Toxicology Abed

8/3/2019 Toxicology Abed

1/31

Toxicology


2/31

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


3/31

Exposure to Toxins

Occurs by various routes:Suicide (50%)

Accidental (30%)Rest are related to:occupational exposure

or homicide

3


4/31

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


5/31

-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.

5


6/31

-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

6


7/31

-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


8/31

-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

8


9/31

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


10/31

Analysis of Toxic Agents

10

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.


11/31

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


12/31

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


13/31

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


14/31

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


15/31

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


16/31

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


17/31

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

17


18/31

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

18


19/31

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


20/31

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


21/31


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


22/31


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


23/31

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


24/31


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


25/31

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


26/31

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


27/31

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


28/31

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


29/31

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

29


30/31

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


31/31

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

Date post:	06-Apr-2018
Category:	Documents
Upload:	abednaim-naim
View:	226 times
Download:	0 times

Toxicology Abed

Documents