peds pharm Flashcards
infants have an increased proportion of water leading to an increase in ______ of _______
volume of distribution
increase volume of distribution requires an increased _______ _____
loading dose
net result (bc infants are MORE sensitive):
[Drug dosing]
loading dose/kg usually the same as for older children and adults
decreased muscle mass causes meds that are dependent on redistribution to have increased initial ______ and increased sustained ______
peak
concentration
ex: muscle relaxants
key to safe drug dosing:
titrate to effect (you can always give more but you cant take it back!)
liver metabolism is ______ in neonates
decreased
diseases such as CF and celiac’s can cause a decrease in ________
P-450
elim 1/2 life is _____ in infants
increased
there are many P-450 substrates from genetics/ethnic differences that are ______ _____ in drug metabolism
clinically significant
Phase I - P-450 is reduced in infants causing decreased ______ and prolonged _______
clearance
half-life
Phase II - synthetic or conjugating reactions convert _______ to ________ for renal excretions
lipophilics to hydrophilics
Phase II reactions are limited in infants leading to increased _____ of ______
risk of toxicity
neonatal RBF is ____ of CO
6%
adult RBF is _______ of CO
15-25%
neonates have ____, _______ tubules
small, undeveloped
_______ is not as useful an indicator of renal fxn as in adults (but commonly used to monitor drugs)
creatinine
______ ______ MUST BE CONSIDERED WHEN DOSING INFANTS
RENAL FUNCTION
paradigm shift
we must protect children FROM research to we must protect children THROUGH research
current legislation requires ____ _____ to be done
[Ethics and Meds Drug Research]
pediatric trials
provide additional 6 months of _____ _____ for pediatric exclusivity
patent time
since 1998, _____ peds clinical drug trials and over ______ failed to show efficacy in children, and over _____ drug label updates specific to children
1000
25%
700
despite labeling, we are within _____ and _____ rights to use these drugs
medical and legal
unapproved does NOT mean ______, ______, _______, or ________
improper, illegal, investigational, or experimental
therapeutic decision must always rely on the ______ _______ _______ and the importance of the benefit for the individual patient
best available evidence
neurons are genetically programmed to ______ ______ if they fail to make synaptic connections on time
commit suicide
this ______ is normal and necessary
apoptosis
anesthetics disrupt _________ ________ (birth - 4 years)
developmental synaptogenesis
this anesthesia induced neuroapoptosis causes two things
- abnormal apoptic death of good neurons
- inhibited apoptic death of weaker neurons
receptors involved:
y-aminobutyric acid (GABAa)
N-methyl-D-aspartate (NMDA) glutamate
Drugs causing AIN
NMDA antagonists - ketamine, N2O, ETOH
GABA agonists - benzos, inhalation agents, propofol
_____ studies have proven this but _____ trials are minimal and indicating it may be clinically insignificant
[Ethics and Meds Drug Research]
animal
human
2016 FDA warning
brain development may be affected with lengthy procedures in children < 3 years and pregnant women in the 3rd trimester. (lengthy = > 3 hrs of exposure)
recent human studies show that a single, short procedure is _____ to cause negative effects
unlikely
but further research is needed
wash-in is more rapid in neonates bc (3)
- higher alveolar ventilation to FRC ratio
- lower tissue/blood solubility
- lower blood/gas solubility
LD 50 much ______ in neonates
lower
________ blood brain barrier and/or ________ myelination
immature
incomplete
caution with centrally acting meds in children _____
< 1 year
EXTREME caution in ______ post-conceptual age
< 48 weeks
use low dose and weigh _____/_____
risks/benefits
vigilant monitoring _______
required
volatiles increase _______ and decrease ________
CBF
CMRO2
current evidence shows that _____ and ______ are best for neuroanesthesia in children ____ MAC and mild ________
iso and sevo
< 1 MAC
mild hyperventilation
BIS monitoring
not reliable in children
(adult goal BIS < 60)
volatiles cause dose dependent CV depression by: (4)
- depressing contractility
- altering conduction
- vascular dilation
- altering PNS, SNS, and reflex responses
volatiles overall have a ______ margin of safety in children
decreased
_____ used, but mostly for CV sx
TEE
neonates compensate _______
poorly
generally, 1 MAC causes _____ drop in SBP in children
30%
EXTREMELY IMPORTANT
______ tolerated much better than halothane
sevo
halothane slows HR leading to ______ rhythm, ________, and then asystole
junctional rhythm
bradycardia
hypercapnia with halothane causes
ventricular ectopy
halothane sensitizes myocardium to _______, especially with ______ anesthesia
catecholamines
light anesthesia
inhalation agents cause dose-dependent ________ _______
respiratory depression
may see paradoxical “rocking horse” pattern where _____ falls, infant ______, and _____ must be considered
FRC
fatigues
EEP
the death spiral
spontaneous ventilation decreases to apnea, then hypoxia and bradycardia ensue
volatiles affect renal fxn by affecting (4)
- CV
- autonomic
- neuroendocrine
- metabolic processes
interferes with P-450 leading to _______ ________ leading to potential renal toxicity
inorganic fluoride
there were past concerns specific to sevo but currently there is
no higher risk than other volatiles
sevo + CO2 absorbent can produce
compound A