TOXICOLOGY

I. What is Toxicology
 Study of poisons and toxic agents
 Four major disciplines in toxicology
o Mechanistic toxicology- elucidates cellular and biochemical effects of toxins
o Descriptive toxicology- uses results from animal experimentation to predict level of
exposure that will harm humans
o Forensic toxicology- concerned with medico-legal consequences of exposure to toxins
o Clinical toxicology- studies relationship between toxin exposure and disease state
 Any substance can cause potential harm if given at a certain dosage
o ED50- effective dose; dose that would be predicted to be effective or have the
therapeutic benefit in 50% of the population
o TD50- toxic dose; dose that would be predicted to produce a toxic response in 50% of
the population
o LD50- lethal dose; dose that would predict death in 50% of the population
 Routes of exposure to toxic agents
o Ingestion, inhalation, transdermal
 Toxicities are associated with suicide, accidental exposure, homicide or occupational exposure
 Acute toxicity is associated with single dose of which is sufficient to cause a toxic effect
 Chronic toxicity is associated with repeated exposure for extended period of time, usually at
doses that are insufficient to cause an acute response
 Toxidromes refers to a constellation of clinical signs and symptoms that suggests a specific
class of poisoning.
II. Toxic Agents
A. Alcohols
 Are common CNS depressants
 Cause disorientation, euphoria, confusion and may progress to unconsciousness,
paralysis and even death
o Ethanol (grain alcohol)
 Is the most common abused drug
 Causes diuresis by inhibiting ADH
 Readily absorbed in the GIT and diffuses easily in tissues
 o Methanol (wood alcohol)
 Is a commonly used solvent and a contaminant of home-made liquors
 It is converted first to formaldehyde, then finally to formic acid in the liver
by alcohol dehydrogenase
o Isopropanol (rubbing alcohol)
 It is rapidly absorbed by the GIT
 It is metabolized by hepatic alcohol dehydrogenase to acetone
o Ethylene glycol (1,2-ethanediol)
 It is a common constituent of hydraulic fluid and antifreeze
 Methods of analysis:
o Flame ionization gas chromatography
o Headspace gas chromatography
 Test for alcohol analysis
o Serum or plasma on blood ethanol levels
o Breath ethanol
o Oral fluid ethanol
o Urine ethanol

Stages of Acute Alcoholic Influence or Intoxication

BLOOD ALCOHOL (%w/v) SIGNS AND SYMPTOMS

0.01-0.05 No obvious impairment, some changes observable on performance
testing
0.03-0.12 Mild euphoria, decreased inhibitions, some impairment of motor skills
0.09-0.25 Decreased inhibitions, loss of critical judgment, memory impairment,
diminished reaction time
0.18-0.30 Mental confusion, dizziness, strongly impaired motor skills (staggering,
slurred speech)
0.27-0.40 Unable to stand or walk, vomiting, impaired consciousness
0.35-0.50 Coma and possible death
≥0.10 Presumptive evidence of driving under influence of alcohol

B. Cyanide
  Characteristic odor of bitter almonds
 Cyanide binds hemoglobin- causing hypoxia, flushing, headache, tachypnea,
dizziness and respiratory depression
 Methods for analysis
o Photometric analysis
o Headspace gas chromatography
C. Carbon Monoxide
 Colorless, odorless, tasteless gas
 Common sources include: car exhausts and cigarette
 Has up to 250 times greater affinity for hemoglobin compared to oxygen
 Produces cherry-red color of the blood
 Methods for analysis
o Gas chromatography
o Spot test for carbon monoxide exposure
o Differential spectrophotometry
D. Arsenic
 Odor of garlic
 Highly keratinophilic, carcinogenic
 Specimen toxicity analysis include: skin, hair or nails
E. Lead
 Analyzed through measurement of blood lead levels
 Can cause toxic effects in brain and can lead to anemia
F. Mercury
 From Greek word “hydrargyrias: which means water silver
 Metallic mercury is liquid at room temperature
 Toxicity: mercury can alter or denature proteins, can cause severe damage in
kidneys, lipophilic and can bind myelin- which is found in neurons
G. Organophosphates
 Found in pesticides and insecticides
 Toxicity is associated with decreased cholinesterase
 Can cause toxicity in the liver
 Pesticides contain organophosphates and carbamates which can inhibit the enzyme
acetylcholinesterase
III. Drugs of Abuse
A. Specimen for Drugs of abuse: urine is often used
B. Methods: Screening- immunoassays; confirmation- gas chromatography- mass spectrometry
C. Common drugs of abuse
a. Barbiturates- sedative hypnotics
 Ultra- short acting: thiopental, methohexital, thiamylal
 Short- acting and intermediate acting: pentobarbital, secobarbital, butalbital,
aprobarbital, amobarbital, butabarbital
 Long- acting: phenobarbital, methobarbital
b. Benzodiazepines- sedative hypnotics
 Short- acting: midazolam, estazolam, flurazepam, temazepam, triazolam
 Intermediate- acting: flunitrazepam
 Long- acting: diazepam, quazepam, alprazolam, chlordiazepoxide, clonazepam,
clorazepate, lorazepam, oxazepam
c. Cannabinoids
 Derived from the leaves of marijuana plant Cannabis sativa
 Cannabis is the most extensively abused drug in the world
 Delta-9-tetrahydrocannabinol is the major psychoactive component of marijuana
 Consumed by smoking the plant leaves, flower buds, and sometimes stems
 THC extracted from glandular hairs of Cannabis flower produced into a resin
known as hashish
 Psychotropic effects: euphoria, distorted perceptions, relaxation
d. Opiates
 Opioid refers to compound involving natural or semisynthetic opiates and fully-
synthetic opioids
 Medically used to relieve moderate to severe chronic pain
 Natural opiates include morphine and codeine
 Natural opiates are derived from the juice and seeds of poppy plant Papaver
somniferum
 Codeine is antitussive and analgesic. It is one of the most frequently prescribed
opiates in the world
 Semisynthetic opiates include: heroin, hydrocodone, hydromorphone, oxycodone,
and oxymorphone
  Fully synthetic opioids include: fentanyl, meperidine, methadone, propoxyphene,
and tramadol
e. Cocaine
 Alkaloid found in a plant, Erythroxylon coca
 Medically used as a local anesthesia; a vasoconstrictor in nasal surgery and to
dilate pupils in ophthalmology
 Available in two forms:
1. Powder- administered through nasal insufflation or snorting
2. Crack- rock crystal that is heated and smoked; term refers to crackling
sounds heard when it is heated
 Benzoylecgonine is the primary metabolite of cocaine
 CNS stimulant
f. Lysergic acid drugs
 Structurally similar to serotonin
 Synthesized from a naturally occurring ergot alkaloid found in the fungus
Claviceps purpurea which grows in wheat and other grains
 Psychedelic drug, hallucinogen
 Dosage forms include: tablet, gelatin, powder, capsule
g. Amphetamines
 Associated with sympathomimetic syndromes
 Stimulants and hallucinogen
 Include amphetamines and methamphetamines
 Designer amphetamines are derivatives of amphetamine
 Representative example is ecstasy (MDMA- methylenedioxymethamphetamine)