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Pharmacokinetics: Pediatrics Allie Punke ([email protected]) The Basics—True or False • Pediatric patients generally require higher doses of lipophilic drugs (like diazepam) due to increased fat content at birth • The Schwartz equation can be used to estimate creatinine clearance, but caution should be used for interpreting the results within the first week of life • Cystic fibrosis patients typically require lower doses of aminoglycosides due to production of thick mucus making it more difficult to eliminate the medication • Hydroxylation is the most developed phase I reaction in pediatric patients. Absorption Pediatrics Absorption • An acid labile drug such as ampicillin is ordered for a neonate. How do you expect the dosing to differ for a neonate versus an adult? • A. An adult will likely require a higher dose due to mature elimination pathways. • B. An infant will likely require a higher dose because the drug will not be absorbed as well. • C. An adult will likely require a lower dose because of the lower total body water content in adults. • D. An infant will likely require a lower dose because the drug will exhibit a higher bioavailability. Absorption • How should phenobarbital, a weak acid, be adjusted for pediatric patients? • A. Dosing should be increased because it is not absorbed as well in pediatric patients • B. Dosing should be decreased because of increased bioavailability • C. Dosing should be increased because pediatric patients are eliminating it much faster • D. Dosing should be decreased because pediatric patients are not able to eliminate it as fast Absorption • The pH is more (acidic or alkaline) at birth? • Patients who are fed Q4 hours each should be expected to have (constant production of acid or a peak in acid production when fed)? • Pediatric patients reach adult gastric output of acid around what age? • The ________, the ___________ the gastric emptying time. • A. Younger, shorter • B. Older, longer • C. Younger, longer Absorption • Patients fed with formula are expected to experience (shorter or longer) gastric emptying times than human milk fed patients. • Because most drugs are absorbed in the _______, pediatric patients most likely should not be given _________. • • • • A. stomach, immediate release B. small intestine, enteric coated C. stomach, sustained release D. colon, immediate release Absorption • What are issues to consider when giving medications by these routes: • Topically • IM • Rectal • Intraosseous Distribution Pediatrics Distribution • Pediatric patients typically require: • • • • A. Smaller doses of hydrophilic drugs such as aminoglycosides B. Smaller doses lipophilic drugs such as aminoglycosides C. Larger doses of hydrophilic drugs such as diazepam D. Larger doses of hydrophilic drugs such as aminoglycosides Distribution • What are some examples of medications that should be used with caution due to displacement of endogenous protein bound substrates (like bilirubin)? Metabolism Pediatrics Metabolism • Which drug is least likely to be affected in a neonate? • • • • A. A drug undergoing hydroxylation B. A drug undergoing glucuronidation C. A drug undergoing oxidation D. A drug undergoing hydrolysis Metabolism • Drugs may undergo different metabolic pathways in pediatric patients due to immaturity of some pathways • How is acetaminophen metabolized in a neonate? • How is theophylline’s metabolism different in a neonate? Elimination Pediatrics Elimination • When should the Schwartz equation not be used in pediatric patients? • Calculate Creatinine clearance for a full term infant who is 24 weeks old. Length=60cm, SCr=0.3 Summary • Pediatric patients have increased total body water and decreased total body fat. Recognize how this can affect drug dosing (i.e. higher doses for water soluble drugs) • Recognize the different routes of administration available and which may or may not be the best • If given the metabolic pathway of a medication, be able to determine if it will likely be affected • Know the Schwartz equation and be able to calculate a CrCl for pediatric patients Questions? Good luck on your exam!