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CA (170,000)
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Chapter Mod 1

PHAR 100 Chapter Notes - Chapter Mod 1: Lauder Brunton, Shennong, Angina Pectoris


Department
Pharmacology and Toxicology
Course Code
PHAR 100
Professor
Bill Racz
Chapter
Mod 1

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Module 1: Basic Principles of Pharmacology
1.1 History
Influence of religion
in ancient times, medicine men were both doctors and priests --> drug therapy was heavily
influenced by both religion and magic. An example of this is Peyote in Mexico used to achieve
a mystical state which contains mescaline.
Influence of Poisons
Paracelsus 16th c “All substances are poisons. There is none which is not a poison. The right
dose differentiates a poison and a remedy.”
1. West and Central Africa: Poisons used in ordeal trials to identify sorcerers. Everyone was
given a poison, and those that did not vomit died and were identified.
2. Amazon: Poison arrows dipped in curare. Causes paralysis and death by preventing
acetylcholine from combining with the receptor, preventing muscle contraction. Curare was
later used by anesthetists during surgery in small doses, and has now been modified to be safer.
3. Russia: Ergot fungus is found on rye in wetter seasons. Ergot is poisonous and causes: a)
burning in the limbs b) constriction of blood vessels c) mental frenzy d) abortion. In modernity,
two active principles have been isolated from Ergot. 1) Ergotamine: treats migraines as a
vasoconstrictor. 2) Ergonovine: used to be used to hasten birth, now used to arrest uterine
bleeding after childbirth.
Early Chinese Medicine
earliest recorded drug experiments are from China in 2700 BC. Emperor Shen Nung tasted all
drugs and classed them by taste. Modern Chinese medical practitioners still believe strongly in
the value of ancient herbs (ie. Shaved antelope horn in place of aspirin)
Early Egyptian Medicine
Ebery Papyrus from 1550 BC was intended to be used as a textbook for med students. Used
Senna as a laxative (still available today)
Early Greek Medicine
In 280 BC Theophrastus wrote a textbook on therapeutics that covered opium. Opium was
found to contain 10% morphine which is still considered the gold standard for pain
management. Opium also contains 0.5% codeine used in OTC drugs like Tylenol.
Spain Persia and Mesopotamia
Maimonides “Never use two drugs where one will do” --> still a fundamental principle of drug
therapy.
Colchicum was first used here for gout. Today the chemical colchicine is extracted from the
plant and is still used today.
Drug Discovery (18th -20th centuries)
25% of modern drugs are derived from plant sources
Drugs acting on the heart:
Digitalis (foxglove): introduced in 1785 by William Withering. Modern drugs using this are
Lanoxin and Digoxin.
Nitroglycerin: introduced in 1867 by Lauder Brunton for treatment of angina pectoris
Quinine: derived from the bark of the south american cinchona tree. Used for arrhythmias
and malaria.
Drugs acting on the Brain:
Reserpine and chlorpromazine: introduced in 1953 to treat mental patients. Derived from
the rauwolfia plant.
LSD: Albert Hoffman in 1943
Anaesthetics: NO intro'd in 1800 by Humphrey Davy

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Paul Erlich: father of chemotherapy. Designed complexes of arsenic and organic molecules which
selectively bound to parasites. Lead to a cure for syphilis in the early 20th C
Gerhard Domagk: Intro'd sulfa drugs in the 30s in German --> first successful synthetic drugs in the
treatment of bacterial disease
Alexander Fleming: Discovered penicillin in 1929 as a treatment for gram-positive bacterial disease
Selman Waksman: Discovered streptomycin in 1943, a turning point in the treatment of TB and
gram-negative bacterial diseases.
SUMMARY OF DRUGS
Hallucinogens: mescaline, LSD
Analgesics (pain relieving
drugs):
morphine, codeine, heroin, aspirin, acetaminophen (Tylenol)
Cardiovascular: digoxin, nitroglycerin, amyl nitrite, quinidine, reserpine
Antimicrobial: organoarsenicals, sulfa, penicillin, streptomycin
Anaesthetics: nitrous oxide, ether
Drugs used in psychiatry: chlorpromazine, reserpine
Other drugs covered: physostigmine (glaucoma)
curare (muscle relaxation) – modified to be safer
ergotamine (migraine) – replaced by better drugs
ergonovine (obstetrics)
senna (purgative)
ephedrine (asthma) – largely replaced by better drugs
colchicine (gout)
quinine (malaria)
1.2: Drug development, trials, and advertising
Major
Stage Sub-stage
Time
Required
(years)
Number of
Compounds Result
Drug
Discovery
Research and
Discovery of Target
2 to 8
(or more) Up to 25,000 Discovery of lead compounds
Preclinical Testing 2 to 6 Start with 30,
reduce to 5
Determine safety and
potentialefficacy
Clinical
Trials
Phase 1 1 year 4 to 5 Safety and tolerability
Phase 2 2 years 2 to 3 Effectiveness, safety
andpharmacokinetics
Phase 3 3 to 5 years 1 Effectiveness and safety
Phase 4 Ongoing 1 Long term safety
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Phase 1: The study is conducted using a small number of health volunteers. Absorption, distribution,
elimination, and adverse effects are studied. Effectiveness of the drug is not studied at this time, only
tolerability.
Phase 2: Determine whether the drug is effective in treating the condition it is recommended for. Uses a
limited number of people, and is given to individuals with the disease in question. Also called “proof of
concept” studies.
Phase 3: Drug is tested in larger numbers of people to study the safety and efficacy of it. If the drug is
found to be safe and effective, it will hit the market. These trials are controlled randomized clinical
trials and last longer than phase 2 studies (months to years) and are multi-centred. Most expensive part
of drug development. Common components of clinical trials: 1) Target Population is carefully defined
2) Inclusion and Exclusion Criteria 3) Ethical Considerations and Consent 4) Comparator 5)
Randomization 6) Blinding 7) What is Measured 8) Compliance 9) Quality of Life Measure 10)
Analysis of the Results
Phase 4: Long term surveillance of the drug after it is released for general use.
Assessing reports on clinical trials:
1. What question is the study designed to answer?
2. How were the patients assigned to treatment and control groups?
3. How were the patients selected?
4. How was the study designed to minimize patient and observer bias?
5. Who makes the observations?
6. Is there a clear definition of the desired therapeutic response?
7. Is the therapeutic response to be measured by objective or subjective criteria?
8. Have the data been subjected to statistical analysis?
9. Has the study answered the question that was initially posed?
10. Were the patients selected for the trial typical of those for whom the drug is now
recommended? If a drug has been tested in a male population only, is it recommended for both
men and women or for men only?
Advertising
for every dollar spent on drugs in Canada, $0.25 goes to advertising (mainly to physicians)
is the popularity of certain drugs based on efficacy or smart advertising?
Techniques:
1) Catch Audience Attention: this is to be drawn to the attention of the physician in most cases,
and involves a well designed poster or pamphlet.
2) Use of celebrities/authorities to endorse products: celebrities or organizations pertaining to the
disease treated.
3) Fear: Illicit fear in the person showing that the drug will help avoid that fearful scenario.
4) Offering an easy solution to problems: how easy and simple it is to treat the disease or ailment
with the drug
5) Before-after techniques: the drug will turn the undesirable before scenario into the desirable
after scenario.
6) Discredit other drugs and praise your own
1.3: Drug Action, Dose-Response Curves, Variability in Response
a drug can be described as a substance received by a biological system that is not received for
nutritive purposes, and which influences the biological function of the organism. This includes
chemicals, biologicals, and herbals are all considered drugs .
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