Pharm Exam 3

Pediatric patients are NOT "little adults"

What fundamental principle explains why pediatric pharmacotherapy differs from adult pharmacotherapy?

Age <30 days old

What age defines a neonate?

Age 1 month to 1 year

What age defines an infant?

Age 1 year to 12 years

What age defines a child?

Age 12-18 years

What age defines an adolescent?

Lack of pediatric clinical trial data

Why do many drug labels state that safety and effectiveness in pediatric patients have not been established?

Body surface area (BSA) relative to body mass is greatest in infants and young children

What body proportion difference significantly affects pediatric pharmacokinetics?

Infancy

During what life stage do the most rapid growth and developmental changes occur?

Quantitative change in body size

What is growth?

Qualitative change in skills or function

What is development?

Genetically controlled development independent of environment

What is maturation?

75-80% total body water

What percentage of body weight is total body water in a full-term neonate?

~65% total body water

To what level does total body water decrease by 3 months of age?

Increase in body fat

What compensates for the decrease in total body water during infancy?

Body fat doubles during the first 5 months

What major body composition change occurs during the first 5 months of life?

Weight triples by age 1 year

What happens to body weight by the end of the first year of life?

BSA and length double by age 1 year

What happens to BSA and length by the end of the first year?

Age 2 years

At what age do the liver and kidneys reach their maximum size relative to body weight?

Peak metabolism and elimination

What occurs when the liver and kidneys reach maximum size relative to body weight at age 2?

Low lipase and absent alpha-amylase

What digestive enzyme deficiency affects preterm infant absorption?

Fat-soluble drugs

Which type of drugs require lipase for absorption?

Decreased vitamin E absorption

What nutrient absorption is reduced because bile acids, lipase, amylase, and protease activity are reduced until about 4 months?

Breastfed infants

Which infants develop intestinal flora more rapidly?

Alkaline gastric pH at birth

What is neonatal gastric pH?

Increased absorption of basic drugs

How does alkaline gastric pH at birth affect basic drugs?

Decreased absorption of acidic drugs

How does alkaline gastric pH at birth affect acidic drugs?

Delayed gastric emptying

What GI characteristic is seen in preterm and full-term neonates?

Neonates and infants

Which pediatric groups have irregular peristalsis that enhances absorption?

Greater duodenal surface area

Why do young children often have enhanced drug absorption?

Decreased muscle mass and blood flow

Why is IM absorption erratic and poor in neonates?

Greater skeletal muscle capillary density

Why can infants absorb IM drugs more efficiently than older children?

Comparable to IV penicillin

How do IM penicillin concentrations compare with IV administration in infants?

Decreased skin thickness, increased hydration, and less subcutaneous fat

What skin characteristics increase percutaneous absorption in neonates and infants?

Much greater percutaneous absorption and toxicity risk

What is the consequence of neonatal skin characteristics on topical drug exposure?

Hexachlorophene

What topical agent caused vacuolar encephalopathy in premature neonates?

Diphenhydramine toxicity

What fatal topical toxicity has been reported in infants treated for eczema?

Hemorrhoidal veins

Rectal drugs are absorbed through which venous system?

Avoidance of first-pass metabolism

What is a major advantage of rectal administration?

Erratic and incomplete absorption

How is rectal absorption characterized in neonates and infants?

Diazepam, valproic acid, and midazolam

Which rectal drugs may be used for seizures when IV access is unavailable?

Altered maternal physiology and the placental-fetal unit

What are the major factors affecting pharmacokinetics during pregnancy?

Increased gastric pH (more alkaline)

How does pregnancy affect gastric pH?

40% decrease in acid secretion

What change in gastric acid secretion occurs during pregnancy?

Decreased absorption of drugs requiring an acidic environment

How does increased gastric pH affect acid-dependent drugs in pregnancy?

Progesterone

What hormone decreases GI motility during pregnancy?

Increased gastric emptying time

How does pregnancy affect gastric emptying?

Peripheral vasodilation, increased skin blood flow, and increased skin water content

Why is percutaneous drug absorption increased during pregnancy?

Increased pulmonary drug absorption

How does pregnancy affect inhaled drug absorption?

Cardiac output and tidal volume increase by ~50%

What pulmonary physiologic changes occur during pregnancy?

Consider dose reductions for volatile anesthetics

What dosing consideration applies to inhaled anesthetics during pregnancy?

Lower tidal volumes and increased respiratory rates

What pulmonary characteristics reduce aerosol drug delivery in infants and children?

Consider higher doses of aerosolized drugs

What dosing consideration may be needed for inhaled drugs in children?

Maternal blood volume increases 30-50%

How does pregnancy affect blood volume?

Total body water increases by about 8 L

How does pregnancy affect total body water?

Body fat increases by 3-4 kg

How does pregnancy affect maternal fat stores?

Increased volume of distribution

How does pregnancy affect Vd?

Dilutional decrease in drug concentrations

What is the consequence of increased Vd during pregnancy?

Decreased albumin concentration

How does pregnancy affect albumin levels?

Increased free concentrations of highly protein-bound drugs

What is the consequence of decreased albumin during pregnancy?

Higher total body water and water:lipid ratio

Why do neonates have increased Vd for hydrophilic drugs?

Increased gentamicin dose

What dosing change may be needed because neonates have increased Vd for hydrophilic drugs?

Immature tissues with less drug binding

Why can neonates have higher free concentrations of tissue-bound drugs?

Lower alpha-1 acid glycoprotein

What plasma protein binding difference exists in preterm infants?

Less albumin than adults

What albumin difference exists in neonates?

Increased free drug concentrations

What is the consequence of lower neonatal albumin levels?

IV administration

Which route provides 100% bioavailability?

Phase I metabolism

Which metabolic phase includes oxidation, reduction, and hydrolysis reactions?

Codeine and tramadol

Which drugs depend on CYP2D6 conversion to active opioid metabolites?

CYP2D6 ultra-metabolizers

Which patients are at risk for toxic morphine levels from codeine or tramadol?

Children <12 years and breastfeeding women

In whom should codeine and tramadol be avoided?

Phase II metabolism

Which metabolic phase consists of conjugation reactions?

CYP3A4, CYP2A6, and CYP2D6 induction

Which CYP enzymes are commonly induced during pregnancy?

CYP1A2 and CYP2C19 inhibition

Which CYP enzymes may be inhibited during pregnancy?

UGT1A4 activity increases 200-300%

What major phase II metabolic change occurs during pregnancy?

Lower lamotrigine concentrations

How does increased UGT1A4 activity affect lamotrigine?

Lamotrigine dose titration upward

What adjustment is often needed for lamotrigine during pregnancy?

Glomerular filtration rate

What does GFR stand for?

First 2 weeks of life

When does neonatal GFR increase rapidly?

Age 2 years

At what age does GFR approach adult levels?

Immature renal system and decreased renal blood flow

Why is renal drug clearance reduced in neonates?

Increased drug half-life

What is the consequence of reduced neonatal renal elimination?

Aminoglycosides, penicillins, and sulfonamides

Which drug classes commonly have prolonged half-lives in neonates?

Age 5-7 months

When does tubular secretion reach adult values?

Directly proportional to age

How is renal excretion generally related to age in pediatrics?

Increased GFR and renal blood flow

How does pregnancy affect renal elimination?

Lithium clearance doubles in the third trimester

What classic example demonstrates increased renal elimination in pregnancy?

Lipid solubility

What drug property most strongly increases placental transfer?

Nonionized state

Which ionization state crosses the placenta more readily?

Unbound (free) drug

Which protein-binding state crosses the placenta most readily?

Low molecular weight

What molecular characteristic increases placental transfer?

P-glycoprotein inhibition

What transporter effect allows more drugs to cross the placenta?

Heparin

Which anticoagulant is relatively safe in pregnancy because it is ionized and crosses poorly?

7-8 weeks gestation

When are fetal liver enzyme systems first present?

First 14 days after conception

When is the embryo relatively protected from exogenous toxicity?

After day 14

When does the embryo become susceptible to drug effects?

First trimester (first 3 months)

What period is most critical for congenital abnormalities and malformations?

Older gestational age increases fetal fat stores

Why do lipophilic drugs affect older fetuses more readily?

Teratogenicity

What is the ability of a drug to cause fetal dysgenesis or developmental abnormalities?

Gestational age, agent, and duration of exposure

What three major factors determine teratogenic risk?

Isotretinoin

Which acne medication is highly teratogenic?