Page 1068 - Basic _ Clinical Pharmacology ( PDFDrive )

1054 SECTION X Special Topics

due probably to increased renal elimination and metabolism. Adherence (formerly called compliance) may be more difficult
For example, the dose per kilogram of digoxin is much higher in to achieve in pediatric practice than otherwise, since it involves
toddlers than in adults. The mechanisms for these developmental not only the parent’s conscientious effort to follow directions but
changes are still poorly understood. also such practical matters as measuring errors, spilling, and spit-
ting out. For example, the measured volume of “teaspoons” can
Special Pharmacodynamic Features in the vary from 2.5 to 7.8 mL. The parents should obtain a calibrated
Neonate medicine spoon or syringe from the pharmacy as these devices
improve the accuracy of dose measurements and simplify admin-
The appropriate use of drugs has made possible the survival of istration of drugs to children.
neonates with severe abnormalities who would otherwise die When evaluating adherence, it is often helpful to ask if an
within days or weeks after birth. For example, administration attempt has been made to give a further dose after the child has
of indomethacin (see Chapter 36) causes the rapid closure of a spilled half of what was offered. The parents may not always be
patent ductus arteriosus, which would otherwise require surgi- able to say with confidence how much of a dose the child actu-
cal closure in an infant with a normal heart. Infusion of pros- ally received. The parents must be told whether or not to wake
taglandin E , on the other hand, causes the ductus to remain the infant for its every-6-hour dose day or night. These matters
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open, which can be lifesaving in an infant with transposition should be discussed and made clear, and no assumptions should
of the great vessels or tetralogy of Fallot (see Chapter 18). An be made about what the parents may or may not do. Nonadher-
unexpected effect of such infusion has been described when the ence frequently occurs when antibiotics are prescribed to treat
drug caused antral hyperplasia with gastric outlet obstruction as otitis media or urinary tract infections and the child feels well after
a clinical manifestation in 6 of 74 infants who received it. This 4 or 5 days of therapy. The parents may not feel there is any reason
phenomenon appears to be dose-dependent. Neonates are also to continue giving the medicine even though it was prescribed
more sensitive to the central depressant effects of opioids than for 10 or 14 days. This common situation should be anticipated
are older children and adults, necessitating extra caution when so the parents can be told why it is important to continue giving
they are exposed to some narcotics (eg, codeine) through breast the medicine for the prescribed period even if the child seems to
milk. be “cured.”
At birth, the function of drug transporters may be very low; Practical and convenient dosage forms and dosing schedules
for example, P-glycoprotein, which pumps morphine from the should be chosen to the extent possible. The easier it is to admin-
blood-brain barrier back to the systemic circulation. Low-level ister and take the medicine and the easier the dosing schedule is to
function of P-glycoprotein at birth can explain why neonates follow, the more likely it is that adherence will be achieved.
are substantially more sensitive than older children to the central Consistent with their ability to comprehend and cooperate,
nervous system depressant effects of morphine. children should also be given some responsibility for their own
health care and for taking medications. This should be discussed
in appropriate terms both with the child and with the parents.
PEDIATRIC DOSAGE FORMS & Possible adverse effects and drug interactions with over-the-
ADHERENCE counter medicines or foods should also be discussed. Whenever a
drug does not achieve its therapeutic effect, the possibility of non-
The form in which a drug is manufactured and the way in adherence should be considered. There is ample evidence that in
which the parent dispenses the drug to the child determine the such cases parents’ or children’s reports may be grossly inaccurate.
actual dose administered. Many drugs prepared for children Random pill counts and measurement of serum concentrations
are in the form of elixirs or suspensions. Elixirs are alcoholic may help disclose nonadherence The use of computerized pill
solutions in which the drug molecules are dissolved and evenly containers, which record each lid opening, has been shown to be
distributed. No shaking is required, and unless some of the very effective in measuring adherence.
vehicle has evaporated, the first dose from the bottle and the last Because many pediatric doses are calculated—eg, using body
dose should contain equivalent amounts of drug. Suspensions weight—rather than simply read from a list, major dosing errors
contain undissolved particles of drug that must be distributed may result from incorrect calculations. Typically, tenfold errors
throughout the vehicle by shaking. If shaking is not thorough due to incorrect placement of the decimal point have been
each time a dose is given, the first doses from the bottle may con- described. In the case of digoxin, for example, an intended dose
tain less drug than the last doses, with the result that less than of 0.1 mL containing 5 mcg of drug, when replaced by 1.0 mL—
the expected plasma concentration or effect of the drug may be which is still a small volume—can result in a fatal overdose. Dif-
achieved early in the course of therapy. Conversely, toxicity may ferent strategies have been developed to prevent these potentially
occur late in the course of therapy, when it is not expected. This fatal errors. For drugs with narrow therapeutic windows (eg,
uneven distribution is a potential cause of inefficacy or toxicity digoxin, insulin, potassium), independent double-checking of
in children taking phenytoin suspensions. It is thus essential dose and volume calculations is widely practiced. A good rule for
that the prescriber know the form in which the drug will be avoiding such “decimal point” errors is to use a leading “0” plus
dispensed and provide proper instructions to the pharmacist and decimal point when dealing with doses less than “1” and to avoid
patient or parent. using a zero after a decimal point (see Chapter 65).