FOR BACHELOR OF PHARMACY STUDENTS

By Tasisa Ketema (B.Pharm, MSc.)

March, 2025
 Introduction
Terms and definitions
 A poison is defined as any agent capable of producing a
deleterious response in a biological system.
 A toxin is any toxic substance that is produced by
biological systems such as plants, animals, fungi, and
bacteria.
 Toxicant is used in speaking of toxic substances that are
produced by or are by-products of anthropogenic (human)
activities.
 Toxicodynamics: The characterization of the molecular,
biochemical and physiological effects of toxicants
 Toxicokinetics: The quantitative relationship between
absorption, distribution, biotransformation, and excretion of
toxicants and their metabolites

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Terms and definitions …con’t
 Chemical idiosyncrasy refers to genetically determined
abnormal reactivity to a chemical.
 Chemical allergy is an immunologically mediated
adverse reaction to a chemical resulting from previous
sensitization to that chemical or to a structurally similar
one.
 Toxicogenomics focused on identifying and protecting
genetically susceptible individuals from harmful
environmental exposures and to customize drug therapies
on the basis of their individual genetic makeup.

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 Introduction cont’t…..
 Toxicology: is the study of toxic effects of chemicals
(poisons) & their adverse effects on biological systems.
 This includes the study of:
 The sources of poisons (identification)
 The chemical and physical properties of poisons
 The mechanism of action of poisons
(Toxicodynamics)
 The absorption, distribution, biotransformation &
clearance of poisons (Toxicokinetics)
 Clinical/postmortem (necropsy) study
 Chronic effects of poisons (carcinogenic, teratogenic,
immunosuppressive and environmental hazards)
 Safety evaluation and risk assessment
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 Introduction cont’t…..
 Toxicology is described as both science and art
 Science: the observational and data gathering phase
 Art: the use of gathered data to predict the risk of
toxicity
 Discovery of fact is science and extrapolations and
hypothesis from little information is an art
 Observation of CCl4 produces hepatocellular carcinoma in
rats is fact and it will do so in humans is prediction or
hypothesis
 Appropriately protecting human populations from risk of
CCl4 induced toxicity is an art

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 Classes of toxicology: based on
research methodology
1. Descriptive Toxicology:- Concerned with toxicity testing
in experimental animals to get information that can be
used to evaluate the risk of chemicals exposure either to
the environment or to the human
2. Mechanistic Toxicology:- Deals with mechanisms of
toxic effects of chemicals
 Useful to
 Predict risks: e.g., physphorylation of ChE
 Rationalize Rx: e.g. oximes for OP poisoning
 Facilitate search for safer drugs: e.g. use of
reversible in stead of irreversible ChEIs

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 Classes of toxicology: based on
research methodology
3. Regulatory Toxicology:- Deals with assessment risk
level of chemicals to be used in living things on the basis
of data provided by descriptive and mechanistic
toxicologists
 Concerned with the formulation of laws and regulations
which are intended to minimize the effect of toxic
chemicals on human health and the environment.
 For example:
 FDA of the US: regulates drug, food, cosmotics and
medical services

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 Classes of toxicology: based on
research methodology
 Environment protection agency: regulates pesticides,
toxic chemicals and pollutants as well as hazardous
wastes
 EFDA of Ethiopia: regulates drug, food, medical
services
 Occupational safety and health adm. Regulates safe
conditions for employees

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 Classes of toxicology: based on
research methodology
4. Predictive Toxicology:- Studies about potential and
actual risks of chemicals
 A tool for licensing new drug/chemical
5. Analytical toxicology
 Identifies the toxicant through analysis of body fluids,
stomach contents, excrement, or skin

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Classes of toxicology: based on specific
medical or social issues
1. Forensic Toxicology:- Concerned about medico legal
aspects of chemical use harmful to living organisms
 Assists postmortem investigations to establish cause of
death
2. Environmental Toxicology:- focuses on the impacts of
chemical pollutants in the environment on biological
organisms, specifically on nonhuman organisms such as
fish, birds, etc
 Studies chemicals that are contaminants of food, water,
soil, or the air

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Classes of toxicology: based on specific
medical or social issues
3. Occupational (Industrial) Toxicology
 Deals with toxicological problems pertaining to exposure as
a result of occupation
 Deals with chemical found in work place (industrial and
agricultural area)
4. Clinical Toxicology
 Deals with diseases caused by toxicants or uniquely
associated with toxic substances.
 Concerned with diagnosis and treatments of poisoning

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Classes of toxicology: based on specific
medical or social issues
5. Developmental toxicology:- Study of adverse effects on
the developing organism that occur any time during the life
span of an organism (from conception until the time of
puberty).
 Teratology is the study of defects induced during
development between conception and birth.
6. Reproductive toxicology :- Study the occurrence of
adverse effects on the male or female reproductive
system that may result from exposure to chemical or
physical agents.

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Classes of toxicology: based on organ/
system effect
1. CVS toxicology
2. Renal toxicology
3. CNS toxicology
4. GIT toxicology
5. Respiratory toxicology etc

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Causes of poisoning
‐ Suicide: common among youth
‐ Homicide: common among illiterates
‐ Accident: common among children
‐ Therapy: both outpatients and inpatients
‐ Occupation: common among factory workers, lab
technicians, mining workers, etc.

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Routes of exposure to toxicity
 Oral
• Most common route of exposure
• Most readily for lipid soluble toxicants
• Small intestine absorbs most toxicants
• Agents that decrease gastric emptying time delay
absorption
• Responsible for suicidal, homicidal, accidental and
therapeutic causes of poisoning

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Routes of exposure to toxicity … cont.
 Inhalational
• Fumes, particulate matters and gases absorbed
through lungs
• Lipid soluble agents have access to be absorbed and
have little respiratory irritation
• Water soluble toxicants primarily irritate upper
respiratory tract, e.g., ammonia
• Only particles < 1μm in diameter can penetrate lower
airways
• Removal of victim from toxic atmosphere reduces
absorption

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Routes of exposure to toxicity … cont.
 Cutaneous
• Lipid soluble agents are highly absorbed
• Inflammation/rubbing increase absorption
• Ice/torniquets retard absorption

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Toxicokinetics
 Toxicokinetics: refers to the study of the time course of
disposition (absorption, distribution, biotransformation,
and excretion) of xenobiotics in the whole organism.

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 A. Absorption
 The process by which toxicants cross body
membranes and enter the bloodstream is referred
to as absorption.
 The main sites of absorption are the GI tract, lungs,
and skin.
 However, absorption may also occur from other sites, such
as the subcutis, peritoneum, or muscle if a chemical is
administered by special routes.

 Mention factors affecting absorption

____________________________________
____________________________________
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B. Distribution
 After entering the blood by absorption or intravenous
administration, a toxicant is available for distribution
(translocation) throughout the body.
 The rate of distribution to organs or tissues is
determined primarily by:
– Blood flow and the rate of diffusion out of the capillary
bed into the cells of a particular organ or tissue
– The affinity of a xenobiotic for various tissues 
redistribution of toxicants
 In general, the initial phase of distribution is
dominated by blood flow, whereas the eventual
distribution is determined largely by affinity
 Mention factors affecting distribution
____________________________________________________
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C. Biotransformation
 Involves the conversion of lipophilic xenobiotics to water-
soluble metabolites which are readily eliminated from the
body.
 The reaction is catalyzed by enzymes in the liver and
other tissues.
 The reactions catalyzed by xenobiotic biotransforming
enzymes are generally divided into two groups, called
phase I and phase II.
Phase I reactions
 Involve hydrolysis, reduction, and oxidation.
 These reactions expose or introduce a polar functional
group (–OH, –NH2, – SH or –COOH), and usually result in
only a small increase in hydrophilicity.

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Phase II reactions
 Involves glucuronidation, sulfation, acetylation,
methylation, conjugation with glutathione
(mercapturic acid synthesis), and conjugation with
amino acids (such as glycine, taurine and glutamic
acid).
 Phase II biotransformation of xenobiotics may or may
not be preceded by phase I biotransformation.
 Most result in a large increase in xenobiotic
hydrophilicity, hence greatly promoting the excretion of
foreign chemicals.

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D. Excretion
 Toxicants are eliminated from the body by several routes
– Urinary Excretion
– Fecal Excretion
 Biliary excretion
Intestinal excretion: from blood into the intestinal
contents
Intestinal wall and flora: mucosal
biotransformation and reexcretion into the
intestinal lumen
– Exhalation
– Other routes of elimination: Cerebrospinal fluid, milk,
sweat and saliva

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Toxicodynamics
 Effects of toxicants in the body by acting on receptors in
most cases
 Toxic effects result from
• Damage to enzyme system
• Protein synthesis disruption
• DNA damage
• Modification of essential biochemical function

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Mechanisms of
Toxicity

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Step 1: Delivery

• Toxicant delivery from the site of exposure to target site/s

– Influenced by toxicokinetics (ADME)
Step 2: Reaction of the ultimate toxicant with the target
molecule
• Frequently involved target molecules may be endogenous
macromolecules like nucleic acids (especially DNA), proteins,
and membrane lipids
• Effects of Toxicants on Target Molecules
– Dysfunction or destruction of Target Molecules
– Neoantigen Formation

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Step 3: Cellular dysfunction and resultant toxicities

• Toxicant-Induced Cellular Dysregulation

– Dysregulation of Gene Expression
– Dysregulation of Ongoing Cellular Activity
• Toxic Alteration of Cellular Maintenance
– Impairment of Internal Cellular Maintenance:
Mechanisms of Toxic Cell Death
– Impairment of External Cellular Maintenance

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 Step 4: Repair or dysrepair
• Molecular Repair
– Repair of Proteins
– Repair of Lipids
– Repair of DNA
• Cellular Repair: A Strategy in Peripheral Neurons
• Tissue Repair
– Apoptosis: An Active Deletion of Damaged Cells
– Proliferation: Regeneration of Tissue
– Side Reactions to Tissue Injury
• When Repair Fails: toxicity results from dysrepair
– Tissue Necrosis
– Fibrosis
– Carcinogenesis

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Dose–Response Relationships
 The characteristics of exposure and the spectrum of
effects come together in a correlative relationship
customarily referred to as the dose–response
relationship.
 There are two types of dose–response relationships:
– Graded dose–response relationship
– Quantal dose–response relationship

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1. Graded dose–response relationship
 Refers to individual dose–response relationship which
describes the response of an individual organism to
varying doses of a chemical
 The measured effect is continuous over a range of
doses
2. Quantal dose–response relationship:
 Characterizes the distribution of responses to different
doses in a population of organisms
 The dose–response relationships are quantal—or “all or
none”— in nature  at any given dose, an individual in the
population is classified as either a “responder” or a
“nonresponder.”

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 2. Quantal dose ………
 Quantal dose–response relationship is used extensively in
toxicology
 It is the most common test applied to variety of
chemicals and is expressed in terms of lethal dose 50
(LD50) or median lethal dose obtained from dose-
response relationships.
 LD50 is often defined as the dosage of lethal to 50%
of the exposed population.
 It is generally determined based on the effect of
exposure to successively increasing dosage levels.

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 2. Quantal dose………
– LD50 response is generally quantal – all or none in
nature
– This means that up on successive increase in dosage
level no responses other than death or no-
death/survival matters.
– LD50 reports only toxicity resulting in death, and
does not take into account organ damage, cancer,
behavioral toxicities and many other effects
considered undesirable.
NB:
– Small increase or decrease in the dosage of toxicant
around the LD50 has got significant effect on the life of
the animal.
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 LD50

Figure: Dose response relationship

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 Segment I: has no slope and is represented by those
doses of the toxicant that elicited no mortality to the
treated population of organisms
 Segment II: represents those dosages of the toxicant
that affected only the most susceptible members of the
exposed population
 Segment III: encompasses those dosages at which most
of the groups of organisms elicit some response to the
toxicant
– Exhibits the steepest slope among the segments
– Around LD50 the graph is more linear and hence is
reproducible (gives same response if tried
repeatedly)

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 Segment IV: encompasses those dosages of the toxicant
that are toxic to even the most tolerant organisms in the
populations
 Segment V: has no slope and represents those dosages
at which 100% of the organisms exposed to the toxicant
have been affected

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Safety testing
 Generally, toxicity test can be divided into two major
categories;
I. General test
• This involves tests for
 Acute toxicities
 Sub-chronic toxicities
 Chronic toxicities
II.Special/specific test
• This involves specific toxicity test on
 Reproduction
 Teratogenicity
 Carcinogenicity,
 Mutagenicity, etc 40
Safety testing….cont.
A) Acute toxicity
• Refers to the effects obtained following a single exposure or
multiple exposures during 24 hours period.
• The exposed animals are then observed for any acute
toxicity over a period of 7 to 14 days

B) Subchronic toxicity
• Refers to results obtained following 30 to 90 days after
exposure.

C) Chronic toxicity
• Refers to study lasting more than 90 days.
• It is conducted to determine the effects of continuous long
term exposure 41
Factors Influencing Toxicity
1. Dose and concentration
 What is there that is not poison?
– “All substances are poison and nothing is without
poison. The right dose differentiates a poison and a
remedy”
Paracelsus (1493-1541)
 Any substance can be toxic given the correct dose and
route of administration (In mouse LD50 of: distilled water
= 44 mL/kg, saline = 66 mL/kg)
 On the contrary, even very toxic substances may not be
toxic at low enough concentration

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2. Routes of administration
 Intravenous administration nearly always leads to most
rapid onset and greatest toxicity.
 Order of toxicity:
– Intravenouse  inhalation  intraperitoneal 
intramuscular  subcutaneous  intradermal  oral 
topical
A. Oral route
 Accounts for 80 % of acute toxic episode resulting from
accidental and intentional ingestion of poisons.
 Key factors in poison absorption are lipophilicity and
presence of the poison in non-ionized form.

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Routes…Cont’d
 Absorption occurs in all areas of the GIT, buccal cavity
through rectum.
 Usually, little absorption occurs in the stomach, most
occurring in small intestine due to large surface area.
 Oral absorption may allow detoxification of toxins by first-
pass metabolism or produce toxins from non-toxic parent
compounds.
B. Inhalation route
 Lung has large surface area and is richly supplied with
blood.
 Poisons absorbed by the lung exist either as vapor or
aerosol.

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Routes…Cont’d
C. Dermal route
 Skin is the largest organ which is most accessible to
poisons but is very efficient barrier.
 Poisons undergoing percutaneous absorption goes
through several layers of the skin to circulation.
 Dermal absorption is determined by nature of the
compound (e.g. corrosive), length of exposure,
condition of the skin (e.g. presence of abrasions).

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3. Metabolism of toxicants
 Metabolism is usually the main detoxification pathway
for xenobiotics/toxicants making more polar and
easily excreted metabolites.
 However, some compounds are metabolized to more
toxic metabolites. E.g. parathion
4. State of Health
 Poisoning occurs both in health and unhealthy
people.
 Renal or hepatic disease: increase toxicity by
altering the pharmacokinetics.
 Head injury: Opiates and other CNS depressants are more
toxic in patients with head injuries.

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4. State of Health… cont.
 Acidosis increases toxicity of tubocurarine and decreases
actions of insulin
 Hypertension may increase toxicity of sympathomimetics

5. Age and maturity

 Most accidental poisonings occur in children under 5 years
 Geriatrics are more susceptible to CNS depressants
 Children are more susceptible to TTCs

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6. Nutritional state and dietary factors
 Absorption is usually highest on empty stomach
 Absorption can be decreased or increased by food
constituents.
 E.g. absorption of tetracycline is decreased by calcium
containing food while that of griseofulvin is increased
by fatty meal.
 Foods rich in tyramine increase the toxicity of
monoamine oxidase inhibitor drugs producing
hypertension crisis.
 Low protein diet or starvation lowers albumin and
increases the concentration of drugs or xenobiotics
normally bound to this protein.

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7. Genetic factors
 What was attributed to idiosyncrasy to describe
individual’s hereditary predisposition to toxicity is now termed
pharmacogenetics.
 Involves polymorphic biotransformation of drugs and
toxins
 Many drugs and some carcinogens undergo metabolism by
acetylation
– Slow acetylators:
 More prone to peripheral neuropathy from
isoniazid
 More prone to systemic lupus erythematosis from
hydralazine and procainamide
 More prone to bladder cancer from exposure to
beta-naphthalene

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 7. Genetic factors Con’t……
– Succinylcholine (muscle relaxant) used during general
anesthesia.
Small segment of population have atypical
pseudocholinesterase, which cannot efficiently
metabolize succinylcholine inactive metabolite
Thus, the concentration of the drug increases 4-7
times higher than normal predisposing this particular
population to life threatening respiratory paralysis
8. Gender
 Most of the time women more susceptible to chemicals
than men
– E.g. absorption of ethanol is greater in women than
men due to reduced activity of alcohol dehydrogenase
in women.
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9. Environmental of exposure
 Temperature: biologicl responses typically slow with
decreasing temperature while duration of response may be
prolonged.
 E.g. atropine is more toxic at higher environmental
temperature as also are other anti-cholinergics.
 Occupation: workers chronically exposed to organic
compounds (solvents, pesticides) are more likely to have
enhanced ability to metabolize drugs and xenobiotics
(increased enzyme induction).

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10. Physical properties of toxicant at time of exposure
 Particle size: <1μm pulmonary absorption
 Solubility
 Physical state of the toxicant: solid vs liquid vs gas
 pH: strong acid/base is highly corrosive
 Stability: paraldehyde (CNS toxicity) when decomposed
forms acetaldehyde (vomiting)

11. Nature of pathology

 Smoking induced functional changes in lungs: reversible
 Lung cancer induced by smoking: irreversible

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12. Site of exposure
 More regenerative tissues: e.g., liver
 Alcohol induced fatty liver: reversible
 Less regenerative tissues: e.g., brain
 Alcohol induced toxic effect on brain: irreversible
13. Concurrent event:
e.g.smoking increases asbestos toxicity

14. Duration of exposure

Examples:
 Acute alcohol toxicity leads to drunkenness, while
chronic to hepatitis
 Acute amphetamine toxicity leads to psychosis, while
chronic leads to hypertension
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Analytical methods in toxicology
 Toxicology lab expected to provide
• Identification of agents/toxicant/ for poisoning
• Detection of drug abuse, i.e.in the victim blood.
• Therapeutic drug monitoring/for low TI drugs-w/c are
potentially toxic/=TDM
 Number of compounds for which true emergency lab
results are needed to guide therapy are few
 For most, victims are treated empirically before lab results
are known

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Analytical methods in toxicology … cont.
 Lab utilization influenced by-2 factors:
• Clinician familiarization with the service
• Turn around time which depends on the facility, e.g.,
chromatography requires longer time than automated
immunoassay kit method

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Analytical methods in toxicology … cont.
 Information necessary for the lab="SATS"+L
• Suspected agent/substance
• Suspected amount
• Time of ingestion and sampling
• Clinical presentation
• Location of victim-where the exposure happens
o gives us information to assess more and how the
poisoning happens.
o to intervene to others who do not come to clinics
while still poisoned.

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Steps in toxicological analysis
1. Pre-analytic phase
• Victim’s history
• Physical examination
• Lab diagnosis
2. Analytic phase
• Toxicological analysis- analyzing the substance using the following
methods.
 Spot tests: color change in urine/blood with specific reagent
 UV spectroscopy: barbiturates
 Immunoassay: recognition by specific Abs (opioids)
 Chromatography
 TLC
 Gas chromatography: for volatile cpds
 HPLC (High Performance Lipid Chromatography): for non
volatile Cpds
 Mass spectroscopy: almost for all (either volatile or not)
 Nuclear magnetic resonance (NMR): most sensitive(i.e, even to
very small amount of substance)but expensive
3. Post-analytic phase
• Results’ interpretation/as to come to conclusion/
• Repeating analysis if needed
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Laboratory specimens
 Laboratory specimens are defined as a biological material
and non-human sources/animals used for
• For diagnostic purposes
• Study or
• Analysis
Types of Specimens
• Urine
• Stomach contents
• Blood
• Non-biologicals (scene residues)-staffs near the victim where
the poisoning occurs, OTC medication, left over medication,
empty bottles ….
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 Laboratory specimens … Cont.
N.B.
 All should be collected before any chemical administration
including drug b/c may complicate the analysis and give
false +ve result.
 Therefore, after maintain the ABCD/supportive therapy/ you
could take specimen prior to administering drug for
symptomatic therapy.

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Choice of specimen
 Depends on:
• Kinetics of the suspected agent
o For not absorbable agent/polar substance/: GI
specimen
o For absorbable agent/non polar toxicant/: blood
specimen
• Lab method
o For qualitative test: urine specimen/gastric contents
o For quantitative tests: serum/whole blood specimen

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Diagnosis of poisoning
 Diagnosis is usually difficult as victims may
• be unconscious-difficult to take history or
• not admit self poisoning
 Suspicious mind is needed in diagnosing poisoned
victim
• ill person who does not respond

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Diagnosis of poisoning: Steps
1. History of the victim-usually 2nd hand info.
• From Living: family members, police, paramedical
personnel/paramedics/
• From non-living: syringes, empty bottles, household
products, OTC medication, left over medication, tablet
• Basic information: SATS (Substance Amount Time
Symptoms)

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Diagnosis of poisoning: Steps …cont.
2. Physical examination
• Vital signs (BP, pulse, Rp, BT)
• GIT (smell, status of peristalsis)
• Eyes (miosis, mydriasis)
• CNS (depression/stimulation)
• Skin (flushing, sweating)
 Consider the possibility of classifying the patient as one
of the known toxidromes
 A toxidrome is a constellation of symptoms or a
syndrome of characteristic features associated with some
drug or class of drugs

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Diagnosis of poisoning: Steps …cont.
3. Laboratory diagnosis
 Electrolyte analysis
 Sodium, potassium, chloride, and bicarbonate should be
measured
 Anion gap= Anion gap = (Na+ + K+)- (HCO3- + Cl-)
 Total serum cation= total serum anion
 Anion gap = (Na+ + K+)- (HCO3- + Cl-)
 Normal 12-16mEq/L
 Elevated anion gap = metabolic acidosis

 Blood glucose test

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Diagnosis of poisoning: Steps …cont.
 Renal function test
 Elevated serum creatinine phosphokinase = kidney
damage
 Arterial blood gases
 Decreased PO2= pulmonary edema
 ECG (QRS, QT, PR)
 X rays
 Liver function test (SGOT, SGPT)
 Rp function test
 Blood glucose
 Hematological tests
 Hematocrit
 Leukocyte count
 Blood clotting

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Diagnosis of poisoning: Steps …cont.
4. Toxicological analysis
 Whole blood: for volatile agents
 Urine
 Gastric contents: unabsorbed toxicants
 Non-biologicals

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Principles of management of poisoning
1. Treating human victim: ensure victim’s ABC
(Airway, Breathing, Circulation)
 Supportive therapy
• Clearing airway of vomit-oral exposure
• Artificial Rp
• Circulatory support
• Maintaining mental function with glucose
 Symptomatic therapy
• Identify toxidroms (signs/symptoms of toxicity)
• Treat each symptom accordingly

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Principles of management of poisoning… cont.
2. Treating the poison victim
a) Removal from skin
Wash
b) Removal from the GIT provided/make sure/that:
• No potential for seizures/convulsion
• Airway is fully protected-conscious victim if not in
obtunded or unconscious .victim may lead to aspiration
• Not too much time elapsed since ingestion
 The toxicant is still in the GI (not absorbed).
• Poisoning is not corrosive (affect the lining or other
organ) or petroleum distillate (lead to aspiration)

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Principles of management of poisoning
Topical decontamination
• Ocular irrigation/bathing: flood the eye with lukewarm
or cool water
• Remove clothing containing the toxin properly disposed
of in airtight wrappings or containers (rescuers care
also!!!)
• Gentle washing of the hair and skin with warm water
and detergent (cutaneous abrasions  dermal
absorption)
Principles of management of poisoning: From
pulmonary route
• If the exposure is inhalational, remove of the patient from the
environment where the toxicant is found
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Principles of management of poisoning: From GIT
Gastric decontamination
1. Emptying the bowel
a) Emesis
• Causes physical removal of GI contents
• Drawbacks include
 Only up to 60% (max.) of the toxicant can be removed-
never completely remove/100%/
 Leads to persistent vomiting for 2-4 h-excess fluid and
electrolyte loss to shock, esophageal and other GI
structure damage, airway blockade etc,,,
 Leads to prolonged delay in administering charcoal
 Aspiration in obtunded/unconscious/victims

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Principles of management of poisoning: From GIT…
 Example
– Syrup of ipecac: 15 to 20 mL given orally with water and
vomiting can be expected within the ensuing 30 min.
– Apomorphine: given parenterally (usually by SC route) at
6 mg for adults and 0.06 mg/kg for children
• Contraindications
 Obtunded/unconscious/victims-b/c it lead to airway
blockade to aspiration
 Caustic ingestion-b/c they are corrosive when they
come out from GI affect the esophagus or the oral
cavity
 Hydrocarbons ingestion: volatile agent access to
respiratory tract lead to aspiration e.g., petroleum
distillate
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Principles of management of poisoning: From GIT…
b) Gastric lavage-washing of the GI
• Intubation(catheter) of esophagus and administration of
250 ml of water/saline/sodium bicarbonate/tannic
acid/potassium permanganate/calcium salts
• Allows immediate administration of charcoal (adv)
• Drawbacks include
 Less effective than emesis (<60%)
 Aspiration-b/c of blocking airway
 Cardiorespiratory dysfunction
 Noxious and labor intensive-for victim and the
professional respectively.
• Contraindications
 Caustic-damage the GIT
 Hydrocarbons-aspiration
 Unprotected airway/unconscious victim/
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Principles of management of poisoning: From GIT…
c. Catharsis-inducing watery/fluidy stool,
i.e.diarrhea
• Used rarely
• Drawbacks
 Dehydration /severe/
 Electrolyte imbalance
 CCF
• Contraindications
 GI hemorrhage-exacerbate during peristalsis,
 Recent bowel surgery-b/c it affects the wound
 Renal failure-route of elimination of agent is kidney
 Corrosives-when they pass through the colon they
affect all the way to the rectum
 Examples:
 Saccharide cathartics (sorbitol): most effective
 Saline cathartics (Na2SO4 , MgSO4) 78
Principles of management of poisoning: From GIT…
2. Inactivating the poison in GIT
i. Adsorbents
Activated charcoal
• Inert substance obtained by organic material combustion
• Treated to increase its surface area
• Not absorbed from GIT
• Chelates most substances except caustics, heavy metals,
hydrocarbons, cyanides
• Drawbacks include
 Constipation-make GI dry b/c of taking up most subs.
 Aspiration

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 Principles of management of poisoning: From GIT…
2. Inactivating the poison in GIT
ii. Demulcents
Egg-white/milk/ice cream
3. Dilution
• Administration of water for chemicals
 1-2 cups(glass) for children
 2-3 cups for adults
• Avoid premature evacuation of stomach unlike emptying tech.
• Recommended for solution or suspension toxicants.
• Not recommended for tablets/capsules-b/c they are easily
dissolved in water
• Contraindicated for obtunded victims-chance of aspiration

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Principles of management of poisoning: From GIT…

4. Whole Bowel irrigation

• New technique
• Not absorbed
• No fluid and electrolyte imbalance
• Flush GIT 5-6h to reduce transit time and limit absorption
• Useful for lithium and iron poisoning/heavy metal poison/
• Sodium sulfate and polyethylene glycol electrolyte solution
 The best and most proffered technique

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 Principles of management of poisoning: From
Circulation
I. Forced diuresis-simplest one
 Procedures
• Use of diuretics (osmotic/loop)-no longer recommended
• Use of large volume of isotonic fluid-HIGHLY PREFFERED
AND RECOMMENDED
• Alteration of urine pH
 Alkaline diuresis with NaHCO3 ↑ urine pH to 7-8
(aspirin)
 Acid diuresis with NH4Cl ↓ urine pH 5.5-6 (no longer
effective for weak bases like amphtamine)

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 Principles of management of poisoning: From
Circulation… cont.
• Complications include
 Fluid and electrolyte imbalance
 Edema
 Acid base disturbances(metabolic)
• Contraindications include
 Renal failure
 Cardiac failure-in case of osmotic diuresis make plasma
fluid higher compromising cardiac function
 Uncorrected fluid and electrolyte imbalance

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 Principles of management of poisoning: From
Circulation… cont.
ii. Dialysis-complex, expensive, risky and may also lead to
death, not routinely used only in sever cases
 Indicated
• Vital function impairment-body temp.,Rp, Bp control is
impaired
• Clinical deterioration (condition or s/s become worse) in
spite of maximum supportive therapy
• Lab confirmation of Lethal blood level
• Renal and or hepatic compromise/failure
• Life threatening complications
• Intoxication with delayed effect (pro-toxicant)-prior to
getting activated need to be removed.
• Multidrug intoxication
84
 Principles of management of poisoning: From
Circulation… cont.
• Contraindicated in
 Toxicants not effectively dialyzable
 Toxicants with specific antidotes
 In shock state-exacerbate the condition
 Coagulopathy for there is a need to heparinization
(anticoagulant)-lead to bleeding w/c exacerbate the shock
state
• Requirements include
 Small molecular size
 Water solubility
 Not bound with plasma proteins
• Types of dialysis
 Peritoneal dialysis
 Hemodialysis

85
 Principles of management of poisoning: From
Circulation… cont.
 Peritoneal dialysis
• Insertion of a catheter into peritoneal cavity
• Uses peritoneum as a dialyzing membrane (partially
permeable)
• Up to 2 L of pre-warmed fluid administered and removed
after 1-2 h
• Advantages include
 Easier procedure
 Less complication  Faster implementation
• Disadvantages include
• Limited role in removal of toxicants
• Abdominal pain-upon inserting the catheter
• Intestinal perforation-upon inserting the catheter
• Peritonitis-upon inserting the catheter

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 Principles of management of poisoning: From
Circulation… cont.
 Hemodialysis
• Insertion of a catheter into blood vessels
• Uses artificial membrane, i.e. the catheter has a dialyzing
membrane
• Up to 100 L of fluid can be administered
• Advantage
 More effective than peritoneal dialysis
• Disadvantages include
 Spontaneous bleeding-during insertion you may miss
the vv lead to bleeding-loss of fluid and electrolyte
balance-hypotension---shock (hypovolumic)
 Venous thrombosis-by extrinsic factor
 Hypotension

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Principles of management of poisoning: From
Circulation… cont.
• Disadvantages ….cont.
 Infection/hepatitis/HIV-if the catheter isn't sterilized
 Anaphylaxis/type-1 hypersensitivity/-since the catheter
is made up of chemicals the victim may be
hypersensitive to one of the chem.
 Electrolyte imbalance
 Death due to equipment failure

88
 Principles of management of poisoning: From
Circulation… cont.
iii. Hemoperfusion
• Exposing to a column containing charcoal (for polar cpds)
or resins (for nonpolar cpds)
• More effective to remove large, lipid soluble or highly PP
bound substances
• Advantages include
 Not limited by water solubility
 Not limited by high molecular weight
 Not limited by protein binding
• Disadvantages include=disadv. of dialysis
 Bleeding
 Thromboembolism
 Hypotension
 Infection  Anaphylaxis

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Principles of management of poisoning: from
tissues
Antidotal therapy
 After toxicant reaches the target receptor, management
methods are much less successful, except for
administration of antidotes
 Antidotes are therapeutic agents that have a specific
action against the activity or effect of a toxicant.
 A relatively small number of specific antidotes are
available for clinical use in the treatment of poisoning.

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Principles of management of poisoning: from
tissues … cont.
 Antidotes fall into 4 categories based on their
mechanism of action:
1. Chemical
 react with poison to form less toxic compound e.g.
chelating agent (CaCl2 forms low solubilty complex with
oxalic acid)
 Sodium nitrite is given to patients poisoned with cyanide
to cause formation of methemoglobin, which serves as an
alternative binding site for the cyanide ion thereby making
it less toxic to the body.

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Principles of management of poisoning: from
tissues
2. Receptor antagonist
 Compete with toxicant for receptor to antagonize its
effects
 E.g. Atropine, an antimuscarinic, anticholinergic agent is
used to antagonize the effects of organophosphate
insecticides, naloxone reverses opiate induced respiratory
depression, etc
3. Dispositional
 Favorably alter absorption, distribution, metabolism or
excretion.
 E.g. N-acetylcystein limits supply of acetaminophen
toxic metabolite by converting it to non-toxic form)

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 4. Functional
 Antagonists that reverse responses such as anaphylactic
reactions leading to bronocho-constriction following drug or
animal toxin exposure (epinephrine produces
bronchocodilation and can restore normal breathing)

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94
Table …Cont’d

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