• Knowledge of animal venoms and plant extracts for hunting,

warfare, and assassination presumably predate recorded history.

PAPYRUS EBERS

• Oldest known writings

• Contains information pertaining to many recognized poisons,
including hemlock, aconite, opium, and metals such as lead, copper,
and antimony.
BOOK OF
JOB
• Speaks of poison arrows (Job 6:4)
• “For the arrows of the Almighty pierce me, and my spirit drinks in
their poison; the terrors of God are arrayed against me.”
HIPPOCRATES

• Added a number of poisons and clinical toxicology principles

pertaining to bioavailability in therapy and overdosage
DIOSCORIDES

• Greek physician in the court of the Roman Emperor Nero, made the
first attempt at classifying poisons into plant, animal, and mineral
poisons in his books De Materia Medica, which contains reference to
some 600 plants
LEGEND - ROMAN KING MITHRIDATES VI OF
PONTUS

• Fearful of poisons that he regularly ingested a mixture of

ingredients as protection against assassination
36
• On the occasion of his imminent capture by enemies, his attempts to
kill himself with poison failed because of his successful antidote
concoction.
• Mithridatic as an antidote or protective mixture.
SULL
A
• Because poisonings in politics became so extensive
• Issued Lex Cornelia, which appears to be the first law against
poisoning and later became a regulatory statute directed at careless
dispensers of drugs
WRITINGS OF MAIMONIDES

• Included a treatise on the treatment of poisonings from

insects, snakes, and mad dogs
• Described the subject of bioavailability, noting that milk , butter and
cream could delay intestinal absorption
CATHERINE DE MEDICI

• Tested toxic concoctions, carefully noting the rapidity of the toxic

response (onset of action), the effectiveness of the compound
(potency), the degree of response of the parts of the body
(specificity and site of action), and the complaints of the victim
(clinical signs and symptoms)
RENAISSANCE
PERIOD
• “all substances are poisons; there is none that is not a poison. The
right dose differentiates a poison from a remedy” – Paracelsus
• Paracelsus (Phillippus Aureolus Theophrastus Bombastus von
Hohenheim) was pivotal standing between the philosophy and magic
willed to us of classic antiquity and the philosophy and science willed
to us by figures of the seventeenth and eighteenth centuries
• Physician-alchemist, formulated many revolutionary views that
remain
integral to the structure of toxicology, pharmacology, and therapeutics today
Paracelsus (Phillippus Aureolus Theophrastus
Bombastus von Hohenheim)

• student of Aristotle - Included numerous references to poisonous plants in

De Historia Plantarum
• He focused on the primary toxic agent as a chemical entity and held that:
• Experimentation is essential in the examination of responses to chemicals
• One should make a distinction between the therapeutic and toxic properties of
chemicals
• These properties are sometimes but not always indistinguishable except by dose
• One can ascertain a degree of specificity of chemicals and their therapeutic or toxic
effects
ELLENBORG

• Warned of the toxicity of mercury and lead from goldsmithing and

Agricola published a short treatise on mining diseases in 1556, the
major work on the subject, On the Miner`s Sickness and Other
Diseases of Miners. This treatise addressed the etiology of miners`
disease, along with treatment and prevention strategies
• Occupational toxicology was further advanced by the work of
Bernardino Ramazzini when he published in 1700 his Discourse on
the Diseases of Workers, which discussed occupations ranging from
miners to midwives and including printers, weavers and potters.
PERCIVAL POTT

• Recognition of the role of soot in scrotal cancer among chimney

sweeps was the first report of polyaromatic hydrocarbon
carcinogenicity. These findings led to improved medical practices,
particularly in prevention.
AGE OF ENLIGHTENMENT

• EXPERIMENTAL TOXICOLOGY accompanied the growth of organic

chemistry and developed rapidly during the nineteenth century
• Magendie, Orfila and Bernard laid the groundwork for
pharmacology, experimental therapeutics, and occupational
toxicology.
ORFILA

• A Spanish physician in the French court, used autopsy material and

chemical analysis systematically as legal proof of poisoning.
• His introduction of this detailed type of analysis survives as the
underpinning of forensic toxicology.
• Published a major work devoted expressly to the toxicity of natural
agents in 1815
MAGENDIE

• A physician and experimental physiologist, studied the mechanisms

of action of emetine and strychnine
• His research determined the absorption and distribution of these
compounds in the body
• One of Magendie`s more famous students, Claude Bernard,
contributed the classic treatise, An Introduction to the Study of
Experimental Medicine.
MODERN TOXICOLOGY

• With the advent of anaesthetics and disinfectants in the late 1850s,

toxicology as it is currently understood began.
1890s and early 1900`s

• The discovery of radioactivity and vitamins, or vital amines, led to

the use of the first large-scale bioassays (multiple animal studies) to
determine whether these new chemicals were beneficial or harmful
to laboratory animals.
ARCHIV FUR TOXIKOLOGIE

• One the first journals expressly dedicated to experimental

toxicology,
of began publication in Europe in 1930
• The same year, the National Institutes of Health (NIH) was
established in the US
• As a response, to the tragic consequences of acute kidney failure
after taking sulfanilamide in glycol solutions, the Copeland bill was
passed in 1938.
• This was the second major bill involving the formation of the U.S.
Food and Drug Administration (FDA)
• The first major US pesticide act was signed into law in 1947. The
significance of the initial Federal Insecticide, Fungicide, and
Rodenticide Act was that for the first time in the US history a
substance that was neither a drug nor a drug nor a food had to be
shown to be safe and efficacious.
AFTER WORLD WAR 2

“ You too can be a toxicologist in two easy lessons, each of ten years.”
Arnold Lehman

• The mid-1950`s witnessed the strengthening of the US FDA`s commitment

to toxicology. The US Congress passed and the president of the US signed
the additives amendments to the Food, Drug and Cosmetic Act.
• The Delaney clause of these amendments stated broadly that any
chemical found to be carcinogenic in laboratory animals or humans could
not be added to the US food supply
• Delaney became a battle cry for many groups and resulted in the
inclusion at a new level of biostatisticians and mathematical
modelers in the field of toxicology.
• Shortly after the Delaney amendment, the first American Journal
dedicated to toxicology, Toxicology and Applied Pharmacology, was
launched.
• The founding of the Society of Toxicology followed shortly afterward.
• The 1960s started with the tragic thalidomide incident, in which several
thousand children were born with serious birth defects, and the
publication of Rachel Carson`s Silent Spring.
• Attempts to understand the effects of chemicals on the embryo and fetus
and on the environment as a whole gained momentum.
• New legislation was passed, and new journals were founded.
• Cellular and molecular toxicology developed as a subdiscipline, and risk
assessment became a major product of toxicologic investigations.
• Currently, many dozens of professional, governmental, and other
scientific organizations with thousands of members and over 120
journals are dedicated to toxicology and related disciplines.
• In addition, the International Congress of Toxicology is made up of
toxicology societies from Europe, South America, Asia, Africa, and
Australia, which brings together the broadest representation of
toxicologists.
• Toxicology has an interesting and varied history. Perhaps as a science that
has grown and prospered by borrowing from many disciplines, it has
suffered from the absence of a single goal, but its diversitification has
allowed for the interspersion of ideas and concepts from higher
education, industry, and government.
• This has resulted in an exciting, innovative, and diversified field that is
serving science and the community at large. Few disciplines can point to
both basic sciences and direct applications at the same time. Toxicology –
the study of the adverse effects of xenobiotics- may be unique in this
regard.
WHAT IS TOXICOLOGY?
TOXICOLOGY

• Study of the adverse effects of chemicals on living organisms.

• TOXICOLOGIST – trained to examine the nature of those effects and assess
the probability of their occurrence.
SIGNIFICANT TERMS IN TOXICOLOGY

• POISON – 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
• POISONING – a clinical toxicity secondary to accidental exposure
• INTOXICATION – toxicity associated with any chemical substance
• 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
DIFFERENT
AREAS OF
TOXICOLOGY
1. MECHANISTIC TOXICOLOGY
2. DESCRIPTIVE TOXICOLOGY
3. REGULATORY TOXICOLOGY
4. FORENSIC TOXICOLOGY
5. ENVIRONMENTAL TOXICOLOGY
6. DEVELOPMENTAL TOXICOLOGY
7. REPRODUCTIVE TOXICOLOGY
8. CLINICAL TOXICOLOGY
MECHANISTIC TOXICOLOGY DESCRIPTIVE TOXICOLOGY

• Identification of cellular, • Concerned directly with toxicity

the and molecular
mechanisms
biochemical, by which chemicals testing, which
exert toxic effects on living organisms information provides for
• TOXIGENOMICS – permits
toxicologists to identify and protect
mechanistic evaluation safety and
genetically susceptible individuals from
harmful environmental exposures, and requirements. regulatory
to customize drug therapies based on
their individual genetic makeup.
REGULATORY TOXICOLOGY FORENSIC
TOXICOLOGY

• Concerned with the basis of • Hybrid of analytic chemistry and

data provided by descriptive fundamental toxicologic
and mechanistic toxicologists, principles that focuses primarily
whether a drug or another on the medicolegal aspects of
chemical poses a sufficiently the harmful effects of the
low risk to be marketed for a chemicals on humans and
stated purpose animals
ENVIRONMENTAL TOXICOLOGY DEVELOPMENTAL TOXICOLOGY

• Focuses on the impacts of chemical • Study of adverse effects on

pollutants in the environment on developing organism that may result
biological organisms, specifically studying the
from exposure to chemical or physical
the impacts on nonhuman organisms agents before conception (either
such as fish, birds, terrestrial animals, parent), during prenatal
and plants. development, or postnatally until the
• ECOTOXICOLOGY – a specialized area
within environmental toxicology, focuses time of puberty.
specifically on the impacts of toxic • TERATOLOGY – study of defects induced
substances on population dynamics in an during development between
ecosystem conception and birth
REPRODUCTIVE TOXICOLOGY CLINICAL TOXICOLOGY

• Study of the occurrence of • Concerned with the disease

adverse effects on the male or caused by or uniquely
female reproductive system that associated with
may result from exposure to substances toxic
chemical or physical agents
ETHICAL DYNAMICS OF TOXICOLOGY

1. Experience & new discoveries in the biological sciences have emphasized the
need for well-articulated visions of human, animal, and environmental health.
2. Experience with the health consequences of exposure to such things as lead,
asbestos, and tobacco has precipitated many regulatory & legal actions &
publicly policy decisions
3. Well-defined framework for discussing our social & ethical responsibilities
4. All research involving humans or animals must be conducted in a responsible
and ethical manner
5. The uncertainty & biological variability inherent in the biological sciences
requires decision making with limited or uncertain information
CLASSIFICATION OF TOXIC AGENTS

• IN TERMS OF THEIR TARGET ORGANS, USE, SOURCE AND EFFECTS;

IN TERMS OF PHYSICAL STATE, CHEMICAL STABILITY/
REACTIVITY, GENERAL CHEMICAL STRUCTURE OR POISONING
POTENTIAL
• TOXIN – generally refers to toxic substances that are produced by biological
systems such as plants, animals, fungi, or bacteria
• TOXICANT – used in speaking of toxic substances that are produced by or a
by-product of human activities
 SPECTRUM OF UNDESIRED
•EFFECTS
ALLERGIC REACTIONS VS. IDIOSYNCRATIC REACTIONS

ALLERGIC REACTIONS – chemical allergy is an immunologically-mediated adverse

reaction to chemical or structurally similar one

IDIOSYNCRATIC REACTIONS – chemical idiosyncracy is genetically determined

abnormal reactivity to a chemical
SPECTRUM OF UNDESIRED
EFFECTS
• IMMEDIATE VS. DELAYED TOXICITY

DELAYED TOXICITY – occur after the lapse of some time

IMMEDIATE TOXICITY – develop rapidly after a single
administration of a substance
 SPECTRUM OF UNDESIRED
•EFFECTS
REVERSIBLE VS. IRREVERSIBLE
EFFECTS
REVERSIBLE EFFECTS – injury caused by a toxic agent that is not permanent
and can be corrected/treated

IRREVERSIBLE EFFECTS – injury caused by a toxic agent that cannot

be repaired in part or full by the injured body
SPECTRUM OF UNDESIRED
EFFECTS
•LOCAL VS. SYSTEMIC TOXICITY
LOCAL TOXICITY – or local effect; 0ccurs at the site of first
contact between the biological system and the toxicant

SYSTEMIC TOXICITY – or systemic effect; requires absorption

and distribution of a toxicant from its entry point to a distant site at which deleterious
effects are produced
FACTORS AFFECTING POISONING EFFECTS

POISON-RELATED FACTORS PATIENT-RELATED FACTORS

• ROUTE OF ADMINISTRATION • AGE

• CONCENTRATION • LIFESTYLE
• SOLUBILITY • TOLERANCE
• EXTENT OF TOXICITY • IDIOSYNCRASY (ADME)
INTERACTION OF CHEMICALS
• ADDITIVE EFFECT
• Observed when two chemicals
are given together occurs when
the combined effect of two
chemicals is equal to the sum of
the effects of each if given alone
• SYNERGISTIC EFFECT
• Occurs when the combined
effects of two chemicals are much
greater than the sum of the
effects of each agent if given
alone
INTERACTION OF CHEMICALS

• ANTAGONISM • TYPES:
• Occurs when two • FUNCTIONAL
administered together chemicals • CHEMICAL
with each other`s actionsinterfere
or one • DISPOSITIONAL
interferes with the action of the
other • RECEPTOR
INTERACTION OF CHEMICALS

• FUNCTIONAL • DISPOSITIONAL
•TWO CHEMICALS • WHEN THE ABSORPTION, METABOLISM,
COUNTERBALANCE EACH OTHER DISTRIBUTION AND
BY PRODUCING OPPOSITE EXCRETION OF A CHEMICAL IS
EFFECTS ON THE SAME ALTERED SO THAT THE
CONCENTRATION AND/OR DURATION
PHYSIOLOGIC FUNCTION OF THE CHEMICAL AT THE TARGET
ORGAN ARE DIMINISHED

• CHEMICAL • RECEPTOR
• (INACTIVATION); SIMPLY A • OCCURS WHEN 2 CHEMICALS THAT
BIND TO THE SAME
CHEMICAL REACTION BETWEEN RECEPTOR
TWO COMPOUNDS THAT PRODUCE LESS OF AN EFFECT WHEN
PRODUCES A LESS TOXIC GIVEN TOGETHER THAN THE ADIITION
PRODUCT OF THEIR SEPARATE EFFECTS
EVIDENCES OF POISONING

• CIRCUMSTANTIAL – deduced from various events or facts but not a strong

evidence
• POST-MORTEM – gathered after an autopsy is performed such as
an examination od tissues, organs, body fluids after death
• EXPERIMENTAL – administering the suspected substance to some living
animal and noting the effect or symptom
• CHEMICAL – detection of suspected substance via analysis of samples of
body fluids collected
• SYMPTOMATIC – poisoning signs or effects are observed
GENERAL KINDS OF POISONS ACCORDING TO
EFFECTS
• IRRITANTS – tissue • CARCINOGENICS –
necrosis
cause on caustic growth of cancer cells
stimulate
effects contact,
• ASPHYXIANTS – cause dyspnea
• NEUROTICS – affect the CNS
• LACRIMATORS – stimulate • ASTHENICS – produce muscular
flow of tears weakness
• STERNUTATORS – • NARCOTICS – produce
cause excessive sneezing mental weakness/depression
GENERAL MANAGEMENT

• Evaluating and supporting the vital

SUPPORTIVE functions (airway, breathing
and
circulation) are mandatory first
CARE steps in the initial management of
drug ingestions.
& • After the patient is stabilized, the
specific issue of poison
ABCs management should be
addressed.
TREATMENT

1. To rule out or treat hypoglycemia, 50ml of 50% dextrose in adults

and 1ml/kg in children intravenously
2. Thiamine 100mg IV push (glucose can precipitate the Wernicke-
korsakoff syndrome in thiamine-deficient patients)
3. Naloxone 0.5 to 2 mg IV push, if opiate ingestion is suspected.
Naloxone may also be administered by the following routes:
inhalation, IM, and intranasal
OBTAINING A HISTORY OF EXPOSURE

• IDENTIFY • PAST MEDICAL HISTORY:

• MEDICATIONS
• NEUROLOGICAL EXAMINATION • ALCOHOL/DRUG ABUSE
• PSYCHIATRIC HISTORY
• CARDIOPULMONARY • ALLERGIES
EXAMINATION • OCCUPATIONAL OR HOBBY
EXPOSURES
• GASTROINTESTINAL • TRAVEL
• PRIOR INGESTIONS
EXAMINATION • SOCIAL HISTORY WITH
POTENTIAL
NEGLECT
FOR DOMESTIC VIOLENCE
OR
• LAST NORMAL MENSTRUAL PERIOD
OR PREGNANCY
ROUTINE LABORATORY ASSESSMENT

• COMPLETE BLOOD COUNT • BLOOD GLUCOSE

• SERUM ELECTROLYTES • URINALYSIS
• BLOOD UREA NITROGEN • ELECTROCARDIOGRAM
• SERUM CREATININE • XRAY
TOXICOLOGY LABORATORY TESTS

ADVANTAGES DISADVANTAGES

• Confirm or determine • Cannot provide specific diagnosis for

presence
the of a particular agent all patients
• Predict the anticipated toxic • All possible intoxicating
effects or severity of exposure to agents
some poisons cannot be screened
• Confirm or distinguish differential • Laboratory drug-detection
or contributing diagnosis abilities
• Occasionally help guide therapy suffer
• Only qualitative determination of
a substance or substances is
necessary
SKIN DECONTAMINATION

• Should be performed when percutaneous absorption of a substance

may result in systemic toxicity
• Or when the contaminating substance may produce local
toxic effects
• The patient`s clothing is removed, and the areas are irrigated
with copious quantities of water
• Neutralization should not be attempted
GASTRIC DECONTAMINATION

• May be attempted when supportive care has begun

• Involves removal of the ingestant with emesis or lavage
• The use of activated charcoal potentially to bind any ingestants, and
the use of cathartics to hasten excretion and thereby limit
absorption
EMESIS

• SYRUP OF IPECAC • CONTRAINDICATIONS

• Within 30 minutes of ingestion
• Children younger than 6 months
of age
• Pts with CNS depression/seizures ;
pts who have ingested a strong
acid, alkali or sharp object; under
coma; ingested hc; ingested subs
with extremely rapid OOA; emesis
after ingestion
GASTRIC LAVAGE

• Infrequently used in patients who are not alert or have a diminished

gag reflex
• Massive ingestions
• CI: ingested acids, alkalis, or hydrocarbons, and who are at risk for GI
perforation or if they are combative
ACTIVATED CHARCOAL

• Adsorbs almost commonly ingested drugs and chemicals and is

usually administered to most overdose patients as quickly as
possible ideally within 1 hour of ingestion
• Not adsorbed: leas, ethanol, iron, lithium, cyanide, ethylene glycol,
mercury, methanol, organic solvents, potassium, strong acids and
strong alkalis
ACTIVATED CHARCOAL

DOSAGE ADVERSE EFFECTS

• Colloidal dispersion • Charcoal aspiration and

• Adults – 25-100g empyema
• Children – 25 – 50g
WHOLE BOWEL IRRIGATION

• Effective under certain conditions particularly when activated

charcoal lacks efficacy
• Isoosmotic cathartic solution –polyethylene glycol
• Dosage: 1 to 2 L/hr orally or bay nasogastric tube until the rectal
effluent is clear
FORCED DIURESIS & URINARY PH
MANIPULATION

• Enhance the elimination of substances, whose elimination is

primarily renal, if the substance has a relatively small volume of
distribution with little protein binding
• Associated with fluid and electrolyte disturbances
• ALKALINE DIURESIS
• Promotes ionization of weak acids, thereby preventing their reabsorption by
the kidney, which facilitates the excretion of such weak acids
 DIALYSIS HERMOPERFUSION
• Anticoagulated is passed
through
blood a column containing
• Enhance activated charcoal or resin
drug elimination particlesclears substances from blood
(ethanol, theophylline, more rapidly than hemodialysis, but
salicylates,
lithium, and long-acting does not correct fluid and electrolyte
barbiturates) abnormalities as does hemodialysis
• For water-soluble drugs • Effective (phenobarbital, phenytoin,
carbamazepine, methoreaxate and
• Life-threatening ingestions theophylline than hemodialysis) less
ethylene of methanol, effective (ethanol & methanol)
glycol, paraquat or • COMPLICATIONs:
leukopenia,
thrombocytopenia, hypocalcemia,
hypoglycemia, hypotension
DOSE-RESPONSE RELATIONSHIP

GRADED RESPONSE QUANTAL DOSE-RESPONSE

• Responder
• Normal frequency distribution
• Hypersusceptible
• resistant
• EFFECTIVE DOSE • SHAPE OF THE DOSE-
• THRESHOLD RESPONSE CURVE
• ESSENTIAL NUTRIENTS
DOSE
• HORMESIS
• THRESHOLD
EVALUATING THE DOSE-RESPONSE
RELATIONSHIP

• DOSE-RESPONSES • MARGINS OF SAFETY AND

• THERAPEUTIC INDEX EXPOSURE
• POTENCY VS. EFFICACY
REFERENCES:

• Lange 2 n d edition (Casarette &

Doull`s Essentials of Toxicology)
• Brex Pharmacy Review 2011
edition
• American Heart Association
Circulation(2010)
• Toxtutor.nlm.nih.gov
• www.ccohs.ca
 AGRICULTURAL POISONS
ORGANOPHOSPHATE ATROPINE, PRALIDOXIME
CARBAMATE INSECTICIDE ATROPINE
HYDROCARBON INSECTICIDE PHYSOSTIGMINE
PARATHION PRALIDOXIME
PARAQUAT BENTONITE, FULLER`S EARTH,
SODIUM SULFATE
BARIUM MAGNESIUM SULFATE,
DDT BENZODIAZEPINES
BARBITURATES
NITROGEN COMPOUNDS:
ANILINE, NITROBENZENE METHYLENE BLUE
 ALCOHOLS & GLYCOL
METHANOL ETHANOL, FOMEPIZOLE, MORPHINE,
VITAMIN B9
ETHANOL DISULFIRAM
ETHYLENE GLYCOL ETHANOL, FOMEPIZOLE, VITAMIN B9
ALDEHYDE
FORMALDEHYDE AMMONIA, SODIUM BICARBONATE
HYDROCARBONS
KEROSENE MINERAL OIL
CORROSIVES
OXALIC ACID, SODIUM PHOSPHATE, CALCIUM GLUCONATE
FLUORIDE
AMMONIA FORMALDEHYDE
BROMINE SODIUM CHLORIDE, AMMONIUM
CHLORIDE
 METALLIC POISONS
Sb, Au, Bi, W Dimercaprol or BAL
Be, Cd, Mn, Se EDTA
Zn, Cr, Ni BAL, EDTA
Cu BAL, penicillamine
As BAL, DMSA, penicillamine
Tl Prussian blue or ferric
ferrocyanide
P CuSO4
Hg Na formaldehyde sulfoxylate,
BAL, DMSA, penicillamine
 ALKALOIDS
ATROPINE PHYSOSTIGMINE
NICOTINE DIAZEPAM
QUINIDINE SODIUM BICARBONATE
ERGOT AND DERIVATIVES TOLAZOLINE, NA
NITROPRUSSIDE
CAFFEINE, THEOPHYLLINE ESMOLOL
STRYCHNINE DIAZEPAM, NEUROMUSCULAR
BLOCKERS, BARBITURATES,
ATROPINE
 ANTISEPTICS
IODINE STARCH SOLUTION, NA
THIOSULFATE
BLEACHING AGENTS NA THIOSULFATE
CATIONIC DETERGENTS ORDINARY SOAP
CHLORATES METHYLENE BLUE
CHLORAMINE-T NA NITRITE, NA THIOSULFATE
PHENOL CASTOR OIL
SILVER SALTS NACL, NA THIOSULFATE, K
FERROCYANIDE
 ANIMAL & PLANT HAZARDS
MUSHROOMS: PENICILLIN
MONOMETHYLHYDRAZINE PYRIDOXINE, METHYLENE BLUE
MUSCARINE ATROPINE
IBOTENIC ACID, MUSCIMOL PHYSOSTIGMINE
RATTLE SNAKE BITE ANTIVENOM, SUCTION &
TOURNIQUET
BLACK WIDOW SPIDER ANTIVENOM
SCORPIONS ANTISERUM
LEAD BAL, EDTA, DMSA, penicillamine,
succimer
 CYANIDES, SULFIDES & CARBON MONOXIDE
CYANIDE Amyl nitrite, Na nitrite, Na
thiosulfate, hydroxybalamine,
100% oxygen, hyperbaric
oxygen
SULFIDES Amyl nitrite, Na nitrite
CO 100% oxygen, hyperbaric
oxygen
COSMETICS:
BROMATES Na thiosulfate
FOOD POISONING
BOTULISM ABE botulinus antitoxin
NITRITES Methylene Blue
SULFITE Epinephrine
MEDICINAL POISONS:
ACETAMINOPHEN NAC
HEPARIN Potamine sulfate
WARFARIN Vitamin K
TRICYCLIC ANTIDEPRESSANTS Physostigmine
BENZODIAZEPINES Flumazenil
BETA BLOCKERS Glucagon
CALCIUM CHANNEL BLOCKER Glucagon, calcium chloride
CONTINUATION---------
DIGOXIN DIGOXIN-SPECIFIC FAB ANTIBODIES
DIGITALIS KCl
IRON DEFEROXIME/DEFEROXAMINE
ISONIAZID PYRIDOXINE
OPIATES NALOXONE, NALTREXONE, NALORPHINE
ATROPINE + DIPHENOXYLATE NALOXONE, NALTREXONE, NALORPHINE
BROMIDES NACl
AMPHETAMINE CHLORPROMAZINE
MAGNESIUM SULFATE CA GLUCONATE
SALICYLATES, PHENOBARBITAL NA BICARBONATEEDROPHONIUM Cl,
NEUROMUSCULAR BLOCKERS NEOSTIGMINE, PYRIDOSTIGMINE
SIGNS AND SYMPTOMS
ODOR SUBSTANCE/S
Shoe polish Nitrobenzene
Fruity odor ethanol
Garlic Arsenic, phosphorous, malathion,
thallium
Mouse urine Coniline
Stale tobacco Nicotine
Bitter almonds Cyanide
Sweet penetrating odor Acetone, chloroform
Pearlike Chloral hydrate
Rotten egg Hydrogen sulfide
Mothballs Naphthalene
Wintergreen methylsalicylate
SKIN DISCOLORATION SUBSTANCE/S
Yellow Picric acid, nitric acid
Bleaching white Phenol
Ash gray Mercuric chloride
Deep brown Bromine
Brown black Sulfuric acid, iodine, silver
nitrate
Bluish gray Silver salts
Blue Cyanotics (opium, aniline,
sulfides)
Pale bonds on fingernails Arsenic
Boiled lobster appearance Boric acid
VOMITUS SUBSTANCE/S
Blue green Copper
Ground coffee Sulfuric acid
Luminous vomit Phosphorous, arsenic
Yellow green chromium
BOWEL CHANGES SUBSTANCE/S
Black Charcoal, bismuth, iron, lead,
magnesium dioxide, silver
nitrate
Clay-like Alcohol, barium
White Aluminum hydroxide
Blue Boric acid, methylene blue,
iodine
Green Indomethacin, iron, cupric
sulfate
Red (also vomit) Hemolytic substances
BLOOD CHANGES SUBSTANCE/S
Blood coagulability Heparin, coumarins,
benzene
Cherry red blood Carbon monoxide, cyanide
Dark red blood Nicotine
Chocolate blood Aniline, nitrites,
nitroderivatives
URINARY CHANGES SUBSTANCE/S
Dark yellow Picric acid
Yellow brown Aloe, senna
Odor of violets Turpentine
Green blue Phenols & derivatives,
methylene blue
Wine or red brown Caffeine, benzene, rifampicin,
lead, mercury, carbon
tetrachloride
DISCOLORATION OF SUBSTANCE/S
GUMS
Blue line gum Bismuth, lead
Black line gum Mercury, arsenic
VISUAL DISTURBANCES SUBSTANCE/S
Purple vision Digitalis, marijuana
Blurred vision Anti-cholinergics
Partial/total blindness Methanol, formic acid,
solanine
Optic neuritis Ethambutol
Blood shot eyes marijuana
RESPIRATORY CHANGES SUBSTANCE/S
Violent sneezing Veratrine
Irritation Sulfur dioxide
Dyspnea Carbon monoxide
General respiratory Opium, barbiturates,
depression benzodiazepine, cyanide
OTHER CHANGES
Alopecia Arsenic
Tinnitus Salicylates, quinine
Ototoxicity Aminoglycosides, loop diuretics
Xerostomia Anti-cholinergics
Bloody sputum Cadmium
Muscular twitching, loss of voice Barium
Loose teeth Mercury, lead, phosphorous
Bleeding gums Arsenic, mercury
Lock jaw Strychnine
Blister formation cantharidin
Clinical Toxicology Lecture (Midterm)

MECHANISMS
OF ACTION
OF POISONS
MECHANISMS OF TOXICITY
• Inhibition of oxygen transport
• Inhibition of electron transport chain
• Corrosivity & Causticity
• Inhibition of enzymes
• Teratogenecity
• Penetration in lipid structures
• Carcinogenecity
• Damage by reactive species
• Neurotransmission damage
INHIBITION OF OXYGEN TRANSPORT

HEMOGLOBIN

CARBON
OXYGEN MONOXIDE

√ (reversible) X (irreversible)
INHIBITION OF ELECTRON TRANSPORT CHAIN
• HYDROGEN CYANIDE + HEMOGLOBIN = HISTOTOXIC HYPOXIA

HEMOGLOBIN BOUND CYANIDE

• BODY
(CELLS)
MITOCHONDRIA Fe Cytochrome
c oxidase

•
ELECTRON TRANSPORT CHAIN •
• X
OXIDATIVE PHOSPHORYLATION

NO ENERGY
 CORROSIVITY & CAUSTICITY
• HYDROLYSIS OF BIOMOLECULES • SAPONIFICATION OF FATS BY
BY AACCIIDDSS
HYBDRAOSXEI
HYDRONIUM IONS PENETRATION IN DEEPER
TISSUES
•+
WATER
•DTSEISSUE
IONS
+
COLLAGEN
Inhibition of enzymes

CATALYTIC REACTION

HEAVY METALS
x √
METALS
 INHIBITION OF REPLICATION & TRANSCRIPTION
• MOA: INDIRECT-ACTING
DIRECT ACTING

METABOLIC ACTIVATION YES METABOLIC ACTIVATION NO

POLYCYCLIC
AROMATIC BETA-
HYDROCARBONS PROPIOLACTONES
ENDOCRINE DISRUPTION
DIRECT ACTING INDIRECT ACTING

HORMONE HORMONE
AGONIST ANTAGONIST
Penetration in lipid structures
• ETHANOL --------------------- --------🡪
MEMBRANE (DIFFUSION) – FILTRATION
• (slightly lipophilic, small, hydrophilic) WATER CHAN NELS
PROTEINS

LIPID BILAYER
Damage by reactive species
• LIPID PEROXIDATION

UPTAKE OF OXYGE-N------------ > OXIDATIVE DAMAGE OF POLYUNSATURATED

ACIDS
FORMATION OF
• LIPID RADICALS
• UNSATURATED LIPIDS
REARRANGEMENT OF
DESTROY THE MEMBRANE LIPIDS----- PRODUCTS
DOUBLE BONDS OF
Neurotransmission Damage

• α-bungarotoxin binds to the acetylcholine receptor at the neuromuscular junction

• Tetrodotoxin concentrated in internal organs of members of the order

Tetraodontiformes blocks Na+ channels

• curare blocks neuromuscular transmission

MOST
POISONOUS
PLANTS
CAN CAUSE EITHER OR BOTH LOCAL AND SYSTEMIC TOXIC EFFECTS.
 JATROPHA/TUBA-TUBA/TUBANG
BAKOD
• SCIENTIFIC NAME: Jatropha curcas L.
• COMMON NAME: Red Physic Nut
• FAMILY: Euphorbiaceae
• POISONOUS PARTS: seeds (saponins – lectin: curcin; phytates, protease inhibitors
and curcalonic acid and phorbol esters), bark, fruit, root, wood (HCN)
• SIGNS & SYMPTOMS: diarrhea (bloody stools), nausea & vomiting, dehydration,
abdominal cramps

ADDITIONAL NOTES: Grows very well on poor soil; From cuttings and seeds easily propagated; Very common in rural areas; Used as a fence;
From mexico; Resistant to drought used for prevention of soil erosion; Used for soap production, manufacture of organic fertilizer, seeds are
source of diesel engines
 BUTA-BUTA
• SCIENTIFIC NAME: Excoacaria agaliocha
Linn.
• COMMON NAME: Blinding Tree
• FAMILY: Euphobiaceae
• POISONOUS PARTS: latex/ trunk saps,
leaves
• LETHAL DOSE: few drops
• SIGNS & SYMPTOMS: blisters, blindness

ADDITIONAL NOTES: Grows in muddy and stony

soil The sap or Milky juice – is caustic and
TALUMPANAY TREE/CACHUBONG
• SCIENTIFIC NAME: Datura metel Linn.
• COMMON NAME: Thorn apple
• FAMILY: Solanaceae
• POISONOUS PARTS: all plant parts (tropanic alkaloids)
• LETHAL DOSE: small dose (toxic tropane alkaloid (anticholinergic substances –
scopolamine, hyoscyamine, atropine)
• SIGNS & SYMPTOMS: Hallucinations (feel out of control or disconnected from their body
and environment), delirium, mental confusion, coma and death

ADDITIONAL NOTES: Hallucinogen, psychedelic – (able to see, hear, smell, feel, taste something that is not present in
reality) Used as a weapon to harm people, usually added in tea in China (Seeds)
Causes Mental and behavioral problems
 DIEFFENBACHI
A
• SCIENTIFIC NAME: Dieffenbachia seguine
• COMMON NAME: Dumbcane
• FAMILY: Araceae
• POISONOUS PARTS: every portion of the plant (needle-like calcium oxalate),
proteolytic enzyme (dumbain)
• LETHAL DOSE: chewed/ingestion
• SIGNS & SYMPTOMS: severe swelling,drooling, dysphagia,respiratory
compromise, dermatitis, intense pain, painful swelling of the mouth

ADDITIONAL NOTES: Causes poisoning effects especially if ingested

*Native Amazonian people – they use the juice of the plants to act as poison in their arrows
 ROSARY PEA
• SCIENTIFIC NAME: Abrus precatorius
• COMMON NAME: jequirity bean
• FAMILY: Fabaceae
• POISONOUS PARTS: all parts esp. seeds
• LETHAL DOSE: can cause death for 72 hours (abrin)
• SIGNS & SYMPTOMS: difficulty in breathing, vomiting, diarrhea, dehydration, pain in
the eyes, abdominal pain

ADDITIONAL NOTES: termed as the COLD-BLOODED KILLER

Seeds – are bright red in color
Entire plant is toxic, beans are highly toxic
 TANGAN-
TANGANNAME: Ricinus communis
• SCIENTIFIC
• COMMON NAME: Castor plant
• FAMILY: Euphorbiaceae
• POISONOUS PARTS: seeds
• LETHAL DOSE: Ricin (4-5 seeds to kill a full-grown adult and just 1 seed would do to
kill a human in 2 days), present as well in other parts but in low concentration;
6000 times more poisonous than cyanide; death within 24 hours
• SIGNS & SYMPTOMS: burning sensation in the throat and mouth, diarrhea,
vomiting, dehydration, pain, drop in blood pressure

ADDITIONAL NOTES: Wrong handling of this plant can cause untimely demise
Cyanide is the most poisonous thing ever
known Oil only – for internal use
 ACONIT
E
• SCIENTIFIC NAME: Aconitum napellus
• COMMON NAME: Devil`s Helmet, monkshood, wolfsbane, leopard bane
• FAMILY: Ranunculaceae
• POISONOUS PARTS: almost all the parts (roots, tubers) –aconitine (alkaloid) both
a cardiotoxin and neurotoxin
• LETHAL DOSE: aconitine (same toxin found in the venom of certain poisonous snakes
and in arsenic, lead and ammonia; the bacteria responsible for tetanus and
botulism)
• SIGNS & SYMPTOMS: burning, vomiting, diarrhea, hypertension, heart irregularities,
coma

ADDITIONAL NOTES: Alkaloid pseudaconitine (poisonous constituent)

In Japan, put this poison in the tips of their arrows for hunting
 ENGLISH YEW
• SCIENTIFIC NAME: Taxus baccata
• COMMON NAME: Yew
• FAMILY: Taxaceae
• POISONOUS PARTS: all parts (taxine alkaloids) except flesh of the fruit
• LETHAL DOSE: 50 grams is enough to kill a human
• SIGNS & SYMPTOMS: muscle tremors, difficulty in breathing, convulsion, collapse,
and worst, untimely demise, paralyze the heart, dry mouth, hypotension

ADDITIONAL NOTES: SOFT, BRIGHT-RED BERRIES THAT ARE palatable especially for birds, only the fruit is non-
toxic.
 BELLADONN
A
• SCIENTIFIC NAME: Atropa belladonna
• COMMON NAME: Deadly nightshade
• FAMILY: Solanaceae
• POISONOUS PARTS: whole plant (berries are the most dangerous part (fruit of a
young plant)
• LETHAL DOSE: 10-20 berries can kill a fully-grown adult; but as small as 1 leaf, where
the poison is more concentrated, can kill a man
• SIGNS & SYMPTOMS: loss of voice, dry mouth, headaches, breathing difficulty,
convulsions, blurred vision, urinary retention, loss of balance

ADDITIONAL NOTES: Benefits: antipyretic, antiseptic, antispasmodic

Children eat these berries thinking these are blueberries that is why there are a lot of children who became victims of this
 PONG-PONG
• SCIENTIFIC NAME: Cerbera odollam Gaertn.
• COMMON NAME: Suicide Tree
• FAMILY: Apocynaceae
• POISONOUS PARTS: seeds (cerebrin – cardiac glycoside)
• LETHAL DOSE: seed ingestion – cardiac arrest despite treatment
• SIGNS & SYMPTOMS: fatal dysrhythmias, nausea, vomiting,
hyperkalemia, thrombocytopenia, hypotension, seizures

ADDITIONAL NOTES: Named after Cerberus– who guarded the gate to the underworld
Found in Coastal salt swamps and other mashy areas; A potent poison used for suicide.
* Phlox – means flame—because of its intense flower colors.
 RHODODENDRON
• SCIENTIFIC NAME: Rhodendron ferruginium L.
• COMMON NAME: alpenrose, snowrose
• FAMILY: Ericaceae
• POISONOUS PARTS: almost all parts especially in leaves (andromedotoxin,
grayanotoxin, rhodotoxin), honey
• LETHAL DOSE: rarely fatal and generally lasts for no more than 24 hours
• SIGNS & SYMPTOMS: bradycardia, loss of balance, salivation exhaustion,
weakness, difficulty in breathing

ADDITIONAL NOTES: Varieties: Pink, violet, red, yellow, white

 JIMSONWEE
D NAME: Datura stramonium
• SCIENTIFIC
• COMMON NAME: Devil`s weed, hell`s bell, devil`s trumpet, devil`s snare
• FAMILY: Solanaceae
• POISONOUS PARTS: Almost all parts (concentrated in leaves and seeds) – chief
alkaloids (atropine, hyoscyamine, scopolamine)
• LETHAL DOSE: 4 grams of leaf can be fatal to a child, alkaloid toxicity (minutes to
hrs); non-fatal ( signs & symptoms – subside 12 – 48 hrs)
• SIGNS & SYMPTOMS: sucking juice of eating roots, leaves will affect the nervous
system, eyes, ears, throat and mouth; extreme thirst, vision impairment, hallucination,
lethargy

ADDITIONAL NOTES: A Powerful hallucinogen.

Toxicity varies – with age, climate and place
 WHITE
SNAKEROOT
• SCIENTIFIC NAME: Ageratina altissima
• COMMON NAME: Richweed, white sanicle
• FAMILY: Asteraceae
• POISONOUS PARTS: plant (tremetol)
• LETHAL DOSE: consumed by animals – eventually the poison is passed on to
toxins (if consumed in large enough)
• SIGNS & SYMPTOMS: severe vomiting, weakness, pain, coma tremors, delirium,
liver failure, constipation

ADDITIONAL NOTES: Tremetone – another poisonous constituent ..

Meat and Milk produced by cows who eat white snakeroot is contaminated with the poison as well , termed it as milk sickness – Nancy Hanks
Lincoln, mother of Abraham Lincoln died in 1818 because of this.
 OLEANDER
• SCIENTIFIC NAME: Nerium oleander
• COMMON NAME: nerium
• FAMILY: Apocynaceae
• POISONOUS PARTS: all parts (digitoxigenin, neriin, oleandrin, olendroside –
concentrated within leaves and stem)
• LETHAL DOSE: chewing the leaves or tasting the nectar of the flower
• SIGNS & SYMPTOMS: irregular heart rate, vomiting, salivation, diarrhea

ADDITIONAL NOTES: Blooms sweet smelling

flowers
 CICUTA
• SCIENTIFIC NAME: Cicuta virosa
• COMMON NAME: Water hemlock, cowbane, poison parsnip
• FAMILY: Apiaceae/Umbelliferae
• POISONOUS PARTS: all parts; thick main stem, roots, seeds (cicutoxin)
• LETHAL DOSE: even if applied in skin –death; can cause death in 15 minutes
• SIGNS & SYMPTOMS: drooling, nausea, vomiting, wheezing, sweating, dizziness,
stomach pain, flushing, lethargy, delirium, uncontrolled bowel movements, difficulty in
breathing, convulsions, heart problems, kidney failure, coma

ADDITIONAL NOTES: Can be fatal in humans,

Severe poisoning and death occurs as early as 1670
 MOST
POISONOUS/TOXIC
ANIMALS
REMEMBER:
VENOMOUS MEANS THE ANIMALS HAVE VENOM THAT CAN TAKE OUT THE LIFE OF THEIR PREY.
POISONOUS MEANS IT CAN CAUSE DEATH OR EFFECTS THROUGH INGESTION OF TOXIC OR
POISONOUS ANIMALS.
 ASIAN TIGER SNAKE
• SCIENTIFIC NAME: Notechis scutatus
• FAMILY: Elapidae
• LETHAL DOSE: (neurotoxin, coagulant, haemolysin, myotoxin); mortality rate
from untreated bites is to be between 40% to 60%
• SIGNS & SYMPTOMS: localized pain in foot and neck, tingling, numbness, sweating,
rapid onset of breathing difficulties, paralysis

ADDITIONAL NOTES: Both venomous and poisonous

Does not only produce toxin from its bite, also stores poison obtain from its toad prey in its
skin
 HOODED PITOHUI
• SCIENTIFIC NAME: Pitohui dichrous
• LETHAL DOSE: skin and feathers – touch – burning and tingling sensation
(homobatrachotoxin, batrachotoxin – extremely potent neurotoxic steroidal
alkaloid)
• SIGNS & SYMPTOMS: slight numbness and tingling, paralysis, cardiac arrest

ADDITIONAL NOTES: Neurotoxin

Originates from the bird`s diet of
beetles One of the world` s toxic birds
 HAWKSBILL SEA TURTLES
• SCIENTIFIC NAME: Eretmochelys imbricata
• LETHAL DOSE: meat (marine turtle poisoning) - chelonitoxin
• SIGNS & SYMPTOMS: nausea, vomiting, diarrhea, other stomach
complaints

ADDITIONAL NOTES: Consume variety of prey like toxic algae, sponges, venomous cnidarians, their flesh can become
toxic.
 CANE TOAD
• SCIENTIFIC NAME: Rhinella marina
• LETHAL DOSE: poison glands (bufotoxin – skin) – paratoid gland (milky liquid) -
ingestion
• SIGNS & SYMPTOMS: frothy salivation, vigorous head shaking, pawing at the mouth
and retching

ADDITI
ADDI ONAL NOTES: Rarely deadly to humans; they have Venom secreting
TIONAL
glands
 POISON DART FROG
• SCIENTIFIC NAME: Dendrobatidae (Dentrobates tinctorius, Dentrobates leucomelas)
• LETHAL DOSE: affects anyone who touches or eats it (assimilate plant
poisons) – allopumiliotoxin, batrachotoxin, epibatidine, histrionicotoxin,
pumiliotoxin
• SIGNS & SYMPTOMS: hallucinations, vasoconstriction, coma

* GOLDEN POISON FROG – a poison dart frog (most poisonous and most toxic in the
world) already endangered

ADDITIONAL NOTES: Small and bright – acts as a warning– the color signifies the levels of alkaloid
present
In Colombia – used in blowgun darts when hunting that is where its name came
 SPANISH FLY
• SCIENTIFIC NAME: Lytta vesicatoria
• LETHAL DOSE: poison (cantharidin - skin)
• SIGNS & SYMPTOMS: blistering, burning pain (contact); ulcers, blistering,
bleeding throughout the digestive tract and can result in death (eaten)

ADDITIONAL NOTES: also known as blister beetle because of its poisoning

effect
COMB STARS
• SCIENTIFIC NAME: Astropecten polycanthus
• LETHAL DOSE: tetrodotoxin – potent neurotoxin;
• SIGNS & SYMPTOMS: paralysis, eventual death from respiratory
failure
 ROUGH-SKINNED NEWT
• SCIENTIFIC NAME: Taricha granulosa
• LETHAL DOSE: tetrodotoxin (flesh)
• SIGNS & SYMPTOMS: numbness throughout the body, cardiac
arrest

ADDITIONAL NOTES: Most poisonous salamander; Produce strong smell -

warning
 STRIATED SURGEONFISH
• SCIENTIFIC NAME: Ctenochaetus striatus
• LETHAL DOSE: accumulates toxin through its diet (maitotoxin); build-up of this toxin
in their flesh causes ciguatera fish poisoning affects 20,000 to 50,000 people each
year
• SIGNS & SYMPTOMS: like any other type of food poisoning but can last from months
to years ; sometimes severe that the condition is misdiagnosed as multiple sclerosis

ADDITIONAL NOTES: Feeding on algae, they sometimes consume tiny

dinoflagellates
 PUFFERFIS
•HSCIENTIFIC NAME: Tetraodontidae
• LETHAL DOSE: liver,kidneys, spikes (tetrodotoxin) – occur 10-45 minutes after
eating
• SIGNS & SYMPTOMS: numbness and tingling around the mouth, salivation,
nausea, vomiting, paralysis, loss of consciousness, respiratory failure

ADDITIONAL NOTES: Cooked only by a licensed chef

Aka blowfish, toadfish
Second most poisonous vertebrae in the world second to golden poison
SYNTHETIC
TOXINS
CLINICAL TOXICOLOGY LECTURE –MIDTERMS
PESTICIDES

INSECTICIDES HERBICIDES FUNGICIDES

RODENTICIDES MITICIDES MOLLUSCIDES

PLANT GROWTH REGULATORS,

LARVICIDES PEDICULOCIDES REPELLANTS, ATTRACTANTS
 EXPOSUR
E
• Oral
• Accidental & Suicidal
• general public exposure
• Inhalation
• Occupational • Dermal
• bystander exposure • Eye contact
I. INSECTICIDES
ACT BY POISONING THE NERVOUS SYSTEMS OF THE TARGET ORGANISMS
 ORGANOPHOSPHATES

• widespread use and high toxicity

• interferes with an important nervous system enzyme, acetylcholinesterase
• nerves continuously send messages to the muscles
• Large exposures can cause acute poisoning.
• Small exposures over time “add up” in the body leading to poisoning.
• Managament/antidote: decontamination, atropine, pralidoxime, diazepam
CARBAMATES
• also interferes with cholinesterase
• broken down by the body
• acute poisoning
• Management/antidote: Atropine
PYRETHROIDS
• Pyrethrum is an insecticide extracted from chrysanthemum flower.
• Active ingredients of pyrethrum are known as pyrethrins.
• Synthetic compounds structurally related to pyrethrins are known as pyrethroids.
• Disrupt voltage-gated sodium channels
• Shows negative temperature coefficient action
• Bind and inhibit GABA
• Occupational exposure – dermal contact
 ORGANOCHLORINE COMPOUNDS

• Effective against a wide variety of agricultural pests as well as against pests that transmit
some of the world`s most serious diseases.
• Acute toxicity is moderate but chronic exposure affects liver and sex hormones

• DDT and its analogs

• Low dermal toxicity; readily absorbed and highly distributed
• Earliest symptom – paresthesia of the mouth, face and tongue; dizziness, tremor of extremities, confusion, and
vomiting follow; convulsions
• Opens the sodium ion channels
• Chronic – target is liver
• Hexachlorohexanes and cyclodienes
• Moderate – high acute oral toxicity
• Readily absorbed thru the skin
• Neurotoxic
• Bind to picrotoxin-binding site on the chloride channel, thereby blocking its opening and antagonizing the
inhibitory action of GABA
 OTHERS
:
• ROTENOIDS
• crop insecticide (applied to plants to control leaf eating caterpillars)
• Inhibits the mitochondrial respiratory chain by blocking transport at NADH-ubiquinone
electron reductase
• NICOTINE
• alkaloid extracted from the leaves of tobacco plants
• Nausea, vomiting, muscle weakness, breathing difficulty, headache, lethargy, and tachycardia; Green
Tobacco Sickness
• AVERMECTINS
• macrolytic lactones that are isolated from the fermentation broth of Streptomyces avermitilis
• Insecticide, parasite control
• Signs & symptoms of intoxication: hyperexcitability, tremors, and incoordination, flowed by ataxia &
coma-like sedation
 II.
HERBICIDES

A PREPLANTING, PREEMERGENT &

POSTEMERGENT
B. CONTACT & TRANSLOCATED
CHLOROPHENOXY COMPOUNDS
• 2,4, di chloro phenoxyacetic acid
• Chemical analogs of auxin
• Chlorophenoxy compounds are well absorbed from the gastrointestinal tract.
• Acute poisoning – vomiting, burning of the mouth, abdominal pain, hypotension,
myotonia, and CNS involvement including coma
BIPYRIDIL COMPOUNDS
• Used to control broad-leaved weeds and grasses in plantations and
fruit orchards, and for general weed control
• Paraquat has life threatening effects on the gastrointestinal tract,
kidney, liver and other organs. The lung is the primary target organ of
paraquat poisoning (acute systemic effect)
• Redox recycling 🡪 oxidation of NADPH (reducing agent) 🡪
cellular depletion
• Diquat – acute toxicity is lower; does not accumulate in the lungs;
target organs (chronic) – GI tract, kidneys, & particularly the eyes
CHLOROACETANILIDES
• Alachlor, acetochlor, and metolachlor
• Used to control herbal grasses and broad-leaved weeds in a number of crops
• Probable human carcinogen
TRIAZINES
• Atrazine, simazine, and propazine
• Used for the preemergent control of broad-leaved weeds
• Low acute oral and dermal toxicity
• Chronic toxicity – decreases body weight gain
 PHOSPHONOMETHYL AMINO
ACIDS
• Glyophosate
• Broad-spectrum non-selective systemic herbicide
• Herbicidal action – inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate
synthase, responsible for the synthesis of an intermediate in the biosynthesis
of various amino acids
• Gastrointestinal symptoms for mild intoxication
• Gastrointestinal bleeding, hypotension, pulmonary dysfunction, and renal
damage (moderate to severe poisoning)
• Glufosinate
• Irreversibly inhibits glutamine synthetase
• Gastrointestinal effects, impaired respiration, neurologic
disturbance, and cardiovascular effects
III. FUNGICIDES
CAPTAN AND FOLPET
• Protectant fungicides
• Chloroalkylthio fungicides
• Potent eye irritants but only mild skin irritants
• Resembles thalidomide
DITHIOCARBAMATES
• Maneb, ziram, zineb, mancozeb
• Metabolite: ethylenethiourea
• Low acute toxicity by the oral, dermal and respiratory routes
• Resembles disulfiram
INORGANIC AND ORGANOMETAL FUNGICIDES
• COPPER SULFATE
• TRIBUTYLTIN
• TRIPHENYLTIN
• METHYLMERCURY
IV.
RODENTICIDES
FLUOROACETIC ACID AND ITS DERIVATIVES
• White and odorless
• High mammalian toxicity
• CNS and CVS
ANTICOAGULANTS
• Coumarin derivatives
• Antagonize the action of vitamin K
• Accidental consumption
 TOXICITY
OF
METALS
CLINICAL TOXICOLOGY
LECTURE
 ESSENTIAL METALS
WITH POTENTIAL
MAJOR TOXIC METALS FOR TOXICITY

METALS RELATED TO
MEDICAL THERAPY
ARSENI
C
• Manufacture of pesticides, herbicides and other agricultural products
• Burning of coal
• Seafood
• 70-180mg – acute toxicity (ingestion) – fever, anorexia, hepatomegaly,
melanosis, cardiac arrhythmia, cardiac failure
• Chronic – skin exposure – skin cancer; liver injury ;
peripheral neuropathy
• Human carcinogen and teratogen
CADMIUM
• Batteries
• Galvanizing alloys
• Paints and plastics
• Food is the major source
• Inhalation –dominant route
• Acute toxicity – Gastrointestinal tract (nausea, vomiting,
abdominal pain)
• Chronic toxicity – renal injury, obstructive pulmonary disease,
osteoporosis, cardiovascular disease and even cancer
• Calcium loss
LEA
D
• Ubiquitous toxic metal
• Paints, toys
• Dose and duration – toxicity
• Children – neurologic, neurobehavioral and developmental effects
• Adults – neurotoxic, nephrotoxic, effects on the blood and
cardiovascular
• Immunosupressive agent
MERCURY
• Aka quicksilver
• Vapor more hazardous than liquid form
• Volcanic eruptions
• Metal mining, coal combustion, water
• Dietary exposure, occupational exposure, accidental exposure
• Inorganic mercury, methylmercury
NICKEL
• metal alloy in stainless steels
• Mining, refineries
• Contact dermatitis
• Nickel carbonyl poisoning
• carinogenic
COPPE
R
• Food
• Beverages
• Drinking water
• Welding
• Gastrointestinal distress—toxicity
• Wilson`s disease
IRON
• Essential metal for erythropoiesis
• Deficiency, accidental acute exposures, chronic iron overload
ZINC
• Gastrointestinal distress
• Neuronal toxicity
ALUMINUM
• Food
• Drinking water
• Mining and welding
• Major target organs: lung, bone ,CNS
• Dialysis dementia
• Alzheimer`s disease
LITHIUM
• Batteries
• Alloys
• Photographic materials
• Space industry
• Ground water contamination
• Readily absorb in GI tract
• Salts are intensely corrosive
PLATINUM
• Automobile catalysts
• Jewelry
• Electronics
• Dental alloys
• Hypersensitivity reactions
• Carcinogen and vice versa
CLINICAL
TOXICOLOGY
MANAGEMENT OF SPECIFIC INGESTIONS
(CASE: SHEET)
FINALS
 1 ACETAMINOPHEN
• AVAILABLE FORMS: tablet
• TOXICOKINETICS: well-absorbed in the GI tract; half-life is b/n 2 & 3 hrs;
less than 5 % is excreted unchanged in the urine
• CLINICAL PRESENTATION:
• Phase I – (12 to 24 hrs postingestion) – N & V, anorexia, and diaphoresis
• Phase II – (1 to 4 days postingestion) - asymptomatic
• Phase III – (2 to 3 days in untreated patients) – nausea, abdominal pain,
progressive
evidence of hepatic failure, coma and death
• LABORATORY DATA: serum acetaminophen levels, baseline liver function
tests, renal function tests, coagulation studies
• TREATMENT: GI decontamination with activated charcoal, antidotal
therapy with NAC
 2

ALCOHOL
S A. ETHYLENE GLYCOL
B. METHANOL
 A ETHYLENE
• AVAILABLE FORMS: solution GLYCOL
• TOXICOKINETICS: ethylene glycol 🡪 glycoldehyde 🡪 glycolic acid
• CLINICAL PRESENTATION:
• Stage I – (0.5 to 12 hrs postingestion) –ataxia, nystagmus, N & V, decreased
deep tendon reflexes, and severe acidosis
• Stage II – (12 to 24 hrs postingestion) – tachypnea, cyanosis, tachycardia,
pulmonary edema, and pneumonitis
• Stage III – (24 to 72 hrs of postingestion) – flank pain, costovertebral angle
tenderness; oliguric renal failure
• LABORATORY DATA: urinalysis
• TREATMENT: gastric lavage, fomepizole, IV ethanol, Pyridoxine +
thiamine, sodium bicarbonate, hemodialysis
 B METHANOL
• AVAILABLE FORMS: solution
• TOXICOKINETICS: methanol 🡪 formaldehyde 🡪 formic acid
• CLINICAL PRESENTATION:
• Stage I – euphoria, gregariousness, and muscle weakness for 6 to 36 hours,
depending on the rate of formation of formic acid
• Stage II – vomiting, upper abdominal pain, diarrhea, dizziness, headache,
restlessness, dyspnea, blurred vision, photophobia, blindness, coma, cerebral
edema, cardiac and respiratory depression, seizures and death
• LABORATORY DATA: serum/blood tests like blood methanol test
• TREATMENT: gastric lavage, IV ethanol, folic acid, fomepizole, sodium
bicarbonate, hemodialysis
 3

anticoagulants
A. HEPARIN/LOW-MOLECULAR-
WEIGHT HEPARIN
B. WARFARIN
C. PRADAXA
 A HEPARIN (LMWH)
• AVAILABLE FORMS: solution for injection
• TOXICOKINETICS: half-life of 1to 1.5 hrs; primarily metabolized in the
liver;
• CLINICAL PRESENTATION: bleeding or bruising
• LABORATORY DATA: PTT, bleeding time, and platelet counts
• TREATMENT: stopping heparin administration for 1 to 2 hours and
restarting therapy at a reduced dose; protamine sulfate
 B WARFARIN
• AVAILABLE FORMS: tablet, solution for injection
• TOXICOKINETICS: well-absorbed after oral administration; half-life is
35 hours; protein binding is 99%, with 5-day duration of activity
• CLINICAL PRESENTATION: minor bleeding, bruising, hematuria,
epistaxis and conjunctival hemorrhage; (most serious bleeding 🡪
GI, intracranial, retroperitoneal and wound site)
• LABORATORY DATA: PT, INR, bleeding time
• TREATMENT: withhold warfarin for 24 to 48 hrs, then reinstitute
therapy with a reduced dosage; phytomenadione; prothrombon
complex concentrates or recombinant factor VIIa to immediately
reverse the INR
 C Pradaxa
• AVAILABLE FORMS: capsule
• TOXICOKINETICS: poorly following oral administration;
absorbed half-life of 12 to 17 hours
• CLINICAL PRESENTATION: minor bleeding, bruising, hematuria, and
epistaxis; (more serious bleeding 🡪 GI, intracranial, retroperitoneal,
and wound site)
• LABORATORY DATA: thrombin clotting time and ecarin clotting time
• TREATMENT: local treatment and withholding one dose;
hemodialysis; charcoal filtration along with either recombinant
factor VII or prothrombin complex concentrates
 4

ANTIDEPRESSANTS A. TRICYCLIC ANTIDEPRESSANTS

B. SELECTIVE SEROTONIN
REUPTAKE INHIBITORS
 A TRICYCLIC
ANTIDEPRESSANTS (TCAs)
• AVAILABLE FORMS: tablets, solution for injection
• TOXICOKINETICS: hepatically metabolized, undergo enterohepatic
recirculation, highly bound to plasma proteins and have an elimination
half-life of approximately 24 hours
• CLINICAL PRESENTATION:
• Mydriasis, ileus, urinary retention and hyperpyrexia
• Tachycardia, conduction blocks, hypotension, and pulmonary edema
• Agitation and confusion, hallucinations, seizures and coma
• LABORATORY DATA: ECG
• TREATMENT: GI decontamination, alkalinization, and.or
phenytoin benzodiazepines, IV physostigmine
 SELECTIVE SEROTONIN
B REUPTAKE INHIBITORS
AVAILABLE FORMS: capsule, tablet, (oSraSlRsoIslu)tion
•

• TOXICOKINETICS: well-absorbed after oral administration; hepatically

metabolized with a half-life between 8 and 30 hours
• CLINICAL PRESENTATION: mild sympatomatology; agitation,
drowsiness and confusion
• LABORATORY DATA: ECG
• TREATMENT: gastric lavage and supportive treatment,
Cyproheptadine
 5 BENZODIAZEPINES
• AVAILABLE FORMS: tablet, oral solution, capsule, parenteral solution
• TOXICOKINETICS: hepatically metabolized
• CLINICAL PRESENTATION: drowsiness, ataxia, confusion
• LABORATORY DATA: ABG, ECG
• TREATMENT: supportive treatment, flumazenil
 6 Beta-adrenergic antagonists
• AVAILABLE FORMS: tablet, capsule, parenteral solution
• TOXICOKINETICS: changes in organ function
• CLINICAL PRESENTATION: hypotension, bradycardia, atrioventricular
block
• LABORATORY DATA: serum electrolytes and blood glucose
• TREATMENT: GI decontamination; glucagon; epinephrine; calcium
salts; high-dose insulin dextrose
 CALCIUM CHANNEL
7 ANTAGONISTS
• AVAILABLE FORMS: tablet, capsule, parenteral solution
• TOXICOKINETICS: onset of action is approximately 30 mins; duration is
6 to 8 hours
• CLINICAL PRESENTATION: hypotension; bradycardia and
atrioventricular block; pulmonary edema and seizures
• LABORATORY DATA: ECG, serum electrolytes
• TREATMENT: GI decontamination, calcium, glucagon, combined
insulin and dextrose administration, phosphodiesterase inhibitors
 8 COCAINE
• AVAILABLE FORMS: powder
• TOXICOKINETICS: well-absorbed after oral, inhalational, intranasal,
and IV administration; metabolized in the liver; excreted in the urine
• CLINICAL PRESENTATION: hypertension, tachypnea, tachycardia,
nausea, vomiting, seizures; respiratory failure, myocardial infarction,
or cardiac arrest
• LABORATORY DATA: urinalysis
• TREATMENT: benzodiazepines, labetalol
 9 CYANIDE
• AVAILABLE FORMS: solutions
• TOXICOKINETICS: rapidly absorbed after oral or inhalational exposure
• CLINICAL PRESENTATION: headache, dyspnea, nausea,
vomiting, ataxia, coma, seizures, and death
• LABORATORY DATA: ECG, ABGs, blood tests
• TREATMENT: cyanide antidote kit; oxygen, sodium bicarbonate,
hydroxybalamin
 10 DIGOXIN
• AVAILABLE FORMS: tablet, solution for injection
• TOXICOKINETICS: well-absorbed; renally eliminated; half-life of 36 to
48 hours; volume of distribution is 7 to L/kg; equilibration between
serum level and myocardial binding requires 6 to 8 hours
• CLINICAL PRESENTATION: confusion, anorexia, nausea and vomiting;
cardiac dysrhythmias
• LABORATORY DATA: ECG, serum tests
• TREATMENT: decontamination; supportive therapy; Digibind
 11 POTASSIUM
• AVAILABLE FORMS: solution/solution for injection
• TOXICOKINETICS: intracellular cation; changes in acid-base balance
produce shifts in serum potassium values
• CLINICAL PRESENTATION: cardiac irritability, peripheral weakness with
minor increases; cardiac dysrhythmias including bradycardia
• LABORATORY DATA: ECG
• TREATMENT: calcium, sodium bicarbonate, glucose and insulin, cation
exchange resins, sodium polystyrene sulfonate, hemodialysis
 12 iron
• AVAILABLE FORMS: tablet, capsule, solution
• TOXICOKINETICS: absorbed in the small intestines
• CLINICAL PRESENTATION:
• PHASE I – nausea, vomiting, diarrhea, GI bleeding, hypotension
• PHASE II – clinical improvement seen 6 to 24 hours postingestion
• PHASE III – metabolic acidosis, renal and hepatic failure, sepsis, pulmonary
edema, and death
• LABORATORY DATA: serum tests, ABGs, liver function tests, CBC,
radiologic tests
• TREATMENT: decontamination, supportive treatment,
deferoxamine
 13 isoniazid
• AVAILABLE FORMS: solution for injection, tablet, capsule
• TOXICOKINETICS: well-absorbed orally; peak levels are within 1 to 2
hours postingestion; hepatically metabolized
• CLINICAL PRESENTATION: lactic acidosis, hypoglycemia, mild
hyperkalemia, and leukocytosis
• LABORATORY DATA: serum tests
• TREATMENT: decontamination, pyridoxine, sodium
bicarbonate
 14 LEAD
• AVAILABLE FORMS: solution, emulsion, aerosol
• TOXICOKINETICS: Slow distribution; half-life is approximately 2
months
• CLINICAL PRESENTATION: nausea, vomiting, abdominal pain,
peripheral neuropathies, convulsions, and coma
• LABORATORY DATA: serum tests
• TREATMENT: EDTA, BAL
 15 OPIATES
• AVAILABLE FORMS: tablet, solution
• TOXICOKINETICS: prolonged half-lives
• CLINICAL PRESENTATION: respiratory depression, decreased level of
consciousness; hypotension, bradycardia, pulmonary edema; seizures
• LABORATORY DATA: ABGs
• TREATMENT: naloxone, nalmefene, nalorphine, naltrexone
 16 SALICYLAtE
S
• AVAILABLE FORMS: solution, tablet
• TOXICOKINETICS: well-absorbed after oral administration; half-life is 6
to 12 hours at lower doses
• CLINICAL PRESENTATION: nausea, vomiting, tinnitus, malaise,
lethargy, convulsions, coma, metabolic acidosis
• LABORATORY DATA: serum tests/blood tests
• TREATMENT: decontamination, alkaline diuresis, hemodialysis, fluid
and electrolyte replacement, vitamin K and frozen plasma