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Chemistry 106
University of Nebraska
Spring 2009
3 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)
KNOW THIS
STRUCTURE!!
p-Aminophenol and related compounds.
Aspirin Substitutes
• Acetaminophen
– Brand names: Tylenol, Datril, etc
– More expensive and more toxic than aspirin
– Analgesic and antipyretic but not antiinflammatory
– 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
Know this structure!!
aspirin
Ibuprofen, an alternative to aspirin for the relief of pain, fever, and inflammation.
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 antiinflammatory 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
LD50 –lethal
dose of 50%
of population
in one week
Toxicities of some analgesics
(ethanol, caffeine, sodium cyanide
included for comparison)
Compound
Ethanol
Phenacetin
Ibuprofen
Naproxen
Aspirin
Methyl salicylate
Acetanilide
Phenol
Salicylic acid
acetaminophen
Caffeine
Sodium cyanide
LD50 (g/kg, mice)
10.60
1.65
1.25
1.23
1.10
.88
.80
.53
.50
.33
.12
.01
Least Toxic
ALL chemical
are toxic-just
depends on
amount that
is consumed
Ex-women
died from
drinking too
much water
Most Toxic
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
Lipitor
Lisinopril
Atendolol
Synthroid
Amoxicillin
Hydrochlorothiazide
Zithromax
Furosemide
Norvasc
analgesic, narcotic
cholesterol lowering agent
antihypersensitive*
antihypersensitive*
thyroid hormone
antibiotic
diuretic, antihypersensitive*
antibiotic
diuretic, antihypersensitive*
antihypersensitive
* Used to treat heart disease and high blood pressure
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
Know This
Structure!!
Alkaloids of opium. These occur in the sap of the poppy.
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
Know this structure
Cocaine and the tropane alkaloids.