This document discusses guidelines for controlling drug development and marketing, including strategies for preventing drug abuse through supply reduction, inoculation, and demand reduction. It also summarizes regulations that have been implemented related to drug labeling, safety testing, and advertising in response to issues like fraudulent patent medicines and the thalidomide tragedy. Current drug scheduling is explained based on abuse potential and medical usefulness.
Drug Use, Regulation, and the LawChapter 3Guid.docx
1. Drug Use, Regulation,
and the Law
Chapter 3
Guidelines for Controlling Drug Development and Marketing
Society has the right to protect itself from the damaging impact
of drug use.
Society has the right to demand safe and effective drugs.
Strategies for Preventing Drug Abuse
Supply reduction
Using drug laws to control the manufacturing and distribution
of classified drugs
Inoculation
Aims to protect drug users by teaching them responsibility and
explaining the effects of drugs on bodily and mental functioning
Demand reduction strategy
Aims to reduce the actual demand for drugs
3
Patent Medicines
The term patent medicines signified that the ingredients were
2. secret, not patented.
The patent medicines of the late 1800s and early 1900s
demonstrated the problems of insufficient regulation of the drug
industry.
Issues Leading to Legislation
Fraud in patent medicines that were sold directly to the public
False therapeutic claims
Habit-forming drug content
5
Image source: Library of Congress Prints and Photographs
Division (Images Ch03_05PatMedKentucky,
Ch03_03PatMedJayne)
Issues Leading to Legislation
Cocaine
Present in many patent medicines
Viewed as a cause of increasing crime
6
Image source: National Library of Medicine, National Institutes
of Health (See image bank for Chapter 6; Image
Ch06_06CocaineDrops)
Reformism
3. Current laws trace back to two pieces of legislation from the
early 1900s
Racist fears about deviant behavior, including drug misuse,
played a role in the development of drug regulation
Laws were developed to regulate undesirable behaviors
7
Image source: Library of Congress Prints and Photographs
Division (Image Ch03_08OpiumPoster1)
Issues Leading to Legislation
Opium and the Chinese
U.S. was involved in international drug trade
Opium smoking brought to U.S. by Chinese workers (myth)
Laws passed against the importation, manufacture, and use of
opium
8
Image source: Library of Congress Prints and Photographs
Division (Image Ch03_07OpiumDen)
Issues Leading to Legislation
In the early 1900s, Collier’s magazine ran a series of articles
attacking patent medicines.
Drug manufacturers have a history of selling ineffective,
addictive and even harmful products to the public.
4. 9
Image source: Library of Congress Prints and Photographs
Division (Image Ch03_06ColliersMagazine)
1906 Pure Food and Drugs Act
Federal government law to protect the public (Dept. of
Agriculture)
Required accurate labeling and listing of ingredients
US Government intervenes in commerce of adulterated or
misbranded drugs and food
Misbranding only refers to the label, not advertising
10
The 1906 Pure Food and Drug Act
Required manufacturers to include on labels the amounts of
alcohol, morphine, opium, cocaine, heroin, or marijuana extract
in each product
Did not prohibit distribution of dangerous preparations
The Sherley Amendment in 1912
Accuracy of manufacturers’ therapeutic claims was not
controlled by the Pure Food and Drug Act.
The Sherley Amendment in 1912 was passed to strengthen
existing laws and required that labels should not contain “any
statement ... regarding the curative or therapeutic effect ...
which is false and fraudulent.”
5. Food, Drug, and Cosmetic Act
The sale and use of Elixir Sulfanilamide led to a tragic accident
that killed over 100 people.
Companies required to file applications with the government
showing that new drugs were safe.
Food, Drug, and Cosmetic Act
A drug is a product intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease
Before marketing, drugs must be shown to be
Safe when used as directed
Effective for their intended use
Food products and ingredients must be
Safe
Pure (unadulterated)
They are not required to show that they are effective or provide
any benefit
14
Food, Drug, and Cosmetic Act (continued)
Required safe tolerances be set for unavoidable poisonous
substances.
Authorized establishment of identity and quality for foods.
6. Durham-Humphrey Amendment
Made formal distinction between prescription and
nonprescription drugs
Established drug classification categories:
Drug is habit-forming
Drug is not safe for self-medication
Drug is a new drug and not shown to be completely safe
Kefauver-Harris Amendments
Passed, in part, as a consequence of the thalidomide tragedy
Drug manufacturers had to demonstrate the efficacy and safety
of drugs
The FDA was empowered to withdraw approval of a drug that
was already being marketed
The FDA was permitted to regulate and evaluate drug testing by
pharmaceutical companies
Thalidomide Tragedy
Regulating New Drug Development
The amended Food, Drug, and Cosmetic Act requires that all
new drugs be registered with and approved by the FDA.
7. Regulation of Pharmaceuticals
1. Purity
The contents of the product must be accurately listed on the
label
FDA encouraged voluntary cooperation and compliance
1912 Sherley Amendment outlawed false and fraudulent
therapeutic claims on labels
21
Regulation of Pharmaceuticals
2. Safety
Originally—no legal requirement that medications be safe
1938 Food, Drug, and Cosmetic Act required pre-market testing
for toxicity
Companies required to submit a New Drug Application (NDA)
to the FDA
Directions must be included
Adequate instructions for consumer OR
Drug can be used only with physician prescription
22
Regulation of Pharmaceuticals
3. Effectiveness
1962 Kefauver-Harris Amendments
Pre-approval required before human testing
8. Advertising for prescription drugs must include information
about adverse reactions
Every new drug must be demonstrated to be effective for the
illnesses mentioned on label
23
Regulating New Drug Development (continued)
The FDA is mandated by Congress to:
Ensure the rights and safety of human subjects during clinical
testing
Evaluate the safety and efficacy of new treatments
Compare benefits and risks of new drugs and determine if
approval for marketing is appropriate
Marketing a New Drug
1) Preclinical research and development
Testing on animals (ED, LD, toxicity)
2) Clinical research and development
Phase One—small doses, healthy volunteers
Phase Two—small number of patients
Phase Three—larger number of patients
3) Permission to market (NDA)
May require 10+ years and $800+ million
25
Regulatory Steps for New Prescription Drugs
9. Regulatory Steps for New Prescription Drugs (continued)
Step 1: Preclinical research and development
Step 2: Clinical research and development
Initial clinical stage
Clinical pharmacological evaluation stage
Extended clinical evaluation
Step 3: Permission to market
Postmarketing surveillance
New Drug Application (NDA)
If there is sufficient data to demonstrate that a drug is safe and
effective, the company submits an NDA as a formal request that
the FDA approve it for marketing.
Exceptions: Special Drug-Marketing Laws
“Fast-track” rule
Applied to testing of certain drugs, such as ones for rare cancers
and AIDS
Orphan Drug Law
Tax advantages for development of drugs to treat “rare
diseases” since this can be otherwise unprofitable
Prescription Drug User Fee Act of 1992
Increase reviewers and decrease review time
Secure and Responsible Drug Disposal Act
10. Addresses the problem that patients were not allowed to return
drugs to DEA registrants
Prescription Drugs were legally “controlled substances” and
people were not allowed to “give” it to other unauthorized
people
Secure and Resposible Drug Disposal Act Explained
The Regulation of
Nonprescription Drugs
In 1972, the FDA initiated a program to evaluate the
effectiveness and safety of nonprescription drugs.
The FDA evaluated each active ingredient in OTC medications
and placed ingredients into three categories:
I. Generally recognized as safe and effective
II. Not safe and effective or unacceptable indications
III. Insufficient data to permit final classification
Switching Policy
The drug must have been used by prescription for 3 years.
Use must have been relatively high during the time it was used
by prescription.
Adverse drug reactions must not be alarming, and the frequency
of side effects must not have increased during the time the drug
was available to the public.
Drug Advertising
Promotional efforts by pharmaceutical companies have a large
impact on the drug-purchasing habits of the general public and
11. health professionals.
As a general rule, the FDA oversees most issues related to
advertising of prescription products. The FTC regulates OTC
advertising.
Direct-to-Consumer (DTC) Advertising
Most physicians surveyed agreed that because their patient saw
a DTC advertisement, he/she asked thoughtful questions during
the visit. Approximately the same percentage of physicians
thought the advertisements made their patients more aware of
possible treatments.
The physicians surveyed indicated that the advertisements did
not convey information about risks and benefits equally well.
Direct-to-Consumer (DTC) Advertising (continued)
Approximately 75% of physicians surveyed indicated that DTC
ads cause patients to think that the drug works better than it
does, and many physicians felt some pressure to prescribe
something when patients mentioned DTC ads.
The physicians surveyed reported that patients understand that
they need to consult a health care provider concerning
appropriate treatments.
The Harrison Act of 1914
Marked the first legitimate effort by the federal government to
regulate and control the production and importation of addicting
substances
12. The Comprehensive Drug Abuse Prevention and Control Act
This 1970 act divided substances with abuse potential into
categories based on the degree of their abuse potential and
clinical usefulness.
Schedules I, II, III, IV, and V
“Scheduling”
Schedule I substances have high-abuse potential and no
currently approved medicinal uses.
Schedule II substances have high-abuse potential but are
approved for medical uses and can be prescribed.
Schedule II–V substances reflect the likelihood of abuse and
clinical usefulness.
Summary of Controlled Substance
SchedulesScheduleCriteriaExamplesIHigh potential for abuse
No accepted medical use
Lack of accepted safetyHeroin,
marijuana, MDMA (Ecstasy)IIHigh potential for abuse
Currently accepted medical use
Abuse may lead to severe dependenceMorphine,
cocaine, methamphetamineIIIPotential for abuse less than I and
II
Currently accepted medical use
Abuse may lead to moderate physical dependence or high
psychological dependenceAnabolic steroids, most
barbituratesIVLow potential for abuse relative to III
Currently accepted medical use
Abuse may lead to limited physical or psychological
dependence relative to IIIXanax, barbital, chloral hydrate,
fenfluramineVLow potential for abuse relative to IV
Currently accepted medical use
13. Abuse may lead to limited physical or psychological
dependence relative to IVMixture with small amounts of
codeine or opium
40
Factors Determining Scheduling
The actual or relative potential for abuse of the drug.
Scientific evidence of the pharmacological effects of the drug.
The state of current scientific knowledge regarding the
substance.
Its history and current pattern of abuse.
What, if any, risk there is to the public health.
Factors Determining Scheduling (continued)
The psychological or physiological dependence liability of the
drug.
The scope, duration, and significance of abuse.
Whether the substance is an immediate precursor of a substance
already controlled.
Principal Issues Influencing Laws Regarding Substance Abuse
If a person abuses a drug, should he or she be treated as a
criminal or as a sick person inflicted with a disease?
How is the user (supposedly the victim) distinguished from the
pusher (supposedly the criminal) of an illicit drug, and who
should be more harshly punished?
Are the laws and associated penalties effective deterrents
against drug use or abuse, and how is effectiveness determined?
14. Strategies for Preventing
Drug Abuse
Supply Reduction
– Attempts to curtail the supply of illegal drugs or their
precursors and exert greater control over other, more
therapeutic drugs
– Includes interdiction, the policy of cutting off or destroying
supplies of illicit drugs
– Limited success
Strategies for Preventing
Drug Abuse (continued)
Inoculation
– Aims to protect drug users by teaching them responsibility
and explaining the effects of drugs on bodily and mental
functioning
Demand Reduction
– Aims to reduce the actual demand for drugs
Suggestions for Reducing Demand
A top priority of prevention is to reduce demand by youth.
Education must be carefully designed for the target population.
Attitudes toward drug abuse must be changed.
Replacement therapy can be useful.
Drug Courts
Designed to deal with nonviolent, drug-abusing offenders
16. 50
Image source: Spike Mafford/Getty Images (Image
Ch03_13DrugTesting)
Pragmatic Drug Policies
The government must develop programs that are consistent with
the desires of the majority of the population.
Programs must consider de-emphasizing interdiction and stress
programs that reduce demand.
State and Local Regulations
Difference in penalties from state to state
Federal law overrides state law
Significant growth in number of Americans in prison
52
Figure from Drugs in Depth box in text
Impact of Drug Enforcement
Budget
International programs
Other federal agencies
In this raid, an international task force seized two tons of
cocaine in the Caribbean Basin.
53
Image source: U.S. Immigration and Customs Enforcement
17. (Image Ch03_14InternationalDrugControl)
Impact of Drug Enforcement
Other costs
Cost of prison population
Crimes committed to purchase drugs
Corruption in law enforcement
Conflicting international policy goals
Loss of individual freedom
Drug use has not been eliminated
54
Effectiveness of Control
About 10-15% of illegal drug supply is seized each year
When supplies are restricted, prices go up
Higher prices and increased difficulty in obtaining drugs may
deter some would-be users
Seized Ecstasy
55
Image source: U.S. Immigration and Customs Enforcement
(Image Ch03_15SeizedEcstasy)
Pragmatic Drug Policies (continued)
Government and society must better understand how laws, used
properly and selectively, can reinforce and communicate
expected social behavior and values.
Programs, such as anti-smoking campaigns, should be
implemented that employ “public consensus” more effectively.
18. Homeostatic Systems
and Drugs
Chapter 4
Homeostasis
Internal and external changes in the environment
Body self-regulates via
nervous system and endocrine system
Equilibrium
Introduction to Nervous SystemsAll nervous systems consist of
specialized nerve cells called neurons and glia (supporting
19. cells).Neurons are responsible for conducting the homeostatic
functions of the brain and other parts of the nervous system by
receiving and sending information.Sending and receiving
information is an electrochemical process.
Transfer of Messages by NeuronsThe receiving region of the
neuron is affected by a chemical message that either excites or
inhibits it.Neuronal message:Impulse moves from the receiving
region of the neuron down the axon to the sending region
(terminal).Chemical messengers (neurotransmitters) are
released.
Transfer of Messages by Neurons (continued)Neurotransmitters
travel and attach to receiving proteins called receptors on target
cells.Activation of receptors causes a change in the activity of
the target cell; the target cells can be other neurons or cells that
make up organs, muscles, or glands.
Sending Messages by Neurons
Figure 4.1: The process of sending messages by neurons.
20. Neurons and NeurotransmittersNeurons can send discrete
excitatory or inhibitory messages to their target cells.Neurons
are distinguished by the type of neurotransmitter they
release.Neurotransmitters represent a wide variety of chemical
substances and functions.Example: Dopamine activates the
pleasure center.
Common NeurotransmittersNeurotransmitterType of EffectCNS
ChangesDrugs of AbuseDopamineInhibitory-excitatory
Euphoria
Agitation
Paranoia
AlteredAmphetamines,
cocaineGABAInhibitoryCognition
Sedation
Relaxation
Drowsiness
DepressionAlcohol, valium-type barbiturates
22. Neurons Dendrites are the receiving regions of a neuron’s cell
body.Each neuron in the central nervous system is in close
proximity with other neurons.Although they are close, neurons
never actually touch.Synapse is the point of communication
between one neuron and another.Synaptic cleft is the gap
between neurons at the synapse.
Neurons (continued)
Figure 4.2: Each neuron may have many synaptic connections.
SynapsesExcitatory synapse initiates an impulse in the receiving
neuron when stimulated, causing release of neurotransmitters or
increasing activity in target cell.Inhibitory synapse diminishes
likelihood of an impulse in the receiving neuron or reduces the
activity in other target cells.
Synapses (continued)A receiving neuron or target cell may have
many synapses.Final cellular activity is a summation of these
many excitatory and inhibitory synaptic signals.
Drug ReceptorsThe chemical messengers from glands and
neurons exert their effects by interacting with special protein
regions in membranes called receptors.Receptors only interact
23. with molecules that have specific configurations.
Drug Receptors (continued)
Figure 4.3: Cell membranes consist of a double layer of
phospholipids.
Drug Receptors (continued)Agonists: Substances or drugs that
activate receptorsAntagonists: Substances or drugs that attach to
receptors and prevent them from being activated
Drug Receptors (continued)
Figure 4.4: Interaction of agonist and antagonist with membrane
receptor.
NeurotransmittersMany drugs affect the activity of neuro-
transmitters by altering their synthesis, storage, release, or
deactivation. Neurotransmitters frequently altered by drugs of
abuse:Acetylcholine
CatecholaminesSerotoninGABAEndorphinsAnandamide
Figure 4.6: Synthetic pathway for catecholamine
neurotransmitters.
Major Divisions of the Nervous SystemTwo major components
24. of the nervous system Central nervous system (CNS) Peripheral
nervous system (PNS)
Central Nervous SystemCNS includes the brain and the spinal
cordCNS receives information from PNS, evaluates information,
then regulates muscle and organ activity via PNSReticular
activating systemReceives input from all the sensory systems
and cerebral cortexControls the brain’s state of arousal (sleep
vs. awake)
Central Nervous System (continued)Basal gangliaControls
motor activityLimbic systemRegulates emotional activities,
memory, reward, and endocrine activityIncludes the nucleus
accumbens, such as reward centerDopamine
Central Nervous System (continued)The cerebral cortexHelps
interpret, process, and respond to information; selects
appropriate behavior and suppresses inappropriate behaviorThe
hypothalamusControls endocrine and basic body functions
Central Nervous System Structure
Figure 4.7: Functional components of the central nervous
system.
Peripheral Nervous SystemConsists of input and output
25. nervesInput to brain and spinal cordConveys sensory info (pain,
pressure, temperature)Output: Two typesSomatic (control of
voluntary muscles)Autonomic (control of unconscious
functions)
Autonomic Nervous SystemSympathetic and parasympathetic
systemThese systems work in an antagonistic fashion to control
unconscious, visceral functions such as breathing and
cardiovascular activity Sympathetic
systemNorepinephrineParasympathetic systemAcetylcholine
Autonomic Nervous System Structure
Figure 4.8
Introduction to the Endocrine SystemThe endocrine system
consists of secreting glands (e.g., adrenal, thyroid,
pituitary)These glands produce substances called hormones
(e.g., adrenaline, steroids, insulin, sex hormones)These
substances are information transferring molecules
Introduction to the Endocrine System (continued)Hormones are
secreted into the bloodstream and carried by the blood to all the
organs and tissues of the body.Hormones affect selected tissues
that are designed to receive the information.Hormones may be
highly selective or very general with regard to the cells or
organs they influence.
27. 5. What are the main components of the 1952 Durham
Humphrey Act? How was this law attempting to protect the
public?
6. What are the main purpose and influence of the Kefauver-
Harris Amendment of 1962? How was this law attempting to
protect the public?
7. What is the main purpose of the Comprehensive Drug Abuse
Prevention and Control Act of 1970?
8. List and briefly describe the 5 levels of drug scheduling
under the controlled substances, schedule I-V”
9. What are the 3 main steps in regulating the development of
new pharmaceutical drugs?
10. Define and describe the 2 main drug prevention strategies:
Supply Reduction and Demand Reduction
28. Week Two
Physiology: Chapter 4
Explain the function of each of the following terms:
Neuron- basic structural unit of the nervous system- Draw and
label a neuron
Dendrite
Receptor
Pre-Synaptic
Synapse/synaptic cleft
Post-synaptic
Neuron, cell body
Axon
Terminal
Terminal vesicles
Neurotransmitters
Reuptake
Metabolizing enzymes
Understanding how receptors function:
Agonist
Antagonist
CNS
Brain Stem
Cerebellum
Cerebral Cortex
RAS
Basal Ganglia
Hypothalamus
Limbic System
29. Hypothalamus
PNS
Somatic nervous system
Sensory information neurons-(afferent)
Motor neurons-(efferent) voluntary actions
Autonomic Nervous system (ANS)
Sympathetic
Parasympathetic
Match the terms in the left column to the short definitions in the
right column:
Abstinence
Experimental use
Situational use
Misuse/ Abuse
Dependency
__________________ Obsessive or compulsive drug use
__________________ Drug use in stressful circumstances
_________________Drug use for curiosity or Peer pressure
__________________Drug use causes problems
30. __________________No drug use at all
Chapter 5 – How and why drugs work
Write a short definition in your own words for the following
terms:
1. Threshold Dose
2. Effect/side effect
3. Safety Margin
4. Lethal Dose
5. Potency
6. Toxicity
7. Metabolize/ biotransformation
8. Half Life
9. Tolerance
31. 10. Cross tolerance
11. Adaptive Process: Pharmacodynamic tolerance (Drug
dependence)
12. Withdrawal
13. Synergistic (potentiate) Drug Interaction
14. Antagonistic Drug Interaction
15. Name 2 main symptoms of Physical Dependence
16. Name 2 main symptoms of Psychological Dependence
Method of Description
Onset
Administration (what happens ) (how
32. fast)
oral
snorting
intraveneous
smoking
17. Elimination and Metabolism:
All drugs are metabolized (broken down) by the
_____________(organ of the body).
18. Most metabolites are excreted out of the body through
_______________.
Reflection Paper: Addiction and Theories
Ksir, C., Hart, C., Ray,O. Drugs, Society and Human Behavior,
Twelfth Edition. McGraw Hill Publisher
Read Chapter 2 of the text, note the definitions and the major
theories about how drug use leads to drug abuse/addiction.
33. What is your favorite theory(s) of Addiction?
Why do people become addicted to alcohol, tobacco and other
drugs (ATOD)?
Write a definition of addiction/dependency:
Nature of addiction/dependency – etiology: what happens to a
person who is addicted/dependent on ATOD (See also chapter 1
“Drug Dependence” and “Stages of Drug Dependence”; Chapter
2 “The vicious Cycle of Drug Addiction)
Bio-Psycho-Social Model: write your favorite explanations of
why someone might become addicted to AOD, based on specific
theories in each of the following categories
Biological causes/factors of addiction/dependency
Psychological causes/factors of addiction/dependency
Social causes/factors of addiction/dependency
The Biopsychosocial Approach
(
Biosphere
Society/ Nation
Culture/Subculture
Community
Family
Individual
Nervous System
Organs
34. Tissues
Cells
Molecules
)The biopsychosocial approach was developed at Rochester
decades ago by Drs. George Engel and John Romano. While
traditional biomedical models of clinical medicine focus on
pathophysiology and other biological approaches to disease, the
biopsychosocial approach in our training programs emphasize
the importance of understanding human health and illness in
their fullest contexts. The biopsychosocial approach
systematically considers biological, psychological, and social
factors and their complex interactions in understanding health,
illness, and health care delivery.
• Biological, psychological, and social factors exist along a
continuum of natural systems, as depicted in the list here.
• Systematic consideration of psychological and social factors
requires application of relevant social sciences, just as
consideration of biological factors requires application of
relevant natural sciences. Therefore, both the natural and social
sciences are ‘basic’ to medical practice. In other words,
psychological and social factors are not merely epiphenomena:
they can be understood in scientific ways at their own levels as
well as in regard to their biological correlates.
• Humanistic qualities are highly valued complements to the
biopsychosocial approach, which involves the application of the
scientific method to diverse biological, psychological, and
social phenomena as related to human health.
• While the biomedical approach takes the reductionistic view
that all phenomena are best understood at the lowest level of
natural systems (e.g., cellular or molecular), the
biopsychosocial approach recognizes that different clinical
scenarios may be most usefully understood scientifically at
several levels of the natural systems continuum.
To apply the biopsychosocial approach to clinical practice, the
clinician should:
• Recognize that relationships are central to providing health
35. care
• Use self-awareness as a diagnostic and therapeutic tool
• Elicit the patient’s history in the context of life circumstances
• Decide which aspects of biological, psychological, and social
domains are most important to understanding and promoting the
patient’s health
• Provide multidimensional treatment
The Biopsychosocial Approach
REFERENCES
Engel GL: The need for a new medical model: a challenge for
biomedicine. Science 1977;196:129-136.
Engel GL: The clinical application of the biopsychosocial
model. Am J Psychiatry 1980;137:535-544.
Frankel RM, Quill TE, McDaniel SH (Eds.): The
Biopsychosocial Approach: Past, Present, Future.University of
Rochester Press, Rochester, NY, 2003.
Borrell-Carrió F, Suchman AL, Epstein RM: The
biopsychosocial model 25 years later: principles, practice, and
scientific inquiry. Ann Fam Med 2004;2:576-582.
Cohen J, Brown Clark S: John Romano and George Engel: Their
Lives and Work.University of Rochester Press, Rochester, NY,
and Boydell and Brewer Limited, Suffolk UK, 2010.
