Flashcards in Buxton Deck (32):
What are 2 disastrous baby med stories?
Thalidomide during pregnancy
chloramphenicol--used in nurseries to prevent spread of staph aureus infections from umbilical stump to stump. Grey baby syndrome b/c of cardiac depression.
Why is it difficult to make drugs for kids that are safe?
pharm moving target
not mini adults (dosing based on weight or surface area) not always predictive
animal studies not always helpful
clinical studies in children unethical
WHat is Clark's rule for dosing?
Weight (lbs)/150 x adult dose = approximate child’s dose
What is Young's rule for dosing?
Age (yrs)/Age +12 x adult dose = approximate child’s dose
What is Fried's rule for dosing?
Age (months)/150 x adult dose = approximate child’s dose
How do you approximate body surface area for dosing calculations?
BSA=[(Height (cm) X Weight (kg))/3600]^1/2
Describe why pediatric patients are a "moving target" for pharm.
Drug metabolizing enzymes
Unique metabolic pathways
Extremely small margin of error for the most fragile patients
What are some stomach differences for infants & drug absorption?
***Gastric acid - approaches adult values ~ 3 mo in full-term infants.
Bioavailability increased for acid-labile drugs (some penicillin derivatives)
Decreased for drugs requiring the acid to be absorbed.
Phenobarbital, furosemide, ampicillin, amoxicillin, ibuprofen
Delayed and unpredictable in newborns - adult values ~ 6 mo.
What is different in the GI tract of an infant that affects drug absorption?
***Digestive enzymes including pancreatic enzymes are low in newborns.
Colonization of the gut occurs rapidly after birth but is highly variable and unpredictable.
Slow in newborns; may be increased in children.
Usually affects the rate but not the fraction of drug absorbed.
The absorptive surface area/BSA is > infants and children vs. adults
HOw is skin absorption different in infants?
Directly related to the degree of skin hydration.
Inversely related to the thickness of the stratum corneum.
Thinnest in premature neonate
Greater extent of cutaneous perfusion
Premature infant has a significantly less effective skin barrier to absorption of drugs and toxins
Ex. Hexachlorophene toxic to immature infants
Newborn skin surface area : body weight is 3x > adult
Describe intramuscular absorption in pediatric patients.
Lipid solubility favors distribution into circulation (rate)
Water soluble at physiologic pH to prevent precipitation
Variable absorption due to blood flow and relative muscle mass
Dispersion driven by muscle contraction (low in neonates and immobility)
Reduced skeletal-muscle blood flow in neonate
Can be extremely painful, cause hemorrhage, nerve damage, abscess, necrosis, fibrosis, and CPK
Describe rectal absorption in pediatric patients.
Absorption is excellent for some agents; less first pass effect
talk about fat & 3rd space in infants.
Larger extracellular and total-body water spaces in neonate and young infants
Adipose stores also have higher ratio of water to lipid
RESULT: Lower plasma levels (relative to weight) for water soluble drugs. Effect on lipid soluble less
INfants have lower plasma proteins. What is the significance of this?
Low in preemies and neonates ( free fraction)
Most important in displacement of bilirubin from albumin resulting in toxicity (kernicterus); brain damage
Can be the result of shift of fetal to adult hemoglobin prior to birth. Exaggerated in the preemie
How are tissue transporters different in pediatric patients?
Tissue transporters - P-glycoprotein ATP-binding cassette family of transporters
Reduced expression in the neonate
Increased cellular uptake of xenobiotic substrates [blood-brain barrier, hepatocytes, renal tubular cells and enterocytes]
Limited data; premature infants probably most affected
Babies don't have drug metabolizing enzymes like adults do. Which drugs should you be especially careful about?
Cause for caution for drugs that have wider therapeutic index in adults
Ex. Methylxanthines, nafcillin, 3rd generation cephalosporins, captopril and morphine
What is the predominant isoform liver in the prenatal period? What is its role?
detoxify dehydroepiandrosterone sulfate (derivative of retinoic acid)
T/F Carbamazepine clearance children > adults
T/FMethylxanthine demethylation exceeds adults by 4 months (and declines in puberty in sex-based divergence)
How do babies deal with morphine?
Glucouronosyltransferase (glucuronidation) is decreased in newborns and young children compared to adolescents and adults
Present by 24 wk gestational age
Morphine glucuronidation correlates with post-conceptional age
Morphine: preemies require increased dose for equivalent analgesia
T/F Clearance of most agents more efficient in prepubescent children than adults (relative to bodyweight)
Premature neonates & neonates have decreased activity of CYP, except for CYP___.
T/F There is more activity in Phase II reactions for pediatric patients compared to adults.
False. Lower activity.
What is the k value for different age groups?
k = 0.45 for infants 1 to 52 weeks old
k = 0.55 for children 1 to 13 years old
k = 0.55 for adolescent females 13-18 years old
k = 0.7 for adolescent males 13-18 years old
How do kids respond to the following drugs?
Warfarin (augmented response in children)
Cyclosporine (cardioprotective effect in neonatal asphyxia)?
Midazolam (Increased T½ & decreased receptor number with age)
Erythromycin (intestinal motilin receptors; prokinetic)
What are some sources of drug toxicity for pediatric patients?
Retrolental Fibroplasia and oxygen (retinopathy of prematurity)
Sulfasoxazole prophylaxis (kernicterus)
Chloramphenicol Prophylaxis (drug accumulation; glucuronidation)
Hexachlorophene (spongiform myelinopathy of the brainstem)
Novobiocin (blockade of glucosyltransferase)
Pentachlorophenate (Diaper Laundry; uncoupler of ox/phos)
Epsom salt enemas (magnesium toxicity)
Benzyl Alcohol (neonatal gasping syndrome; benzoic acid)
What are the possible sources of error for prescriptions for kiddos?
prescription errors in outpatient or ED
sedation errors, like with dental procedures
caregivers administer too much of a med
Which types of errors are most common?
Admin errors are more common than prescription errors.
Which med do you never give a child?
it uncouples oxidative phosphorylation
What is the highest risk for overdose?
If a child has to manage 5 or more meds.
What is a possible solution to medication errors?