Forensic Pharmacology

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Forensic Pharmacology Page 7

by B Zedeck


  61

  the blood-brain barrier. Any benzoylecgonine in brain is from

  cocaine metabolism therein. The half-life of cocaine is about one

  hour, but the half-life of benzoylecgonine is about five to seven

  hours. Cocaine is excreted in urine for about 10 hours, while

  benzoylecgonine can be found in urine as soon as one hour after

  use and for about three days thereafter. Urine drug screens test

  for this metabolite. If benzoylecgonine is detected in urine, use

  of cocaine occurred within the past 72 hours. Cocaine has also

  been found in breast milk. It passes the placental barrier, and

  there is some evidence that it causes fetal abnormalities. When

  both cocaine and alcohol are used at the same time, the two are

  metabolically combined to form cocaethylene, a compound as

  active as cocaine but with a longer half-life. Even though alcohol

  may no longer be detected, finding cocaethylene suggests that the

  individual may have been under the influence of both substances

  at the same time.

  Methamphetamine

  Methamphetamine passes the blood-brain barrier better than

  amphetamine, and there is evidence that chronic use of meth-

  amphetamine can result in permanent damage to dopamine

  neurons. Both pass the placental barrier, and there is some

  evidence that abuse by a pregnant woman can result in fetal

  abnormalities. Methamphetamine is found in breast milk. The

  half-life of methamphetamine and amphetamine is about 10 to

  13 hours. Some methamphetamine is metabolized to amphet-

  amine, and amphetamine-glucuronide can be detected in urine

  for about two days. About 50% of methamphetamine is excreted

  unchanged in the urine over two to three days.

  Cathinone

  After chewing khat leaves, it can take up to two hours to achieve

  peak levels of cathinone. The half-life is about 4.5 hours.

  62 Forensic Pharmacology

  Cathinone is metabolized to norephedrine and norpseudo-

  ephedrine. Cathinone is found in breast milk. Babies of mothers

  who used khat have low birth weights. Methcathinone acts like

  methamphetamine, and effects last four to six hours.

  Most of the CNS stimulants induce similar psychological

  effects, including euphoria, an increased sense of strength and

  self-confidence, and sexual arousal. After the euphoric effect, a

  dysphoria follows, in which the individual feels restless, anxious,

  and depressed, and wants to repeat the experience. The drugs

  adversely affect judgment and decision making, and impair

  psychomotor functions. Physiologically, they increase heart rate,

  blood pressure, body temperature, and respiratory rate. The

  drugs also affect visual acuity by causing dilated pupils. High

  doses can lead to seizures, strokes, and cardiac arrhythmia. The

  latter can lead to sudden death. Prolonged use can result in per-

  sonality changes, psychosis, hallucinations, paranoia, fatigue,

  weight loss, tremors, and depression. Cocaine use creates the

  sensation that bugs are burrowing under the skin, and longtime

  users can damage their skin through scratching. Tolerance may

  develop more with amphetamines than with cocaine; with-

  drawal signs and symptoms include depression, lethargy, and

  anxiety and sleep disorders.

  FORENSIC ISSUES

  The presence of cocaine or benzoylecgonine in blood, urine,

  hair, or other tissues is indicative of cocaine usage. No other

  known substance can give rise to a false positive, and there are

  no legitimate excuses to account for a positive result. There are

  many reports of hospitalized infants and children with positive

  urine test results indicative of exposure to cocaine. The most

  likely route of exposure was secondhand smoke in homes where

  crack cocaine was used.

  Central Nervous System Stimulants

  63

  In murder cases, high blood levels of cocaine or metabolites

  have sometimes served to argue on the defendant’s behalf. If a

  murdered person was shown to have used cocaine, the defendant

  could argue that the killing was done in self-defense. If the defen-

  dant was the one who had used cocaine, the defense attorneys

  could argue that the defendant did not have the mental ability to

  form intent for murder.

  In one actual case, a man and his girlfriend had a fight, dur-

  ing which the girlfriend stabbed the man and he died. She was

  charged with murder. Toxicological analysis of bodily samples

  from the deceased revealed the presence of alcohol in both

  blood and brain at a concentration of 0.19%, and the presence of

  cocaine; benzoylecgonine, the metabolite of cocaine; and coca-

  ethylene, the metabolite of alcohol plus cocaine. At trial, in sup-

  port of an argument for self-defense, testimony emphasized the

  adverse effects of alcohol, cocaine, and cocaethylene on behavior

  and judgment. The woman was acquitted of murder.

  In another case involving alcohol and cocaine, the defendant

  shot three police officers and was charged with attempted mur-

  der. The defendant claims that he had no memory of the events.

  Urine analysis indicated the use of cocaine. Testimony at trial

  emphasized the adverse effects of cocaine on behavior and on the

  inability to form intent to kill. In this case, however, the man was

  found guilty and sentenced to 60 years to life.

  In actual cases involving random employee urine tests that

  were positive for cocaine metabolite, people have offered many

  different ways of explaining the test results. For example, one

  person proposed that cocaine was put in his medication capsules,

  another that cocaine was added to her drink at a party, another

  person claimed that she inhaled cocaine as secondhand smoke

  while looking for someone in a crack house, and a garbage col-

  lector claimed that garbage bags had ripped open and covered

  him with white powder. Other explanations offered in defense

  64 Forensic Pharmacology

  were that urine samples were mixed up at the collection center or

  there were other errors related to chain-of-custody, the sequence

  of steps from point of collection to the reporting of results. These

  arguments have almost never been successful, and the individu-

  als have had to resign from employment.

  A positive screening test result for amphetamines may be

  due to use of amphetamine or methamphetamine-containing

  prescription or over-the-counter drugs. For example, the drug

  Selegiline, which is used to treat Parkinson’s disease, is metabo-

  lized to amphetamine and methamphetamine. The nasal decon-

  gestant pseudoephedrine can cross-react in the test and result

  in a false positive. In the latter case, the confirmatory test is for

  amphetamine.

  Figure 6.4 Methamphetamine that is manufactured illegally is

  usually a crystalline solid known as crystal meth or crystal.

  Central Nervous System Stimulants

  65

  Vicks vapor inhaler, a decongestant, contains l-metham-

  phetamine, listed on the container as levmetamfetamine. Use of


  this product results in only l-amphetamine appearing in urine.

  If d-amphetamine is detected in urine, it could only have come

  from using d-methamphetamine or d-amphetamine-containing

  legal or illegal drugs.

  Many people prepare methamphetamine in their homes (Fig-

  ure 6.4), placing both themselves and their families in peril.

  Oregon has already passed legislation requiring a prescription for

  any cold and allergy medication containing pseudoephedrine,

  the chemical used to make methamphetamine. Congress has

  passed a law requiring that pseudoephedrine-containing prod-

  ucts be sold only from behind the pharmacy counter.

  SUMMARY

  Drugs that stimulate the CNS cause euphoria and an increased

  sense of self-confidence, strength, and sexual arousal.

  Physiological responses include an increase in heart rate, blood

  pressure, temperature, and respiratory rate. The drugs act pre-

  dominantly by increasing the synaptic levels of dopamine and

  norepinephrine. This class of drugs induces predominantly

  psychological dependence rather than physical dependence.

  Withdrawal signs and symptoms consist of dysphoria and

  restlessness.

  7

  Central

  Nervous System

  Depressants

  Central nervous system (CNS) depressants include alcohol,

  barbiturates, benzodiazepines, gamma-hydroxybutyrate (GHB),

  chloral hydrate, glutethimide, and methaqualone.

  THE HISTORY OF DEPRESSANTS

  There is evidence that the Greeks, Egyptians, Hebrews, Japanese,

  Chinese, and Russians made alcoholic beverages thousands of

  years ago. Alcohol (ethanol, ethyl alcohol, and grain alcohol) is

  produced by yeast fermentation of sugar in fruits and grains to

  make wine, beer, or a variety of alcoholic spirits, including gin,

  vodka, and scotch.

  The German chemist Adolph Von Bayer prepared barbitu-

  rates in the 1860s. The first barbiturate, barbital (Veronal), was

  marketed in 1903, and phenobarbital (Figure 7.1) was introduced

  in 1912. Barbiturates used to be common drugs of abuse in the

  1950s and 1960s, but because of their dependence-inducing

  properties and association with suicides and accidental deaths,

  their use has been reduced significantly.

  66

  Central Nervous System Depressants

  67

  Figure 7.1 Phenobarbital is a barbiturate with the chemical formula

  C12H12N2O3.

  In the 1930s, Dr. Leo Sternbach discovered benzodiazepines,

  and in 1954, he developed Librium, the first “tranquilizer,” an

  ambiguous term that is no longer used. Though many people

  suffered serious side effects and developed drug dependence to

  benzodiazepines, these problems were not openly acknowledged

  until the late 1970s. Benzodiazepines are still the most commonly

  prescribed mood altering drugs, seen as alternatives to barbitu-

  rates to treat anxiety, muscle tension, and sleep disorders.

  Dr. Henri Laborit synthesized gamma-hydroxybutyrate

  (GHB) in France in 1960 for use as an anesthetic, based on

  its chemical similarity to gamma-aminobutyric acid (GABA).

  Since it does not block out pain, use of GHB did not become

  widespread. It was discovered in the late 1970s that GHB could

  stimulate the release of growth hormone, and, although contro-

  versial, body builders and weight lifters began using it with the

  goal of reducing fat and increasing muscle mass.

  68 Forensic Pharmacology

  PHARMACOLOGY OF CNS DEPRESSANTS

  CNS depressants inhibit nerve activity, leading to decreased

  anxiety, sedation, uncoordinated movements, and, if the dose

  is high enough, unconsciousness and even death. Sometimes,

  however, the inhibition of nerve activity occurs in a pathway

  that normally inhibits our actions, causing the opposite effect

  of disinhibition, in which intoxicated people say and do things

  they normally would not.

  Alcohol

  Alcohol, taken orally, is absorbed in the stomach but mostly

  from the small intestine into the bloodstream. It first reaches the

  liver, where some alcohol is immediately metabolized (first-pass

  metabolism) by the enzyme alcohol dehydrogenase. Alcohol is a

  water-soluble chemical and distributes throughout body fluids

  but not readily into body fat. Females, who naturally have more

  lipid (fat) tissue per pound of mass, will have a higher BAC than

  males after consuming the same amount of alcohol.

  There are 9.6 grams of alcohol in 1 ounce (30ml) of 80-proof

  (40% alcohol) hard liquor, 13.4 grams of alcohol in one 12-ounce

  can of beer (average alcohol content of 4.67%), and 11.4 grams

  of alcohol in a 4-ounce glass of wine (average alcohol content of

  12%). A 150-pound male who consumes one can of beer over a

  short time period will have a BAC of approximately 0.029%. A

  150-pound female who consumes one can of beer over the same

  time period will have a BAC of approximately 0.036%.

  Though the rates of metabolism and excretion of many drugs

  are measured in terms of half-lives, the elimination of alcohol

  primarily by liver enzymes occurs as a constant amount per time

  regardless of its concentration. On average, the BAC decreases

  0.015% per hour. Thus, it would take about five hours before

  someone’s BAC reached zero if he or she consumed enough

  alcohol to have reached a BAC of 0.075%. Also, if one consumed

  Central Nervous System Depressants

  69

  only one drink per hour, it would require many hours before

  a significant BAC would accumulate. Since alcohol is volatile,

  some is excreted via the breath with each exhalation. This is the

  basis for the breath test (see Chapter 3). Alcohol is also excreted

  in urine, saliva, and sweat.

  There is a relationship between BAC and alcohol’s effects.

  Basically, a BAC of up to 0.05% results in little impairment, but

  with a BAC between 0.05% and 0.10%, some impairment of cog-

  nitive functions, such as attention span, information processing,

  and judgment, is seen. The individual begins to feel euphoric,

  talkative, show increased confidence, and exhibit a loss of inhi-

  bitions. There is a loss of fine motor coordination. Alcohol also

  inhibits the release of antidiuretic hormone from the pituitary

  gland. This causes diuresis, and explains the necessity of hav-

  ing to urinate after consuming alcoholic beverages. A BAC over

  0.10% usually causes ataxia (unsteady balance), slurred speech,

  impaired memory, comprehension, and perception, and vomit-

  ing. Alcohol-induced blackouts, that is, a total amnesia of events

  that can never be recalled, usually occur at a BAC of around

  0.28%. As alcohol is metabolized and eliminated, the individual

  returns to a normal state. Large enough doses can produce stu-

  por, coma, and death.

  Alcohol is toxic to the liver, and prolonged use results in cir-

  rhosis, a condition in which scar tissue replaces normal liver

  tissue, and impairs the ability of the liver to function. Chronic

  use can also result
in permanent damage to the CNS, partly due

  to a poor diet regimen and diminished intake of vitamin B1

  (thiamine).

  Barbiturates

  Barbiturates are used as sedatives, hypnotics, anesthetics, and

  anticonvulsants. They differ in how fast they produce effects

  and how long the effects last. Barbiturates are classified as

  70 Forensic Pharmacology

  ultrashort, short, intermediate, and long acting, and are in

  Schedules II, III, or IV.

  Street names of commonly abused barbiturates describe the

  color and markings on the actual pill. Amytal® (amobarbital):

  blue heavens; Butisol® (butabarbital): bute, stoppers; Lumi-

  nal® (phenobarbital): phennies and phenos; Nembutal® (pento-

  barbital): nembies and yellow jackets; Seconal® (secobarbital):

  red devils and seggies; Tuinal® (amobarbital and secobarbital):

  Christmas trees, rainbows, tooies. Other street names include

  amy’s, block busters, bluebirds, downers, goofballs, pinks, and

  stumblers.

  The Derivation of Proof

  The term proof used for alcoholic beverages dates back to

  colonial days in the United States. President George Washing-

  ton appointed Alexander Hamilton as his first secretary of the

  treasury. Hamilton levied a 10-cents/gal on tax on whiskey.

  The citizens of Pennsylvania—a chief source of whiskey—

  rebel ed, but their famous “Whiskey Rebel ion” was sup-

  pressed. To determine the content of alcohol in the whiskey,

  gunpowder was moistened with the alcohol-containing prod-

  uct and then ignited. If the alcohol content was high enough,

  the product burnt, and this was considered 100 proof. At least

  50% alcohol was required for the gunpowder to burn. The gov-

  ernment said that 100 proof, or 50% alcohol by volume, was to

  be the standard for American liquor. Yet, the 10-cents/gal on

  tax was placed on all whiskey, even if below proof. Today, the

  proof number is always twice the percentage number of the

  concentration of alcohol in the product.

  Central Nervous System Depressants

  71

  Barbiturates are usually taken orally, sometimes with alco-

  hol to increase the intoxicating effect, or by injection. The

  ultrashort-acting barbiturate Pentothal® produces surgical

  anesthesia within about one minute after intravenous admin-

  istration. The onset of action of the short- and intermediate-

  acting barbiturates taken orally for insomnia is from 10 to 60

 

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