Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

810 > PK/PD - Pediatrics > Flashcards

PK/PD - Pediatrics Flashcards

1
Q

Age Classifications

A 
Neonates: Newborn to 1 month
Infants: 1 month to 2 years
Children: 2 years to 12 years
Adolescents: 12 to 16 years old
**FDA established**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Pregnancy Classifications

A

Term Pregnancy: 37-40 weeks
Premature Pregnancy: < 37 weeks
Viable Pregnancy: > 24 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Age Classfications

A

Gestational Age: Time of conception to birth
Postnatal Age: Age since birth
Postmenstrual Age: GA + PNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Weight Classifications

A

Low Birth Weight: < 2500 g: < 35 weeks
Very Low Birth Weight: < 1500 g: < 30 weeks
Extremely Low Birth Weight: < 1000 g: < 27 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Fetal Development

A
  • Embryonic Periods: organogenesis, sensitivity to drug exposure
  • Fetal Periods: organ maturation, less sensitive to drug exposure but still significant
  • *Can affect PK**
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Liver Development

A
  • CYP content ~30-60% of adult values

- Starts developing around week 4 and continues to develop throughout gestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Renal Development

A
  • Develops weeks 5-15
  • Development continues until completed at week 24
  • Functionally matures at birth - can be affected by utero drug exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Milestones

A
  • Weight: doubles in 1st 6 months, triples by first year
  • Body composition: fat, protein, water percentage are constantly changing
  • Organ maturation: major organs mature in the first 2 years
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Pediatric PK Considerations

A

ADME parameters vary greatly by age, even when normalized by weight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pediatric PD Considerations

A

Some evidence supports differing receptor sensitivity and density

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

PK - Absorption

A
  • Total absorption is driven by the rate (affects onset) and extent (determines effective dose) of absorption
  • Drug enters body for therapeutic effects at oral/GI, transmucosal, transdermal, and IM routes
  • Matters since body composition and development stages affect absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Absorption - Oral/GI - pH

A

Normal Adult pH: 1.5-3.5
Birth d/t amniotic fluid pH: 6-8
24-48 hours pH: 1-3
Day 8 pH: ~7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Absorption - Oral/GI - Secretions

A

-HCl secretions mature slowly
-Reaches adult levels at about 2 years of age
-Every drug is optimally absorbed or activity at certain pH
EX: beta lactam antibiotic: high pH: high bioavailability
EX: Weak acids (APAP, Phenytion): high pH: low bioavailability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Absorption - Oral/GI - Gastric Motility/Emptying

A

-Small intestine = major site of absorption
-Prolonged in neonates which affects the rate of absorption
EX: APAP, digoxin has delayed onset
-Clinical factors: gastroenteritis, diarrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Absorption - Oral/GI - Additional Factors

A
  • Intestinal SA - small gut: decreased SA: decreased absorption
  • Diet
  • Biliary function and pancreatic enzymes are underdeveloped which affects lipophilic drug solubility and absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Absorption - Oral/GI - Intestinal Metab/Enzymes

A

-Metabolizing enzymes and drug transporters re not well elucidated
EX: Gabapentin has decreased absorption in those under 5 years old from decreased L-amino transporter activity
EX: Decreased P-gp activity in neonates

17
Q

Absorption - Transmucosal

A
  • SL, nasal, rectal
  • ~50% of rectal blood flow bypasses first pass metabolism
  • Dose loss d/t expulsion
  • Often convenient: Midazolam, APAP
18
Q

Absorption - Skin

A

Neonates and infants have increased skin permeability due to:
-Increases in skin hydration
-Thinner stratum corneum
-Increased subcutaneous perfusion
-Increased BSA:Mass ratio
EX: Steroids (topical OTC hydrocortisone)

19
Q

Absorption: IM

A

-Decreased muscle mass: decreased absorption tissue
-Poor muscle tone: decreased blood flow musculature
-More capillaries
-Evidence shows variable and decreases in absorption
EX: Antibiotics, phenobarbital
Advantages if slow absorption in preferred like with Vitamin K at birth

20
Q

Distribution

A
  • Vd is a ratio of total drug in body to the drug measured in the plasma
  • Depends on hydrophilicity/lipophilicity, plasma protein binding, tissues binding of drug
  • Drug disperses through body in compartments
  • Understanding Vd helps guide loading doses by considering CL and affects on half lives
  • Hydro/lipophilicity of drug determines which compartments it does in to
21
Q

Distribution - Pediatric Compartment Size

A
  • Changes relative to age

- Total body water (decreases with age) and body fat (increases with age) are examples

22
Q

Total Body Water Changes

A

Preterm neonates: 85%
Term neonates: 75%
1 year old: down to 60%

23
Q

Total Body Fat Changes

A

Preterm neonates: 2%
Neonates: 10-15%
1 year: 20-25%

24
Q

Distribution - Plasma Protein Binding

A
  • Neonates have decreases protein binding since there is less proteins, lower affinities, and more competing substrates like bilirubin and FFA
  • Increases Vd, protein maturation occurs at about 10-12 months
25
Q

Distribution Drug Examples (3)

A
  1. Gentamycin - hydrophilic, affects clearance and half life for neonates
  2. Phenytoin - free phenytoin is active, only 40-50% is bound in neonates compared to 80-90% in adults, decreases bilirubin and may end up with more free than bound phenytoin (Take free phenytoin levels)
  3. Ceftriaxone - displaces bilirubin, kernicterus risk, crosses BBB and can cause encephalopathy
26
Q

Metabolism

A
  • Phase I: structural changes, Phase II: conjugation (primarily in liver)
  • Both phases involves enzymes or transporters
  • Genetic polymorphisms can complicate things
27
Q

Metabolism - Pediatric Enzymes

A
  • each enzyme has unique ontogeny
  • CYP3A7 = “neo” enzyme, active form in 0-6 months
  • Others increase over time, though this isn’t linear
  • Takes longer in preterm
  • Reaches adult levels at about 2 years old
28
Q

Metabolism - Phase II Enzymes in Peds

A
  • UGTs have decreased activity - metabolize ~15% of medications (APAP, morphine for examples), matures at about 3 years old
  • Acetyltransferase has decreased activity
  • Sulfation is developed at birth, activity MAY be greater than adults
29
Q

Elimination

A
  • Driven by 3 kidney processes
  • Eliminated from body in final detoxification process from kidney
  • In pediatrics, immature CL increases the half life
30
Q

Elimination - Ped. GFR

A

-Changes over months
-Only receive 5-6% of CO
-Increases after 34 week GA, increases CO and decreases vasculature resistance
-Doubles in first 1-2 weeks, then gradual increase until maturation at about 6 months
GFR, TE, and TA all mature at different rates
Considerations: Infectious disease, CAKUT, excipients

31
Q

SCr Levels by Age

A

Neonates: 0.3-1
Infants: 0.2-0.4
Children: 0.3-0.7
Adolescents: 0.5-1

32
Q

Schwartz Equation

A 
-Used to estimate GFR in those 1-18 years old
Original: K * L / SCr
"Bedside" Schwarts: 0.413 * L / SCr
-Use length, not age
-Original equation overestimates GFR
-EX: gentamycin
33
Q

Elimination - TE/TA in Peds

A
  • 20% of adult capacity at term
  • Increases slowly over first year of life
  • Multiple transporters are involved
34
Q

Pediatric PD

A
  • Different receptor sensitivity (numbers/affinities) at different ages
  • Paradoxical effects: diphenhydramine (awaking effect in kids), antidepressants (depresses)
  • Affect on growth and developments: tetracycline, corticosteroids, fluoroquinolones
35
Q

Pregnancy Kinetics

A
  • Material kinetics affected by pregnancys
  • Absorption: decreased with N/V and increased gastric motility, decreased gastric acid changes bioavailability
  • Distribution: increased total body fluid increases Vd, decreased albumin increases plasma concentrations, feta-placental compartment leads to drug accumulation and increased Vd
  • Metabolism: Increased CO, increased hepatic flow, decreased CYP activity as gestation progresses, increased UGT
  • Elimination: Increased GFR as gestation progresses which decreases half lives and plasma concentrations, tubular changes can also affect clearance (ex: digoxin)
36
Q

Fetal Concerns

A
  • Placental drug transporters = new field of study
  • Synctiotrophoblasts: rate limiting step for transfer across placenta
  • Brush border cell type increases microvilli drug gestation
  • In utero drug exposure: inducing drugs change predictable profiles in drugs like Barbiturates, caffeine, glucocorticosteroids, tobacco
37
Q

Pediatric Dosing

A
  • No single method to determine appropriate dose
  • Most are based on weight, but development isn’t linear and weight can rapidly change and have wide ranges
  • Limitations to developing better models are blood requirements and allometric scaling not being effective for all drugs/age groups
  • Alternatives in Population PK Modeling: avoid “vampirism,” more co-variants, limited knowledge on neonate enzyme ontogeny, need more clinical studies
38
Q

Pediatrics - Vulnerable Population

A
  • Development differences: PK/PD dynamics, dynamic weight, communication barriers
  • Limited buffering capacity (electrolytes, anticoag.)
  • Limited evidence to support safety and efficacy
  • Lack of commercially available, pediatric-friendly dosage forms
39
Q

Pediatric Dosage Forms

A
  • Can’t swallow tablets and weight-based dosing is needed usually
  • Want to minimize administration frequency, impact on lifestyle, and non-toxic excipients
  • Want it to be convenient, reliable, easy, affordable, and stable
  • ANSWER: solutions, suspensions, and dilutions
  • *needs right concentration, standardized concentrations, accurate compounding, crushability (ISMP “Do Not Crush” List), palatability (when possible, sometimes a risk), bulk dispensing ideally**

810 (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions