Drugs: History, FDA, and Society Flashcards
1
Q
What is pharmacology?
A
The basic and clinical applied science that deals with the fate and actions of drugs in the body
2
Q
What are drugs?
A
Any substance used in the diagnosis, prevention, or treatment of disease
3
Q
What is the word pharmacology comprised of?
A
Pharmakon – poison or drugs
Logos – study or discourse of
4
Q
Does the use of medicine date back to prehistoric times?
A
Yes
5
Q
Have humans sought plant and animal products since the earliest time to combat sickness and death?
A
Yes
Many of these products were discovered by errors
Initial treatment caused more harm than good
6
Q
Did people think that certain plants that resembled human parts would cure ailments for those parts? (doctrine of signatures)
A
Yes
Walnuts were thought to cure ailments of the head
Holes in the leaves of Saint Johns Wort resembles pores of the skin
7
Q
What were the oldest prescriptions?
A
Found on clay tablets written by Sumerian physician around 3000 BC (one of the earliest urban societies)
8
Q
Who promotes the idea that disease results from natural causes rather then evil spirits?
A
Hippocrates (5th century BC)
He believed that the body had abilities to recuperate from disease
9
Q
In early years, how were medicines developed?
A
Isolation and use of nature substances from botanical, mineral, and animal sources
10
Q
In modern times, how is medicine developed?
A
Chemical synthesis of compounds that have biological activity
11
Q
What is quinine and how is it used?
A
Found in some tree bark
Still used today as a drug of choice against malaria
The first specific drug used to treat an infectious disease
12
Q
When was the synthesis of arsenicals?
A
1910
13
Q
How did the synthesis of arsenicals happen?
A
Sahachiro Hata and Paul Ehrlich’s synthesized arsenicals by attaching an arsenic atom to a carbon atom
14
Q
What did the synthesis of arsenicals lead to?
A
The use of arsphenamine (first chemotherapeutic agent) to treat syphilis
15
Q
How was digitalis isolated?
A
Use of purple foxglove (digitalis purpurea) in 1783 lead to the isolation of digitalis
16
Q
What was digitalis used for?
A
Made a tea out of it to treat the edema of cardiac “dropsy” (congestive heart failure)
Arteries get blocked or narrowed and the heart had to work harder
Fluid is not getting cycled out of the body
17
Q
Is digitalis still isolated from plants?
A
Yes, it is too difficult and expensive to synthesize chemically
18
Q
When was morphine isolated from opium?
A
1805
19
Q
What is opium used for?
A
A narcotic used for pain control
Has been used as a medical and recreational drug since prehistoric times
Source of opium is the poppy plant (seed pod)
20
Q
Did isolation of morphine lead the way to techniques for the isolation of caffeine, atropine, and strychnine?
A
Yes
21
Q
Where did coffee come from?
A
13th century
Originally native to east Africa
Coffee berries grow on trees
22
Q
What is the caffeine that is extracted from the coffee plant?
A
Coffea arabica
23
Q
How does caffeine work?
A
Stimulating the CNS, heart, and muscles
Relieves mental and physical fatigue and increases mental alertness
24
Q
What is atropa belladonna?
A
Devil’s cherries
Entire plant is extremely poisonous
Only used externally
25
What type alkaloid substances have been isolated from atropa belladonna?
Atropine and scopolamine
26
What is atropine?
Dilates the pupils (medicinal use)
Belladonna plasters often applied after a fall to the injured or sprained part
Ingestion in excess amounts is a poison
27
What is scopolamine?
Extracted from Japanese belladonna
Used for motion sickness, sedative, truth serum, and mydriasis (prolonged or excessive pupil dilation)
28
How was salicylic acid discovered?
Willow bark is a source of salicin, which is metabolized to salicylic acid in the body
29
What are salicin and salicylic acid?
Chemical precursors for aspirin
30
How was aspirin created?
In the 1890s Herman Bayer, converted salicylic acid to the acetyl derivative
Acetylsalicylic acid, also known as aspirin
31
Does willow bark and salicylates increase the risk of bleeding, ulcers, and tinnitus?
Yes
May not be a go-to because of this
32
What is epinephrine?
Also known as adrenaline
It is a hormone and a neurotransmitter
It was the first hormone isolated in 1897, by John Jacob Abel, a researcher at Johns Hopkins University and the father of modern pharmacology
33
Where is epinephrine produced?
Some neurons of the CNS
The chromaffin cells of the adrenal medulla from the amino acids, phenylalanine and tyrosine
34
What is acetylcholine?
It is one of many neurotransmitters in the autonomic nervous system (ANS)
It acts on both the peripheral and central nervous system
It is the only neurotransmitter used in the motor division of the somatic nervous system
35
How does acetylcholine act in cardiac tissue?
Has an inhibitory effect
Lowers heart rate
36
Can acetylcholine be excitatory at neuromuscular junctions in skeletal muscle?
Yes
37
What is sulfa?
An antibiotic
Discovered by changing the chemical makeup of red dye
Was able to arrest infections caused by streptococcal bacteria
The first effective treatments for pneumonia, meningitis, and other bacterial diseases
38
Did sulfa pre-date penicillin?
Yes
39
Did medics during WWII carry sulfa powder and sulfa tablets?
Yes, it greatly reduced mortality
40
Is sulfa used today?
Yes, to treat infections of the urinary tract
41
What is penicillin?
Accidentally discovered that a mold (penicillium notatum) inhibited growth of staphylococcus aureus
Active ingredient was penicillin
Turned into a usable product in 1940
42
What is the FDA?
A regulatory agency that is involved in regulation of drug development
The need for the FDA evolved in response to a public need
Prior to and at the start of the 20th century, tampering and mislabeling of food and drugs was common
43
What was the pure food and drug act in 1906?
Prompted by unsanitary and unsafe conditions in the meat packing industry, Congress created the FDA
44
What were the only requirements of the pure food and drug act?
Drugs meets standards of strength and purity
The burden of proof was on the FDA to show that the drug was false/fraudulent before it could be taken off the market
45
When was the food and drug cosmetic act passed by congress?
In 1938
Happened in response to the strep-elixir incident (mixing drug with anti-freeze)
46
What was the food, drug, and cosmetic act of 1938?
Required proof of a drug’s safety and purity
Mandated that manufacturers obtain pre-market approval from the FDA contingent on demonstrated safety
Regulated labeling and packaging of drug products
47
What was the durham-humphrey act of 1952?
Granted the FDA authority to determine which drugs may be sold without a prescription
FDA examined a drug’s toxicity and the ability for someone to self-diagnose
OTC drugs are sold with lower dosage than their prescription counterparts and used primarily to treat symptoms, not cure diseases
48
What was the 1962 Kefauver-Harris Amendments to the Food, Drug and Cosmetic Act?
Required proof of efficacy as well as safety for new drugs and drugs approved since 1938 (does it work)
Established guidelines for adverse event reporting, clinical testing, and advertising (drugs must be appropriately labeled)
49
What was the orphan drug amendment of 1983?
It provides manufacturers incentives, such as tax deductions for their clinical trials, to manufacture drugs that treat rare diseases (diseases that affect <200,000 people)
Otherwise, they don't have incentive to create them
50
What was the FDA expanded access program (1987, streamlined 2017-2018)?
Began in the AIDS crisis
Intent is to allow FDA to permit pharmaceutical companies to broaden access to investigational products while they are still undergoing clinical trials
Used for cancer medications, AIDS, etc.
51
What is off-label use?
Being prescribed a drug for something that it was not intended to treat
52
What was the expedited drug approval act of 1992?
Allowed accelerated FDA approval for drugs of significant medical need
Required detailed post-marketing surveillance (Phase IV-Clinical Trials)
Example: COVID vaccine
53
What was the FDA modernization act of 1997?
Allowed drug manufacturers to discuss unapproved or “off label” indications for drug products with practitioners
Provided for accelerated drug approvals for life-threatening medical disorders
Made provisions for pediatric drug research
Revised communications between FDA and researchers conducing clinical trials
54
What is the dietary supplement health and education act of 1994?
Dietary supplements are defined as vitamins, minerals, herbs, botanicals, other plant-derived substances, amino acids, concentrates, metabolites and constituents and extracts of these substances
FDA oversees the safety, manufacturing and health claims made by dietary supplements
55
Does the FDA evaluate the efficacy of supplements?
No
56
Does the FDA need to demonstrate that a supplement is unsafe before taking action against it?
Yes
57
What was the federal food, drug, and cosmetic act of 2006?
Required the dietary supplement industry to report all serious dietary supplement-related adverse drug events to the FDA
58
What was the FDA amendments act of 2007?
In response to the safety issues of COX-2 inhibitors (anti-inflammatory drugs) that led to cardiac issues and strokes
Gave enhanced authority to FDA to manage safety of approved drugs
Focused on Risk Evaluation and Mitigation Strategies (REMS) for new and already approved drugs
To ensure that benefits of a drug outweigh the risks
59
Does the FDA regulate drugs sold without a prescription?
Yes, OTC drugs
FDA reviews OTC drugs for misbranding and adulteration
FDA sets guidelines to which OTC drugs are safe and effective
FDA has authority to prevent sales and to withdraw OTC drugs from the market
60
Does the FDA regulate the supplemental product manufacturers?
Yes
To test products for purity
To assure that products do not contain contaminants
To verify that contents within package matched labeling information
61
Does the FDA regulate controlled substances?
Yes
62
What are controlled substances?
Drugs that have some potential for abuse or dependence
63
What was the controlled substances act of 1970?
The Drug Enforcement Administration (DEA) administers the CSA and regulates manufacture and distribution of substances with potential for abuse including opioids (narcotics), stimulants, and sedatives
Before these laws, mixtures containing opium and cocaine were sold over-the-counter (OTC)
64
What happened on March 22, 2016?
The FDA required a boxed or black box warning (strongest warning)
“The serious risks of misuse, abuse, addiction, overdose, and death” for all short-acting opioid pain medications
65
What are some examples of opioids?
Morphine
Hydrocodone
Codeine
66
Was a boxed warning issued before 2016?
Yes, issues in 2013 for labels of long-acting opioid medications (oxycotin)
67
Are opioids meant for long-term use?
No
That is why they were being prescribed generally until recently
68
What is the modern FDA like?
Today’s FDA is one of the strictest and most respected drug regulatory bodies in the world
69
How is the modern FDA responsible for protecting public health?
Assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation
70
How is the modern FDA responsible for advancing public health?
Helping to speed innovations that make medicines more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medicines and foods to maintain and improve their health
71
Does the FDA regulate tobacco?
Yes, they regulate the manufacturing, marketing, and distribution
72
Does the FDA play a role in counterterrorism?
Yes
By ensuring the security of the food supply and by fostering development of medical products to respond to deliberate and naturally emerging public health threats
73
Is the discovery and development of new drugs a lengthy, high risk, and complex process?
Yes
You never know where the drug is going to go
74
How long does it take to develop a new drug in the U.S.?
Approx 10 to 15 years
75
What is the estimated cost of developing a drug in the U.S. from invention to pharmacy?
About 1 to 2 billion dollars depending on what the drug is for
76
Is only 1 of 10 drugs that enter clinical testing is approved and marketed?
Yes
77
What are the phases of drug development?
Synthesis or discovery of new chemicals from the test tube or plant(s)
Safety evaluation in animals and humans
Effectiveness evaluation in humans
Review of new drug application
Post-marketing surveillance to report all adverse effects
78
What is the drug discovery phase?
This phase produces a new molecule
First patents are filed at this stage and granted several years later
79
What is the drug development stage?
The process requires that biological characterization and toxicology animal studies be conducted prior to filing an Investigational New Drug (IND) application
An IND is required at the start of clinical (human) trials (Phase I to III)
At the conclusion of successful clinical trials, the drug company files a New Drug Application (NDA), which is reviewed by the FDA
80
What is the post approval regulation stage?
Once approved, a drug must be monitored for the remainder of its life span (Phase IV)
81
When does the drugs patent expires?
20 years after its application
Abbreviated New Drug Application (ANDA) can be filed before expiration of original patent
82
What is the abbreviated new drug application?
Application for a U.S. generic drug approval for an existing licensed medication or approved drug
Not required to include preclinical (animal and in vitro) and clinical (human) trial data to establish safety and effectiveness
Must scientifically demonstrate that their product is bioequivalent
83
How does a drug demonstrate bioequivalence?
To measure the time it takes the generic drug to reach the bloodstream in 24 to 36 healthy volunteers (rate of absorption and bioavailability)
Must have the same amount of active ingredients in the patient's bloodstream in the same amount of time
84
What is short term toxicity testing?
Testing in animals
General profile screen in mice
Trying to determine the lethal dose (LD50) and the effectiveness dose (ED50)
85
What is the margin of safety?
LD50/ED50 = margin of safety
If LD50 is 10 mg and ED50 is 2 mg then the margin of safety is only 5
10/2 = 5
Lethal dose is only 5x more than the effective dose
86
What is the acceptable margin of safety for humans?
Greater than or equal to 2000
87
What is long term toxicity?
Chronic toxicity studies
Daily dosing rats and dogs from 3 months to 2 years
Observe for toxicities, evaluate blood
Sacrifice the animal, then evaluate histopathology
Many toxic effects appear only after repeated dosing over many months or years
88
What things do they have to ask regarding studies on reproduction?
Does drug prevent ovulation?
Does drug prevent fertilization?
Does drug cause the expulsion of embryo from the uterus?
89
Why are studies done on carcinogenicity?
To determine if the drug will cause cancers
Give rats the drug for over 6 months
Any signs of cancer are enough to stop testing a drug
90
When can an investigational new drug application be submitted?
Submitted if the drug has an impressive margin of safety in mice
Submitted if a drug lacks long-term toxicities
Submitted if a drug does not cause cancer, reproductive effects, or birth defects
91
How long does it take for the FDA to approve the investigational new drug application?
30 days (usually longer)
92
What are the contents of the IND?
Data acquired in animal studies
Protocols for human tests
Chemical structure of the drug
How the drug is synthesized
Formulation of dose form
Packaging information
93
What is phase one of clinical studies?
Begins immediately after IND approval
20 to 100 healthy volunteers (usually healthy males)
Primarily evaluates safety of the drug in humans
Determines pharmacokinetics (what the body does with the drug)
Establishes the dose at which toxicity appears
Trial lasts for several months
Non-blinded trials
94
What is phase 2 of clinical studies?
Given to patients having the condition for which the drug is intended
Up to several hundred patients in the trial
Study of short-term effectiveness and safety and adverse drug events
Establishes therapeutic efficacy, dose-response and dose range, kinetics, and metabolism
The trial lasts for several months to two years
Single-blind trial
95
What is a single blind trial?
Drug of interest is evaluated against a placebo or existing therapy
Participants unaware of what they are receiving
People administering the drug know
96
What is phase 3 of clinical studies?
Patient numbers in the study ranges from several hundred to several thousand and are more heterogenous (diverse)
Confirms drug safety, dosage, and effectiveness
Tries to detect adverse effects undetected in prior studies
Trial lasts one to four years
Randomized, double-blind studies
97
What is a randomized double-blind study?
Participants randomly assigned to either the drug or placebo group
Highest level of research
Neither the participant nor the investigator knows which group the subject is in
Done to make sure there is no placebo effect
It is the most effective design to distill true effects from placebo effects and from natural fluctuations in the course of the disease
98
What is one problem with phase 3?
Small number of patients taking the drug for maybe up to four years compared to potentially millions who will take the drug long term
Drug toxicities which occur at less than 1 in 1000 exposures may not be revealed in Phase 3 clinical trials
Toxicities may only be revealed after marketing
99
When is the new drug application submitted?
After the successful conclusion of the clinical trials
After 8-9 years of animal and human testing
100
What happens when the FDA approved the NDA?
The drug manufacturer can sell the new product as an exclusive proprietary drug
101
When does post-marketing surveillance happen? (phase 4 studies)
Occurs after FDA approval
The drug is monitored for the remainder of its life span
The drug is now used by a much greater number of people than in clinical studies
There is a need to collect additional data to identify side effects
A drug can be pulled off the market if new toxicities are uncovered
102
What happens when a non-life threatening problem occurs with a drug?
Can be addressed by relabeling the drug with new warnings
103
What is a drugs chemical name?
When a drug is being investigated by a drug company, it is identified by this name, which is determined by its chemical structure
Example: Acetylsalicylic acid
104
What is the chemical name of the drug when the structure is unknown?
Then a combination of letters and numbers is used
105
What is the generic (official) name of the drug?
Before any drug is marketed, it is given a generic name that becomes the “official” name of the drug (for e.g., cola)
For each drug, there is only one generic name approved by the U. S. Adopted Names (USAN) Council
All drugs have one generic name but can have many brand names
106
Are generic name capitalized?
No
107
What is the brand or trade (proprietary) name of a drug?
If the compound is found to be useful and will be marketed commercially, then the pharmaceutical company that discovered the drug gives it a trade name (for e.g., Coke)
Trade name = brand name = proprietary name
Trade name is registered as a trademark under the Federal Trade-Mark Law, and is the property of the registering company
Copyrighted name
108
What happens when the drug patent expires?
Other companies can market the generic drug under a trade name of their choosing
Example: cola is the generic name
Coke is a trade name
Pepsi is a trade name
109
Are generic drugs more affordable and have the same efficacy as the brand name drugs?
Yes
110
Previously, who were drugs advertised to?
Physicians via drug reps and in professional journals
111
How do drug manufacturers advertise now?
Directly to the consumer
Through TV, radio, magazines, and the Internet
It gains the consumer’s interest and increases name recognition of brand name drugs
It encourages patients to ask their health care providers for specific medicines
112
What influences drug cost?
Research & development costs including the FDA approval process
Complicated manufacturing process
Extent of coverage and reimbursement for the drug by third-party payers (insurers)
Desired profit margin of the manufacturer
Maximizing profits prior to patent expiration
Export to foreign countries (cost is dictated by the foreign government or negotiated between the manufacturer and that government)
113
Typically, how does overseas drug cost differ from cost in the U.S.?
Lower cost overseas than in the U.S.
114
What is pharmacoepidemiology?
It is the study of drug outcomes as documented in observations of clinical data from large populations of typical patients receiving routine care
Considers the population as the experimental system being studied
115
Why is pharmacoepidemiology important?
It pulls drugs that are harming a population
Example: Vioxx (anti-inflammatory drug) resulting in heart attack and stroke
116
Are medications used in pharmacoepidemiology studied similarly to medications studied in an individual patient?
Yes
117
What are the differences between pharmacoepidemiology and individual patient studies?
True randomization does not occur
The intervening decision-making and behavior of doctors and patients can alter the drugs’ effect
Outcomes are measured in terms of probabilities (or rates) of events
The magnitude of drug experience in the analysis is much larger than that of conventional pharmacology, ranging to millions of patients and millions of person-years of exposure
118
What were the withdrawal of drugs preceded by?
Severe or fatal adverse effects that were unrecognized or underappreciated at the time of approval
They occurred primarily in patient groups underrepresented un clinical trials (elderly, children, pregnant women
119
While there are a modest number of patients studied in conventional pharmacology, what populations does pharmacoepidemiology study?
Large populations
120
While there are direct dose-response relationships in conventional pharmacology, what does pharmacoepidemiology measure?
Probabilities of benefit and risk
121
While conventional pharmacology focuses on biology, what does pharmacoepidemiology focus on?
Behavior of prescribers and patients as well as biology
122
While in conventional pharmacology there are outcomes over a short time frame, how long is the time frame for pharmacoepidemiology?
Longer
123
While rare events are difficult to study in conventional pharmacology, are they easy to study in pharmacoepidemiology?
Yes
Easier to identify rare events
