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

• 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)– 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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