Drugs, Poisons and Forensic ToxicologyRead intro to ch.9 on Anna Nicole Smith’s Death

History of Toxicology

• Paracelsus (1493-1541)– Devised the dose-response

relationship between therapeutic and toxic levels of drugs

• Orfila (1787-1853)– Contributed to the development of

forensic toxicology and the study of poisoning in criminal actions

3 main categories of work for a forensic toxicologist

• identification of drugs such as heroin, cocaine, cannabis;

• detection of drugs and poisons in body fluids, tissues, and organs;

• measuring of alcohol in blood or urine samples

Toxic substances are classified by how people are exposed to them:

• Intentionally: as in drugs taken to treat an illness or relieve pain

• Accidentally: ingested/exposed, as in unintentional overdose due to harmful combinations of meds.

• Deliberately: as in suicide or exposure intended to harm or kill others

Anions• Anions are negatively charged ions• The most important of these is cyanide (CN-)• Cyanide blocks proteins in the mitochondria

affecting metabolism – lactic acid builds up causing lactic acidosis

• The brain's high metabolic rate accounts for its disproportionate vulnerability to cyanide.

• No matter how cyanide gets into your body, it works the same way. In addition to inhaling cyanide gas, it can be swallowed or absorbed through your skin.

• Symptoms– Rapid (fast) breathing. – Dizziness.– Weakness.– Headache.– Nausea and vomiting.– Rapid heartbeat.

Corrosive Poisons

• Cause destruction of body tissues upon contact

• Severity depends on concentration and length of contact time

• If ingested, corrodes digestive tissues and may perforate the gut

• Less commonly used as poisons since they are easy to detect

• Examples: HCl, HNO3, H2SO4 and KOH and NaOH

Gaseous and Volatile Poisons• These are substances that turn into the gas form easily at room temperature to produce toxic vapors

• Most common of these is carbon monoxide – generally formed from the burning of fossil fuels

• CO binds more strongly to hemoglobin than O2 does• Victims therefore asphyxiate• Deaths may be accidental (e.g. faulty gas furnaces or smoke

inhalation in fires) or intentional (e.g. suicides from gas exhaust)

• In accidental deaths, victims are unaware they are being poisoned since CO is colorless and odorless

• Victims become sleepy due to lack of O2 to the brain and lose consciousness

• When CO binds to hemoglobin, it turns it cherry red – so bright red skin is a sign of CO poisoning

Metalloid Poisons

• Metalloids (elements which are intermediates of metals and nonmetals in terms of malleability, ductility, conductivity and luster) include arsenic (As) and antimony (Sb)

• Interferes with cellular respiration• Once a popular poison because it could be

added to food and resulted in symptoms similar to dysentery and cholera – now is less common since traces remain in the hair, nails and bones well after death

• Napoleon was thought to be poisoned with arsenic by his British captors – later found to be baseless claims

• Accidental ingestion still happens since arsenic is found in weedkillers and insecticides

Metal Poisons

• Metals such as mercury (Hg), lead (Pb), lithium (Li) and thallium (Tl) are also toxic – some, like mercury, in fairly low doses

• They create symptoms similar to metalloid poisons

• Sometimes ingested without knowing it in low doses which may accumulate over time (e.g. mercury dumped into water bodies accumulates in fish which we eat)

Pesticides

• Pesticides are substances used to kill “pest” organisms (fungicides, herbicides, insecticides)

• How they act on humans varies because of their differing target organisms (e.g. a herbicide works differently than an insecticide) but may cause vomiting, paralysis and/or convulsions

• Many insect and mammalian poisons are particularly dangerous because they are not host specific and are designed specifically to kill a wide range of organisms

• Because of their widespread agricultural use as well as availability to consumers, accidental exposure by direct exposure to the pesticide is not uncommon

• Pesticides have also been used as poisons deliberately or as a means of suicide

Toxins

• Toxins are poisonous substances produced by an organism (plant, animal, fungus or microorganism)

• Natural toxins are a very diverse group both in terms of how they work and in their chemistry

• May be medicinal, toxic or even recreational

• One important group is the alkaloids (containing nitrogen bases)

A few alkaloid examples

• Atropine (deadly nightshade)

• Atropine blocks nerve cell transmission in the parasympathetic nervous system (the PSN slows the heartbeat and speeds up digestion)

• Symptoms, therefore, include increased heart rate, dilated pupils, and difficulty breathing

A few alkaloid examples• Strychnine (poison berry)• Strychnine prevents the proper operation of the

chemical that controls nerve signals to the muscles

• The chemical controlling nerve signals works like the body’s “off switch” for muscles

• When this “off switch” does not work correctly, muscles throughout the body have severe, painful spasms. Even though the person’s consciousness or thinking are not affected at first (except that the person is very excitable and in pain), eventually the muscles tire and the person can’t breathe.

• This is allegedly one of the most painful deaths imaginable as every muscle in your body contracts

Brown Recluse-venom causes death of soft tissue that may take months to heal and can leave large, deep scars

Brown recluse bite

Controlled Substances

• A drug is a natural or synthetic substance used to produce a psychological or physiological effect

• Today, approximately 23 million people in the US are illicit drug users

• More than 75% of the evidence evaluated by crime labs are drug related

Drug Dependence

• Drug dependence varies based on the nature of the drug, the route of administration, the dose, the frequency of use and the individual’s rate of metabolism

• Psychological needs arise from numerous personal & social factors that stem from the individual’s desire to create a sense of well-being & to escape from reality.

• Certain drugs, when taken in sufficient dose and frequency, are capable of producing physiological changes that encourage their continued use (withdrawal sickness: body chills, vomiting, stomach cramps, convulsions, insomnia, pain & hallucinations)

Categories of Drugs Based on Their Effects on the Central Nervous System

• Stimulants: stimulates brain activity (amphetamines, cocaine, methamphetamines)

• Depressants: Inhibits brain activity (Alcohol, barbiturates, heroin, GHB, Rohypnol, huffing)

• Hallucinogens: alterations in perception and mood without affecting brain activity (Ecstasy, LSD, PCP, cannabis)

• Narcotics: reduce pain by suppressing central nervous system (opiates, heroin, codeine, methadone, oxycodone)

Stimulants: Amphetamine

• AMPHETAMINES-synthetic drugs that stimulate nervous system- “uppers or speed”– once stimulant wears off,

depression may set in.

• Were once used in diet pills since it suppresses appetites – also increases heart rate, blood pressure and temperature

Cocaine• Derived from the coca plant

grown in the Andes mountains of South America and tropical Asia.

• Cocaine has had historical medical use as local painkiller or anesthetic

• Cocaine is a powerfully addictive stimulant drug. The powdered, hydrochloride salt form of cocaine can be snorted or dissolved in water and injected.

• Crack is freebase cocaine and is smoked; inhaling the vapor gets a larger dose of the drug to the bran in less than 15 sec.

Crack cocaine

• This form of cocaine comes in a rock crystal that can be heated and its vapors smoked. The term "crack" refers to the crackling sound heard when it is heated.

• The feeling of euphoria that crack provides fades quickly and leaves the user feeling anxious, depressed and pleasureless.

• Only a small percentage of crack abusers will ever be cured of this drug habit

• Cocaine-related deaths result of cardiac related seizures followed by respiratory arrest.

Methamphetamine

• Produces intense rush or flash followed by pleasure.

• Smokeable form of Meth is “Ice”• Repeated use of amphetamines leads to

strong psychological dependency • Methamphetamine is also produced in

clandestine drug labs (a big problem in the Pacific northwest)

• Chronic users exhibit violent destructive behavior and acute psychosis, similar to paranoid schizophrenia.

DEPRESSANTS- slow down the central nervous system

• ALCOHOL tends to inhibit the mental processes of judgment, memory, and concentration in low doses.

• In 2000, the federal government established 0.08% as the legal blood-alcohol limit. France, Germany, Ireland, Australia and Japan set 0.05%; Sweden is 0.02%.

• A person with 0.08% level is four times more likely to become involved in an car accident as a sober person; at 0.15% you are 25 times more likely.

Hallucinogens: Marijuana• MARIJUANA has been used legally and illegally for 3000 yrs-

references to it in medical and pharmacological uses. • Was used for

– painkiller,– mild sedative,– weakness,– malaria,– constipation,– gout, etc.

• 1964- scientists isolated chemical substance largely responsible for the hallucinogenic properties of marijuana – tetra hydro cannabinol (THC)

• THC content varies in parts of the plant- resin, flowers, leaves.• Marijuana has been authorized for use in medical profession

– Reduction of excessive eye pressure in glaucoma– Lessoning of nausea by anti-cancer drugs.– Muscle relaxer and to increase appetite

LSD & PCP• Lysergic acid diethylamide, a

synthesized form of lysergic acid– Substance derived from ergot

• Drug is very potent, as little as 25 micrograms is enough to start visual hallucination

• Physical dependence does not develop with continued use, but the user may be prone to flashbacks and psychotic reactions even after us is discontinued.

• PCP is often mixed with other drugs, LSD or amphetemines.

• It initially causes the user to feel stronger, invulnerable and detached from reality. Users soon become unresponsive, confused and agitated.

• Long-term daily use can cause severe depression, tendencies toward violence, and suicide.

Narcotics: Morphine/Heroin

• Morphine is extracted from opium (opiates)

• Has medicinal uses as a pain reliever (analgesic). Regular use leads to physical dependence.

• Most addicts prefer a derivative of morphine; heroin.• Heroin has high solubility rate in water- easy street

preparation for intravenous administration for injection.• Process is accelerated by heating in spoon, drawn into a

syringe or eyedropper for injection.

• CODEINE is also present in opium- prepared synthetically from morphine- used as cough suppressant.

• METHADONE- synthetic opiate- used for treatment of heroin addicts- similar drug but less side effects in withdrawal.

• OXYCONTIN-synthetic opiate-used as a painkiller. Doctors write close to 7 million prescriptions for oxycontin annually; it is estimated that close to ¼ million people abuse this drug.

Heroin• Once heroin is produced it

may reduced to powder form

• Heroin is highly soluble in water– This makes street

preparation for intravenous administration rather simple

• In the 1960’s and 70’s, the average bag of heroin sold contained 15-20% heroin. Currently the average purity is 35%.

Drug Identification• So far we have only looked at a small number of

drugs – there are many more, often mixtures of different drugs a forensic chemist may analyze

• These contain active drug ingredients of unknown origin and identity as well as additives- sugar, starch, quinine to dilute potency.

• Forensic chemist or toxicologist can expect any number of known and unknown substances submitted for analysis– this problem makes it difficult for running tests since

multiple tests may be necessary for unknown substance

• Two types of tests are performed; qualitative (presence/absence) and quantitative (amounts)

Drug Identification

• There are 2 general types of tests – qualitative and instrumental

• Qualitative tests such as presumptive, TLC and microcrystalline are fast, easy, relatively cheap, but are qualitative and may be influenced by other chemicals or drugs in the sample

• Instrumental tests are expensive, time consuming, but are more definitive and less influenced by contaminants

Presumptive (Color Tests)• COLOR TESTS many drug tests yield

characteristics of color when brought into contact with chemical reagents.

• Color tests are used as screening tests and not conclusive.

• Impurities may affect the test

2 Primary Color Test Reagents1. Marquis (2% formaldehyde in sulfuric

acid)– Reagent turns purple in the presence of

heroine and morphine and most opium derivatives

– Will become orange-brown when mixed with methamphetamine

Heroin Meth

2 Primary Color Test Reagents2) Scott Test (A:2% cobalt

thiocyanate dissolved in water and glycerin, B: concentrated hydrochloric acid; C: chloroform)

– A powder containing cocaine will turn solution A blue, addition of B will result in a clear pink color, then addition of C the blue color will reappear in the chloroform layer

Microcrystalline Tests

• MICROCRYSTALLINE TEST- drop of chemical reagent is added to small quantity of the drug

• A chemical reaction ensues producing crystals– measure size and shape of crystals– characteristic patterns for known

drugs.• This technique is considerably

more specific than color tests• Hundreds of crystalline tests have

been developed to identify the most commonly used drugs

Cocaine

Methamphetamine

Chromatography

• The techniques of thin layer and gas chromatography are especially well designed for drug analysis.– Since the chromatograph or retention

times must be compared the analysis must have some idea of what to compare the unknown too

– Thus chromatography is a good follow up for either color or microcrystalline tests

Bioterrorism Agents

• Ricin is lethal in humans in quantities as small as 500 micrograms-size of the head of a pin

• It can be inhaled as a powder, ingested in food/drink, or injected into the skin.

• Anthrax is caused by a bacteria that forms spores.

• It can be inhaled, ingested, or absorbed through the skin