Chapter 2 - Drug Regulations

Question 1

Drug Regulation

Answer 1

• Laws govern all aspects of the drug approval, labeling, manufacturing and distribution process.
• Purpose is to protect the public

Question 2

Patent Medicines

Answer 2

Early America saw the rise of patent medicines and a lack of adequate drug regulations

• Drugs had trade names
• Few laws or testing
• False claims
• Mostly harmless, but at worst hazardous or addictive

The need for stricter regulations became apparent in the 1860s when cocaine was synthesized and opiates began to be used painkillers in Civil War.

Question 3

Federal Regulations 1820 - 1914

Answer 3

• 1820 - Physicians established publication of drug standards the United States Pharmacopeia (USP)
• 1848 - Drug Importation Act
  
  • Attempted to stop the entry of unsafe drugs into US
• 1902 - Biologics Control Act
  
  • Standardized the quality of blood-related products
• 1906 - Pure Food and Drug Act (PFDA)
  
  • Set standard for labeling requiring accurate content and purity
• 1912 - Sherley Amendment to PFDA
  
  • Prohibited ‘false and fraudulent’ product labeling.
• 1914 - Harrison Narcotic Act
  
  • First attempt to regulate addictive drugs
    Required prescriptions and mandated increased record-keeping for physicians/pharmacists dispensing narcotics.

Question 4

Early 20th century

Answer 4

Manufacturers did not need to prove that drugs were effective and product safety was not tested.

in 1937 an elixer of sulfanilamide containing a poisonous chemical killed 107 ppl mostly children

Question 5

Federal Regulations 1938 - 1970 - Safe and Effective

Answer 5

• 1938 - The Food, Drug and Cosmetic Act (FDCA)
  
  • Law preventing the marketing of drugs that have not been tested
  • 1951 Dunham-Humphrey Amendment delineated the difference between safer OTC drugs and more dangerous prescription
• 1962 - Harris-Kefauver Amendment to FDCA
  
  • Required drugs to be proven effective and safe before being marketed
  • through well-controlled studies
  • Adverse effects must be reported
• 1970 - The Comprehensive Drug Abuse Prevention and Control Act (Controlled Substance Act)
  
  • Organized regulated drugs into Schedule I, II, III, IV, V and imposed restrictions

Question 6

1980s - Orphan Drugs

Answer 6

• Public placed considerable political pressure on the FDA to find drugs to treat rare or unusual disorders
• Pharma companies not monetary incentives to develop

Question 7

Orphan Product

Answer 7

A drug or biologic for treating a rare disease that affects fewer than 200,000 ppl in US

Question 8

1983 - Orphan Drug Act

Answer 8

Allowed drug manufacturers to be offered developmental grants and tax credits for clinical investigation expenses and 7 years exclusivity.

Question 9

Prescription Drug User Fee Act

Answer 9

• Early 1990s - (HIV/AIDS) officials began to plan how to speed up the approval process
• 1992 - the PDUFA act requires manufacturers to pay fees
• Added revenue allowed FDA to hire more ppl
• Priority drugs receive an accelerated approval process

Question 10

Dietary Supplement Health and Education Act

Answer 10

• 1994
• Controls misleading industry claims must correctly label
• Allows FDA to remove dangerous products from the market
• Regulations of these products remain less stringent than prescription or OTC

Question 11

The early 2000s

Answer 11

• Focus shifts to access
• 2003 - Medicare Prescription Drug, Improvement and Modernization Act
  
  • Provides older adults and those with disabilities prescription drugs benefits and better benefits under Medicare

Question 12

United States Pharmacopeia - National Formulary (USP - NF)

Answer 12

• American Pharmaceutical Association Founded in 1852
• Maintained two compendia
• 1820: U.S. Pharmacopeia (USP)
  
  • Covered all drug products
• 1852: National Formulary (NF)
  
  • Covered all drug ingredients
• These were merged together in 1975 (USP - NF)
• United States Pharmacopeia - National Formulary USP-NF
  
  • Specifies the standardization of drug purity and strength
  • Published annually
  • Drugs in US must conform to standards to avoid possible fees

Question 13

Formulary

Answer 13

List of pharmaceutical products and drug recipes

Question 14

Pharmacopeia

Answer 14

Medical reference summarizing standards of drug purity, strength, and directions or synthesizing

Question 15

US Food and Drug Administration (FDA)

Answer 15

• The regulatory agency that is responsible for ensuring that drugs and medical devices are safe and effective.
  
  • Began with a single chemist appointed by President Lincoln in 1862
  • 1988 - Officially established as part of U.S. Department of Health and Human Services (HHS)

7 branches:

1. Center for Biologics Evaluation and Research
2. Center for Devices and Radiological Health
3. Center for Drug Evaluation and Research - branch of FDA that exercises control over whether prescription and OTC drugs may be used for therapy
4. Center for Food Safety and Applied Nutrition
5. Center for Tobacco Products
6. Center for Veterinary Medicine
7. National Center for Toxicological Research

Question 16

Black Box Warnings

Answer 16

1997 - FDA created black box warnings to regulate drugs with `“special problems” and identifies extreme adverse reactions (ADR)

Question 17

Drug Approval Process

Answer 17

• Established by the FDA
• The amount of time spent by FDA reviewing and approving drugs depends on several checkpoints. Informed consent need to participate in trials.

1. Therapeutic drugs are reviewed in four phases
2. Preclinical investigation
3. Clinical investigation
4. Review of New Drug Application (NDA)
5. Postmarketing surveillance

Question 18

Phase 1: Preclinical Testing

Answer 18

Involves extensive laboratory testing by pharma companies

• evaluated for toxicities, pharmacokinetic properties and useful biologic effects.
• Scientists perform tests on human and microbial cells
• Several species of animals, may take 1-5 years
• Determine drug action and predict whether the drug will cause harm
• Lab tests cannot predict the precise way the human body will respond, therefore, preclinical tests are always inconclusive

When sufficient pre-clinical data gathered, drug developer may apply for permission to begin human testing.

If application approved, drug is awarded Investigational New Drug Status and clinical trials can begin.

Question 19

Phase 2: Clinical Testing

Answer 19

Includes four phases, longest part of approval (2-10 years).

• Phase 1: Testing is conducted on around 20-80 healthy volunteers. If severe side effects anticipated (cancer drugs) then trials done with volunteers who have the disease.
  
  • Proper dose
  • Adverse effects
• Phase 2: Several hundred patients with the disease treated with the drug
  
  • Focus on effectiveness
  • Compare to placebo or another drug used to treat condition
• Phase 3: Large #s of patients with the disease are given drug
  
  • Determine patient variability
  • Potential drug-drug interactions
  • Safety alongside common chronic illnesses
  • Continues over several years and 1000s may be given drug
• Phase 3 completion - manufacturer applies to FDA to obtain conditional approval of New Drug Application
• Phase 4 - Post-marketing surveillance - FDA approval, drug released, observe effects on larger population

Question 20

New Drug Application (NDA)

Answer 20

• Submitted to the FDA after successful testing
• Signals that pharma company ready to sell
• FDA examines data either approved or denied. If denies FDA will specify if drug is “approvable” or “unapprovable”
• # of new drugs approved each year in past decade range from 78-100 while # of new molecular entities (molecularly unique to the market) is 20-30

Question 21

Marketing Surveillance

Answer 21

• The purpose is the survey harmful drug effects in a large population.
• Adverse drug reactions reported by the manufacturer, healthcare providers, and patients to the FDA Adverse Event Reporting System (FAERS)

Question 22

Approval process limitations

Answer 22

• Trials not diverse enough
• Do not test on children or pregnant women
• Adverse effects mat occur at low level so as to be not statistically significant
• Off-label prescribing - healthcare providers may prescribe medication for other indications or doses than tested for

Question 23

Controlled Substance

Answer 23

• In the US a drug whose use is restricted by the Comprehensive Drug Abuse Prevention and Controlled Substances Act of 1970
• Drugs with a potential for abuse categorized into 5 schedules based on the severity
• Hospitals and pharmacies must register with the Drug Enforcement Administration (DEA) to purchase and sell
  
  • Must use an assigned number to purchase scheduled drugs
  • Must maintain records of all quantities purchased and sold
  • Healthcare providers must register to prescribe these drugs
• Drugs with highest abuse potential have added restrictions

Question 24

Dependence

Answer 24

A powerful physiological or psychologic need for a substance

Question 25

Drug Schedules – Classified by Abuse Potential

Answer 25

• Schedule I - Highest potential for abuse. Restricted for use in situations of medical necessity; little to no therapeutic value or used for research (heroin, LSD, marijuana)
• Schedule II - High abuse potential, HR physical/psychological dependence (oxycodone, hydromorphone, fentanyl, methadone, methamphetamines)
• Schedule III - Moderate/Low physical/psychological dependence (Acetaminophen with Codeine, ketamine, anabolic steroids)
• Schedule IV – Low risk dependence (benzodiazepines, zolpidem)
• Schedule V - Lowest potential for abuse including antidiarrheals, antitussives, analgesics (Lomotil, Robitussin AC, Pregabalin)
• *Not all drugs with abuse potential placed into schedules such as
  nicotine, alcohol, caffeine

Question 26

Prescriptive Authority for Nurses

Answer 26

• Advanced practice registered nurses (APRN/APP) allowed to prescribe drugs under state regulations (NP, CNS, PMHNP, CRNA).
• Previously only physician providers or dentist
• Nursing Prescriptive authority came with advanced degree growth Not all states allow APRNs to prescribe medications
• Ability to prescribe is regulated by state laws
• About 1/3 states allow APRNs to prescribe drugs independently
  Other states require healthcare provider collaboration
• Specialty of APRN (APP) affects prescriptive authority

Question 27

Pharmacology in Clinical Practice

Answer 27

Nursing Responsibility - Rights of medication administration

• Monitor client’s condition before & during drug use
• Seek specific information from clients about OTC/illicit drug use
• Evaluate drug effects
• Teach client about self-administration and compliance, explore reasons why client not compliant (cost, side effects)
• Conduct medication reconciliation

Major Goals for Nursing Pharmacology Knowledge

• Eliminate medication errors
• Limit number and severity of adverse drug events (ADE)
• Incorporate knowledge updates as lifelong process