Later On

A blog written for those whose interests more or less match mine.

Child-proofing medications

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Edyta Zielinska has an interesting article in The Scientist on making medications safer for the very young:

In 2005, a mother who had just given birth received codeine to dull the pain associated with childbirth. In her body, the codeine was converted into morphine by a drug-metabolizing enzyme called CYP2D6. Although people carry many variations in the gene for this enzyme, this woman had an unusual difference: she expressed multiple copies of the gene. As a result, the additional CYP2D6 enzymes in her body churned through the codeine so efficiently that her morphine levels spiked and stayed high. Unbeknownst to her doctors, high doses of the drug had passed from her milk into her infant. When the baby was brought back to the hospital with gray skin 12 days after his birth, doctors were puzzled. He was an otherwise healthy baby boy. The next day he died—the concentration of morphine in his blood 30 times higher than expected.

The case highlights not only how variable adults can be in how they metabolize drugs, but also how challenging it is to correctly diagnose and treat infants, whose symptoms and basic physiology differ greatly from those of grown-ups. When babies get sick, they can’t say what’s wrong, what hurts, or whether a treatment has helped. Their most vehement expression—crying—doesn’t always convey whether they are in pain, scared, or simply hungry. What’s most confounding is that the drugs intended to treat their pain react much differently in their small bodies than in those of adults, in some cases rapidly accumulating to high concentrations, in other cases clearing out of their bodies much faster. On top of that, their developmental changes aren’t always linear; sometimes the function of a particular pathway fluctuates throughout childhood before stabilizing at adult levels, making it difficult for doctors to be sure they are getting the dosing right.

A dearth of knowledge about how a child’s physiology changes from birth to adolescence, together with the understudied effects of many drugs in their bodies, makes almost any treatment risky. And yet in the past several years, researchers have begun to tease out how this changing physiology affects a drug’s pharmaco-kinetics: how the drug is absorbed into the bloodstream, how the drug distributes throughout the tissues, and how the drug is metabolized and removed from the body.

Read the accompanying commentary by J. Steven Leeder

Morphine, for example, can be safely given to children following surgery or other physical trauma, as long as certain considerations are taken into account. “Kids are more watery than adults, and adults are fatter,” says Wick Kraemer, a pediatric anesthesiologist at Children’s Hospital of Philadelphia (CHOP). This makes a difference in the metabolism of drugs, such as morphine, that are hydrophilic, or water-loving, allowing them to circulate throughout a baby’s “watery” body more effectively. As a result, morphine will be eliminated from a baby’s body more slowly than from an adult’s, and thus should be readministered less frequently. But as a baby ages, its bodily water percentage also changes, in turn affecting the time it takes for half of the dose to be eliminated. In premature babies, who are typically 85 percent water, the half-life of morphine is 6 to 9 hours; in normal-weight newborns, who are usually 75 percent water, it’s 7 to 8 hours, and in a 6-month old, 3 to 5 hours, says Kraemer. (By comparison, the adult body is about 65 percent water.) But drugs, such as the pain medication fentanyl, that use fat as a vehicle, do not distribute well in the body of a newborn, which can have as little as 1 to 15 percent total body fat.

Those are a few examples of drug pharmacokinetics that are well understood in children. Unfortunately, about 50 percent of the drugs prescribed to children are being administered off-label, which means that their pharmacological properties have never been tested in a child for that indication. (See “Are the Kids Alright?” in this issue.) In addition, there is no such thing “as a typical child,” says Imti Choonara, a pediatric pharmacologist at the University of Nottingham in the United Kingdom. A neonate is as markedly different from a 1-year old as a 1-year-old is from a young teenager, he adds. From day to day and week to week, a newborn’s body changes, and so does the manner in which it processes drugs. And clinical practice hasn’t quite caught up. Physicians are prone to high drug-administration error rates in very young patients. A study of two teaching hospitals published in 2001 found that more potentially serious medication errors were made involving neonates in intensive care units than anywhere else in the hospitals, and the ordering physician was to blame 79 percent of the time. In addition, an outside review of the errors reported that more than 90 percent could have been prevented.1

While much is yet unknown, here are some of the physiological differences between children and adults that make treating kids so difficult. . .

Continue reading. The article is accompanied by a graphic:

Written by LeisureGuy

23 March 2012 at 9:00 am

Posted in Daily life, Medical

2 Responses

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  1. An interesting example to highlight the need for advances in pharmacogenomics and personalised medicine. It’s easy to be forget that whilst medicine is the most advanced it has ever been, with many truly incredible modern therapeutics, so much is not known. Fundamental principles, such as genetic influences on drug metabolism, are still not frequently considered in treatment even though science is very aware of many factors. It’s a shame that translational research from lab to clinic is so slow to occur and unfortunately it’s almost certainly a lack of funding holding this back; a situation unlikely to get better in the near future.

    Great blog by the way.


    24 March 2012 at 3:27 am

  2. I find it interesting in that medicine is learning anew that YMMV and that statistically sound treatments can be disastrous for certain specific individuals. There are big differences between public health (large-scale projects and treatments for the public at large—things like sanitation and polio immunization) and personal medicine (finding the exact medications and treatments that work best for a specific individual).


    24 March 2012 at 5:29 am

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