro-developmental
defects
given situation or setting
• Risk – expected frequency of the occurrence of an
undesirable effect arising from exposure to a chemical or Effects of Poison
Immediate vs. Delayed
physical agents
Immediate Delayed
• Seen after single • Seen after a lapse of time
POISON administration
• deleterious effects Reversible vs. Irreversible
• physical injuries Reversible Irreversible
• death • Reversed by administration of • Permanent damage
• Toxin – natural source the antidote • Carcinogenic and teratogenic
• Toxicants – man made/ artificial source effects
COMMON MAJOR PATHOPHYSIOLOGIC MECHANISMS Local vs. Remote vs. Systemic
CNS stimulation Causes nerve excitability → Seizures → Brain Local Remote Systemic
damage • Same route of • Different route of • Causes
CNS depression Loss of airway protective reflexes and respiratory administration administration widespread
drive → Respiratory depression and site of and site of derangement
Parasympathomimetic Diarrhea action action
effect Urination Example: Example: Example:
Miosis, Muscle fasciculations Phenol, caustic, Paraquat ingestion → Metabolic acidosis
(DUMBELS) Bronchoconstriction, Bradycardia corrosives → skin pulmonary fibrosis due to MUDPHILES
Emesis burn
Lacrimation
Salivation, Sweating MUDPHILES
Sympathomimetic Mydriasis Methanol
effects Agitation Uremia
Tachycardia Diabetic ketoacidosis
(MATHS) Hypertension Paraldehyde
Seizure, Sweating Isoniazid, Iron
Cardiovascular Heart: Cardiac Arrhythmias Lactic acidosis
effects Vasculature: Ethylene glycol
• Vasodilation → hypotension Salicylates
• Vasoconstriction → hypertension
Respiratory effects Aspiration → Bronchospasm Route of administration:
Cellular hypoxia Interference with O2 transport and utilization
Musculoskeletal Muscle breakdown and myoglobinuria → Renal
effects failure, lactic acidosis, hyperkalemia Ingestion
• Accidental and suicidal poisoning
Inhalational
• Occupational exposure
Dermal
• Occupational exposure
Parenteral
• Greatest effect and most rapid response
Module 4 – Toxicology Page 1 of 9 RJAV 2022
, Frequency D. Degree of Disability
Acute Eyes Verbal Motor
• Single administration (+4) Spontaneous (+5) Orientated (+6) Obey commands
• Time: < 24 hours (+3) To sound (+4) Confused (+5) Localizing
(+2) To pressure (+3) Words (+4) Normal flexion
• Acute exposure by inhalation: 4 hours (+1) None (+2) Sounds (+3) Abnormal flexion
Subacute (+1) None (+2) Extension
• Repeated exposure (+1) None
• Time: < 1 month Differential Diagnoses for altered Mental Status:
Sub-chronic 1. Head trauma or other causes of intracranial bleeding
• Repeated exposure 2. Abnormal levels of blood glucose, sodium, or other
• Time: 1-3 months electrolytes
3. Hypoxia
Chronic 4. Hypothyroidism
• Repeated exposure 5. Liver or renal failure
• Time: > 3 months 6. Environmental hyperthermia or hypothermia
7. Serious infections such as encephalitis and meningitis
II. GENERAL MANAGEMENT OF A POISONED PATIENT
Causes Agent Initial Dose
Primary Survey (ABCDE) Hypoglycemia Dextrose
• Adult 50% dextrose, 50mL (25g) IV
• Child 25% dextrose, 2mL/kg IV
History and PE Alcohol intoxication Thiamine 100 mg, in the IV solution or IM
Opioid intoxication Naloxone 0.2-0.4 mg IV or IM
Decontamination *if no response within 1-2 minutes,
give 2 mg IV
Antidotal Therapy Benzodiazepine Flumazenil 0.2 mg IV over 30 seconds
*Pediatric dose Is not established;
starts at 0.01 mg/kg
Toxin Elimination *if no response, give 0.3 mg
**if still no response, give 0.5 mg and
repeat every 30 seconds
PRIMARY SURVEY
E. Exposure/ Environment
Airway
HISTORY AND PHYSICAL EXAMINATION
Breathing
• A.k.a. SECONDARY SURVEY (“AMPLE”)
Circulation
Degree of Disability Allergy
Exposure/ Environment Medication
Past Medical History/ Pregnancy
A. Airway
Last meal
Airway Management
• Optimize airway position Events related to the injury
• Place the neck and head in “sniffing” position
• Apply the jaw-thrust maneuver DECONTAMINATION
• Place the patient in a head-down, left sided position
• CAUTION: Do not perform neck manipulation if neck A. Surface Decontamination:
injury is suspected
• Remove any obstruction or secretions 1. Dermal
• Use of artificial oropharyngeal or nasopharyngeal airway • Remove contaminated clothing
devices • Wash with copious amount of running (tap) water for 30
minutes
B. Breathing Topical Agents for Chemical Exposure to the Skin
Hydrofluoric acid Calcium soaks
Breathing Problems
Oxalic acid Calcium soaks
Ventilatory Failure Paralysis of Ventilatory Muscles: Phenol Mineral oil, Isopropyl alcohol
• Flaccid paralysis: Neuromuscular blockers, White Phosphorus Copper sulfate 1%
Botulinum toxin
• Spastic paralysis: Tetanospasmin,
Strychnine, Saxitoxin, Tetrodotoxin 2. Inhalational
CNS Depression: Alcohols, Sedative-hypnotics, • Remove the patient from the toxic environment → O2
Opioids, Antidepressant, Antipsychotics supplementation
Hypoxia Inert gases: CO2, Methane, Propane, Nitrogen
Cellular hypoxia: CO, Cyanide, 3. Ocular
Methemoglobinemia, H2S, Sulfahemoglobinemia • Wash with BSS/ NSS for 15 minutes of consume 2L
Pneumonia: Aspiration of gastric contents with lids retracted
Bronchospasm Beta-blocker, Hydrocarbon aspiration,
organophosphates and carbamates
B. Gastric Decontamination
C. Circulation
1. Activated Charcoal
• Highly adsorbent powdered material made from a
Circulation Management
distillation of wood pulp
• Check blood pressure and pulse rate and rhythm
• Dose: 10:1 (charcoal to toxin)
• Begin continuous ECG monitoring
• Contraindications:
• Secure venous access
• Unconscious patients
• Draw blood for routine studies
• Begin IV infusion
Module 4 – Toxicology Page 2 of 9 RJAV 2022
TOXICOLOGY
TOXICOLOGY sola dosis facit venenum – “the dose makes the poison”
• Branch of Pharmacology that deals with the study of poison, - a.k.a. deleterious/ toxic
mechanism of toxicity and its treatment., Side effects
Adverse 1. Hypersensitivity
Effects 2. Idiosyncrasy
I. INTRODUCTION TO TOXICOLOGY Effects
3. Tolerance/
- related to therapy Desensitization
Forensic Toxicology Clinical Toxicology 4. Teratogenicity
– medicolegal Mechanistic – diseases cause by
US FDA Pregnancy Risk Classification
aspects of poisoning Toxicology toxicants
(mechansim of Category Animal studies Human studies
action) A Safe Safe
B Safe None
Risk NOT SAFE Safe
Assessment C NOT SAFE None
Regulatory None None
Descriptive
Toxicology D NOT SAFE: benefits outweigh risk
Toxicology
(decides if a X Contraindicated in pregnancy = Teratogenic
(toxicity effects
substance
testing)
possess a risk
Teratogens Presentation
Thalidomide Amelia/ Phocomelia
Warfarin Hypoplastic nose
Tetracycline Tooth discoloration
Environmental Toxicology – Lithium Ebstein’s anomaly
harmful effects of chemicals to ACE inhibitors Renal dysgenesis
the environment/ organisms Methimazole Aplasia cutis
Carbamazepine, Valproic acid Neural tube defects (spina bifida)
Diethylstilbestrol (DES) Clear cell adenocarcinoma of the
RISK ASSESSMENT vagina/ cervix
Phenytoin Fetal hydantoin syndrome
• estimate of potential effects of poison to human health and Ethanol Fetal alcohol syndrome
environmental significance of various types of chemical • Facial anomalies
exposure • Growth retardation
• Hazard – ability of a chemical agent to cause injury in a • Neuro-developmental
defects
given situation or setting
• Risk – expected frequency of the occurrence of an
undesirable effect arising from exposure to a chemical or Effects of Poison
Immediate vs. Delayed
physical agents
Immediate Delayed
• Seen after single • Seen after a lapse of time
POISON administration
• deleterious effects Reversible vs. Irreversible
• physical injuries Reversible Irreversible
• death • Reversed by administration of • Permanent damage
• Toxin – natural source the antidote • Carcinogenic and teratogenic
• Toxicants – man made/ artificial source effects
COMMON MAJOR PATHOPHYSIOLOGIC MECHANISMS Local vs. Remote vs. Systemic
CNS stimulation Causes nerve excitability → Seizures → Brain Local Remote Systemic
damage • Same route of • Different route of • Causes
CNS depression Loss of airway protective reflexes and respiratory administration administration widespread
drive → Respiratory depression and site of and site of derangement
Parasympathomimetic Diarrhea action action
effect Urination Example: Example: Example:
Miosis, Muscle fasciculations Phenol, caustic, Paraquat ingestion → Metabolic acidosis
(DUMBELS) Bronchoconstriction, Bradycardia corrosives → skin pulmonary fibrosis due to MUDPHILES
Emesis burn
Lacrimation
Salivation, Sweating MUDPHILES
Sympathomimetic Mydriasis Methanol
effects Agitation Uremia
Tachycardia Diabetic ketoacidosis
(MATHS) Hypertension Paraldehyde
Seizure, Sweating Isoniazid, Iron
Cardiovascular Heart: Cardiac Arrhythmias Lactic acidosis
effects Vasculature: Ethylene glycol
• Vasodilation → hypotension Salicylates
• Vasoconstriction → hypertension
Respiratory effects Aspiration → Bronchospasm Route of administration:
Cellular hypoxia Interference with O2 transport and utilization
Musculoskeletal Muscle breakdown and myoglobinuria → Renal
effects failure, lactic acidosis, hyperkalemia Ingestion
• Accidental and suicidal poisoning
Inhalational
• Occupational exposure
Dermal
• Occupational exposure
Parenteral
• Greatest effect and most rapid response
Module 4 – Toxicology Page 1 of 9 RJAV 2022
, Frequency D. Degree of Disability
Acute Eyes Verbal Motor
• Single administration (+4) Spontaneous (+5) Orientated (+6) Obey commands
• Time: < 24 hours (+3) To sound (+4) Confused (+5) Localizing
(+2) To pressure (+3) Words (+4) Normal flexion
• Acute exposure by inhalation: 4 hours (+1) None (+2) Sounds (+3) Abnormal flexion
Subacute (+1) None (+2) Extension
• Repeated exposure (+1) None
• Time: < 1 month Differential Diagnoses for altered Mental Status:
Sub-chronic 1. Head trauma or other causes of intracranial bleeding
• Repeated exposure 2. Abnormal levels of blood glucose, sodium, or other
• Time: 1-3 months electrolytes
3. Hypoxia
Chronic 4. Hypothyroidism
• Repeated exposure 5. Liver or renal failure
• Time: > 3 months 6. Environmental hyperthermia or hypothermia
7. Serious infections such as encephalitis and meningitis
II. GENERAL MANAGEMENT OF A POISONED PATIENT
Causes Agent Initial Dose
Primary Survey (ABCDE) Hypoglycemia Dextrose
• Adult 50% dextrose, 50mL (25g) IV
• Child 25% dextrose, 2mL/kg IV
History and PE Alcohol intoxication Thiamine 100 mg, in the IV solution or IM
Opioid intoxication Naloxone 0.2-0.4 mg IV or IM
Decontamination *if no response within 1-2 minutes,
give 2 mg IV
Antidotal Therapy Benzodiazepine Flumazenil 0.2 mg IV over 30 seconds
*Pediatric dose Is not established;
starts at 0.01 mg/kg
Toxin Elimination *if no response, give 0.3 mg
**if still no response, give 0.5 mg and
repeat every 30 seconds
PRIMARY SURVEY
E. Exposure/ Environment
Airway
HISTORY AND PHYSICAL EXAMINATION
Breathing
• A.k.a. SECONDARY SURVEY (“AMPLE”)
Circulation
Degree of Disability Allergy
Exposure/ Environment Medication
Past Medical History/ Pregnancy
A. Airway
Last meal
Airway Management
• Optimize airway position Events related to the injury
• Place the neck and head in “sniffing” position
• Apply the jaw-thrust maneuver DECONTAMINATION
• Place the patient in a head-down, left sided position
• CAUTION: Do not perform neck manipulation if neck A. Surface Decontamination:
injury is suspected
• Remove any obstruction or secretions 1. Dermal
• Use of artificial oropharyngeal or nasopharyngeal airway • Remove contaminated clothing
devices • Wash with copious amount of running (tap) water for 30
minutes
B. Breathing Topical Agents for Chemical Exposure to the Skin
Hydrofluoric acid Calcium soaks
Breathing Problems
Oxalic acid Calcium soaks
Ventilatory Failure Paralysis of Ventilatory Muscles: Phenol Mineral oil, Isopropyl alcohol
• Flaccid paralysis: Neuromuscular blockers, White Phosphorus Copper sulfate 1%
Botulinum toxin
• Spastic paralysis: Tetanospasmin,
Strychnine, Saxitoxin, Tetrodotoxin 2. Inhalational
CNS Depression: Alcohols, Sedative-hypnotics, • Remove the patient from the toxic environment → O2
Opioids, Antidepressant, Antipsychotics supplementation
Hypoxia Inert gases: CO2, Methane, Propane, Nitrogen
Cellular hypoxia: CO, Cyanide, 3. Ocular
Methemoglobinemia, H2S, Sulfahemoglobinemia • Wash with BSS/ NSS for 15 minutes of consume 2L
Pneumonia: Aspiration of gastric contents with lids retracted
Bronchospasm Beta-blocker, Hydrocarbon aspiration,
organophosphates and carbamates
B. Gastric Decontamination
C. Circulation
1. Activated Charcoal
• Highly adsorbent powdered material made from a
Circulation Management
distillation of wood pulp
• Check blood pressure and pulse rate and rhythm
• Dose: 10:1 (charcoal to toxin)
• Begin continuous ECG monitoring
• Contraindications:
• Secure venous access
• Unconscious patients
• Draw blood for routine studies
• Begin IV infusion
Module 4 – Toxicology Page 2 of 9 RJAV 2022
