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

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)

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

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

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

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

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

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

Toxicities of some analgesics (ethanol, caffeine, sodium cyanide included for comparison) CompoundLD 50 (g/kg, mice) Ethanol10.60 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 LD 50 –lethal dose of 50% of population in one week Least Toxic Most Toxic ALL chemical are toxic-just depends on amount that is consumed Ex-women died from drinking too much water

Top 10 Drugs Prescribed in 2004 Hydrocodoneanalgesic, narcotic Lipitorcholesterol lowering agent Lisinoprilantihypersensitive* Atendololantihypersensitive* Synthroidthyroid hormone Amoxicillinantibiotic Hydrochlorothiazidediuretic, antihypersensitive* Zithromaxantibiotic Furosemidediuretic, antihypersensitive* Norvascantihypersensitive * Used to treat heart disease and high blood pressure Medicine/Drugs – interesting facts over $162 billion spent on various medicines in 2002 of this $15 billion spent on OTC drugs

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

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

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

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

Narcotics and Alkaloids Opium alkaloids –Morphine First alkaloid to be isolated (in pure form) Major akaloidof opium (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

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

Narcotics and Alkaloids Acetylation of morphine –Similar to the acetylation salicylic 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

Narcotics and Alkaloids Cocaine –Also an alkaloid –Produced by coca bush of South America –Similar to morphine in medicinal value –Addiction is more psychological rather than physical –Effects include euphoria (well-being, power), depression, and craving

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”)

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

Cocaine and the tropane alkaloids. Know this structure