Developmental differences

Controlled studies of IV verapamil have not been conducted in pediatric patients, but uncontrolled experience indicates that results of treatment are similar to those in adults. Patients less than 6 months of age may not respond to IV verapamil this resistance may be related to a developmental difference of AV node responsiveness. 

Developmental differences in drug absorption between neonates, infants and older children are summarized in Table 1. It must be recognized that the data contained therein reflect developmental differences which might be expected in healthy pediatric patients. Certain conditions and disease states might modify the function and/or structure of the absorptive surface area(s). GI motility and/or systemic blood flow can further impact upon either the rate or extent of absorption for drugs administered by ex-travascular routes in pediatric patients. 

It must be recognized that developmental differences in hepatic drug metabolism occur consequent to reductions in the activity of specific drug-metabolizing enzymes and their respective isoforms. For most enzymes, the greatest reduction of activity is seen in premature infants where immature function may also reflect continued organogenesis. This... 

Finally, developmental differences in pharmacodynamics can be observed in the absence of age-associated changes in the dose versus plasma concentration relationship. Marshall and Kearns demonstrated developmental differences in the pharmacodynamics of cyclosporin. In this study, the IC50 for interleukin-2 (IL-2) expression observed in peripheral blood monocytes obtained from infants less than 12 months of age and exposed in vitro to cyclosporin was approximately 50% of the value observed for older children. In this particular example, the pharmacodynamic differences appeared not to be the consequence of developmental dependence on pharmacokinetics but rather, in the true drug-receptor interaction. 

Overall, the clinical picture of childhood MDD parallels the symptoms of adult MDD (Birmaher et ak, 1996b). There are some developmental differences, however. Symptoms of melancholia (e.g., lack of appetite, insomnia, lack of interest in anything), delusions, suicide attempts, especially high-lethality ones, are all less prevalent in young children and increase with age. In contrast, symptoms of anxiety, behavioral problems, and perhaps auditory and visual hallucinations seem to occur more frequently in children (AA-CAP, 1998 Birmaher et ah, 1996a). Also, it appears that the rate of onset of bipolar disorder is higher in... 

Lea P. M. and Faden A. I. (2001). Traumatic brain injury developmental differences in glutamate receptor response and the impact on treatment. Ment. Retard. Dev. Disabil. Res. Rev. 7 235-248. 

Many differences in overall toxicity between males and females of various species are known (Table 9.1). Although it is not always known whether metabolism is the only or even the most important factor, such differences may be due to gender-related differences in metabolism. Hexobarbital is metabolized faster by male rats thus female rats have longer sleeping times. Parathion is activated to the cholinesterase inhibitor paraoxon more rapidly in female than in male rats, and thus is more toxic to females. Presumably many of the gender-related differences, as with the developmental differences, are related to quantitative or qualitative differences in the isozymes of the xenobiotic-metabolizing enzymes that exist in multiple forms, but this aspect has not been investigated extensively. 

Ideally, the overall benefit to risk ratio would be carefully considered before making a go/no-go decision to prevent the premature termination of drugs which were potentially safer and perhaps more effective than the alternative. Sources of pharmacodynamic variability include genetics (e.g. of transporters or receptors) and demographics (e.g. developmental differences in the abundance of receptors or hormonal influence on the regulation of receptors). 

El-Alfy, A., S. Grisle and D. Schlenk. Characterization of salinity-enhanced toxicity of aldicarb to Japanese medaka sexual and developmental differences. Environ. Toxicol. Chem. 20 2093 —2098, 2001. 

Developmental differences, disease presentation, disease progression, and comorbidities also need to be considered when determining pediatric pharmacotherapy. Even when the mechanism of action and PD response surface may be similar between pediatric and adult populations, differences in therapy may be indicated based on disease progression. For example, hypertension rarely presents as primary finding in children but most frequently as secondary to renal disease or other processes, which frequently impact the pharmacologic goals of therapy. HIV infection and AIDS will result in a 50% 2-year mortality in untreated infants yet typically takes 10 years in adults to wear down the immune system to the point at which opportunistic infections and AIDS take hold. Thus, therapeutic targets must account for these differences especially if these therapies will be used for chronic conditions. 

During each phase, the adolescent typically asserts a new set of developmental differences that create a certain emotional vulnerability for the teenager to manage. 

The Diagnostic and Statistical Manual for Mental Disorders is another tool used by social work practitioners in the assessment process to identify clearly those categories that are applicable to children and to caution the professional on developmental differences that prevent the use of some diagnostic codes with children (American Psychiatric Association, 1994). Goldman (1998) proposes a quick and practical schema that allows the practitioner to apply the DSM-IV diagnoses to children. He proposes that the clinician first confirm the full criteria in the DSM-IV and then consider using the following questions as a way to assess children. 

Hellmann-Blumberg U., Hintz M.F., Gatewood J.M., Schmid C.W. (1993). Developmental differences in methylation of human Alu repeats. Mol. Cell. Biol. 13 4523-4530. 

Schwartz, A., Palti, Y., and Meiri, H. 1990. Structural and developmental differences between three types of Na channels in dorsal root gangfion cells of newborn rats. J. Membr. Biol. 116, 117-128. 

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