Drug Evaluation and Approval Flashcards
(80 cards)
When was the Penicillin Structure described?
1945
What was synthesized based on the Penicillin structure?
More Beta-Lactams
Ampicillin
Carbenicillin
Methicillin
When was the mechanism of penicillin described?
1965
Describe the Discovery of Aspirin.
Willow Bark had been used as an analgesic and antipyreti for centuries - Hippocrates wrote about using willow leaves for fever. (400 BC)
Salicylic Acid - the active ingredient was isolated in the 1700s.
Were able to synthesize in the 1800s.
SA was very hard on the stomach. Topically used to burn off warts.
**Felix Hoffman (Bayer Pharmaceuticals) - Acetylated SA **to make Acetylsalicylic Acid (Aspirin) started selling in 1899.
Aspirin became the “wonder drug” intially used for Pain/Inflammation and Fever and later routinely used as an Antiplatelet (1980s).
Mechanism of Action was not descibed until the 1970s.
Antiplatelet Propertied discovered -1940s
Describe the Discovery of Anti-Retrovirals.
AIDS (Acquired Immune Defiency Syndrome) - was first identified in 1981.
100% Mortalilty Rate
Mid-1980s - Discovered how contracting HIV leads to the developement of AIDS. At this time everyone who got HIV developed AIDs.
**Very Few Antiviral drug on the market at this time. (ONLY Herpes and Influenza)
**
The fight against AIDs was considered an internation emergency and significant resources were directed to research.
In a few years, researchers determined:
HIV was a retrovirus.
Key Enzyme in its replication was a reverse Transcriptase.
Started researching drugs to inhibit Reverse Transcriptase.
AZT (Azidothymidine) was found efficacious in treating the virus. Was Previously a failed anti-cancer drug in the 1960s.
AZT Approved by 1987 (Record Time)
Resistance soon Developed but other therapies were found.
1996 - Combination Therapy made HIV very treatable.
What are the steps in HIV replication and what drugs target these steps?
Step 1: Attachment/ Entry; CCR5 Inhibitor Drugs
Step 2: Transcription; Reverse Transcriptase Inhibitors
Step 3: Integration into Genome; Interase Inhibitors
Step 4: Assembly/Maturation; Protease Inhibitors
What are the 2 fundamental approaches for drug discovery?
Compound-Centered - 20th Century
Target Centered - 21st Century
What is the Compound-Centered Approach for drug discovery?
Test promising compund for pharmacologic activity.
Without fully characterized your target.
Receptors were not characterized until the 1970s.
What are the 2 technologies that the Compound-Centered Approach is facilitated by?
Combinatorial Chemistry
High throughout screening.
What are all the sources of compounds in the compound centered approach?
Natural Products: Penicillin, Opioids
Endogeneous Compounds: Cortisol, Insulin
Re-purposing Existing Known Compounds
Describe the Process of Combinatorial Chemsitry?
Use a known compound Precursor (Opium).
Machine that allows for the generation of a large number of compounds from a small number of precursors.
Can then be screened for effectiveness.
Describe the process of High-Troughput Screening?
Automated System that allows for the rapid screening of thousands of compounds.
Assay for:
Receptor Binding
Biochemical/Cellular Target
What is the target-centred approach fo drug discovery characterized by?
Identify/Characterize the target first, then design a dig that “hits that target”.
Rational Drug Design
What techniques is target-centered drug discovery facilitated by?
Understanding the mechanisms of the disease.
Ability to full characterize receptors through protein crystallography.
What drug is used in immunotherapy of cancer?
Pembrolizumab
How does the Pembrolizumab and Immunotherapy work?
Pembrolizumab targets programmed cell death protein (PD-1)
Tumours bind to PD-1 and Turn of the T-Cell Immune response to the timour.
Pembrolizumab prevents this - T Cells remain activated to attack tumour cells.
How long does a patent last in Canada?
20 years from the Date of Issue.
What do you do after you discover a drug molecule?
Patent It
What is a patent?
A patent grants exclusivity to the holder of the patent for marketing of the product, and protects the intellectual property behind that product.
What is a Generic Version of a drug refer to?
A drug that has been copied after the patenting period.
What are the effects of increasing or decreasing patent protection?
What was done to address uncertainty with patenting?
20 Year Patent starts ticking as soon as it is issued, however what is it takes 18 years to bring said dug into the market.
New Rule: Allows 8 years exclusivity post-market approval.
If it took 18 years, you would still get 8 years Exclusivity of drug.
How can a patent be challenged in Canada?
If a generic manufacturer can prove that a manufacturer is not marketing their product then they can infringe upon the patent.
Why do drug companies want fast evaluation and approval processes?
The longer it takes to gain approval to sell the drug, the less time the company will have exclusive sales.
Patent Clock Starts Ticking
