Forensic Pharmacology

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Forensic Pharmacology Page 8

by B Zedeck


  minutes, and the effects last up to six hours. Barbiturates dis-

  tribute to body fat and are found in breast milk. They may cause

  drowsiness, slow heartbeat, and shortness of breath in babies of

  nursing mothers who are taking these drugs.

  Barbiturates are metabolized in the liver via hydroxylation and

  glucuronide conjugation. Short-acting barbiturates are excreted

  in the urine as metabolites for about one to four days, while long-

  acting barbiturates are excreted for two to three weeks.

  Barbiturates overdosing may occur readily. Since tolerance

  develops to the behavioral effects but not to the respiratory

  effects, increasing the dosage may result in death. Also, because

  of amnesia-causing effects, people forget that they took their

  medication and may proceed to take additional doses, which may

  lead to respiratory depression and death.

  Benzodiazepines

  Trade names of some benzodiazepines are Ativan® (lorazepam),

  Dalmane® (flurazepam), Halcion® (triazolam), Klonopin®

  (clonazepam), Librium® (chlordiazepoxide), Restoril® (temaze-

  pam), Serax® (oxazepam), Valium® (diazepam), Versed®

  (midazolam), and Xanax® (alprazolam). Some street names

  include benzos, downers, and goofballs. The “date rape drug”

  Rohypnol® (flunitrazepam) has its own group of names, includ-

  ing forget-me pill, Mexican valium, mind erasers, R2, roches,

  roofies, rope, and rophies (Figure 7.2). Except for Rohypnol®,

  which cannot be sold in the United States, the benzodiazepines

  are listed as Schedule IV drugs.

  72 Forensic Pharmacology

  Figure 7.2 Photographed above is a box of Rohypnol tranquillizer

  pills, powerful sedatives normally prescribed as sleeping pills for

  insomniacs, which have unfortunately gained notoriety as a “date

  rape” drug. Rohypnol causes sleepiness and memory loss when

  dissolved in an alcoholic drink; therefore, a blue dye has been added

  to the pills to prevent this from occurring unnoticed.

  Benzodiazepines are grouped into categories depending on

  how fast they take effect and how long the effects last. The short-

  acting benzodiazepines flurazepam, temazepam, and triazolam

  are used to manage insomnia, and the long-acting alprazolam,

  chlordiazepoxide, diazepam, lorazepam, and clonazepam are

  used for the treatment of generalized anxiety.

  Benzodiazepines are lipid soluble and are found in breast

  milk. They are metabolized in the liver and excreted as glucuro-

  nide metabolites at different rates. For example, the half-life of

  triazolam is 2 to 5 hours, while that of diazepam varies between

  Central Nervous System Depressants

  73

  20 and 100 hours, and that of an active metabolite of diazepam

  (desmethyldiazepam), between 36 and 200 hours. This means

  that diazepam metabolites may be in the bloodstream up to

  200 hours after a single dose. Many of the benzodiazepines are

  converted to the same active metabolite. For example, diaz-

  epam, temazepam, and chlordiazepoxide are all metabolized to

  oxazepam.

  Gamma-hydroxybutyrate

  GHB, a Schedule I drug, is synthesized by mixing gamma buty-

  rolactone (GBL; street names: blue nitro, fire water, gamma G)

  and sodium hydroxide. GBL is a solvent in many commercial

  products and is not listed as illegal. If ingested, GBL is rapidly

  converted in the body to GHB. Another solvent, 1,4 butanediol

  (BD) (street names: Sucol B, zen), is metabolized in the body to

  GHB. GHB is a natural metabolite of GABA.

  GHB is used to treat cataplexy, a sudden onset of muscle weak-

  ness, in narcolepsy patients. It has been used as a hypnotic, anes-

  thetic, and aphrodisiac, and is used to treat alcohol withdrawal.

  Some street names include cherry meth, eclipse, EZ lay, fantasy,

  G, Georgia home boy, great hormones at bedtime, grievous

  bodily harm, liquid ecstasy, nature’s Quaalude, and poor man’s

  heroin (Figure 7.3). According to a 2004 NIDA survey, 0.7% of

  eighth graders, 0.8% of tenth graders, and 2.0% of twelfth grad-

  ers used GHB at least once during the preceding year. In 2002,

  there were 3,330 emergency room admissions related to GHB,

  second only among club drugs to the hallucinogen methylene-

  dioxymethamphetamine (MDMA).13

  GHB used orally is rapidly absorbed, and peak effects occur

  in 20 to 40 minutes. The effects last for about three hours. The

  half-life is approximately 20 minutes. About 5% of the dose is

  eliminated in urine, mostly in the first four hours. Since GHB

  is odorless and tasteless, it can be added to someone’s drink

  74 Forensic Pharmacology

  without detection. It causes a rapid induction of deep sleep and

  amnesia, and is used as a date rape drug. GHB is a common

  drug at rave parties.

  Barbiturates, benzodiazepines, and GHB affect the activity

  of the neurotransmitter GABA, resulting in more chloride ions

  entering the neuron and making it more resistant to excitation.

  As a consequence, the output of excitatory neurotransmitters,

  including norepinephrine (noradrenaline), serotonin, and dopa-

  mine, is reduced.

  Figure 7.3 Gamma-hydroxybutyrate (GHB) is manufactured in illicit

  home laboratories. The chemicals above were confiscated from a GHB

  lab in Germany.

  Central Nervous System Depressants

  75

  Other CNS Depressants

  Chloral hydrate, glutethimide, and methaqualone also produce

  a depressant effect. Chloral hydrate is dangerous to use as an

  anesthetic, but it has been used to treat persons undergoing

  withdrawal from heroin, GHB, and alcohol. A mixture of chlo-

  ral hydrate and alcohol is termed a “Mickey Finn” and has been

  used as a date rape drug.

  Glutethimide (Doriden®) was introduced in 1954 as a substi-

  tute for barbiturates. Its street names include CB, glue, and goof-

  balls. The combination of glutethimide and codeine is called

  “doors and 4s” and “pancakes and syrup.” The combined eupho-

  ria resembles that of heroin, and effects can last for about eight

  hours.

  Methaqualone was marketed by William H. Rorer, Inc., under

  the trade name of Quaalude, and later by the Lemmon Company

  as Lemmon “714” tablets. Street names include bandits, drunken

  monkey, ludes, magwheels, quay, 714, sopors, and wagon wheels.

  Methaqualone was used during the 1960s and 1970s on many

  college campuses, and there were many reports of overdoses and

  deaths. The use of methaqualone has diminished greatly since

  the late 1980s.

  Though some differences between CNS depressant drugs do

  exist, as a group the effects induced are very similar. They cause

  a state of intoxication, with signs and symptoms of euphoria,

  mental confusion, loss of motor coordination, blurred vision,

  slurred speech, nausea, vomiting, impaired judgment, decreased

  attention span, and amnesia. The drugs also decrease blood pres-

  sure, heart rate, and respiration.

  Tolerance and psychological and physical depe
ndence do

  develop. Withdrawal effects from CNS depressants include anxi-

  ety, tremors, sweating, sleep disturbances, nausea, vomiting,

  and headache. Hallucinations and seizures are possible. Dosage

  must be reduced gradually. A condition specific to the effects of

  76 Forensic Pharmacology

  alcohol is delirium tremens. This may begin as late as 14 days

  after cessation of alcohol consumption. The signs and symptoms

  include confusion, delusions, fever, sweating, increased blood

  pressure, and seizures. Withdrawal effects can be treated symp-

  tomatically with benzodiazepines, antiseizure medication, and

  nutritional supplements.

  All of the CNS depressants can pass through the placenta.

  Newborn babies with dependent mothers may be physically

  dependent themselves and have withdrawal symptoms that

  include tremors, irritability, hyperactivity, and feeding and

  breathing problems. There may be birth defects such as fetal

  alcohol syndrome, which consists of abnormal facial features, a

  small head, mental retardation, and poor coordination.

  Combined use of any of the drugs in this category increases

  the risk of death. While a single drug may not depress respiration

  markedly, a combination of drugs can do so. The antidote for

  benzodiazepine overdose is an intravenous injection of Romazi-

  con® (flumazenil).

  FORENSIC ISSUES

  In the 1970s, Marcelline Burns and Herbert Moskowitz set out

  to standardize field sobriety tests. They selected 10 psychophysi-

  cal tests in use at that time and, along with the Los Angeles

  police and sheriffs departments and the California Highway

  Patrol, tested each for accuracy in predicting whether a person

  had a BAC of 0.10% or higher. Of the 10 different tests, the one-

  leg stand, the walk-and-turn test, and the horizontal gaze nys-

  tagmus test proved to be of value in detecting lack of sobriety.

  These three tests, under the sponsorship of the National High-

  way Traffic Safety Administration (NHTSA), were further devel-

  oped under experimental conditions and under field conditions.

  It was found that if one failed the one-leg-stand test, the officer

  Central Nervous System Depressants

  77

  would be correct 65% of the time in stating that the person’s

  BAC was above 0.10%; if the walk-and-turn test was failed, the

  officer would be accurate 68% of the time; and if the horizontal

  gaze nystagmus test was failed, accuracy would be 77%. If both

  horizontal gaze nystagmus and the walk-and-turn tests were

  failed, accuracy increased to 81%.14 All states have established a

  BAC of 0.08% as the cutoff value for determining driving while

  intoxicated, or DWI.

  Examples of actual cases involving alcohol include DWI,

  motor vehicle accidents (involving alcohol in either pedestrian

  or driver), rape, personal injury (tripping or falling), burglary,

  theft, assault, and attempted murder. In many cases, it was nec-

  essary to calculate the BAC at the time of the accident or other

  event that had occurred hours before the breath or blood sample

  was taken (a process known as “back extrapolation”).

  In one particular case, a young man attacked a public figure

  with a knife. He was immediately apprehended and charged with

  attempted murder. At trial, testimony revealed that during the

  previous 24 hours, the man had consumed enormous amounts

  of alcohol and had used marijuana. The defense argued that this

  amount of alcohol plus marijuana had impaired the defendant’s

  judgment and perception, and that he could not have been able

  to form the intent to kill. Testimony involved the pharmacology

  of both drugs, calculation of the BAC at about 0.40%, and the

  effect of both drugs on the defendant’s mental capabilities. The

  jury returned a verdict of guilty of assault and weapons posses-

  sion, but not attempted murder. The man was sentenced to 5 to

  15 years.

  In some states, lawsuits known as “dram shop” cases arise

  when someone injured by a driver under the influence of alco-

  hol sues the bar or restaurant that had earlier served alcohol to

  the driver while the latter was visibly intoxicated. Testimony in

  those cases focused on the number and type of drinks served, the

  78 Forensic Pharmacology

  interval of drinking, when the last drink was served, the time of

  the accident, and the rate of alcohol metabolism.

  The barbiturate butalbital is sold in combination with aspi-

  rin or acetaminophen (Fiorinal® or Fioricet®, respectively) for

  treatment of migraine and chronic tension headaches. When

  providing a urine sample, consumption of either of these drugs

  must be mentioned.

  The benzodiazepine Rohypnol® has a rapid onset of action

  and has been used as a date rape drug. The victim will have no

  memory of any events that occurred while under the influence

  of the drug. The effects begin in about 20 to 30 minutes and peak

  in about two hours.

  GHB can be formed from GABA and is found naturally in

  human tissues. In non-GHB users, however, GHB is usually not

  detected in blood or urine samples. Also, since GHB appears to

  form in blood postmortem, a finding of GHB is not indicative

  of use unless there is evidence of oral intake. Because of its short

  half-life, GHB is not found in blood 8 hours after use or in urine

  after 24 hours. However, lack of GHB after these intervals is not

  indicative that GHB was not used in an alleged rape. There are

  many reports of GHB being involved in overdoses, motor vehicle

  accidents, and deaths.

  SUMMARY

  CNS depressants are drugs that decrease brain activity, result-

  ing in both behavioral and physiological changes. The effects

  of alcohol on coordination, speech, and cognitive functions are

  familiar to most people. The effects of barbiturates are similar

  to alcohol. In low doses, barbiturates act as sedatives: increased

  doses have a hypnotic or sleep-inducing effect; and still larger

  doses have anticonvulsant and anesthetic activity, and can lead

  to respiratory depression, coma, and death. Barbiturate addicts

  Central Nervous System Depressants

  79

  must be withdrawn from the drug gradually to avoid severe with-

  drawal symptoms such as convulsions. The benzodiazepines,

  introduced as alternatives to barbiturates to manage insomnia

  and anxiety, can also induce amnesia and have been used as date

  rape drugs. GHB, which causes an alcohol-like effect and amne-

  sia, is found at rave parties and has been used as a date rape drug.

  Tolerance and psychological and physical dependence develop

  to CNS depressants.

  8

  Opioids

  There are many different opioids, and this chapter will focus

  on a few that are most commonly abused. Opium is the milky

  latex that seeps out of cuts made into the unripe seed capsule

  of the poppy plant, Papaver somniferum (Figure 8.1). Opium

  contains two pharmacologic groups of chemicals: the phen-


  anthrenes, which includes morphine, codeine, and theba-

  ine; and the benzylisoquinolines, which includes papaverine

  and noscapine. The poppy plant grows in Burma, Thailand,

  Cambodia, Laos, India, Pakistan, Afghanistan, Turkey, Mexico,

  Brazil, and Colombia.

  The effects of opium have been known as far back as 3,000

  b.c. In 1803, the German pharmacist Frederick Sertürner iso-

  lated morphine from the poppy plant. He named the drug

  morphine after Morpheus, the Greek god of dreams, and, in

  1832, codeine was isolated. Heroin was synthesized in 1874.

  Many years ago, these drugs were termed narcotics, because

  of their ability to produce sleep. Today, the word narcotic is

  sometimes used incorrectly to denote all drugs of abuse. The

  natural opium-derived drugs are more correctly termed opi-

  ates, and together with other natural (opioid-like endorphin

  80

  Opioids

  81

  Figure 8.1 Opium is collected by slitting the seed capsule of an

  unripe opium poppy. A milky substance containing opium oozes out

  and soon hardens. The hardened substance is then scraped off and

  purified.

  82 Forensic Pharmacology

  peptides present in brain tissue) and synthetic drugs that have

  morphine-like activity, are called opioids. Opioids are used for

  their analgesic (pain relief), antidiarrheal, and antitussive, or

  cough suppressant, effects.

  There are many synthetic derivatives of morphine and codeine

  in use today medicinally, including hydrocodone (Hycodan®

  and Vicodin®), hydromorphone (Dilaudid®), and oxycodone

  (Percodan®, Percocet®, and OxyContin®, a controlled-release

  form with street names of hillbilly heroin and poor man’s

  heroin). Other compounds that have morphine-like activ-

  ity include meperidine (Demerol®), methadone (Dolophine®,

  synthesized in Germany during World War II because of a

  shortage of morphine), propoxyphene (Darvon®; street names

  include pink ladies and pumpkin seeds), and fentanyl (Dura-

  gesic®, also known as Apache, China white, goodfellas, mur-

  der 8, and Tango and Cash). A designer drug variation of

  fentanyl, called 3-methylfentanyl, is 6,000 times more potent

  than morphine. Dextromethorphan is an antitussive available

  over the counter in many products, including Coricidin HBP®,

 

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