Week 1: Section 18, Chapter 97. pp 2265 - 2276 (Pediatric Pharmacotherapy)

Question 1

True or False:

Children undergo considerable physiologic changes between birth and adulthood. Although most follow the same general pattern of growth, the TIMING OF MATURATION varies from child to child.

Answer 1

True

Question 2

All aspects of pharmacokinetics are affected by growth and development. Drug absorption is altered by a variety of mechanisms, with the most significant differences noted during the ____.

Answer 2

first months of life.

Question 3

The greatest degree of drug distribution change occurs during the _____.

Answer 3

first year of life.

Question 4

Drug distribution is affected by changes in (7)

Answer 4

1. Organ size
2. Body water content
3. Fat stores
4. Plasma protein concentration
5. Acid-base balance
6. Cardiac output
7. Tissue perfusion

Question 5

True or False:

Metabolic function is highly dependent on ____.

Answer 5

patient’s age.

Question 6

Drug elimination is reduced during _____, resulting in slower rates of clearance for many commonly used drugs.

Answer 6

infancy

Question 7

The effects of puberty can alter the ____ or _____ of many drugs administered during this period.

Answer 7

efficacy or toxicity

Question 8

(In pediatrics) For most dose calculations, _____ is used to account for growth and development.

Answer 8

weight

Question 9

Children do not grow in a predictable, linear fashion, but rather in PERIODIC BURSTS, with additional variation caused by differences in (3)

Answer 9

1. Genetic predisposition
2. Nutritional intake
3. Environment

Question 10

This refers to the research on the impact of growth and development on pharmacokinetics and pharmacodynamics.

Answer 10

Developmental pharmacology.

Question 11

ASA is no longer used in children because of its association with ______ syndrome.

Answer 11

Reye’s syndrome (causing mitochondrial damage and resulting in hepatic failure)

Question 12

NSAIDs are not recommended for use in infants younger than 6 months f age because of an increased risk for _____.

Answer 12

renal impairment.

Question 13

True or False:

In neonates, gastric acid production is DECREASED, giving a higher, nearly neutral pH in the stomach.

Answer 13

True.

Therefore: Great absorption tof acid-labile drugs (PCN, erythromycin). Less absorption for weakly acid drugs (Phenobarbital, phenytoin)

Question 14

Amylase activity is minimal at birth and remains low until the ______.

Answer 14

third month of life.

Question 15

Pancreatic lipase activity is detectable by _____ weeks AOG, but remains low at birth and throughout the next 2 - 3 months.

Answer 15

32 weeks

Question 16

This is present at birth and accounts for greater percentage of fat absorption during early life.

Answer 16

Gastric lipase

Question 17

Adult values for gastric emptying and intestinal transit time are generally reached by _____-

Answer 17

4 - 8 months of age

Question 18

Reduction of splanchnic blood flow may cause damage to the gut lining from _____ drug formulatios.

Answer 18

hyperosmolar.

Therefore, enteral route of drug administration is delayed until patient is receiving 1/4 to 1/2 of nutritional needs through enteral feedings.

Question 19

Intestinal enzymatic activity does not approach adult values until age ____.

Answer 19

2 - 3 years old

Question 20

Why Vitamin K is administered IM in newborns?

Answer 20

Vitamin K per IM has slow absorption (due to immature vasculature, small size muscle, etc). It will protect the neonate from belle ding for 1 month. Until such time he is getting Vitamin K from breastmilk or infant formula.

Question 21

Transdermal drug absorption is higher in neonates because of (4).

Answer 21

1. Greater skin to body surface area ratio
2. Thinner stratum corneum
3. Better epidermis hydration
4. Greater perfusion

Question 22

The use of Betadine (Povidone-Iodine) in neonates is associated with _____ dysfunction.

Answer 22

thyroid

Question 23

EMLA cream is a mixture of these two drugs.

Answer 23

lidocaine and prilocaine.

Question 24

EMLA cream should be applied ____ prior to circumcision, while lidocaine should be applied ____.

Answer 24

1 hour…. 30 minutes

Question 25

These patch medications are used to treat ADHD in pediatrics (2).

Answer 25

Methylphenidate, clonidine

Question 26

These patch medications are used to treat severe pain in pediatrics (2).

Answer 26

lidocaine, fentanyl

Question 27

These are preferred formulation for rectal administration. They do not require an extended time for dissolution.

Answer 27

Gels and liquids.

Question 28

Emperic antibiotic therapy for sepsis and meningitis consists of __ (2).

Answer 28

ampicillin and aminoglycoside. | Combination of these is very effective in the neonatal period when drug distribution into the CNS is much higher.

Question 29

Administration of drugs with a high binding affinity for albumin, such as sulfonamides, during neonatal period can result in competition with bilirubin for binding sites. The resulting increase in unbound bilirubin can lead to ______, neurologic damage caused by deposition of bilirubin in the brain, primarily in the basal ganglia.

Answer 29

kernicterus

Question 30

Phase 1 reactions include (4)

Answer 30

1. Oxidation 2. Reduction 3. Hydroxylation 4. Hydrolysis

Question 31

This enzyme plays a major role in drug metabolism, including that of erythromycin.

Answer 31

Cytochrome P-450 (CYP) 3A enzymes.

Question 32

This is the primary metabolic enzyme in utero.

Answer 32

CYP3A7.

Question 33

CYP3A7 can be found in

Answer 33

Endoplasmic reticulum of fetal hepatocytes. Has a role in transformation of DHEA and detoxification of retinoid acid derivatives (from maternal serum across the placenta).

Question 34

The lack of ______ activity has a profound impact on the ability of newborns to metabolize benzyl alcohol, a common preservative in injectable drug products.

Answer 34

alcohol dehydrogenase

Question 35

This termed is referred to benzoyl alcohol toxicity.

Answer 35

Gasping syndrome

Question 36

Phase II reactions include (3)

Answer 36

1. Glucuronidation 2. Sulfation 3. Acetylation

Question 37

This enzyme is responsible for glucuronidation of both drugs and endogenous substances. They are low levels in fetal circulation.

Answer 37

UGT (5'-diphosphate glucoronosyltransferase

Question 38

The reduced ability of infants to perform glucuronidation has been known for many years as a result of ____.

Answer 38

chloramphenicol "gray baby syndrome"

Question 39

This is the primary enzyme responsible for chloramphenicol metabolism.

Answer 39

UGT2B7

Question 40

This is responsible for fetal metabolism of thyroid hormones.

Answer 40

SULT1A1

Question 41

This enzyme is responsible for metabolism of steroid hormones.

Answer 41

SULT2A1

Question 42

This enzyme is responsible for metabolism of catecholamines.

Answer 42

SULT1A3

Question 43

The primary site for SULT enzyme development takes place in the

Answer 43

liver. Except for SULT2A1... occurs primarily in fetal adrenal gland.

Question 44

Adverse effects of morphine (3)

Answer 44

1. Hypotension 2. Respiratory depression 3. Constipation

Question 45

The ability of kidney to filter, excrete, and reabsorb substances is not maximized until the age of ___./

Answer 45

1 year

Question 46

Glomerular filtration rate at birth, for full term neonates.

Answer 46

2 - 4 ml/min

Question 47

Normal GFR for adults.

Answer 47

100 - 120 ml/min

Question 48

Name 2 renal eliminated drugs

Answer 48

Aminoglycosides and vancomycin

Question 49

In neonates, tubular secretion is also decreased. A decrease in tubular secretion also results in prolonged elimination half-life for drugs such as (4)

Answer 49

1. PCN 2. Cephalosporins 3. Furosemide 4. Digoxin

Question 50

This drug has been used for many years in the management of SVT in neonates.

Answer 50

Digoxin

Question 51

These (2) are not always useful indicators of renal function in neonates.

Answer 51

BUN and serum creatinine

Question 52

This is often used as an additional measure of renal function in neonates.

Answer 52

Urine output.

Question 53

Normal urine output for neonates.

Answer 53

1 ml/kg/hr

Question 54

One of the most common method to calculate for creatinine clearance in pediatrics is ____.

Answer 54

Traub and Johnson Method

Question 55

These maturational changes can result in clinically significant differences in response to common therapies. (3)

Answer 55

1. Receptor conformation 2. Receptor Density 3. Receptor Affinity 4. Signal Transduction

Question 56

Infants have long been suspected to be relatively resistant to the effects of B-adrenergic AGONISTS, including (3)

Answer 56

1. Dopamine 2. Dobutamine 3. Epinephrine

Question 57

This is a serious dermatologic reaction in children associated with the use of lamotrigine.

Answer 57

toxic epidermal necrolysis

Question 58

Name 2 theories associated for the greater incidence of serious dermatologic reactions in children.

Answer 58

1. Dose-related toxicity | 2. Immune-mediated hypersensitivity response

Question 59

Pediatric drug references provide most doses in units per weight; with the exception of _____ (agents), which are dosed by body surface area.

Answer 59

Chemotherapeutic

Question 60

A recent study of clonidine clearance in the early postnatal period suggests that both age and weight should be used to optimize clonidine doses in newborns being treated for _____.

Answer 60

neonatal abstinence syndrome

Question 61

True or False: Older children and adolescents should transition to adult dosing whenever the calculated weight-based dose exceeds the usual adult dose.

Answer 61

True

Question 62

This is a part of the FDA Modernization Act of 1997. It was developed to address the lack of pediatric study data, including medication prescribing information.

Answer 62

Pediatric Exclusivity Program

Question 63

This rule gave the FDA the ability to require manufacturers to conduct clinical trials of drugs that would be used in a significant number of patients.

Answer 63

1998 Pediatric Rule

Question 64

This act extended the previous incentives and created a mechanism for funding studies of older, off-patent medications that are often used in children.

Answer 64

Best Pharmaceuticals for Children Act of 2002

Question 65

In 2007, the WHO passed a resolution calling for better medications for children. WHO initiated the _____ program with the goal of increasing medication availability for children.

Answer 65

Make Medicines Child-Sized program