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1 History of Pharmacology PHARMACOLOGY

Dr. Macaraig | June 14, 2013 1st 2013-2014

OUTLINE o H.P. Rang, PHARMACOLOGY, 7th ed

I. Introduction o C.R. Craig, Modern Pharmacology with Clinical Application
II. Contributions of Cultures
A. Ancient Chinese
o Koda-Kimble, Applied Therapeutics: The Clinical Use fo
B. Egyptian Drugs, 10th ed
C. Greek  Computation: Prefinal Grade
D. Central and South American o Exemption: Prefinal Grade >=85%
E. European and South American Parallelism
F. Roman Table 1. Computation of the Prefinal Grade.
G. Parallelisms in Traditional Chines Medicine
III. Medicine in the Middle Ages
A. Alchemy
Long Exams 60%
B. Arab Pharmacy Quizzes 10%
C. Significant Advances
IV. Nineteenth Century
Preceptorial 10%
V. The Discipline of Pharmacology Grade
VI. Twentieth Century Attendance 2%
VII. Pharmacology in the Philippines
Participation 8%
OBJECTIVES Manual Grade 2%
At the end of the lecture, the student should be able to:
1. Learn lessons from the past. “those who cannot remember the past are Laboratory 8%
doomed to repeat it” – George Santayana Grade
2. Glimpse of pharmacology – prelude to the Introductory Lectures
3. Transition from vacation “petiks” mode to the academic “level up” mode
Leader 2%
References: Faculty 6%
Craig and Stilzel, Modern Pharmacology
Lüllmann, Color Atlas of Pharmacology © 2000 Thieme ICS 10%
http://chemistknight.com/ TOTAL 100%
http://www.ancientegyptianfacts.com/ancient-egyptian-medicines.html

Legend: Italicized – quoted from the lecturer; bold – emphasis, or from references  Computation: Final Grade
o Prefinal Grade = 85%
ORIENTATION o Final Exam = 15%
 Pharmacology: The study of substances that interact with living  Submission of Manuals
systems through chemical processes, especially binding to o After each long examination usually Friday of the Exam
regulatory molecules and activating or inhibiting normal body week by 5pm
responses o Formulary should also be submitted together with the
 Weight of Pharmacology manuals
o Total Academic Load: 21.33% o Example:
 Objectives of the Course Amlodipine
o To discuss the general principles of pharmacology  Therapeutic Classification: Anti-HPNive, anti-anginal
o To analyze the pharmacokinetics, pharmacodynamics, uses,  Pharmacologic Classification: Ca-channel blocker-
adverse effects of different drugs acting on the different Dyhydropiridine
organ systems  MOA: blocks L type Ca channels in heart & blood vessels
o To prepare students in second year to prescribe drugs to  Side Effects: headache, flushing, edema, palpitations
patients on a rational basis  Preparations: 5mg, 10mg tab
o To discuss pharmacologic changes in pregnant women,  Dose: 5-10mg once a day
children and elderly  Brand Name: Norvasc
o To introduce students to complementary and alternative
medicine and toxicology
 Course
o Didactic lectures
o Laboratory sessions (prescription writing, case discussions,
presentations, formulary)
o Laboratory experiments
o Integrated Case Study
 Course Material
o Prescribed Textbook: Bertram G. Katzung, BASIC & CLINICAL
PHARMACOLOGY (12th ed)
o Gold Standard: Goodman & Gilman’s THE
PHARMACOLOGICAL BASIS OF THERAPEUTICS (12th ed)
o Harrison’s PRINCIPLES OF INTERNAL MEDICINE (18th ed)
o Nelson’s TEXTBOOK OF PEDIATRICS (19th ed)

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I. INTRODUCTION
A. Terms
 Pharmacology – branch of medicine concerned with drug action
 Drug – any man-made, natural, or endogenous molecule which
exerts a biochemical and/or physiological effect on the cell,
organ, or organism.
B. Early Human History
• Natural bond formed between religion and drug use
 “mediators” known as priests, shamans, holy persons, and
witches stood between this world and the spirit world
 More became known about the effects of drugs, thus
importance of divine intervention receded
o Curative powers of natural products became understood
 Information learned from treating patients showed that a
regularity prevailed in the natural world that was independent
of supernatural whim
 This became the cornerstone for the formation of a science-
based practice of medicine
II. CONTRIBUTION OF CULTURES
A. Ancient Chinese
 Wrote extensively on medical subjects
 Pen Tsao (2700 BC) –classified medicinal plants and compiled
plant mixtures to be used for medical purpose- their own
formulary based on ancient writings
 Shennong (“Divine farmer”, Emperor of Five Grains)
o Legendary ruler and culture hero who became a demigod
o One of the Three Sovereigns (“Three Emperors”) who lived
5,000 years ago
o Thought to have taught the practices of agriculture and use
of herbal drugs
B. Egyptian Medicine
 Ebers papyrus (1550 B.C.) – contains 800 prescriptions, with
similar components as the present:
o Active substance
o Vehicle – animal fat or ointments, water, milk, wine, beer,
honey for liquids
o Preparation – mixed, pounded, boiled, strained, left
overnight
o How to be used – swallow, inhale, gargle, applied externally,
given as enema
 For Example:
o 1/8 cup figs and grapes, bread dough, pit corn, fresh Earth,
onion, and elderberry –cure for diarrhea in ancient Egypt
Figure 1. Writings believed to be that of the Egyptian physician made a
god, Imhotep.
PHARMA 1.1
 Cathartics and purgatives – ejection of GIT contents drove out
the disease-producing evil spirit
 Curatives: all types of plants, nearly all animal parts, mineral
compounds
 Herbs played an important role; also mentioned in Ebers
papyrus;
o Opium, cannabis, myrrh, frankincense, fennel, cassia,
thyme, henna, juniper, aloe, linseed, castor oil
 Garlic – important healing agent
 Coriander and Cumin were also considered also effective
 Some medicines were imported from abroad
C. Greek Medicine
 Observed from the Iliad and the Odyssey
 Battle wounds covered with powdered plant leaves or bark
which contained tannins acting as an astringent and pain
reducer
 Mandrake root – has atropine like substances, inducing a
twilight sleep that protected Ulysses from Circe
 The oriental hellebore containing the cardiotoxic Veratrum
alkaloids was smeared on arrow tips for a more powerful kill
 Great fascination with toxic plant extracts led to increased
knowledge on poisonous aspects of drugs (science of
toxicology)
 Plato’s description of death of Socrates:
o Accurate display of toxicity of juice of hemlock fruit
o Described paralysis of sensory and motor nerves
o Followed by CNS depression and respiratory paralysis
o Precisely matches actions of the hemlock alkaloid, coniine
(we now know that this is the one responsible for the death
of Socrates
D. Central and South American Medicine
 In Indian cultures, drugs were important in rites, religions,
history, and knowledge
 Treated patients with blend of religious rituals and herbal
remedies
 Incantations, charms, and appeals to deities were as important
as the application of poultices, decoctions, and infusions
E. European and South American Paralellism
 Early drug practitioners blended herbs, plants, animals, and
minerals into foul-smelling and ill-flavored concoctions
 Searched for improved formulations to improve taste and
cosmetic properties to ensure patient compliance
o Hence, the beginnings of the discipline of pharmacy –
science of preparing, compounding, and dispensing
medicines
o pharmacognosy – identification and preparation of crude
drugs from natural sources
F. Roman Medicine
 Keen on things that would lead to the direct improvement of the
quality of life of the people in their empire
 Built roads, aqueducts and sewers for belief that water may be a
source of illnesses
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 PHARMA 1.1
 In the early years, there was no separate medical profession:
each head of household is responsible for knowing herbal cures
and medicine to treat illnesses in his household
 Roman write Pliny wrote:
o "Unwashed wool supplies very many remedies…..it is
applied….with honey to old sores. Wounds it heals if dipped
in wine or vinegar….yolks of eggs….are taken for dysentery
with the ash of their shells, poppy juice and wine. It is
recommended to bathe the eyes with a decoction of the liver
and to apply the marrow to those that are painful or
swollen”.
 Believed in a healthy mind equaling a healthy body. If you kept
fit, you would be more able to combat illness. Money spent on
keeping fit rather than on doctor. Figure 3. The Five Elements as seen in the human body. Traditional Chinese
 Believed that illness had a natural cause, bad health was a teachings suggest that if one has a weak heart, one must strengthen the
result of bad water and sewage kidney. This is apparent in people with heart problems also having with edema.
*Note: The spleen is the nourishing organ in the body.
 Polypharmacy: Using several drugs with combined properties to
adjust for patient’s deficiency; tendency of physicians to Table 2. Applications or interpretations of the Five Elements
prescribe large numbers of drugs where one or two would be
sufficient; Problem encountered: drug interactions.
o Traced back to Claudius Galen (A.D. 131-201), considered
greatest European physician after Hippocrates
 Believed drugs had essential properties; warmth,
coldness, dryness, or humidity
 Formulated these rules and laws before factual
information was available for its justification
 Used healing power of nature to develop treatments to
restore balance of four humours
 Believed in use of opposites  By the first century A.D. it was clear to physicians and
Eg. Fever treated with something cold; protopharmacologists that there was variation from one
Weak people treated with physical exercises to biological extract to another
strengthen muscles;  Thus it was reasoned that they must obtain standardized and
uniform medicinal agents
Breathing problems, given singing exercises

F. Parallelisms in Traditional Chinese Medicine III. MEDICINE IN THE MIDDLE AGES

 Medical knowledge in the Middle Ages appeared to have stood
 Principles: Yin and Yang, Five Elements still. After the demise of ancient Roman, Greek, and Egyptian
 Yin and Yang civilizations, the momentum started by these people in
o Harmony of opposites medicine tended to stagnate and it did not develop at the same
o If you are a male, you have something female in you and vice pace until the Seventeenth/Eighteenth Centuries
versa  The Roman Catholic Church dominated what direction the
 Example: A male that is caring for the children (a female medical world took. Any differing views could veer towards
quality) heresy with the punishments that entailed
o If you are hot, there is something cold in you and vice versa
o Everything should exist in balance A. Alchemy
 Auroelus Philippus Theophrastus Paracelstis Bombast von
Hohenheim (1493 - ?) (A.K.A. Paracelsus) - the illustrious
physician and exponent of the hermetic philosophy
o The first physician to use opium and mercury and to
recognize the value of sulphur

B. The Arab Pharmacy

Figure 2. Yin and Yan symbol. The unison of the black and white sides with the
 It was in the Arab period that appeared the first establishments
black and white dots is said to represent a harmony of opposites.
in which pharmacy was practiced as a profession quite apart
from that of healing but this was by no means universal
 The Five Elements: Wood, Fire, Earth, Metal and Water
o First public pharmacy was opened in Baghdad
o The interrelationships of nature are seen as very important
o By the 17th century, it had become the usual method in the
(a concept of Taoism)
large towns
o In smaller places, it was still customary for patient to
prepare his own infusions and decoctions
 The majority of physicians prepared their own compounds

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 PHARMA 1.1
 Rhazes: attempted to classify chemical substances and carried milkmaid who caught cowpox got blisters on her hands.
on original investigations on specific gravity by means of Jenner concluded that the cowpox somehow protected the
hydrostatic balance milkmaids. He then started to unethically experiment with
o “I have prepared an extract of turbith and found its action his theory, injecting the cowpox virus to his participants
similar to that of scammony. I have also prepared in the without obtaining a formal consent.
same way an extract of colocynth pulp. I used to mix it with
kernels of almonds and tragacanth and sugar. Thus
administering it, is less repugnant”
 Avicenna (Ibn Senna): world renowned author of the “Canon”
o founder of the Greco-Arabic school of medicine
o Canon of Avicenna was the most popular text-book in
medicine, and authoritative and used by the Universities of
Europe till as late as 1650
o First authority to describe one of the parasitic infestations of
the body, and also the first to note the sweet taste of urine
of diabetic patients
o Introduced the gilding and silvering of pills
 Avenzoar (A.K.A. Abhomeron): opposed to mystcism and
astrology and left several important works which influenced
Figure 4. Smallpox was responsible for an estimated 300–500 million deaths
pharmacy and alchemy for several centuries
during the 20th century. After vaccination campaigns throughout the 19th and
o Contradicted some of the teachings of Galen 20th centuries, the WHO certified the eradication of smallpox in 1979.A vial of
the organism remains contained at the CDC in Atlanta, USA.
B. Significant Advances
 Joseph Lister: “Father of Antiseptic Surgery”; made the link  Louis Pasteur: 3 great accomplishments
between lack of cleanliness in hospitals and deaths after o He showed that airborne microbes were the cause of
operations disease
 Ignaz Semmelweiss: Hungarian doctor that studied ward o He helped to develop more vaccines
cleanliness and the link between germs and good post-operative o His career showed how conservative the medical
health with his findings on postpartum sepsis establishment was at the time
o Deaths on the wards Semmelweiss was in charge of fell from  Sir Alexander Fleming
12% to just 1% by increasing hygienic practices. o Discovered Penicillin by accident. He correctly observed that
 Antoine-Laurent Lavoisier: “Father of modern chemistry” and the mold Penicillium notatum inhibited the growth of
an eminent physiologist Staphylococcus, a bacteria in the glass plates he was working
o Discovered true nature of respiration when he found that it on
was a process whereby oxygen is taken up by blood in the o 10 years later, Howard Florey and Ernst Chain, working at
lungs Oxford University, isolated the bacteria-killing substance
found in the mould- Penicillin.
IV. 19th CENTURY
 Methods became available for the isolation of active principles
from crude drugs. The development of chemistry made it
possible to isolate and synthesize chemically pure compounds
that would give reproducible biological results.
 Friedrich Wilhem Adam Serturner (1783-1841): In 1806,
isolated the first pure active principle when he purified
morphine from the opium poppy
 Many other chemically pure active compounds were soon
obtained from crude drug preparations, including:
o emetine by Pelletier (1788–1844) from ipecacuanha root
o quinine by Carentou (1795–1877) from cinchona bark
o strychnine by Magendie (1783–1855) from nux vomica; and, Figure 5. Penicillin and sulphonamides were used during the two world wars.
o in 1856, cocaine by Wohler (1800–1882) from coca Penicillin in particular was the wonder drug that saved a countless number of
 The isolation and use of pure substances allowed for an analysis soldiers.
of what was to become one of the basic concerns of
pharmacology, that is, the quantitative study of drug action.  Francoise Magendie & Claude Bernard, through laboratory
 It was soon realized that drug action is produced along a studies of animal physiology, provided an environment
continuum of effects, with low doses producing a less but conducive to the creation of similar laboratories for the study of
essentially similar effect on organs and tissues as high doses - pharmacological phenomena.
The appearance of toxic effects of drugs was frequently a o Rudolph Bucheim (1820-1879) established one of the first
function of the dose-response relationship. laboratories devoted almost exclusively to drug research.
 Edward Jenner: Vaccination for smallpox  Lived in Dorpat, Estonia, late 1840s
o Rural milkmaids did not get smallpox. He believed that  This laboratory, built in Bucheim’s home, was devoted to
milkmaids only got a weak version of smallpox – the non-life studying the actions of agents such as cathartics, alcohol,
threatening cowpox – but did not get smallpox itself. A chloroform, anthelmintics, and heavy metals
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 Bucheim believed that “the investigation of drugs is a
task for pharmacologist and not for a chemist or
pharmacist, who until now have been expected to do
this.”
 Much more was required to raise the discipline to the same
prominent position occupied by other basic sciences
o This included the creation of chairs in pharmacology at other
academic institutions and the trainign of sufficient number
of talented investigators to occupy these positions
o Task of training new investigators was accomplished largely
by Bucheim’s pupil and successor at Dorpat, Oswald
Schmiedeberg (1838-1921), the most prominent
pharmacologist of the nineteenth century
 Conducted his own outstanding research on
pharmacology of diuretics, emetics, cardiac glycosides,
and so forth
 Wrote an important medical textbook and trained
approximately 120 pupils from more than 20 countries
 Many of these new investigators either started or
developed laboratories devoted to experimental
pharmacology in their own countries
 John Jacob Abel: One of Schmiedeberg’s most outstanding
students.
o Founder of American pharmacology
o Occupied the chair of pharmacology first at the University of
Michigan and then at Johns Hopkins University.
o Examined the chemistry and isolation of the active principles
from the adrenal medulla (monobenzyl derivative of
epinephrine) and the pancreas (crystallization of insulin)
o Also examined mushroom poisons, investigated the
chemotherapeutic actions of arsecincals and antimonials,
conducted studies on tetanus toxin, and designed a model
for an artificial kidney
o Founded the following journals:Journal of Experimental
Medicine, Journal of Biological Chemistry, Journal of
Pharmacology and Experimental Therapeutics
o His devotion to pharmacological research, enthusiasm for
the training of students in his new discipline, and
establishment of journals and scientific societies proved
critical to the rise of experimental pharmacology in the
United States.
PHARMA 1.1
 In the past 100 years, the expansion of medical information has
come about largely through the contributions of the biological
sciences to medicine by a systematic approach to the
understanding and treatment of disease.
 The experimental method and technological advances are the
foundations upon which modern medicine is built.
VII. PHARMACOLOGY IN THE PHILIPPINES
 Scholars from UP and UST were sent to the USA to learn about
pharmacology
 Colleges of Medicine set up their own department of
Pharmacology
 Local research on the drugs for common local conditions
 Dr. Romulo P. Guevara, Sr.
o First Head, UERMMMCI Dept of Pharmacology
o Special training in US:
 Graduate work in Pharmacodynamics, Experimental
Therapeutics, and Bioassays from Cornell, Harvard, Johns
Hopkins, Michigan State, Pennsylvania and Yale
Universities
o 41 publications on such familiar agents as Tiki-tiki, digitalis
ergot, castor oil, tangan-tangan oil, antimicrobials, pitressin,
emetine, piperazine, morphine, serotonin, atropine, and
hydroxytryptamine
 During time of the war, there was Beri Beri, a Vitamin B
deficiency. Tiki-Tiki is a Vitamin B complex and was used
to wipe out Beri Beri.
 Philippine Society for Experimental and Clinical Pharmacology
o Started in the 1970s by eight universities in the Philippines,
University of the East being one of them
o This society is now linked with several societies abroad. It is
linked with the International Society of Pharmacovigilance
o Ethnopharmacology is not going back to the old times, but
seams what we learned in the past with the present
scientific methods and technology that we have.
 Eg. Balbas pusa: used to treat hypertension.
 Concepts from Traditional Chinese medicine and Tibetan
medicine are also being studies today

V. THE DISCIPLINE OF PHARMACOLOGY

 Pharmacology, as a separate and vital discipline, has distinct
interests from the other basic sciences and pharmacy. Its
~Tomorrow begins in the East~
primary concern is not the cataloguing of the biological effects
that result from the administration of chemical
 Pharmacology is concerned with the dual aims of:
o (1) providing an understanding of normal and abnormal
human physiology and biochemistry through the application
of drugs as experimental tools and
o (2) applying to clinical medicine the information gained from
fundamental investigation and observation
VI. THE 20TH CENTURY
 Sir James Black: developed propanolol which became the
world’s most widely sold drug for hypertension and heart
disease. The development of Propanolol is now considered to be
one of the most important medical events of the Twentieth
Century.
o Black later joined Smith, Kline and French and while he was
working for them he developed he second major medical
find – cimetidine, which was used to treat peptic ulcers

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