Forensic Biology Quiz 5 (13,9, and 16)

Drug Metabolism

The body's process of chemically transforming drugs to make them easier to eliminate

Most drugs are?

lipophilic (fat-loving) - they can stay in the body too long

The body converts fat to…

hydrophilic (water-loving) forms = easier to excrete in urine

Where does drug metabolism occur?

The liver (main detox organ)

Also occurs in:

Blood

Kidneys

Intestines

Lungs

Transformation of molecules happens with enzymes

Enzymes

• Biological catalysts

• In the Drug Metabolism Context:

  Molecular scissors that cut drugs apart

  Molecular glue that attaches things to drugs

• Esterases (break ester bonds)​

  Oxidases (add oxygen = increases attraction to water)​

  Transferases (transfer groups from one molecule to another)​

Phase 1 of Metabolism= Functionalization

• Makes small chemical changes to the drug

• Adds or exposes functional groups that like water! (-OH, -NH2, -COOH)

• Makes the drug slightly more water-soluble

• Key reaction- hydrolysis

• Many drugs have ester bonds

  Ester bond + Water + Enzyme → Two Metabolites

  Common: Cocaine, heroin, aspirin, local anesthetics

Phase 2 of Metabolism- Conjugation

• Attaches large, water-loving molecules to the drug for excretion

• Makes drug MUCH more water-soluble

• Common conjugation reactions:

  • Glucuronidation (adding glucuronic acid)

  • Sulfation (adding sulfate groups)

  • Acetylation (adding acetyl groups)

Cocaine and ester bonds

• 2 Ester bonds

• Creates different metabolites depending on which enzyme breaks which bond.

• Important: These metabolites are MORE water-soluble so they can be cleared.

Why this matters for forensic toxicology

Problem: Parent drugs often have SHORT half-lives

• Cocaine: ~60 minutes

• Heroin: ~3-5 minutes

• By the time someone gets tested, the drug might be gone!

Half-life: the time it takes a drugs concentration to be reduced by half

Solution: Look for metabolites instead!

• Metabolites last MUCH longer

• Benzoylecgonine (cocaine metabolite): detectable for 2-4 days

• Morphine (heroin metabolite): detectable for 2-3 days

Fat-soluble parent drugs will be stored in fat and leak into blood stream/converted into metabolites making the detection time of metabolites much longer

Inactive metabolites

No pharmacological effect (Just waste products)

Active metabolites

• Still have drug effects (sometimes stronger!)

• Can contribute to toxicity

• Clinical significance: Active metabolites can make intoxication worse or last longer

Drugs interact during metabolism

• Example: Cocaine + Alcohol

  Normally: Cocaine → Benzoylecgonine

  With alcohol present: Cocaine + Ethanol → Cocaethylene

• Cocaethylene:​

  MORE toxic than cocaine alone​

  Increases cardiac risk & Lasts longer in the body​

  Unique marker that BOTH substances were present​

  This is why polysubstance use is so dangerous!​

Specimen selection matters

Blood

• Reflects recent/current drug levels

  Shorter detection windows

  Urine

• Reflects drug use over longer period

  • High metabolite concentrations

  • Longer detection windows

  • Most common for drug screening

  Hair

• Reflects drug use over months

  • Good for historical use patterns

  • Not good for recent use

Example-Cocaine

• Cocaine in blood: 4-6 hours

  • Benzoylecgonine in urine: 2-4 days

  • Benzoylecgonine in hair: months

Forensic Toxicology

• Detecting and identifying drugs/poisons in body fluids, tissues, and organs to determine their influence on behavior

• Bachelor's degree in chemistry, pharmacology, or another scientific field. Some universities now offer master's degrees and doctoral degrees in forensic toxicology.

• Work in crime laboratories and medical examiners’ offices, hospital laboratories and health facilities

Toxicology of Alcohol

• Alcohol, or ethyl alcohol

• Alcohol is the most heavily abused legal drug

• Affects the central nervous system, particularly the brain.

• Blood alcohol concentration has been shown to be directly proportional to the concentration of alcohol in the brain.

Alcohol Absorption

• Alcohol appears in the blood within minutes and slowly increases in concentration while being absorbed from the stomach --> small intestine --> bloodstream.

• Alcohol becomes distributed in the watery parts of the body (about 2/3 of body volume)

• Fat, bones, and hair are low in water content = hold little alcohol

• Lab will explore these items a bit!

• The type of beverage affects absorption time.

• For example, beer is absorbed more slowly than 80 proof alcohol because of the carbohydrates in beer.

• Food also impact's absorption!

• For an average human drinking on an empty to modestly full stomach, alcohol is absorbed entirely into the bloodstream 30-90 minutes

• When drinking on a full stomach, the absorption time can be as long as 2-3 hours

Alcohol Distribution

• Postmortem, if blood is not available other watery portions of the body, e.g., brain, cerebrospinal fluid, or vitreous humor, can be used.

Alcohol Metabolism

• Reaction to metabolize alcohol is Oxidation (shifts electrons between molecules)

• Blood alcohol concentration is defined as percent weight per volume. Hence, 0.10% is equivalent to 0.10 grams of alcohol per 100 milliliters of blood.

• The elimination or “burn-off” rate of alcohol varies, but 0.015%/hour is the average.

• if your blood level of alcohol is 0.10%, it takes about 6.5 hours for you to come down to zero.

Alcohol Elimination

• About 5% of the alcohol is excreted in the breath, urine, and sweat.

• Humans have a closed circulatory system consisting of a heart, veins, capillaries, and arteries

• Arteries carry blood AWAY from the heart

• Veins carry it towards the heart

• Capillaries are tiny vessels that connect the two with the cells of the body. Exchange of molecules happens in the capillary beds

The Respiratory System

The trachea connects the nose and mouth to the bronchial tubes. The bronchial tubes divide into numerous branches that terminate in the alveoli sacs in the lungs.

Alcohol and the circulatory system

• Alcohol is absorbed from the stomach and small intestines into the bloodstream.

• Alcohol is carried to the liver for metabolism

• Blood, carrying alcohol, moves to the heart and is pumped to the lungs.

• The lungs bridge with the circulatory system.

• Exchange takes place between fresh air in the lung's alveoli sacs and spent air in the blood in the capillaries surrounding the sacs.

• If alcohol is present in the blood, it will also be exchanged.

BAC

• The amount of alcohol exhaled in the breath is in direct proportion to the blood concentration and is directly proportional to alcohol in the brain.

• The current legal measure of drunk driving in the United Stated is a blood-alcohol concentration of 0.08 percent, or 0.08 grams of alcohol per 100 milliliters of blood.

Breath Testers

• Breath testers operate on the fact that 1 milliliter of blood contains nearly the same amount of alcohol as 2,100 milliliters of alveolar breath.

• Designed to analyze breath as it flows through a chamber exposed to infrared radiation

Fuel Cell Detecting

• Converts energy from a chemical reaction into an electromagnetic current.

• Alcohol present in the sample will be converted to acetic acid and this reaction is measured

• The strength of the current flow between electrodes is proportional to the concentration of alcohol in the breath

Field Sobriety Testing

• Used to decide if a test for alcohol is justified.

• Walk and turn, and the one-leg stand are considered reliable and effective

• Horizontal Gaze Nystagmus (Ne-stagmus)- involuntary jerking of the eye as it moves from side to side.

• Subjects follow a pen light from side to side. The more intoxicated, the less the eye moves before jerking begins.

• Usually people are unaware it’s happening and cannot control it. (drugs can also cause this)

• A portable, handheld, roadside breath tester may be used to determine a preliminary breath-alcohol content.

• These testers use fuel-cell detectors and are not admissible in court proceedings as proof of intoxication.

Testing Blood for Alcohol Content

• Gas chromatography = most widely used approach for determining alcohol levels in blood

• Comparing the EtOH peak with a standard control

• Hospital or clinical labs normally measure alcohol content by looking at metabolites as a way to estimate time.

• These instruments measure the conversion of alcohol to acetaldehyde by alcohol dehydrogenase.

Collection and Preservation of Blood

• Postmortem, alcohol may be produced during decomposition, creating an elevated blood alcohol level.

• Collect from several places and compare- remember that alcohol spreads evenly through all watery places in the body.

• Alcohol attributed to drinking can be determined if all the samples are relatively the same in all places.

• Vitreous humor and urine do not experience post-mortem increases

Alcohol and Law

• All 50 states have established Per se Laws= any individual at a specified blood alcohol concentration (normally 0.08%) = intoxicated.

• At 0.08% a driver is four times more likely to become involved in an accident. At 0.15% the chances rise to 25 times.

Detecting Non-Drug Poisons

• Heavy metals such as arsenic, bismuth, antimony, mercury, and thallium:

• Dissolving the tissue in hydrochloric acid and dipping a copper strip in it will reveal a silvery dark coating if metals are present (Reinsch test)

• Carbon monoxide is another common poison encountered. Carbon monoxide prevents the normal transport of oxygen throughout the body.

• In a healthy, middle-aged individual, a carbon monoxide blood saturation greater than 50-60% is considered fatal.

• Using Mass Spec, the amounts of carbon monoxide to oxygen ratios can be measured on hemoglobin from a blood sample

The Drug Recognition Expert (DRE) Program

• During the 1970s, the Los Angeles Police Department developed clinical and psychophysical exam 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 to certify an officer as a drug recognition expert (DRE).

• The DRE program incorporates standardized methods for analyzing blood pressure, pulse, or pupil size, etc. to decide whether they have taken one or more drugs.

• Typically, a standardized form is utilized