Unit 1: Introduction to Pharmacology



Unit 1: Introduction to Pharmacology

Many substances that historically have been used for murder, magic and folk medicine are currently clinically acceptable drugs. Synthetic chemistry started in the 1930’s but Mother Nature has been working for over 3.5 billion years.

Now, scientists hang by ropes in the Rain Forests to collect spiders, dive below ice caps for fish to obtain antifreeze that preserves organs for transplantation and search the desert for viper poison for high blood pressure medicine.

In his book, "Medicine Quest, In search of Nature's Healing Secrets", Marc Plotkin pleads with a shaman to treat a woman collapsed in the jungle with diabetic symptoms.  The shaman  finally makes a thick red liquid potion to treat the woman.  He gives her two teaspoons a day and after three days, the woman  was working in her garden and the gangrene was healing.

Marc Plotkin is an ethnobotanist, a plant hunter, and a shaman’s apprentice in search of natural compounds to treat diseases.

Interesting Quotes:

1.      "Nature distributed medicine everywhere. - Pliny the Elder circa A.D. 77 Plotkin, Mark J. "Medicine Ques, In search of Nature’s Healing Secrets "  p. xi (read first paragraph)

2.      "The difference between a deadly poison and a life-saving medicine can be very small; in fact, it is sometimes merely a question of dosage: Dr. R.E. Schultes, 1980 died 2001 from p. 3 Plotkin, Mark J. "Medicine Quest, In search of Nature’s Healing Secrets"

3.      Remember that "The dose is the poison" Paracelsus – the Grandfather of Pharmacology Levine, Ruth R. “Pharmacology, Drug Actions and Reactions.”  p. 8,9.   

I.  Pharmacology is the study of chemical agents (xenobiotics – drugs substances foreign to the body) and living organisms (different cell types) and all aspects of their interactions i.e. a biological response.  These xenobiotics may include: pollutants, food additives, contaminants and DRUGS.

A.  These substances can be:

1. Absorbed through the lungs, skin, or the gastrointestinal tract

2. Metabolized in liver

3. Excreted via skin, lungs, kidneys, or intestines

B.  Primitive man identified edible and poisonous plants and animals that were:

1. used for  executions, euthanasia, murder and hunting

2. appetite suppressants, stimulants and psychedelic

C.     Physicians used drugs as therapeutic agents

1. Opium has been used for 5000 years

2. Cocaine for 2000 yrs, appetite suppressants

3. Egyptian remedy for colicky babies was poppy pods (i.e. opium -> morphine)

D.  Interest and concerns:  take drugs over long time

1. Oral contraceptives

2. Insulin

3. Drugs of abuse

4. Food additives

5. Economic insecticides Fertilizers

6. Industrial pollutants (air, water)

7. All these substances foreign to the body are known as xenobiotics.

E. Medicines as old as human race combat illnesses/plants around them ease pain:  

1. aspirin (from the Willow Tree)

2. alcohol

3. opium

4. quinone  (cinchona bark)

5. ipecac (amoebic dysentery)

F. Poisons- helped provide valuable discoveries –

1. elucidate info. about neurotransmitters, synapse etc.

2. curare (arrow poison)

3. veratrine,

4. ouabain not absorbed in gut very well so can eat animals killed this way

5. Witches, North American Indian Medicine Men and Shaman (South American Medicine Men) used potions from the natural world around them for Magic and Medicine.

G.  Examples of uses for Toxins or Poisons currently being investigated for medicinal purposes: can be man-made or natural products

1. Poisons from Brazilian viper venom – high blood pressure medicine, eriostatin

2. Protein from the Asian pit viper – inhibits melanoma

3. Venom of Israeli scorpion – inhibits brain cancer

4. Venom from the Cameroon red tarantula – neurological disorder

5. Venom from American S.W. Gila monsters – stimulate insulin production

H. Toxins work by:

1. attaching to healthy cells

2. entering  cells

3. exerting deadly effects – causing cells to malfunction and/or die

4. Toxins can be used to treat cancer, Tay-Sachs disease and as pain relievers.

5. Poisons have Antiviral Activity

I. Other Toxin Examples

1. Cordyceps fungus related to the toadstool Fungus grows on exoskeleton à goes inside and devours nonvital organs part of brain, fungus eats the insect, spread lots of spores- this is source of cyclosporin which is an  immunosuppresant which allows surgery especially organ transplants.

2. Tropical Insects: N1 811 does suppress immune system or antibodies and AIDS à blocks reproduction

3. Crab Spider eats Bee: must kill or be stung

4. Gila Monsters:  Molecule that controls level of sugar in blood, Diabetes kills more than 4 times more people than Breast Cancer

5. African Vipers: anticoagulant, Coagulation is a 32 step cascade multi-step process

6. Cone Snails: kill by shooting out poison, can be effective pain killer, it is an opiate derivative (opiates are addictive, have confusing side effects, this poison has none of the opiate drawbacks

J. Rainforest:  22 years

1. Spices make food better

2. Mace: more important to kill bacteria

3. Spice Trade:  “Origin of democracy”

4. Magii:  Frankensense and Muir, Incense, goodies

5. Muir = “Gift of Life”, strong antibiotic properties

Marc Plotkin asks these questions:

1. What happens now?

2. Magic, Black Magic, Dosage, Healing Earache, Dandruff, Aching Back, Diabetes,

3. "How to Bring Cultures and Medicines Together?"

4. Problem: “The Culture is Dying and Disappearing faster than the Rain Forests”

5. N.W. Amazon, South Central Amazon, Brazil, Suriname Medicine Men usually resent each other and do not work together.

6. Nature more important than before à final unique molecules

7. 3 x 109 ways to make molecules: Western Medicines need cures for depression, schizophrenia and other mental illness

More Resources to answer some questions:

1.

2. Shaman’s Apprentice program with Harvard Medical School

3.  "Amazon Conservation Team" .org

.Unit 1 (continued) History of Pharmacology

(Medicines and Religions have been intertwined over the years, “If we want to see ahead, we must look back”  -Albert Szent-Gyorgyi years  (pg. 1Levine, Ruth R. “Pharmacology, Drug Actions and Reactions.”)

I.  Egypt and Babylonia 1600 B.C. Papyrus listing and characterizing 700 diseases

A.     Egyptians used mythology for their welfare

B.      Materia Medica (p.458, Levine, Ruth R. “Pharmacology, Drug Actions and Reactions.”): remedies for disease, sources, nature and preparation of drugs

C.     Babylonians believed the world was full of hostile demons

1. Code of Hammurabi- “eye for an eye, tooth for a tooth” 2123 – 2081 BC

2. Transmitted the foundations of medicine to India and Greece

D.    India: Sushruta (500B.C.) Hindu Prof. Of medicine:

1. 1st aseptic surgery, 1st skin graft – he described 1100 diseases

2. smallpox vaccination

3. All this unknown in Europe for 2000 years

II.  India and Greece

A.     medicine and religion are a close alliance until the Code of Hammurabi.

B.      Greece: medicinal pharmacy "History of Plants" 300 B.C.

 1st ethics Hippocrates 400B.C. :  freed medicine from mysticism and philosophy “Father of Medicine”  with emphasis on medical ethics.

C.    Dioscorides: Nero’s surgeon described 600 plants This was the chief source of pharmacological knowledge till 16th century "Father of Materia Medica" (later in Europe)

D.    Anatomy & Physiology

Sensory and motor nerves

E.      Erasistratus 0 AD antiquity, function of arteries – physiologist

Herophilus: anatomist 19 centuries before Harvey "Circulation of Blood"

F.      Roman Era: Galen "described humors" blood phlegm yellow and black bile and earth air fire, water

G.    Middle Ages: no significant developments in Europe till 1500 AD Paracelsus

H.     Greeks (B.C./A.D.)

I.         Many advances were made with Arabs and Jews

J.      Crusades later brought these discoveries to Europe

 

III. Arabs

A.  Arabs made many contributions: precision in observation, control in experimentation meticulous record keeping.  They developed The Experimental Method

B.  Moslems: 1st apothecary shop, 1st pharmacy school, 1st standards regulations of drugs.

C.  15th century alchemy of Arabs – Europe relatively pure substances for medical use Sulfur, Iron, Arsenic and Laudanum "tincture of opium" (the active part morphine), Mercury was used to treat syphilis.

D.  Standards established, storage and preparation of drugs was standardized, 1st consumer protection punished by law if deceptive practices occurred.

IV. 13th century medicinals come to Europe

Paracelsus: "Grandfather of Pharmacology"

"the dose is the poison"

A. Rise of Pharmacology:

1. Wm. Harvey 1600 "circ. of blood"

2. Toxicity of drugs/poisons in animals

3. Crude drug –> active principal –> characteristic Effect

4. Controlled studies led to: DOSE --> RESPONSE i.e. the amount of drug --> produces a biologic effect or response.

5. 1806 1st isolation of the active principal component i.e.  white crystalline morphine from opium (poppies) Columbia study of natural drugs (organic chemistry begins)

6. Site of Drug Action

1856 curare acts at junction of nerve-muscle

7. Cellular Mech. Of Drug Action – receptor (composed of chemicals)

8. Fate of Drugs in Body Chemical conversion in body or excretion

B.  Modern Era

1. Ether Morton 1819 – 1868

2. Antiseptic Lister 1827-1912

3. Chemotherapy Ehrlich 1854-1915 p. 15

4. Insulin Banting & Best 1921

5. "Basis for Rational Therapy of Disease"

Humans concerned with digestive organs specifically bowels

17th cent. England – bimonthly purging for good health, many substances used for murder, magic, and folk

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