Chemistry 106 University of Nebraska Spring 2009

1. Chemistry 106 University of Nebraska Spring 2009 3 April 2009 Exam 4 next week

2. Aspirin Substitutes • p-aminophenols • Acetanilide(1886) used to treat fever but too toxic – caused serious form of anemia • Phenacetin(1887) used as an analgesic until banned by FDA (1983) – caused kidney damage and blood disorders • Acetaminophen(1893) can cause kidney damage if taken in too large of doses or in combination with alcohol (Tylenol)

3. KNOW THIS STRUCTURE!! p-Aminophenol and related compounds.

4. Aspirin Substitutes • Acetaminophen • Brand names: Tylenol, Datril, etc • More expensive and more toxic than aspirin • Analgesic and antipyretic but not anti-inflammatory • Does not contain a carboxylic acid group

5. Aspirin Substitutes • Ibuprofin • Approved as OTC drug in 1984 • Brand names: Advil, Motrin, etc • Anti-inflammatory, antipyretic, analgesic • Not a p-aminophenol or a salicylate • Acts by inhibiting prostaglandin synthase (similar to aspririn) • Same painkilling effect as aspirin at 1/3 the dosage

6. Know this structure!! aspirin Ibuprofen, an alternative to aspirin for the relief of pain, fever, and inflammation.

7. Aspirin Substitutes • Naproxin • Approved in 1994 • Inhibits cycloxygenase enzymes which form prostaglandins (similar to aspirin but a different class of compound) • Commercial name: Aleve • Anti-inflammatory, analgesic and antipyretic

8. Commercial Pain Relievers • Aspirin, Ibuprofen, Naproxen-nonsteroidal anti-inflammatory drugs (NSAID’s) • All drug have trade names and generic names (acetominophen sold as Tylenol, etc) • Many pain relievers contain multiple active ingredients • Excedrin: Aspirin and acetaminophen • Many also contain caffeine • Acts as a stimulant

9. Toxicities of some analgesics (ethanol, caffeine, sodium cyanide included for comparison) Compound LD50 (g/kg, mice) Ethanol 10.60 Phenacetin 1.65 Ibuprofen 1.25 Naproxen 1.23 Aspirin 1.10 Methyl salicylate .88 Acetanilide .80 Phenol .53 Salicylic acid .50 acetaminophen .33 Caffeine .12 Sodium cyanide .01 LD50 –lethal dose of 50% of population in one week Least Toxic ALL chemical are toxic-just depends on amount that is consumed Ex-women died from drinking too much water Most Toxic

10. Medicine/Drugs – interesting facts • over $162 billion spent on various medicines in 2002 • of this $15 billion spent on OTC drugs Top 10 Drugs Prescribed in 2004 Hydrocodone analgesic, narcotic Lipitor cholesterol lowering agent Lisinopril antihypersensitive* Atendolol antihypersensitive* Synthroid thyroid hormone Amoxicillin antibiotic Hydrochlorothiazide diuretic, antihypersensitive* Zithromax antibiotic Furosemide diuretic, antihypersensitive* Norvasc antihypersensitive * Used to treat heart disease and high blood pressure

11. Natural Pain Relievers • Human body produces natural pain relievers Enkephalins • Produced in the brain in minute amounts • Small polypeptides • 1000 time more effective than morphine • Very short duration

12. Medicines versus Drugs • Drug • Connotation of narcotics, addiction, and crime • Illicit, illegal chemicals • Medicine • Connotation of physicians, healing, and wellness • respectable, useful chemicals

13. Narcotics and Alkaloids • Narcotic • Substance that in small doses dulls the senses, relieves pain, and induces sleep but in excessive doses causes stupor, coma, and/or convulsions • Alkaloid • Any number of basic, bitter-tasting, nitrogen containing compounds found in seed plants

14. Narcotics and Alkaloids • Poppy plant used for centuries to produce opium (dried sap from poppy plant) • Opium contains a mixture of alkaloids with narcotic effects and other compounds

15. Narcotics and Alkaloids • Opium alkaloids • Morphine • First alkaloid to be isolated (in pure form) • Major akaloidofopium (10% by weight) • Analgesic and cough suppressant in small quantities • High addictive producing both apathy and euphoria • Codeine • Another alkaloid in opium • Very powerful cough suppressant but less potent analgesic • Papaverine • Useful for relaxation of smooth muscles (blood vessels, intestine, stomach, bladder, etc) • All these alkaloids are 1) addicting and 2) powerful constipating agents

16. Know This Structure!! Alkaloids of opium. These occur in the sap of the poppy.

17. Narcotics and Alkaloids • Acetylation of morphine • Similar to the acetylationsalicylic acid to form acetylsalicylic acid (aspirin) • Morphine is acetylated to form diacetylmorphine • More powerful narcotic and cough suppressant than morphine • Also powerfully addictive • Diacetylmorphine is known as Heroin • Morphine and heroin produce physical addictions addiction (sweating, dilated pupils, goose flesh, etc) in addition to psychological addiction

18. Narcotics and Alkaloids • Cocaine • Also an alkaloid • Produced by coca bushof South America • Similar to morphine in medicinal value • Addiction is more psychologicalrather than physical • Effects include euphoria (well-being, power), depression, and craving

19. Narcotics and Alkaloids • Cocaine • An ingredient in Coca Cola when first introduced • Like all bases, will react with acids to form a salt • Cocaine hydrochoride is similar to table salt in some physical properties (water soluble, thermostable, small granules) • Reacting cocaine hydrochloride with a base forms cocaine itself (known as “free base”) • Cocaine (“free base”) has quite different properties than table salt • The “free base” easily vaporizes which allows for inhalation to produce a sharper, more intense sensation • Solid cocaine forms a solid sheet which cracks into clumps or rocks (individual lumps are termed “crack cocaine”)

20. Narcotics and Alkaloids • Cocaine is a class of alkaloid known as tropane alkaloid • Others include atrioine and scolopamine • Both found in the nightshade family of plants • Both affect the nervous system • Atropine is active ingredient in belladonna, a poison used in Middle Ages • Scolopamine still used today in some OTC sedatives and motion-sickness drugs

21. Know this structure Cocaine and the tropane alkaloids.