Ch. 12 Toxicology

Pharmacokinetics of Alcohol

"drug-movement" •Alcohol appears in the blood within minutes after it has been taken by mouth and slowly increases in concentration while it is being absorbed from the stomach and the small intestine into the bloodstream. •When most of the alcohol has been absorbed, a maximum alcohol level is reached called the Cmax (concentration maximum) in the blood; and elimination through metabolism then dominates. • For an average human drinking on an empty to modestly full stomach, alcohol is absorbed entirely into the blood stream 30-90 minutes after the completion of drinking. When drinking on a full stomach the Cmax can be as long as 2-4 hours

Alcohol Elimination

Elimination of alcohol throughout the body is accomplished through oxidation and excretion. •Metabolism through Oxidation, takes place almost entirely in the liver. •Alcohol is excreted unchanged in the breath, urine, and perspiration. The elimination or "burn-off" rate of alcohol varies, but 0.015%/hr. is an average.

Drug Drug interactions

Metabolism -one drug can effect the rate of metabolism of another. Causes an increase in Cmax above the therapeutic level Example: Heroin and Fentanyl Drug protein equilibrium -Alcohol can act as a "chaser" by dislodging drugs in there protein bound state, thereby increasing Cmax of the drug. Antibiotics and Alcohol consumption end result is a lowering of the antibiotic concentration resulting in potential for resistant bacteria to develop

The Significance of Toxicological Findings

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 based on the drug concentration. For many drugs, blood concentration levels are readily determined and can be used to estimate the pharmacological effects of the drug on the individual • The concentration of a drug in urine is a poor indicator of how extensively an individual's behavior or state is influenced by the drug. • Before drawing conclusions about drug-induced behavior, the analyst must consider other factors including age, health, and tolerance. • Often, 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 behavior and motor skills.

Blood Alcohol Concentration (BAC)

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. Experimental evidence has verified that the amount of alcohol exhaled in the breath is in direct proportion to the blood concentration

Forensic toxicologists

responsible for detecting and identifying the presence of drugs and poisons in body fluids, tissues, and organs. not only work in crime laboratories and medical examiners' offices, but may also work in hospital laboratories and health facilities to identify a drug overdose or monitor the intake of drugs. A major branch of forensic toxicology deals with the measurement of alcohol in the body for matters that pertain to violations of criminal law.

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"- Dated material. HPLC-MS or GC-MS most widely used for analysis

Role of the Toxicologist

• Beyond the analysis of alcohol, the toxicologist is confronted with a maze of drugs and poisons. • The toxicologist is originally presented with body fluids and/or organs and is normally requested to examine them for the presence of drugs and poisons. • Without supportive evidence, such as the victim's symptoms, a postmortem pathological examination, or an examination of the victim's personal effects, the toxicologist is forced to use general screening procedures with the hope of narrowing thousands of possibilities to one. • In addition, the toxicologist is not dealing with drugs at the concentration levels found in powders and pills, having been dissipated and distributed throughout the body. • Furthermore, the body is an active chemistry laboratory as few substances enter and completely leave the body in the same chemical state.

Breath Testers

• Breath testers operate on the fact that at 34C, the ratio of alcohol in the blood to alcohol in alveolar breath is approximately 2,100 to 1. • Breath testers that operate on the principle of infrared light absorption are becoming increasingly popular within the law enforcement community. • Many types of breath testers are designed to analyze an individual's breath as it flows through a chamber in the breath tester and is exposed to infrared radiation. • It's the degree of the interaction of the infrared light with alcohol in the breath chamber that allows the instrument to measure a blood alcohol concentration in breath. • Some breath testing devices also use fuel cells.

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 centimeter per month, analyzing segments of hair for drug content may define the timeline for drug use. • The chronology of drug intake may be distorted by drugs penetrating the hair's surface as a result of environmental exposure, or drugs may enter the hair's surface through sweat.

The Drug Recognition Expert (DRE) Program

• 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. • To ensure that each subject has been tested in a routine fashion, each DRE must complete a standard Drug Influence Evaluation form. • The DRE program usually cannot determine which specific drug was ingested. • Hence, it is the production of reliable data from both the DRE and the forensic toxicologist that is required to prove drug intoxication

Testing Blood for Alcohol Content

• Gas chromatography offers the toxicologist the most widely used approach for determining alcohol levels in blood in forensic labs or hospital labs. • Once blood is removed from an individual, its preservation is best ensured when it is sealed in an airtight container after an anticoagulant and a preservative have been added and stored in a refrigerator.

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 characteristic fragment pattern that can be used for identification and or just the parent mass (molecular weight) of the compound. • Typically for a living person, it's the blood that is tested for drug content; however, urine drug testing for drugs is becoming common for job and employees in the work place.

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.

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. • Some of the consumed Alcohol is metabolized initially in the stomach by an enzyme called Alcohol dehydrogenase. • Blood, carrying alcohol, moves to the liver then 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. It's in the alveoli sacs that alcohol is in equilibrium with the blood. • In the alveoli sacs carbon dioxide and alcohol are exhaled during breathing.

Field Tests

• 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 Law

• The American Medical Association and the National Safety Council have been able to exert considerable influence in convincing the states to establish uniform and reasonable blood-alcohol standards. • Between 1939 and 1964 a person having a blood-alcohol level in excess of 0.15 percent w/v was to be considered under the influence, which was lowered to 0.10 percent by 1965. • In 1972 the impairment level was recommended to be lowered again to 0.08 percent w/v. • Starting in 2003, states adopted the 0.08 percent 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.

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 behavior. • Alcohol, or ethyl alcohol, is a colorless liquid normally diluted with water and consumed as a beverage. • Like any depressant, alcohol principally affects the central nervous system, particularly the brain.

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.