PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
PHARM 100 – Module 1
Section 1: History of Drug Use and Development
• Drugs have been used since before recorded history; a few were useful but majority of
useful clinical drugs have been developed in the past 250 years
Historical Influences on Modern Pharmacology
• Civilizations
o Ancient Greece: opium was found to contain to important substances
▪ Codeine: used for pain relief, Tylenol, over the counter (0.5%)
▪ Morphine: relieve intense pain (10%)
o Ancient Egypt: papyrus text on use of drugs specifically senna
o Ancient China: earliest recorded drug experiments, drugs classified according
to taste
• Poison: when used in ancient times led to drug developments
o Curare: used on the tips of arrowheads VS anesthetic in surgery
(muscle relaxation)
o Ergot: violent contractions, constriction of vessels, hallucinations vs migraine
treatment and no longer for enhancing birth
• Religion: medicine men were physicians and priests, therapy influenced by religion and
magic, most substances used to alter state of consciousness to communicate with gods
o Peyote cactus similar to LSD
Drug Discovery
• ¼ of drugs today are derived from plant sources and the rest are obtained through
chemical synthesis in a laboratory
Drugs Acting on the Brain
• Reserpine and Chlorpromazine
o Discovery: came from the extracts of the rauwolfia plant used to reduce
tension, anxiety and blood pressure, aggressive animals became placid when
taken
o Therapeutic uses: management of mentally ill patients (anxious, tense, hostile),
difficult to prescribe
o Benefits: large social benefit, returning back to everyday life
• Lysergic Acid Diethylamide (LSD)
o Discovery: came from originally trying to synthesize improved components
of ergot
o Contribution: supported the idea that certain mental illnesses might be due to
production of potent substances that caused a disturbance
• Anesthetics
,PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o Nitrous oxide: laughing gas, inhaled and became belligerent and fought, gashed
leg but felt no pain used in extraction of teeth (Wells)
o Ether: similar to nitrous oxide, used in a surgical operation, complete success
(Morton)
Drugs Acting Against Infectious Disease
• Organoarsenicals (Ehrlich, 1900): arsenic and organic compounds that bound to
parasites, led to dramatic cure for syphilis, Father of Chemotherapy
• Sulfa Drugs (Domagk, 1930): first successful drug treatment of bacterial diseases
antibacterial
• Penicillin (Fleming, 1940): first antibiotic, used in WWII
• Streptomycin (Walksman, 1950): turning point in treatment of tuberculosis
Section 2: Drug Development, Drug Trials and Drug Advertising
Drug Development Process
• Drug Discovery: identifying a biological target for the potential drug is the first step
o For example, a target could be when activated it causes an increase in
blood pressure
o Once a compound binds well to the target it is then studied for pharmalogical
effects at various levels
o If the compound shows promise it is then identified as lead and enters more
detailed studies for safety and efficacy
• Preclinical
o Is it safe and effective?
o Conducted prior to testing drugs on humans
o Two main categories
▪ Toxicology: determine effect of drug on organ systems other than
targeted organ (adverse effects), all drugs have some toxicity dose
▪ Pharmacology: determine mechanisms of action of new drug
• Clinical Trials: Initial Steps
1. Submit proof of safety and efficacy to government regulatory agency
2. Methodology in humans is required
3. Submission evaluated, if satisfied permission will be given to begin investigation of
drugs in humans
• Phase 1: 20-100 volunteers
o Conducted in a limited number of healthy people
o Absorption, distribution, elimination, and adverse effects evaluated
o One or two doses administered
o Effectiveness not assessed
• Phase 2: 100-500
o Conducted in patients with disease that’s targeted
,PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o Determine effectiveness in treating condition recommended for (still limited)
o Careful attention to safety
• Phase 3: 1000-5000
o Controlled randomized clinical trials, main study used for licensing and
marketing of drug
o Test the drug in larger number of people to obtain more info on safety and
efficacy
o Usually longer
o Conducted at centers in many cities
o Most expensive part
o Determine if safe and effective
• Basic Elements of Phase 3 Trials
o Target population: have to be carefully defined, for whom the drug is intended
▪ Inclusion/exclusion: define the characteristics of the patients used in the
study (is and is not eligible), tries to eliminate all other variables other
than drug
▪ Consent: informed consent must be obtained, consists of document that
outlines purpose of study, procedures used, potential risks and benefits
• They have to fully understand what they are getting into
o Study population random allocation: ensures patients are assigned to treatment or
control by chance, randomization, ensures different characteristics are equally
distributed which maximizes comparability, removes potential bias
o Treatment: patients receive experimental drug
o Blinded assessment: double blind manner neither investigator nor subject is
aware of treatment
o Control: drug that the treatment is compared to
▪ Placebo: does not contain the active drug but is identical to appearance,
colour, taste and size
▪ Gold standard: drug that is accepted by the medical community as best
available treatment for specific disease, this is what control group receives
(placebo used if unavailable)
o Outcome: result should be measured in an objective and reliable manner (same
time, day, person, and technique)
o Additional Components
▪ Compliance: how often the patient actually took the drug, need to have so
trials are valid, generally asked to return unused drugs
▪ Quality of life: measures impact of drug on this, hope is to improve,
considered when determining the usefulness
▪ Result analysis: experimental drug compared to control using statistics,
sometimes very small
• Health Canada Review
, PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o At successful completion of phase 3 trials, the new drug application with results
will be submitted to regulatory body
o Results are again reviewed and if deemed effective and toxicity is acceptable then
it will be granted approval
• Manufacturing
o Generic vs brand name:
▪ Chemical names are too complex so generic name is selected for
placement on market
▪ Patent for brand name is applied for, which gives company exclusive
rights for 20 years on market
▪ Patent life begins when it is filed (10-12 years is normal for effective life)
▪ After it expires other companies can make copies
o Bioavailability studies
▪ New brand names and generic will contain identical active ingredient as
original brand name in the same amount and dosage
▪ Compares blood levels after administration of original and new to make
sure they are bioequivalent
▪ Strict regulations are in place so that this happens
• Phase 4: Post-Approval
o Tests over longer periods of time, in different groups of people and
in combination with other treatments
o Post marketing surveillance for delayed or less frequent risks
Drug Advertising
• Advertising is what convinces physicians to prescribe a new drug and patients to take it
• For every dollar spent, 25 cents go to promotion of drugs
• Advertising influences prescribing habits of physicians
• Lack of info on adverse effects of drugs is a major deficiency of drug
advertisement Advertising Techniques
• Before-after: show person in an undesirable situation then a picture of the person taking
drug in a desirable situation
• Fear: illicit fear then provide drug to abate it
• Easy solution: focuses on how easy it is to treat something specifically with drug
• Catch attention: add is designed in a way that draws the eye
• Authorities/celebrities endorse: trusting, admire
• Discredit others, praise your own: make the new drug look better than any other on the
market that treat the same thing
Section 3 – Drug Action
Drug Targets
– Module 6
PHARM 100 – Module 1
Section 1: History of Drug Use and Development
• Drugs have been used since before recorded history; a few were useful but majority of
useful clinical drugs have been developed in the past 250 years
Historical Influences on Modern Pharmacology
• Civilizations
o Ancient Greece: opium was found to contain to important substances
▪ Codeine: used for pain relief, Tylenol, over the counter (0.5%)
▪ Morphine: relieve intense pain (10%)
o Ancient Egypt: papyrus text on use of drugs specifically senna
o Ancient China: earliest recorded drug experiments, drugs classified according
to taste
• Poison: when used in ancient times led to drug developments
o Curare: used on the tips of arrowheads VS anesthetic in surgery
(muscle relaxation)
o Ergot: violent contractions, constriction of vessels, hallucinations vs migraine
treatment and no longer for enhancing birth
• Religion: medicine men were physicians and priests, therapy influenced by religion and
magic, most substances used to alter state of consciousness to communicate with gods
o Peyote cactus similar to LSD
Drug Discovery
• ¼ of drugs today are derived from plant sources and the rest are obtained through
chemical synthesis in a laboratory
Drugs Acting on the Brain
• Reserpine and Chlorpromazine
o Discovery: came from the extracts of the rauwolfia plant used to reduce
tension, anxiety and blood pressure, aggressive animals became placid when
taken
o Therapeutic uses: management of mentally ill patients (anxious, tense, hostile),
difficult to prescribe
o Benefits: large social benefit, returning back to everyday life
• Lysergic Acid Diethylamide (LSD)
o Discovery: came from originally trying to synthesize improved components
of ergot
o Contribution: supported the idea that certain mental illnesses might be due to
production of potent substances that caused a disturbance
• Anesthetics
,PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o Nitrous oxide: laughing gas, inhaled and became belligerent and fought, gashed
leg but felt no pain used in extraction of teeth (Wells)
o Ether: similar to nitrous oxide, used in a surgical operation, complete success
(Morton)
Drugs Acting Against Infectious Disease
• Organoarsenicals (Ehrlich, 1900): arsenic and organic compounds that bound to
parasites, led to dramatic cure for syphilis, Father of Chemotherapy
• Sulfa Drugs (Domagk, 1930): first successful drug treatment of bacterial diseases
antibacterial
• Penicillin (Fleming, 1940): first antibiotic, used in WWII
• Streptomycin (Walksman, 1950): turning point in treatment of tuberculosis
Section 2: Drug Development, Drug Trials and Drug Advertising
Drug Development Process
• Drug Discovery: identifying a biological target for the potential drug is the first step
o For example, a target could be when activated it causes an increase in
blood pressure
o Once a compound binds well to the target it is then studied for pharmalogical
effects at various levels
o If the compound shows promise it is then identified as lead and enters more
detailed studies for safety and efficacy
• Preclinical
o Is it safe and effective?
o Conducted prior to testing drugs on humans
o Two main categories
▪ Toxicology: determine effect of drug on organ systems other than
targeted organ (adverse effects), all drugs have some toxicity dose
▪ Pharmacology: determine mechanisms of action of new drug
• Clinical Trials: Initial Steps
1. Submit proof of safety and efficacy to government regulatory agency
2. Methodology in humans is required
3. Submission evaluated, if satisfied permission will be given to begin investigation of
drugs in humans
• Phase 1: 20-100 volunteers
o Conducted in a limited number of healthy people
o Absorption, distribution, elimination, and adverse effects evaluated
o One or two doses administered
o Effectiveness not assessed
• Phase 2: 100-500
o Conducted in patients with disease that’s targeted
,PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o Determine effectiveness in treating condition recommended for (still limited)
o Careful attention to safety
• Phase 3: 1000-5000
o Controlled randomized clinical trials, main study used for licensing and
marketing of drug
o Test the drug in larger number of people to obtain more info on safety and
efficacy
o Usually longer
o Conducted at centers in many cities
o Most expensive part
o Determine if safe and effective
• Basic Elements of Phase 3 Trials
o Target population: have to be carefully defined, for whom the drug is intended
▪ Inclusion/exclusion: define the characteristics of the patients used in the
study (is and is not eligible), tries to eliminate all other variables other
than drug
▪ Consent: informed consent must be obtained, consists of document that
outlines purpose of study, procedures used, potential risks and benefits
• They have to fully understand what they are getting into
o Study population random allocation: ensures patients are assigned to treatment or
control by chance, randomization, ensures different characteristics are equally
distributed which maximizes comparability, removes potential bias
o Treatment: patients receive experimental drug
o Blinded assessment: double blind manner neither investigator nor subject is
aware of treatment
o Control: drug that the treatment is compared to
▪ Placebo: does not contain the active drug but is identical to appearance,
colour, taste and size
▪ Gold standard: drug that is accepted by the medical community as best
available treatment for specific disease, this is what control group receives
(placebo used if unavailable)
o Outcome: result should be measured in an objective and reliable manner (same
time, day, person, and technique)
o Additional Components
▪ Compliance: how often the patient actually took the drug, need to have so
trials are valid, generally asked to return unused drugs
▪ Quality of life: measures impact of drug on this, hope is to improve,
considered when determining the usefulness
▪ Result analysis: experimental drug compared to control using statistics,
sometimes very small
• Health Canada Review
, PHARM 100 - Midterm Notes . – Module 1TO
– Module 6
o At successful completion of phase 3 trials, the new drug application with results
will be submitted to regulatory body
o Results are again reviewed and if deemed effective and toxicity is acceptable then
it will be granted approval
• Manufacturing
o Generic vs brand name:
▪ Chemical names are too complex so generic name is selected for
placement on market
▪ Patent for brand name is applied for, which gives company exclusive
rights for 20 years on market
▪ Patent life begins when it is filed (10-12 years is normal for effective life)
▪ After it expires other companies can make copies
o Bioavailability studies
▪ New brand names and generic will contain identical active ingredient as
original brand name in the same amount and dosage
▪ Compares blood levels after administration of original and new to make
sure they are bioequivalent
▪ Strict regulations are in place so that this happens
• Phase 4: Post-Approval
o Tests over longer periods of time, in different groups of people and
in combination with other treatments
o Post marketing surveillance for delayed or less frequent risks
Drug Advertising
• Advertising is what convinces physicians to prescribe a new drug and patients to take it
• For every dollar spent, 25 cents go to promotion of drugs
• Advertising influences prescribing habits of physicians
• Lack of info on adverse effects of drugs is a major deficiency of drug
advertisement Advertising Techniques
• Before-after: show person in an undesirable situation then a picture of the person taking
drug in a desirable situation
• Fear: illicit fear then provide drug to abate it
• Easy solution: focuses on how easy it is to treat something specifically with drug
• Catch attention: add is designed in a way that draws the eye
• Authorities/celebrities endorse: trusting, admire
• Discredit others, praise your own: make the new drug look better than any other on the
market that treat the same thing
Section 3 – Drug Action
Drug Targets
