Gremlin: PKPD

Question 1

Compared to adults, peds have (higher/lower/same) gastric pH

Answer 1

Higher (more basic) → impact on drug stabiity

drugs that are acidic are more likley to be ionized in peds → lower absorption → higher mg/kg dose needed

Question 2

Compared to adults, peds have (higher/lower/same) gastric emptying rate

Answer 2

decreased rate of gastric emptying → decreased rate of drug absorption rate

during first week of life, gastric empyting rate and subsequently drug delivery increases, however this doesn’t bring it up to adult levels. Just makes it less worse

Question 3

Compared to adults, peds have (higher/lower/same) frequency and amplitude of intestinal contractions

Answer 3

reduced frequency and amplitude of intestinal contractions (age < 6 months) → reduced rate of absorption

Question 4

Compared to adults, neonates have (higher/lower/same) amplitude of rectal contractions

Answer 4

higher amplitude of contractions → derease time that durg is able to be absorbed → decreased F

Question 5

Compared to adults, infants have (higher/lower/same) drug permeabilty (percutaneous)

Answer 5

enhanced drug permeability ← high perfusion rates, greater degree of hydration

Question 6

Compared to adults, children have (higher/lower/same) capillary density

Answer 6

higher capillary denisty → icreased IM F

Question 7

Compared to adults, neonates have (higher/lower/same) TBW %

Answer 7

Higher: 75-85% vs 55-60%

Question 8

Compared to adults, neonates have (higher/lower/same) ECF

Answer 8

higher: 35-45 % vs. 20%

Question 9

Compared to adults, infants have (higher/lower/same) muscle/fat

Answer 9

Reduced
- increased Vd of hydrophilic drugs → lwoer [ ] → higher mg/kg dose than adults
- decreased Vd of lipophilic drugs → higher [ ] → lower mg/kg dose than adults

Question 10

Compared to adults, peds have (higher/lower/same) [ ] of circulating proteins (albumin and alpha1-acid glycoprotein

Answer 10

decreased [ ] of ciruclating proteins -> increased free fraction of drug

Question 11

Compared to adults, peds have (higher/lower/same) binding affinity of albumin

Answer 11

lower -> increased free fraction of drug

Question 12

d/t displacement of bilirubin, which drugs should specifically be avoided in peds < 2 months and what is the AE we’re avoiding

Answer 12

• avoid: ceftriaxone and sulfoamides
• don’t want bilirubin deposits in brain (kernicterus)

Question 13

Peds CYP3A4 considerations

Answer 13

CYP3A4 does not reach adult acitivty levels until age 1 → decreased CYP3A4 metabolism for pts under 1

Question 14

Peds 2C19 consdierations

Answer 14

more active during first 6 months of life → higher rates of metabolism of CYP2C19 drugs in pts under 6 months → shorter half life → more frequent dosing

Question 15

Peds APAP considerations

Answer 15

The UGT pathway is responsile for production of toxic byproduct, however pts under 12 years have a more active SULT pathway ← protiective from APAP overdose

Question 16

peds drug elimination consdierations

Answer 16

• renal elimination
  
  • Decreased renal blood flow
  • Decreased eGFR: reach adult at 1-2 year and then go over adult level before reverting to adult at age 12
  • Decreased tubular secretion: reach adult by 1 year
• → slower clearance, longer half life → less frequent dosing