LECTURE 1 - Introduction to Pharmacology
Sunday, January 21, 2024
12:32 PM
LEARNING OUTCOMES:
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Define pharmacology
Discuss the interdisciplinary nature of pharmacology
Compare and contrast therapeutics and pharmacology
Compare and contrast conventional drugs, biologics, and natural health products
Identify the advantages and disadvantages of prescription and over the counter (OTC) drugs
Identify key Canadian drug regulations that help to ensure the safety and efficacy of medications
Discuss the role of Health Canada and the Health Products and Food Branch (HPFB) of Health Canada and its
Therapeutic Products and Directorate in the drug approval process
Describe the stages of approval for therapeutic and biologic drugs in Canada
PHARMACOLOGY
• Effective use of drugs and medications by a health care team depends on being able to
apply knowledge related to anatomy & physiology, pathophysiology, chemistry,
microbiology
PHARMACOLOGY - the study of MEDICATIONS
DRUG - substance capable of producing a BIOLOGIC RESPONSE
MEDICATION - a drug given for the purpose of producing a THERAPEUTIC RESPONSE
• Classifying a substance as a drug or a medication is not always simple
THERAPEUTICS - a branch of medicine concerned with the prevention of disease and treatmen
of suffering
• Pharmacotherapeutics refers to using medications (to prevent disease and treat
suffering)
The CLASSIFICATION OF DRUGS
• Traditional medications
• Biologics
• Natural health products
TRADITIONAL Medications
• Produced by a pharmaceutical manufacturer
○ Aspirin - in Canada, "Aspirin" remains a trademark, so generic aspirin is sold as
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• Biologics
• Natural health products
TRADITIONAL Medications
• Produced by a pharmaceutical manufacturer
○ Aspirin - in Canada, "Aspirin" remains a trademark, so generic aspirin is sold as
ASA (AcetylSalicylic Acid)**
BIOLOGIC Medications
• Agent produced by animal cells and microorganisms
○ Hormones, antibodies, vaccines
NATURAL Medications
• Natural health products
○ Natural plant extracts
○ Vitamins, minerals
○ Dietary supplements
PRESCRIPTION DRUGS
• Require a dispensing order (a prescription) from a qualified health care professional
PRIOR to patient receiving drug
Patients MUST receive authorization to receive the drug, Why…..?
• Drugs may be too harmful for self-administration
• Drugs may treat complex diseases
• May require skill to administer
• Drugs may be addictive*
○ In 2017, 1-in-10 (11%) students in grades 7-12 (an estimated 98,300 in Ontario)
report using a prescription opioid pain reliever (Percocet, Percodan, Tylenol #3,
Demerol, Dilaudid)
• Drugs may treat complex diseases
• May require skill to administer
• Drugs may be addictive*
○ In 2017, 1-in-10 (11%) students in grades 7-12 (an estimated 98,300 in Ontario)
report using a prescription opioid pain reliever (Percocet, Percodan, Tylenol #3,
Demerol, Dilaudid)
○ In 2017, about 3% of students grades 7-12 (an estimated 23,000 in Ontario) report
using a drug typically used to treat Attention-Deficit/Hyperactivity Disorder (ADHD
in children (Adderall, Ritalin, Concerta, Dexedrine) WITHOUT a prescription
BENEFITS to Prescription Drugs
• Health care provider can examine and diagnose patient prior to ordering medication,
ensuring that the order is appropriate for patient and condition
• Dose and frequency of dispensed drug can be controlled
• Patient provided with education about drug including dosing, interactions, adverse effect
• Maximize therapy
• Patient follow-up
OVER-THE-COUNTER (OTC) DRUGS
• Drugs that can be obtained by patients WITHOUT consultation with a health care provide
BENEFITS to OTC Drugs
• Cost-effective
• Convenience
• Quick relief
• Self-treatment -- patients can treat themselves for common conditions by following
directions on packaging
• Usually have a high margin of safety and few adverse effects
• Do NOT require authorization from healthcare provider
• Must carefully follow directions
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• Quick relief
• Self-treatment -- patients can treat themselves for common conditions by following
directions on packaging
• Usually have a high margin of safety and few adverse effects
• Do NOT require authorization from healthcare provider
• Must carefully follow directions
• No monitoring from healthcare provider needed
RISKS to OTC Drugs
• **no drug is without risk**
• Patient may not choose proper medications
• No assistance from health care provider
• May interact with food, herbals, prescription, or other OTC drugs
• May be ineffective or harmful
PRESCRIPTION DRUGS VS. OTC DRUGS
• Reclassification
○ Prescription drugs can be changed to OTC drugs
○ Decision initiated by manufacturer or mandated by FDA
○ High safety margin must exist
OTC DRUGS
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Self medication
Off the shelf
For general public use
If not taken properly, can lead to
worse patient condition
BOTH
• FDA regulated
• Drugs
• Potential side
effects
SUPPLEMENTS
• Herbal and dietary supplements are not drugs
• Not subjected to the same regulatory process
• Can cause side effects and interact with medications
• Not tested by FDA for safety
CANADIAN DRUG REGULATIONS
PRESCRIPTION DRUGS (Rx)
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MD prescription
Pharmacy
Prescribed use for 1 person
Prescription drugs require more
patient education
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Herbal and dietary supplements are not drugs
Not subjected to the same regulatory process
Can cause side effects and interact with medications
Not tested by FDA for safety
CANADIAN DRUG REGULATIONS
• Created to protect the public from drug misuse and to provide mechanism for quality
assurance for safety and efficacy
• Health Products and Food Branch (HPF B) of Health Canada is responsible for ensuring th
safety and quality of drugs, biologics and natural health products
• Standard is set by Food and Drug Act and Regulations:
○ Therapeutic Products Directorate (TPD)
§ Federal authority that regulates pharmaceutical drugs
§ Manufacturer must provide substantive evidence of a drug's safety, efficacy
and quality, per Food and Drug Act and Regulations, to TPD for approval
§ TPD approval required for drug to be marketed in Canada
○ Biologics and Genetic Therapies Directorate
§ Parallel branch to TPD that regulates biologics and radiopharmaceuticals
○ Natural and Non-Prescription Health Products Directorate
§ Parallel branch to TPD that regulates natural health products
CANADIAN DRUG APPROVAL PROCESS
A seven-step process that includes preclinical and clinical trials, pre-market review and approv
and post-market evaluation:
1. Preclinical trials
○ Using cultured cells, living tissues and small animal models
2. Clinical trial application and testing
○ Phase I - healthy subjects -- evaluate safety of drug and possible adverse effects
○ Phase II - small group of patients with target condition
○ Phase III - large group of patients with target condition
3. Manufacturer completes New Drug Submission (NDS) to Health Canada
CANADIAN DRUG APPROVAL PROCESS
A seven-step process that includes preclinical and clinical trials, pre-market review
and approval and post-market evaluation:
1. Preclinical trials
○ Using cultured cells, living tissues and small animal models
2. Clinical trial application and testing
○ Phase I - healthy subjects -- evaluate safety of drug and possible adverse
effects
○ Phase II - small group of patients with target condition
○ Phase III - large group of patients with target condition
3. Manufacturer completes New Drug Submission (NDS) to Health Canada
○ Outlines test data obtained from clinical trials, indication, adverse effects,
production and packaging
4. Review of NDS submission
○ Committee of drug experts reviews NDS to identify benefits and risks
5. Health Canada shares information about drug with health care providers and
consumers
6. Issuance of DIN and notice of compliance
○ If approved, Health Canada issues a Drug Information Number (DIN) and a
Notice of Compliance to manufacturer (both are required for marketing of
a drug)
7. Evaluation of drug safety and efficacy
○ Health Canada continues to evaluate drug safety and efficacy through
quality assurance (QA) processes
THALIDOMIDE
• The release of thalidomide in the 1950s and 1960s led to the world's most
publicized pharmaceutical disaster
• Thalidomide was invented in the early 1950s by scientists working for a German
pharmaceutical company ChemieGrunenthal, who believed the drug could
succeed as a sleeping pill and a sedative and it was marketed in 1957, first in
Germany and then throughout Europe
• The release of thalidomide in the 1950s and 1960s led to the world's most
publicized pharmaceutical disaster
• Thalidomide was invented in the early 1950s by scientists working for a German
pharmaceutical company ChemieGrunenthal, who believed the drug could
succeed as a sleeping pill and a sedative and it was marketed in 1957, first in
Germany and then throughout Europe
• Thalidomide was marketed internationally to pregnancy women in the late
1950s and early 1960s as a treatment for morning sickness
• Horrifically, it killed an estimated 80,000 children around the world before they
were born, and 20,000 more who survived were born without limbs, with
severe nerve damage, and an array of other ailments
• By 1960, thalidomide was marketed in 46 countries, with sales nearly matching
those of aspirin
Thalidomide Babies
• Australian obstetrician Dr. William McBride discovered that the drug also
alleviated morning sickness. He started recommending this off-label use of the
drug to his pregnant patients, setting a worldwide trend
• McBride began to associated this so-called harmless compound with severe
birth defects in the babies he delivered with deformities such as phocomelia as
a consequence of thalidomide use
• Other effects included deformed eyes and hearts, deformed alimentary and
urinary tracts, blindness, and deafness
Removal from the Market
• It took some time before the increasing number of babies being born with
malformations was connected with thalidomide, despite the existence of
reports of birth defects associated with the drug
• Initially the phenomenon was blamed on nuclear weapon testing and lack of
healthy nutrition and behaviour of the mothers
• When a German newspaper published that 161 babies were adversely affected
by thalidomide, marked the beginning of the end, leading the makers of the
drug to finally stop distribution within Germany. Other countries followed, and
by March of 1962, the drug was banned in most countries where it was
previously sold
FDA Refusal
• ChemieGrunethal approached Smith, Kline & French (SFK), with a request to
market and distribute the drug in the United States, however said marketing
and distribution of the drug were denied by the FDA
• FDA inspector Frances Kelsey considered the application for thalidomide
contained incomplete data on its safety and effectiveness. ChemieGrunethal
applied for its approval 6 more times, through different distributors and
manufactures, and 6 more times Frances Kelsey refused
Thalidomide Distribution in the US
• Clinical trials were not under supervision nor needed approval by the FDA at the
time, which resulted in about 2.5 million doses being distributed in the United
applied for its approval 6 more times, through different distributors and
manufactures, and 6 more times Frances Kelsey refused
Thalidomide Distribution in the US
• Clinical trials were not under supervision nor needed approval by the FDA at the
time, which resulted in about 2.5 million doses being distributed in the United
States
• Smith, Kline, and French and other pharmaceutical companies conducted
animal tests and ran clinical trials of the drug in the United States involving
about 20,000 people, including pregnant women
• A total of 17 children in the United States were born with thalidomide-induced
malformations
Time for a Change
• FDA inspector Frances Kelsey, who prevented the drug's approval within the
United States was praised as a hero and received the President's Award for
Distinguished Federal Civilian Service by John F. Kennedy
• The tragedy surrounding thalidomide helped motivated profound changes in
the FDA. By passing the Kefauver-Harris Amendments Act in 1962, legislators
tightened restrictions surrounding the surveillance and approval process for
drugs to be sold in the United States, requiring that manufacturers prove they
are both safe and effective before they are marketed
Children of Thalidomide
Many children in the 1960s were born with phocomelia as a side effect of the drug
thalidomide, resulting in the shortening or absence of LIMBS