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Thera X > 4 Pediatric Clinical Pharmacology Steinberg > Flashcards

4 Pediatric Clinical Pharmacology Steinberg Flashcards

1
Q

What is a Neonate?

A

First 28 or 30 days of postnatal life

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2
Q

What is an Infant?

A

One month to 1-2 years of age

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3
Q

What is a Child?

A

1-2 to 11 years old

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4
Q

What is a Preadolescent?

A

11-13 years old for boys; 10-12 years for girls

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5
Q

What is Adolescent?

A

11-20 years

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6
Q

What is a Term Infant?

A

38-42 weeks

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7
Q

What is a Preterm Infant?

A

36-38 weeks

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8
Q

What is Premature Infant?

A

30-36 weeks

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9
Q

What is Extremely Premature Infant?

A

< 30 weeks

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10
Q

How does pH dependent diffusion differ in infants?

A

At birth, newborns have a more alkaline gastric pH (6-8) d/t to residual amniotic fluid in the stomach and inability of the stomach to express acid. Gastric acid production increases over the next 24-48 hrs to achieve adult pH levels

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11
Q

What are the implications of the pH differences in newborns?

A

Acid-labile drugs such as penicillins will have greater stomach epithelial permeation and/or decreased decomposition, and higher extent of oral absorption in neonates and young infants than in adults, while lower bioavailability of weak acids

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12
Q

What is gastric emptying time like in infants?

A

Irregular and unpredictable gastric emptying time and peristalsis seen in neonates and young infants; via rapid antral concentrations in 1st week, then slows. Biphasic gastric emptying pattern. Gastric emptying time 6-8 hrs in neonates vs ~2 hrs in adults; adult values by 6-8 months of age

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13
Q

What are the implications with the slower gastric emptying in infants?

A

Complete but delayed/slow absorption of digoxin, phenobarbital, etc.

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14
Q

What is iron absorption capacity like in infants?

A

Iron absorption mediated by DMT1. Very low absorption in 0-6 months, increases linerally after birth

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15
Q

What is the intestinal surface area and absorption like in infants?

A

Shorter bowel length compared to adult (though more microvilli present). Short-gut syndrome. Protein-calorie malnutrition

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16
Q

What are the implications of intestinal surface area and absorption?

A

Sustained-release products that portray extended time-release profile may have incomplete bioavailability

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17
Q

What is Exocrine function like in infants?

A

Function is reduced in the neonate (low lipase production; increased circulating bile acids, but low transporter-mediated secretion of bile acids into the biliary canaliculi –> low luminal bile acid salts)

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18
Q

What are the implications of neonates decreased lipase production?

A

Fat malabsorption of nutrients (e.g. vitamins A, D, E, and K) and lipid-soluble drugs

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19
Q

What is Intramuscular Absorption like in infants?

A

Gluteus maximus, deltoid, etc. Should not be used in young infants (important nerve tracks); anterior thigh

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20
Q

What is Percutaneous Absorption like in neonates?

A

Enhanced in neonates (Decreased thickness of the stratum corneum, increased water content of the skin)

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21
Q

What is rectal absorption like in neonates?

A

Ease of administration; necessary route in neonates. Anus and bottom third of rectum: venous drainage via azygous vessels and straight to vena cava - NO hepatic 1st pass effect

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22
Q

Where does a premature baby carry most of its water?

A

Extracellularly

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23
Q

What is total protein like in neonates for drug protein binding?

A

Lower in neonates and infants

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24
Q

What is plasma albumin like in neonates?

A

Low. Goes up in infancy

25
Q

What is the blood pH like in neonates?

A

Low. Increases in infancy

26
Q

What is tissue binding like in infants?

A

Infants have ~3x the number of myocardial receptors for digoxin as do adults (and 2x higher dissociation constant) leading to different pharmacodynamic response (less sensitive) for any given dose; PK differences also seen. Therefore, typical doses of digoxin to treat cardiac arrhythmias or heart failure in young infants are 8-15mcg/kg/day, as compared with 2-4 mcg/kg/day for adults

27
Q

What are the Phase 1 (hydroxylation/demethylation) hepatic reactions like in neonates?

A

Low in neonates. Much higher in children > 6 months old than the adult

28
Q

Which hepatic enzyme is highest in children < 10 years?

A

UGT2B7

29
Q

Which hepatic enzymes goes down with age while another goes up?

A

CYP3A7 decreases until its absent by ~1 year of age. CYP 3A4 is low and eventually goings up after age 1 year

30
Q

What is Theophylline metabolism like for neonates?

A

< 2 weeks have very low metabolism (50% of drug is excreted in urine unchanged). 45% by 31 days of age. 10% excreted unchanged after 1 year of age. Require a higher dose of theophylline in children 1-9 years of age

31
Q

What is Tramadols concentration like in infants?

A

Very high concentration in < 6 months, slowly decreasing with age (metabolism increases)

32
Q

What is Chloramphenicol like in neonates?

A

Decreased glucuronidation of Chloramphenicol in neonates –> accumulation of high concentrations (grey-baby syndrome)

33
Q

What is the benefit of Higher Sulfation Capacity in young children?

A

Lower incidence of liver damage from acetaminophen overdose in young children than in adolescents and adults (less reactive metabolite formed and more conjugated)

34
Q

What is Morphine metabolism like in the young?

A

Lower glucuronidation –> less early formation of morphine-6-glucuronide (more potent than morphine). M-6-G metabolite contributes to the pharmacodynamic effect in children, adolescents and adults. With immature BBB, neonates more sensitive to morphine. Higher serum concentrations of parent compound, morphine, are needed in the newborn (paradox)

35
Q

At what age does the fetus begin making urine?

A

9-12 weeks gestational age

36
Q

What is the Vancomycin PK clearance vs. weight?

A

As weight increases, so does vancomycin clearance

37
Q

How does vancomycin clearance relate to SCr?

A

The higher the SCr, the lower the amount of vancomycin cleared (reaches zero at SCr 1.8 in the young)

38
Q

What are some attempts to reduce variability in pediatric dosing?

A

Fixed doses or downsizing adult doses (e.g. Clark’s Rule). mg/kg dosing. mg/m2 (BSA dosing). Normalization to adults via allometric methods. Allometric relationship, more general description. Population pharmacokinetic modeling and derived equations, with Bayesian parameter and dose adjustment

39
Q

How does the weight-based pediatric dosing of Digoxin compare to adults?

A

Pediatric clearance is MUCH higher, requiring a higher ug/kg/day dose (triple the adult amount)

40
Q

How does the weight-based pediatric dosing of Tobramycing compare to adults?

A

Clearance is a lot higher in pediatric patients, causing them to have a higher mg/kg/day dose

41
Q

How does the weight-based pediatric dosing of Ceftazidime compare to adults?

A

Clearance is a lot higher in pediatric patients, causing them to have a higher mg/kg/day dose

42
Q

How does the weight-based pediatric dosing of Indomethacin compare to adults?

A

Clearance is a lot higher in pediatric patients, causing them to have a higher mg/kg/day dose

43
Q

When is BSA dosing useful?

A

For drugs with hepatic metabolism, fat solubility, large Vd. Less useful for renally-cleared drug, polar, relatively small Vd

44
Q

Why is BSA dosing potentially dangerous in infants?

A

Surface area to volume ratio changes dramatically, therefore BSA dosing will equate to much higher mg/kg dose than in older children and adults

45
Q

What is Valganciclovir dosing based on for posttransplantation?

A

BSA and CrCl. Pediatric dose (mg) = 7 x BSA x CrCl

46
Q

What are Allometric Methods?

A

Attempt to normalize PK parameters or dose to a typical adult size or age

47
Q

What is the surface area like for newborns?

A

Around that of adults at birth, then greatly increases by age 1, after that it slowly declines back to that of an adult

48
Q

What is the Allometric 3/4 power dosing like for pediatric patients?

A

Relatively constant equation for doing in pediatric patients, better than “per kilogram” dosing

49
Q

What is Acyclovir clearance like in children?

A

Dosed based on weight. As weight increases, so does clerance

50
Q

What is Propylene Glycol PK like in neonates?

A

Applied as a cosolvent for drugs often given to neonates, e.g., acetaminophen, phenobarbital, lorazepam, lopinavir, ritonavir

51
Q

What is the metabolism of Propylene Glycol like?

A

Metabolized to carbon dioxide and H2O through metabolic intermediates including lactic and pyruvic acids

52
Q

What is clearance of Propylene Glycol like in neonates?

A

Increases with increased birth weight

53
Q

What are concentrations of Paracetamol like in neonates?

A

Concentrations decrease as gestational age increases

54
Q

What are concentrations of Phenobarbital like in neonates?

A

Concentrations decrease as gestational age increases

55
Q

What is the effect of TCAs and MAOIs in children?

A

Lack of effect. Neurodevelopmental delay of NE system

56
Q

What is the effect of Opioid Analgesics in children?

A

Higher sensitivity in neonates. Higher opioid receptor expression

57
Q

What is the effect of Oral Anticoagulants in children?

A

Increased Warfarin effects. Lower Cp of Vit K-dependent clotting factors

58
Q

What happens with liver mass as a percent of body weight as we age?

A

Decreases with age

Thera X (25 decks)

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