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8/3/2019 Toxicology Abed
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Toxicology
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Toxicology
Study of poisons. There are four major disciplines:
1. Mechanistic: elucidate the cellular and
biochemical effects of toxins.2. Descriptive: uses results of animal
experiments to predict harmful effects tohumans.
3. Forensic: concerned with medicolegalconsequences of exposure to a toxin.
4. Clinical: the study of interrelationships
between toxin exposure and disease states(diagnosis & therapeutic intervention)2
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Exposure to Toxins
Occurs by various routes:Suicide (50%)
Accidental (30%)Rest are related to:occupational exposure
or homicide
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Routes of Exposure
Toxins enter the body by several routes:
1. Ingestionmost often seen in a clinical setting
to exert a systemic effect, they must beabsorbed into circulation
most are absorbed by passive diffusion
If not absorbed they may produce localeffects, such as diarrhea, bleeding, ormalabsorption of nutrients
2. Inhalation
3. Transdermal absorption4
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-relationship
Poisonany substance that causes a harmfuleffect upon exposure.
Dose is a key issue.There are various toxic effects from
drugs based on dose includingdeath.
Dose-response implies that there willbe an increase in the toxic responseas the dose is increased.
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-relationship
Not all individuals display a toxic response at thesame dose.
Cumulative frequency histogram of the % ofpeople producing a toxic response over a range
of concentrations
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-relationship
TD50 is the dose that would be predicted to
produce a toxic response in 50% of the
population.ED50 is the dose that would be predicted to
be effective or have a therapeuticbenefit in 50% of the population.
LD50
is the dose that would predict death in7
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-relationship
The therapeutic index is the ratio of theTD50 to the ED50.
A high therapeutic index is preferable to a
low one: this corresponds to a situation in which
one would have to take a much higher
dose of a drug to reach the lethal thresholdthan the dose taken to elicit thetherapeutic effect.
Drugs with a large therapeutic index havefew toxic adverse effects
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Toxicity
Acute toxicity:associated with a single, short termexposure to a substance, the dose is
sufficient to cause immediate toxiceffect.
Chronic toxicity:associated with repeated exposure forextended periods, at a dose that are
insufficient to cause immediate acute9
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Analysis of Toxic Agents
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Two-steps procedure Screening test:
which is a rapid , simple analysis that is
qualitative procedure to detect specific drug orsubstance.
Sensitive but lack specificity
Assy: E.g. immunoassays
Confirmatory test:
test utilizing more specificity- and quantitative
Thin layer chromatography and gaschromatography.
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Agents
Alcohol:Exposure to alcohol causes: disorientation,
confusion
and euphoria
can progress to unconsciousness,
paralysis and with high-level exposure ,even death.
common depressant of the central
nervous system.11
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Alcohol:
There is biotransformation ofalcohols to toxic products
Alcohol Aldehyde AcidChronic consumption of alcoholover a long period leads to
accumulation of lipids inhepatocytes, which may progressto alcoholic hepatitis and finally to
liver cirrhosis12
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Alcohol:
EthanolThe economic impact is estimated to exceed
$100 billion
one of the top 10 causes of hospitaladmissions
20% of all hospital admissions have some
degree of alcohol-related problems80,000 Americans die each year, either
directly or indirectly, as a result of alcohol
Consumption of large quantities has been
associated with compromised function in13
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Alcohol:
Methanol: Common solvent ingested accidentally
Death can occur due to the formation of formic acidleading to severe acidosis
CNS depressant Isopropanol:
rubbing alcohol, metabolized by liver to acetone
CNS depressant
Ethylene glycol: common component of anti-freeze.
Causes crystallization of calcium oxalate within therenal system and cause tubular damage if dosage
high.14
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Determination of Alcohol
Specimen: serum, plasma, whole bloodDo not use alcohol to clean area for
veinpuncture specimens must be capped at all times to
avoid evaporation
Methods:
Gas chromatography.Enzymatic method
Ethanol + NAD Acetaldehyde + NADH15
ADH
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Carbon Monoxide
By product of incomplete combustion of carboncontaining substances (gasoline engines,furnaces and wood or plastic fires.)
Colorless, odorless and tasteless gas that isabsorbed into the blood from inhaled air.
Toxic effect is due to its affinity for heme (Hb,myoglobulin, etc).
Hb affinity has the most effect due to theproduction of carboxyhemoglobulin (~ 200 Xgreater affinity)
Major toxic effect of carbon monoxide are seenin or ans with hi h O demand brain & heart16
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determination
1. Spot test: using 5 ml of 40% NaOH mixed with 5
ml of 1/20 aqueous dilution of whole
blood a pink color if CO present at 20% or
greater value
2. Quantitative method Gas chromatography,
and spectrophotometeric methods
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Caustic Agents
Occupational or household exposure ofcleaning agents.
Aspiration and ingestion present the
greatest hazard Ingestion produces lesions in the
esophagus and gastrointestinal tract,
which may produce perforations Corrective therapy for ingestion is usually
by dilution
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Cyanide
Supertoxic substance that exist as a gas,solid or in solution.
Exposure can occur through inhalation,ingestion, or transdermal absorption.
Found in insecticides and rodenticides
Toxic effect involves its ability to bind hemeiron.
Cyanide clearance is mediated by enzymaticconversion to thiocyanate, a nontoxic productrapidly cleared by renal filtration.
Method for analysis: Ion specific electrode19
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Metals and Metalloids
Arsenic:exist bound or as primary constituent of
organic and inorganic compounds.
Found naturally and can be manmadeforms.
Environmental exposure or occupational
Absorption of arsenic depends on theform.
Toxicity related to the binding ability to
protein.20
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Metals and Metalloids
CadmiumMetal found in industrial processes
(electroplating)
Pigment found in paints and plastics.
Significant environmental pollutant.
Exposure occurs through inhalation,
toxicity related to ability to bind toprotein & tends to accumulate in thekidneys.
Assay: atomic absorption21
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Metals and Metalloids
LeadCommon environmental contaminant
Use to be used in household paint and
gasoline.
Exposure can occur in various route- mostis through dietary ingestion of contaminated
material.Toxicity related to ability to bind to
macromolecular structures.
Distributes into the bones and soft tissue.22
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LeadLead toxicity has various physical
effects (neurological, decreased
intelligence).Potent inhibitor of many enzymes (Vit.
D, heme synthetic pathway) resulting in
changes in bone and calciummetabolism and in anemia.
Assay: chromogenic reaction
Most common method Graphite furnace23
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Metals and Metalloids
MercuryExposure occurs through inhalation and
ingestion (contaminated food)
Toxicity related to ability to bind proteinresulting in a change of structure andfunction.
Inhibits a number of enzyme activities.Many biological effect most noted is
renal.
Assay: AAS24
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Pesticides
Substance that are intentionally used tokill or harm an undesirable life form.
Categorized as insecticide and herbicides
which are used to control of vector-bornedisease and pest and to improveagricultural productivity.
Contamination of food is the major routeof exposure.
Inhalation, transdermal absorption and
ingestion through hand-to mouth contact25
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Pesticides
Actions of most are nonselective andresult in toxic effect to various organs.
Wide variation of pesticides that range
from salts to heavy metals. Organophosphate and carbamates
function by inhibition of acetylcholine
esterase.Acetylcholine is a neurotransmitter and has
many effects in the body.
Test utilized to test for toxic pesticides-26
Toxicology of Therapeutic
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Toxicology of TherapeuticDrugs
Analyze the overdose effects ofpharmaceutical drugs.
Salicylates:Aspirin: analgesic, antipyretic, and anti-
inflammatory drug.
Various bodily effects: Because aspirin is an acid leads to metabolic
acidosis.
Assay: Gas or liquid chromatography,
Immunoassay & Chromogenic method27
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Amphetamines
Amphetamine and methamphetamines aretherapeutic drugs used for narcolepsy andattention deficit disorder.
Stimulants with high abuse potential.
Produce an initial sense of increased mentaland physical capacity
Overdose results in hypertension, cardiac
arrhythmia, convulsions and possibly death.
Assay for amphetamine requires urinespecimen,
immunoassay is a screening test,28
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Anabolic Steroid
Chemical compound that is chemicallyrelated to male sex hormonetestosterone.
Used to increase muscle mass andenhance performance.
Various physical effects including toxichepatitis with chronic use, enlarge heart,
atherosclerosis. Assay: gas chromatography with mass
spectrometry
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Cocaine
Effective local anesthetic with few side effects attherapeutic concentration.
At High levels it is a potent CNS stimulator.
Alkaloid salt that can be administered by IV and/or inhaled in free base form.
Primary product of hepatic metabolism isbenzoylecgonine in urine.
Detected in urine 4-7 hrs after use and detectedup to 3 days after single use and 20 days inchronic use.
Confirmation test is done by gas30
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Opiates
Capable of analgesic and anesthesia Derived from opium poppy, naturally
occurring substances include opium,
morphine, and codeine. Heroin and hydromorphone are common
synthetic substances.
High abuse potential. Acute overdose present with respiratory
acidosis due to depression of respiratory
center and cardiac damage31