Day 3: Dr. Peterson

Question 1

What is the length for a full term prego and at what week will they try to revive the baby if it must be born?

Answer 1

Full term is 40 weeks

At 23 weeks they will try to revive the baby if born

**A 20 week baby will weight around 400g

Question 2

What are the pediatric dosing options?

Answer 2

Age-based dosing

Body weight- based

Body surface area- bases

Question 3

What are the pros and cons of age-based dosing?

Answer 3

Pro
It’s practical
Easy to use (parents can just quickly see how much to give child based on age no math needed)

Cons:
Assumes that maturational effects on drug disposition is conistent across the age category (EX: a child who is 1 is grouped in the same as a 3)
This is a con because there can be large PK differences between a 1 and 3 year old.

Question 4

What are the stages and age/definition for development?

Answer 4

Fetus: > 8 weeks in womb

Neonate: birth to 4 weeks
Premature < 37 weeks gestation

Infant: 4 weeks to a year

Child: 1 to 12 years

Adolescent: 12 to 18 years

Question 5

What are the pros and cons of weight based dosing?

Answer 5

Pros:
Practical
Easy to assess (what’s used most often)

Cons:
Does not account for PK of age

Underweight pets can be underdosed, while over weight pets can be overdosed

Question 6

What are the pros and cons of body surface area-based dosing?

Answer 6

Pros: Gold standard

More accurate than weight based for pets

Decreases risk of over-dosing in older children

Cons:
Difficult to calculate

Many different formulas for BSA and it might give different answers

Can over dose neonates

Question 7

What is the equation for BSA?

Answer 7

Sqrrt ((Height (cm) x weight (kg)) / 3600

Question 8

What is the number one problem with oral route for ped patients?

Answer 8

The drugs taste badly so the children do not want to eat it

Question 9

How does the pH of a peds stomach affect absorption?

Answer 9

At birth the pH of the stomach is neutral (not much acid in stomach)

The pH will drop over 2 years until it reaches adult values

While the stomach is not a primary site of absorption for most drugs it affects their stability.
EX: A drug like B-lactams and macrolides are acid labile (meaning that acid will break them down). As an adult when the drug hits the stomach we break it down which means less drug is available to be absorbed. For a baby when it hits the stomach they don’t break it down meaning that MORE drug is available to be absorbed. Need to lower doses for these drugs

Question 10

What are the differences in gastric emptying for ped patients?

Answer 10

You get delayed gastric emptying = reduced motility and peristalsis.

This means that even after they take the drug it will sit in their stomach and not go to where it should be absorbed

Some drugs can increase the time and allow for better absorption

Question 11

Can you still give oral drugs to ped patients?

Answer 11

Yes, even tho they have differences the overall oral BA of drugs in adequate and they can be given

Question 12

Can you use Muscular route for neonates?

Answer 12

Yes, we give vaccines this way but it does have its problems for drugs

It’s unreliable because blood flow varies over the first 2-3 weeks of life and this causes unpredictable systemic absorption

Question 13

Can you use rectal route for absorption in peds patients?

Answer 13

Not very good for neonates and young children

In kids the rectum is alkaline while adults are more neutral

Also propagation (lots of pooping) of lower GI in infants (if they are always going to the bathroom and cant control themselves the drug will be expelled out)

**only really used if oral route can not be done

Question 14

What is important to note about topical absorption in neonates?

Answer 14

They have faster and higher systemic concentrations than adults

Reasons why:

Very thin skin

Poorly keratinised

Well-hydrated stratum corneum

Large surface area

***watch application of lidocaine and corticosteroids

Question 15

What can happen from topical terroir toxicity?

Answer 15

thinning of the skin

Glucose abnormalities (inc blood glucose)

Immunosuppressive

Adrenal crisis (HPA axis toxicity)
      Hypothalamus —> Pituitary—> adrenal gland —-> Cortisol (then negative feedback to hypothalamus

Question 16

What is different about the metabolism in neonates and children?

Answer 16

Their hepatic blood flow (therefore the liver’s ability to metabolize meds) is decreased at birth

The hepatic enzymes are also immature the first year of life (CYPS)

**how can test liver function? You can do ALT/AST but that only shows dmged liver cells, there for you can run INR which can be a marker for the cofactors needed in the clotting cascade

Question 17

How is the rectal route in terms of metabolism for children and neonates?

Answer 17

You have to watch where you insert it, since they have anatomical differences if you place it in the wrong spot you can get a lot fo first pass metabolism

Question 18

How is distribution in neonates and children different?

Answer 18

When you are born you have a much higher fraction of total body water

This will cause hydrophilic drugs to have a larger distribution and lower plasma concentration in neonates and young infants

In terms of body fat stores are limited in premature and newborn infants but it does not change the Vd

Question 19

What is the difference in the fraction of unbound drug for neonates and infants vs children and adults?

Answer 19

Neonates and infants have MORE unbound drug

The reason is because their liver isn’t at full function so less albumin is produced (main protein that is binds drugs)

EX: a drug Ike phenytoin which has high protein binding will not be able to bind because there is less albumin so more free unbound drug is in the body. This means you need to lower the dose when given to the baby.

Question 20

How does exertion of a neonate and new born differ from that of an adult?

Answer 20

Nephrogenesis do not begin until 9 weeks of gestation and is completed by 36 weeks

This means that preterm neonates will have a very low GFR but as you age it will increase

**wadult capacity is achieved in first 1-2 years of life

Question 21

What is the process of breaking down a RBC?

Answer 21

RBC —> Heme —> Bilirubin —> bind to albumin—-> travels to the liver —-> gets conjugated —-> goes into bile —> to small intestine —> then into poop

Question 22

Why does bilirubin cause a problem in neonates ?

Answer 22

A RBC in a baby is only 80 days so they have more breakdown also since they have poor liver function they have less albumin to carry it to the liver to excrete it. Also when it gets reabsorbed into the body it compounds the problem

***this is an issue because it will build up inside the neonate and cause them to have jaundice

Question 23

Why do you put a child with jaundice into sun light?

Answer 23

You do this because phototherapy is an indirect way to cause conjugation of the bilirubin so it can be excreted

Question 24

What are some medications that can cause Hyperbilirubinemia?

Answer 24

Sulfonamides (cant give to someone older than 30 days)

Contrast media

Bumetanide (loop diuretic)

Ceftriaxone (must be older than 30 days)

Ibuporfen (shouldn’t give to kids less than 6 months) it can displace bilirubin

Question 25

What are the consequences of hyperbilirubinemia in peds?

Answer 25

Jaundice

Bilirubin encephalopathy - results in high concentration in blood and CNS (can lead to mental retardation)

Can also have neurologic sequelae
Cerebral palsy

Hearing loss

Gaze abnormalities, upward gaze

Dental enamel dysplasia