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 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