14.1: Forensic Pharmacology and Forensic Toxicology

• Clinical pharmacology – is concerned with the effects of drugs on humans.

• Forensic toxicologist – a scientist who works on cases where drugs are involved in death or injury.

  • Forensic toxicologist has several tasks that must be accomplished to reach conclusions about the role of a drug in causing death.

    • Determine the identity of all drugs and poisons present in the body.

    • Determine the quantities of all drugs and poisons present at the time of death.

    • Determine which metabolites (secondary products of drugs as they are acted on by the liver) of these drugs are present.

    • Determine what interactions (e.g., synergisms) may exist among the particular combination of drugs that are present.

    • Help determine the history and patterns of drug use by the person involved and the role that drug dependence or addiction may play.

    • Help determine the role that tolerance may play.

• Drugs –  a chemical or chemical mixture that is designed to have one or more physiological and/or psychological effects upon a person.

• Poison – a substance that has a toxic (life-threatening) effect on a person.

14.2: Pharmacokinetics

• Pharmacokinetics – concerned with how drugs move into and out of the body.

Four Processes of Pharmacokinetics

1. Absorption – These include oral, intramuscular, intravenous, rectal, topical, subcutaneous, and inhalation.

2. Distribution – Blood reaches every cell in the body and drugs are distributed via the bloodstream.

3. Metabolism – a process whereby a drug or other substance is chemically changed to a different but related substance, called a metabolite. It serves at least three purposes:

   1. It may deactivate the drug so that it has fewer or milder effects on the body.

   2. The metabolite may be more water soluble than the parent drug. This makes it easier to eliminate the drug through urination.

   3. It may convert the drug into a substance that can be used by the body’s cells for energy. This also aids in the elimination of the drug.

4. Elimination – through urine excretion; exhaled from lungs; by perspiration and respiration.

14.3: Drug Actions – Pharmacodynamics

• Pharmacodynamics – the study of how drugs act in the body.

• Agonist – a drug that binds to a receptor and causes it to exert its function on the cell.

• Antagonist –  drugs that may bind to a receptor but not cause it to exert the action of the cell to which the receptor is attached.

14.4: Dependence, Tolerance, and Synergism

Addiction and Withdrawal

• When a person becomes addicted to a drug, there will be a potent craving for it. The person’s whole life becomes a constant search for the money to buy the drug or for the drug itself.

• If there is a physical dependence on the drug then the person will undergo withdrawal syndrome.

  • Withdrawal Syndrome – a well-defined set of physical symptoms, including high temperature, physical discomfort, pain, etc.

• If the person is psychologically dependent on the drug, there will be no withdrawal syndrome but the subject will be quite uncomfortable and will demonstrate symptoms of deprivation of the drug.

Tolerance

• Chemical tolerance – a phenomenon whereby the body’s organ systems adapt to the drug.

• If the drug is stopped, it may take a long period for the body to recover. In some cases of extreme tolerance build-up, the sudden withdrawal of the drug can be fatal.

Synergism

• The drugs work together to magnify their effects or create effects that would not have occurred otherwise – called synergism.

• One of the most well-known synergisms in toxicology is that of alcohol and barbiturates.

  • Barbiturates are CNS depressants. They slow down many functions of the body and may induce drowsiness or sleep.

  • Alcohol is also a CNS depressant, but its mechanism of action is different from barbiturates.

• When alcohol and barbiturates are taken together, the depressant effects are greatly magnified over what they would be if the alcohol and drugs were taken separately. This combination is lethal.

• Synergism is easiest to detect if someone takes two drugs and has effects that would not be expected from either one of the drugs.

14.5: Identification of Drugs in the Body

1. Sampling

   1. The types of samples taken from the body for drug identification are dictated by the condition of the body and the most likely place for the drug to congregate.

   2. If the person is alive, then blood, urine, and, increasingly, hair is the preferred samples. If the person is dead then all of the above may be available.

   3. If the person took the drug and then died shortly thereafter, some of the undigested or partially digested drugs may remain in the stomach.

   4. It is usually good scientific practice to use urine samples to screen for the possible presence of a drug but to use blood for determination of the concentration of the drug and confirmation of its presence.

2. Extraction

   1. Liquid Phase Extraction

   2. Solid Phase Extraction

3. Screening

   1. A type of preliminary test for drugs in body fluids. They are designed to give a preliminary result that indicates that a drug may be present but they do not confirm the presence of a particular drug. Screening tests fall into two general categories:

   2. Chromatographic tests are usually thin-layer chromatography or gas chromatography.

   3. Immunoassay Techniques

      1. Enzyme Multiplied Immunoassay Test (EMIT)

      2. Radioimmunoassay (RIA)

4. Confirmation

   1. Once a screening test has been completed, any drugs that appear to be present must be confirmed with the use of mass spectrometry.

5. Cut Off Levels

   1. Every analytical technique has a detection limit. This is because every instrument creates some electronic noise that shows up in the chart or graph of the analysis.

   2. If the signal that indicates the presence of a drug is too weak, it will not be seen above the noise. To avoid the possibility that noise will be mistaken for a signal, each laboratory sets a cut-off level for each drug.

   3. If a drug is found at a level at or below this cut-off, the result will be reported as “drug not detected.”

14.6: Ethyl Alcohol

Two independent measuring systems:

1. Blood alcohol concentration (BAC)

2. Breath alcohol concentration (BrAC)

Pharmacokinetics of Alcohol

• Once alcohol is ingested, it is absorbed quite rapidly into the bloodstream.

• Several factors determine the rate at which alcohol is absorbed from the gastrointestinal tract into the blood:

  • Nature of drink

  • Rate and speed of drinking

  • Contents of the stomach at the time of drinking

• Once alcohol gets into the blood it circulates rapidly through the body, and it will be distributed to all parts of the body in approximate proportion to the water content of each part.

• Metabolism accounts for more than 90% of elimination. It takes place mainly in the liver, which has an enzyme, alcohol dehydrogenase that first converts ethyl alcohol to acetaldehyde and then to acetic acid.

  • Acetic Acid – is used by cells for energy and forms carbon dioxide and water.

• The amount of alcohol that gets into the breath from the alveoli is proportional to the amount of alcohol in the blood and is governed by Henry’s law.

  • Henry’s Law –  states that when a volatile substance, such as alcohol, is dissolved in a liquid, such as blood, and then that liquid is brought in contact with a closed air space, such as alveolar breath, the ratio of the concentration of alcohol in the blood and breath is a constant at a given temperature.

14.7: Measurement of Alcohol in the Body

• Blood– is the preferred medium for alcohol measurement because it provides the best surrogate for brain alcohol levels and because of this, most states have statutes that relate sanctions for drunk driving to blood alcohol levels.
  

• Breath Alcohol Testing – the most widely used method for alcohol testing in use today, especially given its near universal use in drunk-driving cases.

  • Preliminary Breath Testing – Most of the PBTs work by either chemical oxidation or by fuel cell technology. Those that work by chemical oxidation operate using similar principles to the Breathalyzer although potassium permanganate may be employed in place of potassium dichromate.

  • Evidentiary Breath Testing

    • Intoxilyzer uses infrared spectroscopy for the measurement of alcohol.

14.8: Field Sobriety Testing

• Drug Recognition Experts – specially trained police officers that can administer a battery of field sobriety tests to a driver.

A typical protocol calls for three tests.

1. Horizontal Gaze Nystagmus –  the subject is asked to follow with his or her eyes only, a pencil or other object as the officer moves it slowly back and forth across the subject’s field of vision.

2. The “walk and turn” whereby a person must walk in a straight line putting one foot directly in front of the other and then turn around and come back.

3. Close one’s eyes and touch one’s nose with the tip of a finger.

• Driving a car means that the subject is in the driver’s seat with the engine turned on and the car in motion on a road or other surface.

• Operating a car means that the subject is in the driver’s seat and the engine is turned on but the car can be in the park—it doesn’t have to be in motion.

• Drugged Driving – driving under the influence of drugs.

• Drunk Driving – driving under the influence of alcohol.