Chapter 38 Introduction To Chemotherapeutic Drugs Chapter 38 Introduction To Chemotherapeutic Drugs.
Chapter 7 Drugs
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Transcript of Chapter 7 Drugs
Chapter 7
Drugs“Having sniffed the dead man’s lips, I detected a
slightly sour smell, and I came to the conclusion that he had poison forced upon him.”
—Sherlock Holmes, in Sir Arthur Conan Doyle’s
A Study in Scarlet
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Drugs and Crime
A drug is a natural or synthetic substance designed to affect the subject psychologically or physiologically.
“Controlled substances” are drugs that are restricted by law
Controlled Substances Act is a law that was enacted in 1970; it lists illegal drugs, their category and their penalty for possession, sale or use.
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Controlled Substances Act
Schedule I—high potential for abuse; no currently acceptable medical use in the US; a lack of accepted safety for use under medical supervision
Schedule II—high potential for abuse; a currently accepted medical use with severe restrictions; abuse may lead to severe psychological or physical dependence
Schedule III—lower potential for abuse than the drugs in I or II; a currently accepted medical use in the US; abuse may lead to moderate physical dependence or high psychological dependence
Schedule IV—low potential for abuse relative to drugs in III; a currently accepted medical use in the US; abuse may lead to limited physical or psychological dependence relative to drugs in III
Schedule V—low potential for abuse relative to drugs in IV; currently accepted medical use in the US; abuse may lead to limited physical or psychological dependence relative to drugs in IV
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Examples of Controlled Substances and Their Schedule Placement
Schedule I—heroin (diacetylmorphine), LSD, marijuana, ecstasy (MDMA)
Schedule II—cocaine, morphine, amphetamines (including methamphetamines), PCP, Ritalin
Schedule III—intermediate acting barbiturates, anabolic steroids, ketamine
Schedule IV—other stimulants and depressants including Valium, Xanan, Librium, phenobarbital, Darvon
Schedule V—codeine found in low doses in cough medicines
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Human ComponentsUsed for Drug Analysis
Blood
Urine
Hair
Gastric Contents
Bile
Liver tissue
Brain tissue
Kidney tissue
Spleen tissue
Vitreous Humor of the Eye
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Identification of Drugs
PDR—Physicians’ Desk Reference
Field Tests—presumptive tests
Laboratory Tests—conclusive tests
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Physicians’ Desk Reference
PDR—a physicians’ desk reference is used to identify manufactured pills, tablets and capsules. It is updated each year. This can sometimes be a quick and easy identifier of the legally made drugs that may be found at a scene. The reference book gives a picture of the drug, whether it is a prescription, over the counter, or a controlled substance; as well as more detailed information about the drug.
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Drug IdentificationScreening or presumptive tests Spot or color tests Microcrystalline test—
a reagent is added that produces a crystalline precipitate which is unique for a certain drug.
Chromatography
Confirmatory tests Spectrophotometry
Ultraviolet (UV) Visible Infrared (IR)
Mass spectrometry
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Presumptive Color Tests
Marquis—turns purple in the presence of most opium derivatives and orange-brown with amphetamines
Dillie-Koppanyi—turns violet-blue in the presence of barbiturates
Duquenois-Levine—turns a purple color in the presence of marijuana
Van Urk—turns a blue-purple in the presence of LSD
Scott test—color test for cocaine, blue
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Chromatography
A technique for separating mixtures into their components
Includes two phases—a mobile one that flows past a stationary one.
The mixture interacts with the stationary phase and separates.
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Paper Chromatography
Stationary phase—paper Mobile phase—a liquid solvent
Capillary action moves the mobile phase through the stationary phase
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Spectroscopy
Spectroscopy—the interaction of electromagnetic radiation with matter.
Spectrophotometer—an instrument used to measure and record the absorption spectrum of a chemical substance.
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SpectrophotometryComponents
A radiation source A frequency selector A sample holder A detector to convert electromagnetic
radiation into an electrical signal A recorder to produce a record of the signal
Types Ultraviolet Visible Infrared
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Infrared Spectometry
Material absorbs energy in the near-IR region of the electromagnetic spectrum.
Compares the IR light beam before and after passing through a transparent sample.
Result—an absorption or transmittance spectrum Gives a unique view of the substance; like a fingerprint
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Mass Spectrometry
Gas chromatography has one major drawback, it does not give a specific identification. Mass spectrometry cannot separate mixtures. By combining the two (GCMS), constituents of mixtures can be specifically identified.
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Mass Spectrometry
In a mass spectrometer, an electron beam is directed at sample molecules in a vacuum chamber. The electrons break apart the sample molecules into many positive charged fragments. These are sorted and collected according to their mass-to-charge ratio by an oscillating electric or a magnetic field.
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Mass Spectra
Each molecular species has its own unique mass spectrum.
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IR Spectrophotometry andMass Spectrometry
Both work well in identifying pure substances.
Mixtures are difficult to identify in both techniques
Both are compared to a catalog of knowns
Chapter 8
Toxicology:Poisons and Alcohol
“All substances are poisons. There is none which is not. The right dose differentiates a poison and remedy.”
—Paracelsus (1495-1541). Swiss physician and chemist
—Jhn Trestrail from “Criminal Poisoning”
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Toxicology
Definition—the study of the adverse effects of chemicals or physical agents on living organisms.
Types:Environmental—air, water, soilConsumer—foods, cosmetics, drugsMedical, clinical, forensic
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Forensic Toxicology
Postmortem—medical examiner or coroner
Criminal—motor vehicle accidents (MVA) Workplace—drug testing Sports—human and animal Environment—industrial, catastrophic,
terrorism
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Toxicology
Toxic substances may: Be a cause of death Contribute to death Cause impairment Explain behavior
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The Severity of the Problem
“If all those buried in our cemeteries who were poisoned could raise their hands, we would probably be shocked by the numbers.”
—John Harris Trestrail, “Criminal Poisoning”
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Aspects of Toxicity
Dosage The chemical or physical form of the substance The mode of entry into the body Body weight and physiological conditions of the
victim, including age and sex The time period of exposure The presence of other chemicals in the body or
in the dose
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Lethal Dose
LD50—refers to the dose of a substance that kills half the test population, usually within four hours
Expressed in milligrams of substance per kilogram of body weight
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Toxicity Classes
LD50 (rat,oral) Correlation to Ingestion by 150 lb Adult Human
Toxicity
<1mg/kg a taste to a drop extremely
1-50 mg/kg to a teaspoon highly
50-500 mg/kg to an ounce moderately
500-5000 mg/kg to a pint slightly
5-15 g/kg to a quart practically non-toxic
Over 15g/kg more than 1 quart relatively harmless
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Federal Regulatory Agencies
Food and Drug Administration (FDA)
Environmental Protection Agency (EPA)
Consumer Product Safety CommissionDepartment of Transportation (DOT)
Occupational Safety and Health Administration (OSHA)
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Symptoms of Various Typesof Poisoning
Type of Poison Symptom/Evidence Caustic Poison (lye) Characteristic burns around the lips and
mouth of the victim Carbon Monoxide Red or pink patches on the chest and
thighs, unusually bright red lividity Sulfuric acid Black vomit Hydrochloric acid Greenish-brown vomit Nitric acid Yellow vomit Phosphorous Coffee brown vomit. Onion or garlic odor Cyanide Burnt almond odor Arsenic, Mercury Pronounced diarrhea Methyl (wood) or Nausea and vomiting, unconsciousness,
Isopropyl (rubbing) alcohol possibly blindness
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Critical Informationon Poisons
Form Common color Characteristic odor Solubility Taste Common sources Lethal dose Mechanism Possible methods of administration Time interval of onset of
symptoms.
Symptoms resulting from an acute exposure
Symptoms resulting from chronic exposure
Disease states mimicked by poisoning
Notes relating to the victim Specimens from victim Analytical detection methods Known toxic levels Notes pertinent to analysis of
poison List of cases in which poison was
used
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To Prove a Case
Prove a crime was committed Motive Intent Access to poison Access to victim Death was caused by poison Death was homicidal
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Forensic Autopsy
Look for: Irritated tissues
Characteristic odors
Mees lines—single transverse white bands on nails.
Order toxicological screens Postmortem concentrations should be done at the
scene for comparison
No realistic calculation of dose can be made from a single measurement
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Human Specimens for Analysis
Blood
Urine
Vitreous Humor of Eyes
Bile
Gastric contents
Liver tissue
Brain tissue
Kidney tissue
Hair/nails
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Alcohol—Ethyl Alcohol (C2H5OH)
Most abused drug in America About 40% of all traffic deaths are alcohol-related Toxic—affecting the central nervous system, especially
the brain Colorless liquid, generally diluted in water Acts as a depressant Alcohol appears in blood within minutes of consumption;
30-90 minutes for full absorption Detoxification—about 90% in the liver About 5% is excreted unchanged in breath, perspiration
and urine
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Rate of Absorption
Depends on:amount of alcohol consumed
the alcohol content of the beverage
time taken to consume it
quantity and type of food present in the stomach
physiology of the consumer
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BACBlood Alcohol Content
Expressed as percent weight per volume of blood
Legal limits in all states is 0.08% Parameters influencing BAC:
Body weight Alcoholic content Number of beverages consumed Time between consumption
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BAC
Burn off rate of 0.015% per hour but can vary:
MaleBAC male = 0.071 x (oz) x (% alcohol)
body weight Female
BAC female = 0.085 x (oz) x (% alcohol) body weight
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Henry’s Law The concentration of alcohol in breath is proportional to
that in the blood. This ratio of alcohol in the blood to the alcohol in the
lungs is approximately 2100 to 1. In other words 1 ml of blood will contain nearly the same amount of alcohol as 2100 ml of breath.
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Field Tests Preliminary tests—used to determine the degree of
suspect’s physical impairment and whether or not another test is justified.
Psychophysical tests—3 Basic Tests Horizontal gaze nystagmus (HGN): follow a pen or small
flashlight, tracking left to right with one’s eyes. In general, wavering at 45 degrees indicates 0.10 BAC.
Nine Step walk and turn (WAT): comprehend and execute two or more simple instructions at one time.
One-leg stand (OLS): maintain balance, comprehend and execute two or more simple instructions at one time.
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The Breathalyzer More practical in the field Collects and measures alcohol content of alveolar breath
Breath sample mixes with 3 ml of 0.025 % K2Cr2O7 in sulfuric
acid and water2K2Cr2O7 + 3C 2H5OH + 8H 2SO4 2Cr2(SO4)3 + 2K2SO4 + 3CH3COOH + 11 H2O
Potassium dichromate is yellow, as concentration decreases its light absorption diminishes so the breathalyzer indirectly measures alcohol concentration by measuring light absorption of potassium dichromate before and after the reaction with alcohol
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Generalizations During absorption, the concentration of alcohol in arterial
blood will be higher than in venous blood. Breath tests reflect alcohol concentration in the pulmonary
artery. The breathalyzer also can react with acetone (as found
with diabetics), acetaldehyde, methanol, isopropyl alcohol, and paraldehyde, but these are toxic and their presence means the person is in serious medical condition.
Breathalyzers now use an infrared light absorption device with a digital read-out. Prints out a card for a permanent record.