EXAM2 L3

Question 1

Environmental Exposures Renaissance:

Answer 1

Infectious Agents
Fire Byproducts
Heavy Metals

Question 2

Environmental Exposures today:

Answer 2

Infectious Agents
Fire Byproducts
Heavy Metals
Industrial chemicals
Chlorination byproducts
Vehicular Emissions
Pesticides

Question 3

T/F: 66% of drugs have never been tested on pregnant women

Answer 3

True

Question 4

Thalidomide Disaster

Answer 4

Was prescribed for morning sickness, caused significant increases in phocomelia, a birth defect consisting of no limns, or tiny flipper-like arms and legs, serious facial deformities, and defective organs

Question 5

T/F: Exposure to xenobiotics are poorly understood

Answer 5

True

Question 6

T/F: Xenobiotic target moves even further due to the environment

Answer 6

True

Question 7

1962 Kefauver-Harris Drug Amendments did what?

Answer 7

Required efficacy and safety demonstration for FDA approval and marketing

Question 8

Legislative incentives/mandates in place to promote pediatric development

Answer 8

FDA: Pediatric plan, BPCA, PREA
EU: Pediatric investigation plan (PIP)
WHO: Make medicines child size

Question 9

Several practical challenges have discouraged the testing of drugs in pediatric populations including the lack of:

Answer 9

incentives for companies to study drugs in neonates, infants and children
Technology to monitor patients and assay very small amounts of blood
Suitable pediatric clinical infrastructure for drug trials

Question 10

What percent of approved drugs have pediatric labeling

Answer 10

20-30%

Question 11

Ways the FDA has encouraged pediatric studies

Answer 11

Financial incentive to conduct studies
Increased studies resulted in new labeling for 40 drugs
For approval of selective number of new drugs pediatric studies have been required

Question 12

Developmental changes occurring from conception to adulthood is considered to be

Answer 12

Moving target

Question 13

Why pediatric studies are difficult

Answer 13

Children are not mini adults
Animal studies not always predictive
Clinical studies in children fraught with ethical and financial hurdles
Admin. of drug can be probelmatic

Question 14

BCS: Classification is based on what three factors that influences the drug’s bioavailability from a peroral formulation:

Answer 14

Solubility
Intestinal permeation acorss the intestinal barrier (in vitro vs in vivo)
Dissolution rate

Question 15

T/F: There is an urgent need to expedite the development of pediatric formulations

Answer 15

True

Question 16

PBCS stands for

Answer 16

Pediatric Biopharmaceutics Classification System

Question 17

PBCS Class 1

Answer 17

(pediatric volume = 25ml): rapid dissolution (t50 = 15 min) for immediate release

Question 18

PBCS Class 2:

Answer 18

(Subclasses a,b,c for acidic, basic and neutral drugs); Dissolution criteria are critically needed

Question 19

BCS: Class 3:

Answer 19

Very rapid dissolution

Question 20

BCS Class 4:

Answer 20

Same as BCS Class 2

Question 21

T/F: Because Disposition drives safety and efficacy, there is a need for consideration of distribution , metabolism and elimination in the system-BDDCS

Answer 21

True

Question 22

T/F: Low clearance rates are associated with higher toxicity

Answer 22

True; Dose lowering adjustments and higher hydration rates should be required in children carrying these phenotypes

Question 23

What factors govern regulation of transporter expression and activity during growth and development?

Answer 23

Nuclear receptor regulation
Endocrine changes

Question 24

Major Challenges in Studying Pediatric Drug Transporters

Answer 24

Limited availability of quality pediatric tissue (all age groups) for protein quantification and assessment of transporter function
Lack of transporter-specific probes to assess in vivo function
Ethical and practical challenges with performing nontherapeutic studies in children

Question 24

Biological challenges with pediatrics:

Answer 24

Ontogenic changes Compositional Changes

Question 25

Clinical Challenges with pediatrics:

Answer 25

Clinical Trials Caregiver Requirements

Question 26

Formulation Challenges with pediatrics:

Answer 26

Dosage Form Selection Flexibility in Dosing Excipient Selection Taste Masking

Question 27

Differences between EMAs and FDAs view on pediatric trials

Answer 27

EMA will not allow a products release, including adult formulation, if their pediatric investigation Plan (PIP) isn't satisfactory

Question 28

Paradigm shift for industry

Answer 28

Changed from protecting children FROM research to protecting children THROUGH research

Question 29

The safety and Toxicology of Excipients for Pediatrics Database

Answer 29

Collaboration between EMA and NICHD Draws considerable attention to use of traditional excipients, particularly co-solvents for pediatrics vs. adults Encouraging greater use of solid dosage forms

Question 30

Factors important in mini-tablet platform formulation

Answer 30

Ability to incorporate BCS Class I and III Easy translation to market formulation Minimal Excipients Same or Similar Manufacturing Conditions Fractional Factorial DOE approach

Question 31

Pharmaceutical Film Advantages

Answer 31

Acceptable for patients with dysphagia Ease and accuracy of dosing Increased stability compared to solutions/suspensions Faster onset of action Life cycle management

Question 32

Pharmaceutical Film Disadvantages

Answer 32

Difficult to manufacture Moisture sensitive Limited dosing capacity Increased packaging costs

Question 33

Challenges that remain in pediatric pharmacology

Answer 33

Age based dosage form selection Need for descriptive pharmacology in pediatric patients Animal models need to be refined for prediction Enable clinical studies in children by tackling ethical and financial hurdles Better means of drug admin. are needed