LESSON 1 o Testing or analysis of a toxicant or

agents in bodily fluids

What is TOXICOLOGY?
o LD50, LC50
 “Branch of science that deals with o TLV - Threshold limit values
poisons” 4. Descriptive Toxicology
 “The science of poisons and the effects o Conduct toxicity testing in order to
of chemicals on living organisms” gather product information on
 “The medical science of studying product acceptance , safety and
poisons” regulation
5. Forensic Toxicology
POISON o Concerned with medico-legal cases
o e.g. crime scenes
 Any substance that can cause injury,
disease and death. 6. Mechanistic Toxicology
o Deals with the MECHANISM OF
 Any drug is poisonous if taken in
TOXIC ACTION (MOTA) of
sufficient quantities
substances
EX: Luana Suares 2013 Died of Water
Intoxication LESSON 2 INTRODUCTION TO POISONS
INTOXICATION Toxicity associated with any SOURCES OF POISONS
substance
1) INDUSTRIAL
HAZARD Likelihood that an injury may occur
 POLLUTANTS
RISK Frequency that a harmful effect may  HYDROCYANIC ACID
happen  CARBON DIOXIDE/MONOXIDE
 CHLOROFLUOROCARBONS
OVERDOSE Intentional exposure to toxic agent
2) HOUSEHOLD
POISONING Accidental exposure to toxic agent  INSECTICIDES/PESTICIDES
Branches of Toxicology  CLEANING AGENTS
3) ENVIRONMENTAL
 LEAD
 SULFUR DIOXIDE
 NITROGEN
 OZONE
4) PHARMACOLOGIC/MEDICINAL
 CLINICALLY USED SUBSTANCE
1. Clinical Toxicology  SUBSTANCES FOR ABUSE
o The analysis and assessment of
KINDS OF POISONS
overdose and poisoning effects to
the patient ACCORDING TO PROPERTY
2. Environmental Toxicology A. CORROSIVES
o The study of the impact of  Local destruction of parts but not
pollutants to human health poisonous if diluted.
3. Experimental Toxicology  ACIDS , BASES
B. TRUE POISONS
  Highly toxic  Subcutaneous
 No medicinal value  Absorption through the skin
C. CUMULATIVE POISONS  Inhalation
 Increases the intensity of a poison as
the dose increase Quantitative Toxicity
ACCORDING TO MODE OF ACTION Median Lethal Dose (LD5)
A. LOCAL Median Lethal Concentration (LC50)
 Destroy or cause serious injury to Threshold Limit Value (TLV)
mucous membrane or tissues TYPES OF POISONING
 Corrosives (e.g. Acids & Bases) A. ACUTE
KINDS OF LOCAL EFFECTS  Taken in excess in a single dose or small
 CORROSION doses with high frequency resulting to
 IRRITATION death or injury over a short span of
 SPECIFIC EFFECT time.
Localization of Poisons  e.g. Sleeping pills
The remote action of poison following B. CHRONIC
absorption on certain organs  Produced by taking over the course of a
Factors Affecting Absorption of Poison long period of time producing gradual
 Solubility of Poison but progressive deterioration of tissue
 Character of the Surface to which functions.
the poison is applied  e.g. Heavy metals
 Quantity of blood in the blood CLASSIFICATION OF TOXIC EFFECTS
vessels A. PHARMACOLOGICAL – exaggeration of
Conditions which Modify the Action of Poisons effects
 Physical state B. PATHOLOGICAL- injury to tissue
 Age C. GENOTOXIC –damage to DNA
 Sex D. CHRONIC
 Idiosyncrasy E. ACUTE
 Habit F. IMMEDIATE – rapid effects after
 Mental & Physical State exposure
 Condition of the stomach G. DELAYED – occurrence of effects over a
 Character and amount of stomach period of time
contents H. DIRECT – caused directly by a specific
B. SYSTEMIC substance
 Follow local action, absorbed into the I. INDIRECT – effects are only
bloodstream, furthermore, produces consequences of the direct effects.
harmful effects on vital organs. EVIDENCE OF POISONING
 E.g. Heavy Metals  CIRCUMSTANTIAL
Routes  Circumstance or deduced from
 Oral various consequences and facts
 Intravenous  SYMPTOMATIC
  Exhibited by the patient
 CHEMICAL
 Evidence by means of chemical
analysis (e.g. tyrotoxin,
tyrotoxicon)
 ANTE-MORTEM
 Obtained right before death
 POST-MORTEM
 Examinations of organs or
tissues after death
 Blackening and severe
corrosion (corrosives)
 Discoloured lips (caustic alkali)
 Swollen lips (ammonia)
 Whitened mucous membrane
(oxalic acid)
 Dessicated inflammation
(cantharides)
 EXPERIMENTAL
 Obtained by administering a
suspected substance to some
living animals and observing the
effects
 Discoloration of the feces
 Discoloration of the urine
FECAL EVIDENCE
• ANTACIDS – WHITISH SPECKS
• ANTICOAGULANTS – RED TO BLACK
• BISMUTH AND IRON – BLACK
• PIRVINIUM PAMOATE – RED
• RIFAMPICIN – RED
• SALICYLATES – RED TO BLACK
URINARY EVIDENCE
• CASCARA SAGRADA – RED IN ALKALINE
URINE
• CHLOROQUINE – YELLOW TO BROWN
• CHLORPROMAZINE – PINK TO RED
• FURAZOLIDONE – YELLOW TO BROW
• METRONIDAZOLE – DARK
• NITROFURANTOIN – YELLOW TO
BROWN
• RIBOFLAVIN & RIFAMPICIN – YELLOW
LESSON 3 MOTA
A. RECEPTOR THEORY
 According to Paul Erlich
 Specific or selective for a
particular tissue or organ
 Cell possess receptors
(proteins, cell membrane
surface, nucleus) which forms
complexes with poisons.
 Cause physiologic change in the
cell
B. CHANGE IN ENZYME SYSTEMS
 Disruption of enzyme activity
 Direct action on
substrate or a cofactor
 Inhibition of enzyme
 Similar structure of enzyme acts
on a substrate
 Competitive inhibition
 Inactive enzymes
 Alter enzyme structures
C. CHANGE IN MEMBRANE STRUCTURE
 Interfere with the normal
activities of the membrane:
 transport of nutrients,
 expulsion of toxic products
COMMON PATHOPHYSIOLOGICAL
MECHANISMS
A. INTERFERENCE OF OXYGEN
B. DEPRESS OR STIMULATE CNS
C. AFFECT ANS
D. AFFECT THE LUNGS
E. AFFECT CV
F. LOCAL DAMGE
G. DELAYED EFFECTS
ELIMINATIONOF POISONS
A. SALIVA
B. URINE
C. SWEAT
D. BILE  Trade and generic name of the
E. PANCREATIC JUICE poisons
 Route of exposure
F. FECES
 Formulation and name of
G. RENAL IS USALLY THE ROUTE OF manufacturer
ELIMINATION  Action taken to eliminate poison
H. GASEOUS POISONS MAY BE PROMPTLY  Occupation and hobbies
REMOVED BY THE LUNGS  WHEN?
 Time of exposure
DIAGNOSIS OF POISONING
 Differential diagnosis as to the
 Dependent on: onset of the poison
 Consciousness of the patient  Routines
 Physical examination  HOW MUCH?
 Past history  Amount of exposure and strength
 Chemical identification of poison
 Quantification of compound in  Place of exposure
question  WHY?
 CONSCIOUSNESS  Poisoning
 Overdosing
 Admittance
 PHYSICAL FINDING
 Poisoning
 Vital signs
 SIGNS
 Heart rate
 Vomiting
 Respiration rate
 Convulsions
 Temperature
 Coma
 Blood pressure
 Pupilodilation/pupilocostriction
 Documents and Pertinent
 Slow/rapid respiration
Evidence
 Delirium
 Dyspnea
MANAGEMENT OF POISONING: GENERAL
 Cyanosis
PRINCIPLES
 IDENTIFICATION OF PATIENT AND
A. Separation of patient from the poison
TOXIC AGENT  Remove the patient from contaminated
 WHO IS THE PATIENT? area
 HOW IS THE PATIENT?  Remove clothing, if the area of
 Obtaining the history (for non life exposure is local
threatening cases)  Induce vomiting for non-corrosives
 Symptomatic patients are B. Provide supportive therapy
transferred to the nearest health  Use of ventilator
care facility  Use of cardiovascular support
 Asymptomatic patients: C. Give antidotes
 Age  Give universal antidotes
 Medication taken  Give specific antidotes
 Past history
 Last meal MANAGEMENT OF POISONING: PREVENTING
 Events that lead to the ABSORPTION
poisoning/overdose
A. Induce vomiting
 WHAT?
  stimulation of medullary
chemoreceptor trigger zone (CTZ) LESSON 4
 Syrup of Ipecac (Cephalis ipecacuanha) ANTIDOTES
 Contraindicated for corrosives,
 agents which neutralize or counteract
hydrocarbons
the effects of poisons
 unconscious or altered consciousness
Kinds of Antidotes
 convulsive
B. Gastric Lavage Mechanical
 large-bore tube through the mouth, into  Remove poisons or prevent absorption
the esophagus and stomach by coating or suspending the poison
 Pumped in with 250mL aliquots of saline or  Examples:
water
 Stomach pump or tube
 Less effective
 employment of emetics,
 Alternative for emesis
cathartics
C. Activated Charcoal
A. EMETICS
 Adsorption of poison or toxin
 Delay GI absorption 1. LOCAL EMETICS
 stimulation or irritation of terminal
D. Cathartics
 enhances the transit of materials through
nerve filaments, reflex stimulation of
the GIT the vomiting center of the medulla
 generally, utilized after specific antidotes oblongata
are given  Example:
FIRST AID TREATMENT FOR POISONING Mustard (Brassica nigra and Sinapis
alba)
A. Removal of poison from point of
2. SYSTEMIC EMETICS
contact
 produce effects through circulation
1. Eyes - wash with saline, milk
 Example:
2. Skin - wash with running water Ipecac syrup
3. Mouth - remove contents of mouth Emetine
B. Removal of victim from poisonous Apomorphine hydrochloride
fumes B. CATHARTICS
1. Allow the victim to have fresh air  agents which produce intestinal
2. Loosen all tight-fitting clothing evacuation, generally used after a
3. If breathing is not detected, start chemical antidote
artificial respiration  Castor Oil - contraindicated for
4. Use oxygen if available cantharides, copper salts, phosphorus
C. Inducing vomiting  Magnesium sulfate (Epsom salt)
1. Give syrup of ipecac  Sodium sulfate (Glauber’s salt)
Dosing:
 Adults - 30mL
 Child over 1 year - 15mL
 Child less than 1 year – 10ml Physiological
2. Contraindications:  agents which act by opposing the
o Unconscious patients
effects of the poison combat symptoms
o Convulsive
 Example:
o Ingested corrosives
o Ingested hydrocarbons
 Atropine to morphine
  Barbiturate to cocaine
 Caffeine to morphine
Chemical Antidotes
 agents which acts chemically to form
non-toxic compounds
 action is usually by precipitation,
neutralization, oxidation or chelation
1. Acids & corrosives - antacids
2. Barium salts - sodium sulfate, magnesium
sulfate
3. Alkaloids - potassium permanganate
4. Heavy metals - milk, egg white
5. Mercury – dimercaprol
A. CHELATION
 CHELATE
 formation of a large compound
containing a ligand bonded to acentral
metal atom
1. DIMERCAPROL
 Also known as British Anti-Lewisite
(BAL)
 Metal acceptor to prevent or
reverse activation
 A/E:
3mg/Kg dose: Anorexia, restlessness,
body malaise, itching, salivation, elevated BP
5mg/Kg dose: Vomiting, convulsions,
stupor or coma
 Contraindications:
Not for Iron or selenium poisoning
Not for patients with hepatic and renal
issues
2. CALCIUM EDETATE
 Also known as Calcium disodium
versenate
 Only for metals that cannot be
displaced by calcium
 (e.g.) Lead, iron, zinc, manganese,
beryllium, copper
3. PENICILLAMINE
 Also known as Cuprimine
 A product of hydrolysis of penicillin
 Usually for the removal of copper and
lead
4. DEFEROXAMINE
 chelates iron to FERRIOXAMINE
 given aif the Iron serum levels exceeds
400mcg/Dl
5. SUCCIMER
 also known as Dimercaptosuccinic acid
or DMSA
 analog of dimercaprol
 Isolated from Streptomyces pilosus
 A/E: Anorexia, N&V, diarrhea
6. TRIENTINE
 Also known as
TRIETHYLENETETRAMINE
 for copper chelation, second line
treatment
LESSON 5
Specific Poisons
 Corrosives
 Maybe referred as acids
MOTA:
 Direct chemical reaction, the tissue protein
is converted to acid proteinate (e.g.
Hemoglobin to Hematin) and is
precipitated. The action to the tissue will
cause reflex loss of vascular tone
 Caustics
 Maybe referred as bases
MOTA:
 combine with proteins to form proteinates
and form soap, produce soft liquefactive
necrosis, can also cause loss of vascular
tone
 Corrosives and Caustics
 Principal Manifestation: CORROSION
 Ingested: severe burning pain in the tissues
that come into contact
Evidence: Brown to yellow stains
Probable cause of death: Asphyxia from the
edema of the glottis
  Inhaled: coughing to choking, dizziness,
weakness, cyanosis, hemoptysis
Evidence: shortness of breath for several
weeks
Probable cause of death: Asphyxia from the
vapor
 Skin Contact: penetrating burns, necrosis
Evidence: yellow to brown stains
 Eye Contact: penetrating burns,
conjunctival edema, corneal destruction,
pain
Evidence: redness of the eyes, blindness
TREATMENT: Corrosives and Caustics
 General Measures:
 Dilution with milk (100x)
 Gastric lavage is not the first option
 Relieve pain with morphine
 Prevent edema of the glottis
 Maintain blood pressure
 EYE - Dilute with milk for at least 15 minutes
 SKIN - Flowing water for at least 15 minutes
 INHALATION - Artificial respiration