Key Differences in Pediatric Pharmacology

One of the first things you learn about pediatric pharmacology is that children are not simply small adults. The way that kids process, excrete and metabolize drugs is completely different than it is in adults and warrants a closer look. Unfortunately, there’s not an abundance of research on the way medications interact with pediatric physiology. We do know, however, that the responses children have to medications are much more variable and dynamic than we ever thought possible. Additionally, adverse reactions can be very specific and even different than what occurs in adults.

Dosing is often by weight in pediatric pharmacology

One of the first things to know about pediatric pharmacology is that many of the medications you give will be dosed by weight. So, if you’re not comfortable doing dosage calculations, now is the time to get comfortable.  In addition to understanding the concept behind these types of calculations, you’ll want to review all the metric conversions along with teaspoons to mls, mls to ounces and kg to pounds.

Four key factors in pediatric pharmacology

We’re going to look at pediatric pharmacology in four key ways: absorption, distribution, metabolism and excretion. Ready?

Absorption

In the pediatric population,  the key take-away is that the absorption is going to be much more erratic in children than it is in adults. It also will vary based on if they’re an infant, baby, toddler, preschooler, adolescent, etc. 

Variability of gastric pH

One reason absorption is so variable in children is due to the variability of gastric pH, which differs based on the stage of development. There’s a lot of evidence on this topic and, to be honest, I found quite a bit of contradictory information. But the general consensus is that pH is pretty neutral at birth, then it drops down and gets more acidic in about 24-48 hours, but then it goes back up towards neutral before becoming acidic again. The main takeaway that I want you to understand is that the gastric pH fluctuates during this timeframe and slowly becomes more acidic, up until about 2 years of age. Understanding gastric pH is important when it comes to medications such as penicillin. Penicillin will have higher peak concentrations in newborns, with their neutral pH, than in infants or children whose gastric pH is more acidic. For this reason, medications like penicillin have highly variable doses based on the age of the child.

Bile secretion

Another factor that affects absorption is bile secretion. In the first two to three weeks of life, bile secretion hasn’t yet optimized. As the bile salt concentration increases, so will the solubility of the drug. An example of this is the medication hydrocortisone, which is a poorly-soluble medication. Because of this change in the bile salt concentrations, drugs like hydrocortisone may need to be dosed differently as the child matures and bile secretion becomes optimal.

Intestinal permeability and gastric emptying

Then there’s the issue of intestinal permeability which is higher at birth, and reduces in those first few weeks of life. Along with intestinal permeability, gastric emptying times exhibit variability as well. For example, newborns have delayed gastric emptying and irregular peristalsis, so the absorption of PO medications are going to be absorbed more erratically than they would be in an older child or adult. When looking at gastric emptying times, the longer a medication sits in the stomach, the less absorption occurs (this is because most absorption takes place in the small intestine). This is just one of the reasons you’ll see different dose ranges for children of different ages. 

Other factors in pediatric pharmacology

In addition to those GI factors that play a role in how medications are absorbed in pediatric patients, we also have factors such as the thin strata corneum and variable blood flow at the site of intramuscular or subcutaneous injections. Let’s say you’re giving a neonate an intramuscular injection. The blood flow in the muscles of neonates is highly variable, so absorption is going to be highly variable as well. It could be delayed and then there could be a sudden increase in blood flow, resulting in a rapid absorption of that medication that could lead to levels that are too high. 

Looking at topical medications, infants and young children have thinner skin and larger body surface area relative to their size than adults, which means medications like a hydrocortisone cream can have vastly different effects in children and can even lead to systemic toxicity. A great example of this is topical lidocaine, which is typically used as a local anesthetic. However, it can have systemic effects, so you’d be very careful using this in children and would never apply it over a broad surface area. 

Yet another key difference in children is the blood-brain barrier, which isn’t fully developed in young infants. So, medications that act on the CNS can have unpredictable results in children with more significant side effects. 

Distribution

So now let’s talk a little about distribution of pharmacological agents in the pediatric populations. Medications are going to be distributed differently in children due to things like differences in body composition, total body water and the ratio of fat to lean muscle. When we look at the total body water (TBW) of a newborn, it’s about 80% compared to about 60% in adults. So, a newborn is going to require higher doses of hydrophilic (water-loving) drugs. Infants also have immature livers, meaning they have decreased levels of plasma proteins binding to drugs, which leads to higher levels of unbound drugs in systemic circulation. This is why, if your pediatric patient is taking a potentially toxic drug such as phenytoin, you want to monitor very closely to ensure the plasma concentration is within normal range.

Yet another factor that plays a role in the distribution of drugs is the frequent changes in the ratio of body fat to lean muscle as the child develops. As children grow and change, some medications (such as seizure medications) will need to be monitored regularly, especially during times of great physical change during growth spurts and puberty.

Metabolism

The metabolism of drugs is highly complex and variable over that first year of life. The key take-away is that when the body is undergoing a lot of physiologic change (such as a  premature infant who is developing rapidly) there is more likely to be variation in the pharmacokinetics of medications. So, what you’ll likely see is that drugs are re-dosed routinely based on the child’s age, body size, etc. The dose that a child takes when they’re six months old is probably not going to be the same dose they take when they’re six years old. Just know that dosing is quite variable in this population. 

Excretion

The excretion of drugs – how we eliminate it from the body — is affected in great part by the renal system. The glomerular filtration rate (GFR) in newborns is only about 30-40% of adult values. So, medications that are excreted by the kidneys are going to be excreted more slowly. This means dosing intervals and amounts are going to be continually evaluated, monitored and adjusted for medications that rely on renal clearance. For example, digoxin is a medication used to treat children with congenital heart conditions. A child on digoxin will need frequent evaluation of their renal function as they mature and renal function improves to ensure he is on the proper dose of this important medication.

Safe pediatric medication administration

Always always always check your medication rights. Then, with children, check them again. 

• Right patient
• Right medication
• Right dose 
• Right time for administration
• Right route
• Right documentation

Want to take your safe medication practice even further? Download my “Bulletproof Medication Administration” cheat sheet here.

Key takeaways 

Pharmacokinetics in the pediatric patient are highly variable and dependent on many factors.

Triple check your doses because with a child there is no room for error. Check your basic medication rights, or check out my Bulletproof Medication Administration cheatsheet that takes patient safety to an even higher level.

One last thought before you head back out into the sunshine. A lot of times you have to be very creative when you’re giving medications to kids. You’ve got to get them to comply and trust you, so a lot of what you do in pediatrics will be dependent on the developmental age of the child. For my best tips for giving meds to children, listen to podcast episode 116.

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