Chemistry 106University of Nebraska

Spring 2009

3 April 2009Exam 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 cyanideincluded for comparison)

Compound LD50 (g/kg, mice)

Ethanol 10.60Phenacetin 1.65Ibuprofen 1.25Naproxen 1.23Aspirin 1.10Methyl salicylate .88Acetanilide .80Phenol .53Salicylic acid .50acetaminophen .33Caffeine .12Sodium cyanide .01

LD50 –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

Hydrocodone analgesic, narcoticLipitor cholesterol lowering agentLisinopril antihypersensitive*Atendolol antihypersensitive*Synthroid thyroid hormoneAmoxicillin antibioticHydrochlorothiazide diuretic, antihypersensitive*Zithromax antibioticFurosemide diuretic, antihypersensitive*Norvasc antihypersensitive* 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

relieversEnkephalins

• 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