Chapter 7 & 8 Drugs and Toxicology

1. Chapter 7 & 8Drugs and Toxicology “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

2. Define • Drug • Controlled Substance • Illicit Drug • Prescription Drug • Over the Counter Drug • Poison Kendall/Hunt Publishing Company

3. Drug • A natural or synthetic substance designed to affect humans or animals psychologically or physiologically. Kendall/Hunt Publishing Company

4. Controlled substance • Identified under the Federal Schedules of the Controlled Substances Act Kendall/Hunt Publishing Company

5. Illicit Drug • An illegal substance used for pleasure but not necessarily defined in the Federal Controlled Substance Act Kendall/Hunt Publishing Company

6. Prescription Drug • A doctor must prescribe a drug for a specific reason. • Misuse makes it an illicit drug. Kendall/Hunt Publishing Company

7. Over the Counter (OTC) • No restrictions on purchase • Misuse of these can and does occur • Pseudoephedrine misuse leads to curtailed access Kendall/Hunt Publishing Company

8. Poison • Almost anything can be a poison if used inappropriately • Poison Control Center frequent calls • Children’s Tylenol • Children’s Vitamins with iron Kendall/Hunt Publishing Company

9. Chapter 7 & 8Drugs and Toxicology “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

10. Drugs Students will learn: • How to apply deductive reasoning to a series of analytical data. • The limitations of presumptive (screening) tests. • The relationship between the electromagnetic spectrum and spectroscopic analysis. • The dangers of using prescription drugs, controlled substances, over-the-counter medications, and illegal drugs. Kendall/Hunt Publishing Company

11. Drugs Students will be able to: • Chemically identify illicit drug types. • Classify the types of illicit drugs and their negative effects. • Discuss the federal penalties for possession and use of controlled substances. • Explain the need for confirmatory tests. Kendall/Hunt Publishing Company

12. Drugs • Describe IR, UV-VIS spectroscopy, and GC-MS • Present and interpret data with graphs. • Use the Physicians’ Desk Reference (PDR) to identify pills. • Use technology and mathematics to improve investigations and communications. Kendall/Hunt Publishing Company

13. 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. Kendall/Hunt Publishing Company

14. 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 Kendall/Hunt Publishing Company

15. 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 Kendall/Hunt Publishing Company

16. Identification of Drugs • PDR—Physicians’ Desk Reference • Field Tests—presumptive tests • Laboratory Tests—conclusive tests Kendall/Hunt Publishing Company

17. 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. Kendall/Hunt Publishing Company

18. Product Inserts: use the guide to help you interpret your example. Answer these questions on notebook paper. • 1. Scan your product insert • A. List the generic name and indications • B. List contraindications (and describe what that means) • C. List warnings and adverse reactions • D. Describe dosage • 2. Describe “black box warnings” and give 7 examples…check the handout for these. • Does your product have a black box warning?

19. Screening 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 Drug Identification Kendall/Hunt Publishing Company

20. 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 Presumptive Color Tests Kendall/Hunt Publishing Company

21. 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. Kendall/Hunt Publishing Company

22. Types of Chromatography • Paper • Thin Layer (TLC) • Gas (GC) • Pyrolysis Gas (PGC) • Liquid (LC) • High Pressure Liquid (HPLC) • Column Kendall/Hunt Publishing Company

23. Paper Chromatography • Stationary phase—paper • Mobile phase—a liquid solvent Capillary action moves the mobile phase through the stationary phase Kendall/Hunt Publishing Company

24. Thin Layer Chromatography • Stationary phase— a thin layer of coating (usually alumina or silica) on a sheet of plastic or glass • Mobile phase— a liquid solvent Kendall/Hunt Publishing Company

25. Retention Factor (Rf) • This is a number that represents how far a compound travels in a particular solvent • It is determined by measuring the distance the compound traveled and dividing it by the distance the solvent traveled. • If the Rf value for an unknown compound is close to or the same as that for the known compound, the two compounds are likely similar or identical (a match). Kendall/Hunt Publishing Company

26. Phases Stationary—a solid or a viscous liquid that lines a tube or column Mobile—an inert gas like nitrogen or helium Analysis Shows a peak that is proportional to the quantity of the substance present Uses retention time instead of Rf for the qualitative analysis Gas Chromatography Kendall/Hunt Publishing Company

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28. Uses of Gas Chromatography • Not considered a confirmation of a controlled substance • Used as a separation tool for mass spectroscopy (MS) and infrared spectroscopy (IR) • Used to quantitatively measure the concentration of a sample. (In a courtroom, there is no real requirement to know the concentration of a substance. It does not affect guilt or innocence). Kendall/Hunt Publishing Company

29. 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. Kendall/Hunt Publishing Company

30. Mass Spectrometer • A machine used to weigh molecules • A molecular scale Kendall/Hunt Publishing Company

31. How is MS used? • A mass spectrometer helps scientists • ID molecules • Determine how many molecules are present • Determine what atoms are in a molecule • Determine how the atoms are arranged Kendall/Hunt Publishing Company

32. Pocket change sorted Kendall/Hunt Publishing Company

33. Sorting and Counting POCKET CHANGE MIXTURE OF MOLECULE AND FRAGMENTS Mixture of different molecule fragments Sort fragments by mass Show amount of each fragment on bar graph • Penny, nickel, dime, quarter, half dollar, dollar • Sort change by value or size • Stack them up to sort them visually Kendall/Hunt Publishing Company

34. Molecular fragments sorted Kendall/Hunt Publishing Company

35. HOW? Using ions • An ion is an electrically charged atom or molecule • Molecules must be charged to be measured by a mass spec • A mass spec “weighs” molecules by electrically attracting and repelling ions with carefully controlled charges and force fields. Kendall/Hunt Publishing Company

36. Let’s get charged up! • First, the mass spec ionizes (or charges) the molecules • It also breaks apart the big molecule into pieces…like tearing apart a jigsaw puzzle • This is called ionization Kendall/Hunt Publishing Company

37. Sort it out! • It sorts all of these charged particles out by size Kendall/Hunt Publishing Company

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39. Like a pinball machine…a certain amount of force sends the ball where you want it • A different size ball requires different force Kendall/Hunt Publishing Company

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41. What do the patterns tell us?MOLECULAR FINGERPRINTS Scientists recognize the pieces and assemble them to identify the compound. MS Fragments...pieces of a puzzle Each compound produces a unique spectrum.

42. Mass Spectra Each molecular species has its own unique mass spectrum. Kendall/Hunt Publishing Company

43. Spectroscopy • Spectroscopy—the interaction of electromagnetic radiation with matter. • Spectrophotometer—an instrument used to measure and record the absorption spectrum of a chemical substance. Kendall/Hunt Publishing Company

44. Spectrophotometry Components • 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 Kendall/Hunt Publishing Company

45. 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 Kendall/Hunt Publishing Company

46. 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 Kendall/Hunt Publishing Company

47. Blood Urine Hair Gastric Contents Bile Liver tissue Brain tissue Kidney tissue Spleen tissue Vitreous Humor of the Eye Human ComponentsUsed for Drug Analysis Kendall/Hunt Publishing Company

48. Challenges of Tox • Drugs must be isolated from body components, such as urine, blood, brain vitreous humor, stomach contents, liver, bile, brain Kendall/Hunt Publishing Company

49. Challenges of Tox • Drugs in the body are changed chemically as the body metabolizes the drug. Scientists must understand the process and look for the metabolites. Kendall/Hunt Publishing Company

50. Challenges of Tox • If the patient is alive, testing must be fast to provide medical care. • The quantity of drug present is often important. Remember, the difference between medicine and poison is often the dose. Kendall/Hunt Publishing Company