Unit 1: Medicinal Plants
9 days
Read on your own: Introduction to
Pharmacology
Course Goals
• Help scholars obtain an understanding of how
drugs and medicines are
– Found
– Isolated
– Produced
– Abused
• Help scholars understand different classes of
drugs and how they work in the body
Course Structure
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Unit 1 – Medicinal Plants
Unit 2 – Psychopharmacology
Unit 3 – Depressants and Stimulants
Unit 4 – Drugs that relieve Pain
• 11 Lab Activities and/or Case Studies
• 3 Research Projects
Classroom Policies
• School rules apply
• Respect the space, manager, and your peers
• All deadlines are final – work should be
submitted electronically if the scholar is not
present
Test Format
• 30 multiple choice questions
• Choice of 6 free response questions
Pharmacology Reference Book
• No textbook available
• Lecture materials were primarily pulled from
the following textbooks
– A Primer of Drug Action 9th edition: Julien
– Economic Botany 3rd edition: Simpson and
Ogorzaly
Website, Notes, Projects
• All notes, lectures, and activities are available
on the class website
• askmrspierce.pbworks.com
January 6th: Medicine throughout
History
History of Medicine
• 75% of world’s population still depends on
traditional herbal medicine
• 10% of major medical drugs in the U.S. have a
primary ingredient extracted from plants
today
• 25% of common medicines contain some
compounds from plants
History of Medicine
• Fungi are the source of penicillin (discovered
1941)
• Many plant compounds have provided blue
prints for synthetic drugs
History of Medicine
• Early drugs were found by trial and error
• Passed by word of mouth
History of Medicine
• Sumerian drawings of opium poppy (2500
B.C.)
History of Medicine
• Code of Hammurabi (1770 B.C.)
• Tablets carved under the direction of the King
of Babylon
• Mention many plant medicines
History of Medicine
• Egyptians recorded knowledge of illness and
cures on temple walls
• Also on the Ebers papyrus (1550 B.C.)
• Contains over 700 medicinal recipes
• Include – cannabis, aloe, castor, mandrake,
and several gum and resin producing shrubs
• Mandrake was used as an anesthetic (contains
atropine and scopolamine)
History of Medicine
• Golden Age of Greece had many major
advancements in the field of pharmacology
• Hippocrates (460 – 377 B.C.)
• Father of Medicine
• Illness caused by bodily problems, not evil
spirits
• Discussed between 300 and 400 species of
plants that provided medicinal drugs
History of Medicine
• Aristotle
– compiled a list of medicinal plants
• Theophrastus
– Father of Botany
– Provided first account of opium poppy and its
effects
• Dioscorides
– 5 volume work titled De Materia medica
– Described preparation of 1000 simple drugs
History of Medicine
• Middle Ages saw little advancement
• Not much academic interest in Europe
• Monks used early Greek writings to produce
herbals
• Printing press in 1439 made herbals more
wide spread
Renaissance
• Study of human anatomy renewed
• Surgical procedures were improved
• Paracelsus (1493 – 1541)
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Publicly burned Greek works
Said God put plants on Earth to be used by humans
Said plants had signs of what they were useful for
Doctrine of Signatures
• Red sap = treatment for blood disorder
• Brain-like convolutions of walnut = good for brain
17th and 18th Centuries
• Edward Jenner
– Vaccination in 1796
• William Withering
– Foxglove extracts as remedies for heart problems
in 1775
19th Century
• Progress was made in surgical procedures
• Joseph Lister
– Promoted the use of chemicals to prevent
infection
20th Century
• ‘miracle’ drugs produced
• Morphine, quinine, ephedrine
• Chemists began task of determining the
structures of these compounds
• Determined how to synthesize them
Natural Medicines
• Less studied in the U.S. than elsewhere over
the last 50 years
• Old fashioned or folkloric
• Biochemistry can synthetically make
compounds
Plant Biodiversity
• Only 1 in 10,000 randomly screened plants
make it to market
• National Cancer Institute is expanding its
testing program for natural products
• Currently has teams in all major rainforest
areas of the world
• In many parts of the world illness is treated
holistically
• Illness is viewed as an imbalance
January 7th: Chemistry of Plant Derived
Medicines
Chemistry of Plant Medicines
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Two major classes
Alkaloids
Steroids
Often the medicinally active compound occurs
with one or more sugar molecules attached
• Called glycosides
Steroids
• Four carbon rings = backbone
• Addition of diverse chemical groups at
different places on the backbone leads to
diversity of compounds
• Adding sugar = steroidal glycosides
Steroids
• Occur in several groups of angiosperms
• Secondary products (no direct physiological
function)
• Often have pronounced effect on animals
(especially vertebrates)
• Herbivory deterrent
Milkweed and Monarchs
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Asclepias is toxic to humans
Contains abundant steroidal glycosides
Eaten by monarch caterpillars
Store compound in their body
Butterflies are toxic to vertebrate predators
(birds)
Alkaloids
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Diverse group
Multi-cyclic chemicals
Contain nitrogen
Usually exhibit alkaline reaction
Occasionally enter into primary metabolism of
plants, so may not be a secondary product
Alkaloids
• Many are extremely poisonous to humans
– Locoweed
– Nightshade
– Hemlock
– Nicotine
• Can alleviate physiological problems when
ingested in small quantities
• Important to standardize safe dose
January 8th: Plants that were formerly
important to medicine
Human Diseases
• Leprosy
– Disfiguring
• Painful death
• Malaria
– Killed more people throughout recorded history
than all other diseases and wars combined
• First drugs used to treat these diseases came
from plants
Leprosy
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Leprosy was long considered to be incurable
Leper colonies
Caused by bacterium
Similar to tuberculosis
The Vedas mentioned over 2000 years ago an
oil (chaulmoogra) that helped in curing
leprosy
• Europeans did not pay serious attention
Leprosy
• Source of chaulmoogra oil was unknown to
western medicine
• Joseph Rock led expedition to find the species
of plant that produced the chaulmoogra fruit
in the 1920’s
• Found trees in India that produced
chaulmoogra, and sent seeds to Hawaii where
cultivation began
Leprosy
• Chaulmoogra was only successful treatment
until sulfa drugs were produced in 1946
Malaria
• Bronze Age Greek skulls show evidence of
malaria
• Well documented throughout history
• During WWI more people died from malaria
than from enemy fire
• In 1999, CDC estimated that 310-500 million
people were infected with malaria worldwide
• ~1 million people died in 1999 (primarily kids)
Malaria
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Believed to be transmitted through the air
Root of name
Actually transmitted by a mosquito vector
Infectious agent is a protozoa called
Plasmodium
• Fever, chills, anemia, and spleen enlargement
Malaria
• In the middle of the 17th century Jesuits in
South America found that local people had a
remedy
• Steeped bark of Cinchona trees in water
• Indian name for this drink was ‘quina’
• Protestants believed that the Jesuits were
trying to poison them, and would not try the
drug
Malaria
• Oliver Cromwell died of malaria rather than
take the “Jesuits’ powder”
• Cinchona was not universally accepted until
1681
• Quinine (the active ingredient) was not
isolated until 1820
Malaria
• The Dutch finally established productive
plantation in Java of a particularly potent
species
• Gave them a monopoly on the world supply of
quinine
• During WWII the U.S. and Europe were cut off
from supplies
• U.S. sent expeditions to Bolivia
Malaria
• One of these expeditions was successful
• Quinine was successfully synthesized in 1944
• This reduced the need for natural quinine
• Some Plasmodium strains are becoming
resistant to synthetic compounds
• Renewed interest in natural compounds
Malaria
• Original basis for drinking gin and tonic in the
evenings
• British originated the drink because the bitter
component of tonic water in quinine
• Served as a prophylactic dose
Malaria
• New antimalarial compound has been recently
found in Artemisia annua (Asteraceae)
• A wormwood related to the plant used to
make absinthe
• Has been used in China since 168 B.C.
Ephedrine
• Originally made by soaking the dried stems of
ma-huang, Ephedra sinica (a gymnosperm)
• Prescribed in China for centuries as a
stimulant, and treatment for high blood
pressure, asthma, and hay fever
Ephedrine
• After 1920 western medicine accepted
Ephedra as a decongestant
• Bronchodilator
• Similar structure to adrenaline
• Initially caused the death of many children
from cardiac arrest
White Willow
• Salix alba (Salicaceae)
• Soaked leaves of this plant were often placed
on body parts to relieve aches
• Salicin (the active ingredient) was isolated in
1827
• Salicin and salicylic acid are stomach irritants
• Acetylsalicylic acid, produced in Germany in
1898, can be ingested easily
White Willow
• This compound, called Aspirin, is the most
widely used medicine in the world
• New physiological actions are being
discovered and described even today
Cocaine
• Not often thought of as a medicine
• Has historically been used as a calmative and
local anesthetic
• Coca, Erythroxylum coca, is native to the
Andes
• Indians have chewed the leaves for thousands
of years
Cocaine
• Reduces feelings of hunger, pain, and fatigue
• First used as a medicine in 1884 when one of
Freud’s assistants found that a cocaine
solution numbed his tongue
• Used as local anesthetic in eye surgery and
dentistry
• Cocaine has never been synthesized
• Lidocaine and procaine (Novocain) have
January 12th: Plants that are important
in medicine today
Steroids
• Many animal hormones are steroids
• To produce hormones for therapy can be
expensive and labor intensive
• Between 1936 and 1940 it was discovered
that certain yam plants had steroids called
saponins
• These looked almost identical to human sex
hormones, with only 1 additional ring added
Saponins
• These tubers can be collected and used to
produce large amounts of saponins
• Then microorganisms are added that cleave
off side groups and add others
• This produces synthetic hormones at a
relatively inexpensive price
Saponins
• Most of these hormones are used in birth
control pills and fertility drugs
Digitalis
• 2 of every 5 American dies from heart related
illness
• Dropsy used to be a disease caused by
retention of fluid in the tissues, likely cause by
congestive heart failure
• William Withering is credited with finding
purple foxglove (Digitalis purpurea)
compounds that cured this type of disease.
Digitalis
• The two active compounds were isolated in
1928
• They are still used in heart treatment today
Alkaloids
• Pain is a necessary warning
• Drugs that numb pain, without causing
unconsciousness, are called analgesics
• One of the oldest and best sources of
analgesics is the opium poppy
Opium
• Fossilized poppy capsules have been found in
prehistoric settlements around the
Mediterranean
• Representations of the poppy appear in
ancient Egyptian, Greek, and Roman artwork
• Used as a calming agent for at least 2600
years
Opium
• Most opium production is in Nepal, India,
Laos, and Cambodia
• Only about 4% of the crop is harvested for
legitimate medical uses
• Cultivation is illegal in most countries
(including ours)
• High amounts of opium are currently being
grown in Afghanistan
Opium
• Harvested by slashing capsule and collecting
the latex
• Used to be used in powdered form
• Now subjected to chromatography to separate
the chemical components
• Over 26 different alkaloids have been
seperated from the opium poppy
• Only 3 are commonly used in medicine
– Morphine, Codeine, Papaverine
Morphine
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Most abundant in the opium poppy
VERY addictive
Most potent painkiller
Very helpful during early times when no
anesthetic was available for surgery
• Often given during labor and delivery during
the 1930’s and 1940’s
Codeine and Papaverine
• Less habit forming
• Often over the counter
• Used for the treatment of internal spasms
• Traditionally used for treatment of diarrhea
• Also used for cramping
January 13th: Tropane alkaloids and
Balladonna
Tropane Alkaloids
• First isolated from Atropa belladonna
• Atropine, scopolamine, and hyoscyamine
• All have similar complex nitrogen ring
structure
• Nightshade has been used since the time of
the Ancient Greeks
• Named for Atropos (one of the fates who cut
the thread of life)
Tropane Alkaloids
• Belladonna is the common name which was
derived from the medieval practice of putting
drops into the eyes
• This dilated the pupil, and made women look
charming
Tropane Alkaloids
• Soothe the smooth muscle system and relieve
cramping
• Also has some cardiac physiological effect
• Dilate pupils
• Relieve pain and infection in the urinary tract
Hellebore
• Not all alkaloids come from the potato family
• A lily species indigenous to North America
• Have two compounds used to decrease blood
pressure
• Used by Native Americans
• Adopted by Europeans
January 14th: Cinchona, Rauwolfia,
Snakeroot, and Cancer Drugs
Cinchona
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Known primarily as a source of quinine
Produces about 30 other alkaloids
Quinidine
Useful in treating heart disease
Helps regulate irregular rhythyms
Rauwolfa
• Mentioned in the Vedas of India
• Noted that snakeroot was used to treat
hypertension
• Indian people have chewed on snakeroot for
centuries for its calming effect
• Can also be used to treat mental illness
Rauwolfia
• Most important chemical obtained from
snakeroot is reserpine
• Replaced electric shock and injections of
insulin as a replacement for schizophrenia
treatment
• Also helpful for its calming effects in other
mental disorders
• Mostly obtains from crops in India, Pakistan,
and Java
Cancer Drugs
• Many have proved to be plant alkaloids
• Work by interfering with cell mitotic division
Common Periwinkle
• Used in its native region for centuries to treat
diabetes
• In 1957 was found to be effective in treating
and curing some forms of childhood leukemia
Mayapple
• Found in forests of Canada and the Eastern
United States
• Used by native Americans to treat skin
disorders, tumorous growths, and as a
purgative
• Used today to treat testicular, lung, and breast
cancers
Autumn Crocus
• Mainly used to alleviate pain from gout
• Also interferes with mitotic cell division
Pacific Yew
• Yews are commonly know as ‘trees of death’
• Genus name Taxus is derived from the Greek
word for toxin
• Used to treat ovarian cancer
• Not cost effective to synthesize, but Taxol, a
multicyclical alcohol, can be extracted from
yew bark
• Trees were being lost to deforestation
• Became #1 selling cancer drug in 2000, sales
over $3 billion
January 15th: Other Plants of Medicinal
Use
Plantain
• 2 species have psyllium in their seed husks
• A colloid mucilage used for intestinal
problems
• Ground powder pulls water out of the
intestinal tract which forms a smooth, bulky
mass that is unaffected by bacteria
• Relieves irritations caused by diarrhea and
constipation
Aloe
• A member of the liliaceae
• Soothing gels
• Used for skin conditions
Ipecac Syrup
• Used in many households to induce vomiting
• Member of the coffee family
• Used in poison control kits
Chymopapain
• From papayas
• Sister enzyme to papain (meat tenderizer)
• Injected into slipped disks, dissolves disk and
alleviates pressure
• Prevents surgery
January 20th: Dietary Supplements
Herbal Medicine
• Use of herbs to treat illness, fatigue, and
depression has increased dramatically in the
last 40 years
• Several contributing factors:
• Prescription drugs are expensive
• Aura of being more natural and less invasive
• Don’t need a physician to purchase
Regulation
• Cons:
– Increase expense
– Deprive some people of medicine
– Claim they are already safe
– Claim they are already extensively used
• Pros:
– Differ widely in content
– Contain contradicting compounds
Herbiogenic Death
• Serious complications, underscore the major
concern with consuming unregulated
bioactive compounds
• Several deaths have occurred from ephedra
being used as a diet
Interactions
• St. John’s Wort reduces the efficacy of birth
control pills
Germany
• Has regulation of all bioactive compounds that
has been shown to be very effective
• Makes herbal use safe for public
• Still available and inexpensive
China
• Herbal medicines have been used for
thousands of years
• Chinese scientists are currently attempting to
isolate and test these compounds
• Looking to folk medicine for new cures
U.S.A.
• Private and governmental agencies are
conducting screening process for new drugs
• Conservation concerns