Intro to Pediatrics - Block 4 Flashcards
What are the classifications of a pre-term vs term newborn?
Pre-term: <37 weeks
Term: >37 weeks
Classifications of neonates?
Birth - 1 month
Classification of Infant?
1 month - 2 yr
Classifications of a child?
2-12 YO
Classification of adolescent?
12-18 YO
Growth charts used from birth to 36 months?
- Length
- Weight
- Head circumference
Growth charts use for 2-20 YO?
- Height
- Weight
- BMI
Describe the development of neonates and how they get older?
- Babies would lose water weight within the first 7 days of life do to stress and adjustment.
- Birth weight is regained by 10 days, however, if 10% of birth weight that is an indication for dehydration or malnutrition
- Babies have a lot of water and as they age they gain more protein and fat
How do vitals differ in neonates than infants and adolescents?
HR: generally higher
RR: generally higher
BP: generally lower
What is the difference between PK and PD?
PK: what the body does to the drug (ADME)
PD: What the drug does to the body (Ligand, receptor, tissue)
How does the PK change in pediatrics?
ADME varies by age even when normalized by body weight
How does PD change in pediatrics?
Differences receptor sensitivity and density
PO factors that impact absorption?
- Gastric pH
- Gastric motility
- Bowel length and absorptve area
- Enzymes and bile salts
- Microbial flora
GI/PO factors that impact absorption in neonates?
Gastric motility and emptying: reduced gastric emptying and poorly coordinated intestinal cotractility
* Adult pattern onset at 6-8 months
* Drug absorption is dependent on disintegration, dissolution, and formulation
Intestinal drug-metaolizing enzymes: Lower
Biliary function and pancreatic enzymes (amylase and lipase): Underdevelopment affects ability to solubilize lipophilic drugs
Gastric factors that impact absorption in neonates?
Neonates have higher gastric pH:
* Acid labile drugs are less broken down -> increased F
* Weak acids are neutralized -> decreased bioavailability
Gastric pH will decrease at age 2
Rectal factors that impact absorption in neonates?
Increased pulsatile contractions -> decreased holding time
Transdermal facotrs that impact absorption in neonates?
Enhanced skin permeability due to:
1. Greater skin hydration
2. Subcutaneous perfusion
3. Increased BSA to mass ratio
Intramuscular facotrs that impact absorption in neonates?
Erractic yet effective due to reduced skeletal muscle blood flow and contraction offset by high density of capillaries
Gastric pH in neonates (compared to adults)
Increased:
* Decreased F (weak acids)
* Increased F (weak bases)
Gastric emptying time in neonates (compared to adults)
Increased delaying absorption
CYP3A4 acitivity in neonates (compared to adults)?
Decreased (increased F)
GST acitivity in neonates (compared to adults)?
Increased (decreased F)
Intestinal drug transporters in neonates (compared to adults)?
Decreased (decreased F)
Hydration of epidermis in neonates (compared to adults)?
Increased (increased F)
TBW in infants and adults?
Premature: 85%
Full term: 78%
Adults: 60%
ECF volume in infants and adults?
Premature: 50% of BW
4-6 month old: 35%
1 YO: 25%
Adults: 19%
Plasma protein in neonates?
Decreased plasma protein concnetration
Lower binding capcity of protein
Decreased affinity of proteins for drug binding
Competition for certain binding sites by endogenous compounds
Body fat contents in neonates?
Gradually increases as body water decreases
What is Vd?
Amount of drug that leaves the plasma into other compartments that dependent on:
1. Hydro or lipophilicity of drug
2. PPB
3. Tissue binding
High: extensive drug distribution
Low: drug remain in the plasma
Body water and fat ration in neonates (compared to adults)?
Increased:
* High Vd (hydrophilic drugs)
* Low Vd (lipophilic drug)
PPB in neonates (compared to adults)
Decreased (Increased free drug)
Describe the distribution of gentamicin in neonates?
Hydrophilic drug and high Vd: requiring more drug to maintain serum concentration
What is the difference between Phase 1 and 2?
Phase 1: covalent modification of drug to increase polarity (oxidation, reduction, hydrolysis)
Phase 2: Conjugation of polar groups to increase polarity
- Both used to enhance elimination
Most important organ for drug metabolisn?
Liver
Ezyme activity of neonates?
No CYP development (decreased phase 1)
Phase 2: GST activity
Hepatic metabolism in neonates (compared to adults?
Slower in neonates and infants than children and adults
What are the components of renal clearance?
Glomerular filtration + tubular secretion - tubular reabsorption
* Adult GFR reached at 1 yr
* Tubular mechanisms take longer than 1 yr to develop
How do we calculate eGFR?
Renal excretion in neonates (compared to adults)?
Dosage adustment based on elimination (neonates)?
Decreased elimination: decreased dose and increased intervals
Increased elimination: increased dose and decreased intervals
How would you dose pediatrics?
Predominately in children less than 2 YO
* doses normalized by body weight or BSA and allometric scaling is used in >2YO
