Toxicology

(Part 2)

Drug Absorption
-Drug Absorption from the GI tract is dependent on the rate & amount of intact drug and the rate that it reaches
circulation after oral administration. Rate is affected by:
a. Solubility- is the maximum amount of a substance that will dissolve in a given amount of solvent at a specified
temperature.
b. Absorption across membrane
c. Gastric emptying-test that measures the time it takes for food to empty from the stomach and enter the small
intestine.
d. Metabolic Rate-the amount of energy used in a certain period.

Structure of GI Tract
-The GI tract has three major regions: the stomach, small intestine and the large intestine.

Stomach – the mucosa contains many folds that increase the surface area available for drug absorption. -The high
blood supply and the fact that a drug can potentially reside in the stomach for several hours can provide
optimum conditions for the absorption of acidic drugs.

Small Intestine – is the most important GI site for drug absorption. The intestinal mucosa provides an extremely large
surface area; villi and microvilli aids drug absorption (about 30’ long in an adult)

Large Intestine - like the stomach, lacks the villi and microvilli of the small intestine; serves as a site for the absorption of
drug that has not been completely absorbed in the small intestine (about 6’ long in an adult)

Mechanisms of Drug Transport across the GI Barrier

-The majority of drugs cross the membrane by passive diffusion.

Passive Diffusion
- Drug transport rate is determined by the physical and chemical properties of the drug, and its concentration gradient
across the membrane.
-Passive diffusion is the process by which molecules diffuse from a region of higher concentration to a region of lower
concentration.
-It is the most important mechanism for passage of drugs through membranes.
-Drug entering the blood stream will be carried away from the site of absorption by the gastrointestinal blood supply
and will become diluted by:
a. Distribution in a large volume of blood.
b. Distribution into body tissue.
c. Metabolism and excretion.
d. Protein binding in the blood.

Physiological Factors Influencing Drug Absorption

- Surface area of the absorption site pH of the GI fluids
-Gastric emptying rate: can be stimulated by hunger, anxiety, body position and liquid consumption; Fatty foods, high
bulk diet, depression and various drugs and alcohol retard it.
-Intestinal motility
-Drug stability in the GI system
-Dietary components
-Disease states

Drug Metabolism
-Metabolism is the fundamental mechanism of drug elimination.
-Metabolism aids drug excretion processes and may affect the pharmacological response of a drug by altering its
potency and/or duration of action
-Metabolism can occur in the plasma as well as organs other than the liver such as the GI tract, kidneys and lungs.

Factors Affecting Metabolism

a. Age
-Young children and elderly people usually have a lower metabolic capacity
b. Diseases
-Diseases can affect all of the ADME processes.
-Liver and kidney diseases probably have the greatest effect on drug concentrations by affecting metabolism and
excretion.
c. Weight
-The weight of a patient affects drug concentrations in the blood since it determines the volume into which the drug is
distributed.
-Drug metabolism tends to be faster in males than in females.
d. Genetic Factors
-Gender and race differences in enzyme activity can affect drug metabolism
e. Diet
-Diet may influence the metabolism of some drugs.
-Exposure to other drugs (particularly alcohol) markedly affects the metabolism of certain drugs.

Excretion of Drugs
-The excretion of drugs and metabolites terminates their activity and presence in the body. -Elimination can
occur by various routes. The kidney plays a major role with the excretion of drugs and/or their metabolites
into the urine.
-Drugs may also be excreted in the faeces, bile, lungs sweat, saliva and breast milk.

Drugs
What is a drug?
-A drug can be defined as a natural or synthetic substance that is used to produce physiological or psychological effects
in humans or other higher order animals.
-Narcotic drugs are analgesics, meaning they relieve pain by a depressing action on the central nervous system.
*This affects functions such as blood pressure, pulse rate and breathing rate.
*The regular use of a narcotic drug will invariably lead to physical dependence.
*The most common source for these narcotic drugs is opium, extracted from poppies.
Illicit Drugs
-Illicit drugs refer to highly addictive and illegal substances such as heroin, marijuana and meth. -While the decision to
use one of these drugs for the first time is usually a voluntary one, an unexpected addiction can make the decision to
quit later significantly harder.
-Illicit drugs fall into two categories. The first category is comprised of those drugs that are illegal to process, sell,
and consume.
-These include cocaine, methamphetamine, and heroin.
-The second class includes those drugs that are legal to process, sell, and consume when prescribed by a physician, but
are then misused by the person to whom the drugs have been prescribed, or are used by individuals not under a
prescribing doctor’s care, and who may have obtained the drugs by illegal means.
-Drugs in the second category can include prescription pain medication and prescription sedatives.

“NIDA 9”
Methamphetamine
Cocaine
Opiate
Benzodiazepam
THC
Methadone
Barbiturates
PCP
Illicit Drugs

CNS Depressants:
Narcotics (opiates)
Sedatives, hypnotics (PCP, Quaalude)
Tranquilizers (Valium)

CNS Stimulants
Cocaine
Amphetamines

Hallucinogens
Mescaline,
Psilocybin,
LSD, PCPTHC
Steroids
Inhalants

Illicit Drug Use

-The hazards of illicit drug use are the increase in infections, disease, and overdose
-Medical complications that are commonly seen among addicts are brain, skin, and lung abscesses; inflammation of the
lining of the heart, hepatitis, and AIDS.

Signs of an Overdose
-Respiratory depression
-Cold, clammy skin
-Confusion
-Convulsions
-Severe drowsiness
-Constricted pupils

Drug Groups

Hallucinogens
-A class of drugs is hallucinogens; marijuana is the most well-known member of this class.
-Hallucinogens cause marked changes in normal thought processes, perceptions, and moods. -Marijuana is the most
controversial drug in this class because its long-term effects on health are still largely unknown.

Marijuana
Other Names:
Cannabinoids
Marijuana Blunt
dope,
ganja,
grass,
herb,
joints,
Mary Jane,
pot, reefer, sinsemilla,skunk, weed
Swallowed/Smoked:14 days - 11weeks

Marijuana
-The chemical substance largely responsible for the hallucinogenic properties of marijuana is known as
tetrahydrocannabinol, or THC.
-The THC content of Cannabis varies in different parts of the plant, generally decreasing in the following sequence: resin,
flowers, leaves, with little THC in the stem, roots, or seeds.
-The THC-rich resin is known as hashish.
-Marijuana do not cause physical dependency, the risk of harm is in heavy, long-term use.

Other Hallucinogens
-Other hallucinogens include: LSD, mescaline, PCP, psilocybin, & MDMA (Ecstasy).
-LSD is synthesized from lysergic acid, & can cause hallucinations that can last for 12 hours.
-Phencyclidine, or PCP, is often synthesized in clandestine laboratories & is often smoked, ingested, or sniffed. -PCP
is often mixed with other drugs, such as LSD, or amphetamine, & is sold as a powder (“angel dust”), capsule, or
tablet.
-Oral intake of PCP first leads to feelings of strength and invulnerability, which may turn to depression, tendencies
toward violence, & suicide

Opiates
-Morphine is readily extracted from opium and is used to synthesize heroin.
-Addicts frequently dissolve heroin in water by heating it in a spoon, and then inject in the skin.
-Heroin produces a “high” that is accompanied by drowsiness and a sense of well-being that generally last for three to
four hours.
-Codeine is also present in opium, but it is usually prepared synthetically from morphine.
-OxyContin, with the active ingredient oxycodone, is not derived from opium or morphine, but does have the same
physiological effects on the body as do opium narcotics.
-OxyContin is prescribed to a million patients for treatment of chronic pain.
-Methadone is another well-known synthetic opiate.
-Methadone, which is pharmacologically related to heroin, appears to eliminate the addict’s desire for heroin while
producing minimal side effects.

Depressants
-Depressants are another class of drugs.
-Depressants are substances used to depress the functions of the central nervous system.
-Depressants calm irritability and anxiety and may induce sleep.
-These include alcohol (ethanol), barbiturates, tranquilizers, and various substances that can be sniffed, such as airplane
glue, model cement, or aerosol gas propellants such as Freon.
-Alcohol (ethyl alcohol) enters the body’s bloodstream and quickly travels to the brain, where it acts to suppress the
brain’s control of thought processes and muscle coordination.
-Barbiturates, or “downers,” are normally taken orally and create a feeling of well-being, relax the body, and produce
sleep.
-Tranquilizers, unlike barbiturates, produce a relaxing tranquillity without impairment of high-thinking faculties or
inducing sleep.
-Sniffing has immediate effects such as exhilaration, but impairs judgment and may cause liver, heart, and brain damage,
or even death.

Heroin Usage
-In 1974 estimated users were 246,000.
-Between the years there was an estimate of 28,000-80,000 new users
-Between 1995 and 2001 the number of new users was greater than 100,000Today there has been a reported 3.7 million
people in the US alone who reported using heroin at least once in their lifetime.

Oxycodone
-The tablet is either taken orally or crushed and sniffed or dissolved in water and injected
-This drug is often stolen and prescriptions are often forged.

Hydrocodone
-It is used as a cough suppressant and analgesic
-DEA has this drug listed as the most frequently encountered opiate pharmaceutical that is submitted for drug evidence
to federal, state and local forensic laboratories.
-Abusers obtain the is drug by theft, doctor shopping, fraudulent prescriptions, and fake call in prescriptions

Dextropropoxyphene
-Related to Morphine
-First marketed in 1957
-Used to help moderate to mild pain
-There is 150 tons produced in the United States annually
-25 million prescriptions have been written.
-This drug is among the top 10 drugs reported by the medical examiner in drug abuse deaths.

Stimulants
-Amphetamine and methamphetamine, often injected intravenously, causes an initial “rush,” followed by an intense
feeling of pleasure, followed by a period of exhaustion and a prolonged period of depression. -Cocaine, extracted
from the leaves of Erythroxylin coca, causes increased alertness and vigour, accompanied by the suppression of
hunger, fatigue, and boredom.

Cocaine
-Crack is cocaine mixed with baking soda and water, then heated.
-Crack is often smoked in glass pipes, and, like cocaine, stimulates the brain’s pleasure center.

Date Rape Drugs

-Substances that are often used as club drugs include, but are not limited to, MDMA (Ecstasy), GHB (gamma
hydroxybutyrate), Rohypnol (“Roofies”), ketamine, and methamphetamine.
-GHB and Rohypnol are central nervous system depressants that are often connected with drug-facilitated sexual
assault, rape, and robbery.

Ecstasy
-Adam, clarity, ecstasy, lover's speed, peace, STP, X, XTC Swallowed
-Referred to as party drugs
-Drugs that are commonly found at bars, night clubs, raves and techno parties.
-Causes a comma in minutes associated with sexual assaults
-Methylenedioxymethamphetamine, also known as MDMA or Ecstasy, is a synthetic mind-altering drug that exhibits
many hallucinogenic and amphetamine-like effects.
-Ecstasy enhances self-awareness and decreases inhibitions; however, seizures, muscle breakdown, stroke, kidney
failure, and cardiovascular system failure often accompany chronic abuse.

Ketamine
-Ketamine is primarily used as a veterinary animal anaesthetic that in humans causes euphoria and hallucinations.
-Ketamine can also cause impaired motor functions, high blood pressure, amnesia, and mild respiratory
depression

Alcohol Related Deaths

Of the 40,000 auto accidents in the United States50% are drunk drivers 60% of pedestrians killed have high blood
alcohol levels

Toxicology of Alcohol
-The analysis of alcohol exemplifies the primary objective of forensic toxicology—the detection and isolation of drugs in
the body for the purpose of determining their influence on human behaviour.
-Alcohol, or ethyl alcohol, is a colourless liquid normally diluted with water and consumed as a
beverage. -Like any depressant, alcohol principally effects the central nervous system, particularly the
brain.

Alcohol Levels
-Alcohol appears in the blood within minutes after it has been taken by mouth & slowly increases in concentration while
it is being absorbed from the stomach & the small intestine into the bloodstream.
-When all alcohol has been absorbed, a max alcohol level is reached in the blood; and the post-absorption period
begins. -The alcohol concentration slowly decreases until a zero level is again reached.

Factors affecting outcome on individual consumption:

a. Time taken to consume the drink
b. Alcohol content
c. Amount consumed
d. Food presence in the stomach
*The extent to which an individual may be under the influence of alcohol is usually determined by either measuring the
quantity of alcohol present in the blood system or by measuring the alcohol content in the breath.

Alcohol Levels
-Elimination of alcohol throughout the body is accomplished through oxidation & excretion. -Oxidation takes
place almost entirely in the liver, while alcohol is excreted unchanged in the breath, urine, and perspiration.
-Experimental evidence has verified that the amount of alcohol exhaled in the breath is in direct proportion to the blood
concentration.

Alcohol & the Circulatory System

-Humans have a closed circulatory system consisting of a heart, arteries, veins, and
capillaries. -Alcohol is absorbed from the stomach and small intestines into the blood stream.
-Alcohol is carried to the liver where the process of its destruction starts.
-Blood, carrying alcohol, moves to the heart and is pumped to the lungs.
-In the lungs, carbon dioxide and alcohol leave the blood and oxygen enters the blood in the air sacs known as
alveoli. -Then the CO2 & alcohol are exhaled during breathing.

Alcohol Breath Testers

-Breath testers that operate on the principle of IR light absorption are becoming increasingly popular within the law
enforcement community.
-Many types of breath testers are designed to capture a set volume of breath.
-Captured breath is exposed to IR light.
-It’s the degree of the interaction of the light with alcohol in the captured breath sample that allows the instrument to
measure blood alcohol concentrations in breath.

Alcohol Field Testing

-Law enforcement officers typically use field sobriety tests to estimate a motorist’s degree of physical impairment by
alcohol and whether or not an evidential test for alcohol is justified.
-The horizontal gaze nystagmus test, walk and turn, and the one-leg stand are all considered reliable and effective
psychophysical tests.
-A portable, handheld, roadside breath tester may be used to determine a preliminary breath-alcohol content.
Alcohol and the Law
-The AMA. & the National Safety Council has been able to exert considerable influence in convincing the states to
establish uniform & reasonable blood-alcohol standards.
-Between 1939 and 1964 a person having a blood-alcohol level in excess of 0.15 per cent w/v was to be considered
under the influence, which was lowered to 0.10 per cent by 1965.
-In 1972 the impairment level was recommended to be lowered again to 0.08 per cent weight/volume.

Alcohol and the Law

-Starting in 2003, states adopted the 0.08 per cent per se level.
-To prevent a person’s refusal to take a test for alcohol consumption, the National Highway Traffic Safety Administration
recommended an “implied consent” law.
-Adopted by all states by 1973, this law states that the operation of a motor vehicle on a public highway automatically
carries with it the stipulation that a driver will submit for a test for alcohol intoxication if requested or be subject to loss
of the license.

Collection and Preservation of Blood for Alcohol Testing

-Blood must always be drawn under medically accepted conditions by a qualified individual. -It is important to
apply a non-alcoholic disinfectant before the suspect’s skin is penetrated with a sterile needle or lancet.
-Once blood is removed from an individual, it is best preserved sealed in an airtight container after adding an
anticoagulant and a preservative.

Field Testing
-Law enforcement officers typically use field sobriety tests to estimate a motorist’s degree of physical impairment by
alcohol and whether or not an evidential test for alcohol is justified.
-The horizontal gaze nystagmus test, walk and turn, and the one-leg stand are all considered reliable and effective
psychophysical tests.
-A portable, handheld, roadside breath tester may be used to determine a preliminary breath-alcohol content.

Anabolic Steroids
-These are synthetic compounds that are chemically related to the male sex hormone testosterone. -Anabolic
steroids are often abused by individuals who are interested in accelerating muscle growth. -Side effects include
unpredictable effects on mood and personality, depression, diminished sex drive, halting bone growth, and liver
cancer.

Drug Control Laws

-The U.S. federal law known as the Controlled Substances Act will serve to illustrate a legal drug-classification system
created to prevent and control drug abuse
-This federal law establishes five schedules of classification for controlled dangerous substances on the basis of a drug’s:
potential for abuse potential for physical and psychological dependence medical value

Schedules of Classification
a. Schedule I drugs have a high potential for abuse and have no currently accepted medical use such as heroin,
marijuana, methaqualone and LSD.
b. Schedule II drugs have a high potential for abuse and have medical use with severe restrictions such as cocaine, PCP,
and most amphetamine and barbiturate prescriptions
c. Schedule III drugs have less potential for abuse and a currently accepted medical use such as all barbiturate
prescriptions not covered under Schedule II, codeine, and anabolic steroids.
d. Schedule IV drugs have a low potential for abuse and have a current medical use such as darvon, phenobarbital, and
some tranquilizers such as diazepam (valium) and chlordiazepoxide (librium).
e. Schedule V drugs must show low abuse potential and have medical use such as opiate drug mixtures that contain
nonnarcotic medicinal ingredients.

Collection & Preservation

-Generally common sense is the best guide, keeping in mind that the package must prevent the loss of the contents
and/or cross-contamination.
-Often the original container in which the drug was seized will suffice.
-All packages must be marked with information that is sufficient to ensure identification by the officer in the future and
establish the chain of custody.

Drug Identification
-The challenge or difficulty of forensic drug identification comes in selecting analytical procedures that will ensure a
specific identification of a drug.
-This plan, or scheme of analysis, is divided into two phases.
a. Screening test that is nonspecific and preliminary in nature to reduce the possibilities to a manageable
number. b. Confirmation test that is a single test that specifically identifies a substance.

Screening Tests
-A screening test is normally employed to provide the analyst with quick insight into the likelihood that a specimen
contains a drug substance.
-Positive results arising from a screening test are considered to be tentative at best and must be verified with a
confirmation test.
-The most widely used screening tests are thin-layer chromatography, gas chromatography, and immunoassay.
-Physical Tests: boiling point, melting point, density, and refractive index
-Crystal Tests: treatment with a chemical reagent to produce crystals
-Chemical Spot Tests: treatment with a chemical reagent to produce colour changes
-Chromatography (thin-layer or gas)-used to separate components of a mixture

Confirmatory Tests
-Gas chromatography/mass spectrometry GC/MS is generally accepted as the confirmation test of choice. -The GC
separates the sample into its components, while the MS represents a unique “fingerprint” pattern that can be used
for identification.
-Once the drug is extracted and identified, the toxicologist may be required to provide an opinion on the drug’s effect on
an individual’s natural performance or physical state.

The Analytical Scheme

-The forensic toxicologist must devise an analytical scheme that will successfully detect, isolate, and specifically identify
toxic drug substances.
-Once the drug has been extracted from appropriate biological fluids, tissues, and organs, the forensic toxicologist can
proceed to identify the drug substance present.
-Drug extraction is generally based on a large number of drugs being either acidic or basic.
-The strategy used for identifying abused drugs entails a two-step approach: screening and confirmation.

Drug Recognition Expert (DRE)

-During the 1970s, the Los Angeles Police Department developed clinical and psychophysical examinations that a trained
police officer could use to identify and differentiate between types of drug impairment.
-This program has evolved into a national program to train police as drug recognition experts. -Normally, a three- to
five-month training program is required to certify an officer as a drug recognition expert (DRE). -The DRE program
incorporates standardized methods for examining suspects to determine whether they have taken one or more
drugs.

Specimens for Analysis

a. Adipose Tissue-Insecticides, Thiopental
b. Bile-Codeine, Morphine
c. Blood- Alcohols, CO
d. Brain-Volatile Poisons
e. Kidney-Heavy metal
f. Specimens for Analysis
g. Liver-Most Toxicants
h. Lung-Methadone, Gases, Inhalants
i. Stomach/Intestine Contents-All toxicants taken orally
j. Urine-Most Toxicants
k. Vitreous Humor-Digoxin, electrolytes, glucose

Detecting Drugs in Hair

-Drugs present in blood diffuse through the capillary walls into the base of the hair and become permanently entrapped
in the hair’s hardening protein structure.
-As the hair continues to grow, the drug’s location on the hair shaft becomes a historical marker for delineating drug
intake.
-Given that the average human head hair grows at the rate of 1 centimetre per month, analyzing segments of hair for
drug content may define the timeline for drug use.

Drug Identification
The challenge or difficulty of forensic drug identification comes in selecting analytical procedures that will ensure a
specific identification of a drug.
This plan, or scheme of analysis, is divided into two phases.
a. Screening test that is nonspecific and preliminary in nature to reduce the possibilities to a manageable
number. b. Confirmation test that is a single test that specifically identifies a substance.

Preliminary Analysis
-The unknown substance may be any one of a thousand or more commonly encountered drugs, the analyst employs
screening tests to reduce these possibilities to a small and manageable number.
-This objective is often accomplished by subjecting the material to a series of colour tests that will produce characteristic
colours for commonly encountered illicit drugs.
-Microcrystalline tests can also be used to identify specific drug substances by studying the size and shape of crystals
formed

Conformational Determination
-Once this preliminary analysis is completed, a conformational determination is pursued.
-Forensic chemists will employ a specific test to identify a drug substance to the exclusion of all other known chemical
substances.
-Typically infrared spectrophotometry or gas chromatography-mass spectrometry is used to specifically identify a drug
substance.

Qualitative vs. Quantitative

-Another consideration in selecting an analytical technique is the need for either a qualitative or a quantitative
determination.
-The former relates just to the identity of the material, whereas the latter requires the determination of the per cent
composition of the components of a mixture.

The Screening Step

-A screening test is normally employed to provide the analyst with quick insight into the likelihood that a specimen
contains a drug substance.
-Positive results arising from a screening test are considered to be tentative at best and must be verified with a
confirmation test.
-The most widely used screening tests are thin-layer chromatography, gas chromatography, and immunoassay.

The Confirmation Step

-Gas chromatography/mass spectrometry is generally accepted as the confirmation test of choice. -The GC separates
the sample into its components, while the MS represents a unique “fingerprint” pattern that can be used for
identification.
-Once the drug is extracted and identified, the toxicologist may be required to provide an opinion on the drug’s effect on
an individual’s natural performance or physical state.

Nondrug Poisons
-Heavy metals such as arsenic, bismuth, antimony, mercury, and thallium are only occasionally encountered because
severe environmental protection regulations restrict their availability to the general public.
-Carbon monoxide is one of the most common poisons encountered in a forensic laboratory. -To measure the
concentration of carbon monoxide in the blood spectrophotometric methods determine the amount of
carboxyhemoglobin relative to oxyhemoglobin or total hemoglobin; or a volume of blood can be treated with a reagent
to liberate the carbon monoxide, which is then measured by gas chromatography.

Significance of Findings
-Once a drug is found and identified, the toxicologist determines its influence on the behaviour of the individual. -For
many drugs, blood concentration levels are readily known and are used to estimate the pharmacological effects of the
drug on the individual.
-When dealing with a living person, the toxicologist has the added benefit of knowing what a police officer may have
observed about an individual’s behaviour and motor skills.