peds week 2 pharm Flashcards
When does pharmacologic maturation occur?
between 3-6 months of age
Drug Absorption
There is no structural difference between infants, children, and adults that affect GI absorption of drugs
There are differences in the neonate related to pH (less acidic), gastric emptying and gastric transit time (markedly slower)
Protein binding in neonates
The neonate has a qualitative and quantitative reduction in protein binding
There is a decrease in the number of plasma proteins and a decrease in the affinity of proteins for drugs in the neonate
This contributes to the apparent larger volume of distribution in comparison to adult proportions
Do neonates have less protein binding and a larger volume of distribution that adults?
Yes..
Neonates and infants have larger distribution of volumes for water-soluble drugs and smaller distribution volumes for lipophilic drugs due to higher percentage of total body water
Plasma protein binding of drugs decreases the apparent volume of distribution, and tissue binding increases the apparent volume of distribution.
the physiologic nadir of hemoglobin
Infants go through a period of anemia following birth (3- 6 months) with the destruction of fetal hemoglobin and the concurrent but slow production of RBC’s
Total body water, extracellular fluid and blood volume are relatively _____ when comparing the neonate with the child or adult on a per kg scale
Larger
This initial larger volume of distribution may explain why the neonate requires higher per kg dose of drugs to reach the desired effect
the neonate requires_____ per kg dose of drugs to reach the desired effect
higher
The infant’s brain receives a _____ proportion of cardiac output (in comparison to the adult) and the resultant brain concentration of many drugs is ______ in the infant than in the adult
large, higher
Post conceptual age –
weeks of age at birth + weeks of age since birth
Drug metabolism
The ability to metabolize drugs develops to the same degree in the same time period after birth in the premature infant and the full term infant
Postnatal age (not gestational age) is more important in determining maturity of drug metabolism
Hepatic enzyme systems are ______ developed or absent at birth
Phase I &II processes are ____ but ____ within a few days after birth
Conjugation reactions are developed by ___ months
Hepatic enzyme systems are incompletely developed or absent at birth
Phase I &II processes are limited but develop within a few days after birth
Conjugation reactions are developed by 3 months
The ultimate elimination of most drugs or their metabolites is by
renal excretion
Clearance of most drugs reaches adult values by 3 months of age
Is the uptake of inhaled anesthetics more rapid in infants and small children than in adults?
Yes, uptake is more rapid
Va / FRC
Va / FRC
5:1 in infants
1.4:1 in adults
True/False: Distribution of cardiac output is higher to the vessel-rich group (the brain) vs. adults
True
Effects of Shunting R>L
Slows uptake of agent
TOF, TGA, TA, TAPVR
Partial pressure of agent increases more slowly
Over-pressuring can be dangerous
Slow on means slow off!
Overpressuring can be dangerous because if you get significant cardiovascular depression from anesthetic overdose, it can be equally difficult to decrease the anesthetic concentration
Effects of Shunting L>R
Uptake is faster
ASD, VSD, PDA, BT Shunt
Increase depends on size of shunt
Large (>80%) more rapid increase in agent partial pressure
Small (<50%) change is negligible
There is an _____ relationship between MAC of inhalation agents and age
There is an inverse relationship between MAC of inhalation agents and age
MAC increases the first month of life
MAC starts to decrease after 6 months of life
True/False: In the first week of life, the neonate’s response to pain is diminished
True
Incidence of bradycardia, hypotension, and cardiac arrest during induction is ______ in infants than in adults
Greater
This is due to the increased amount of agent administered and increased sensitivity of the cardiovascular system
The baroreceptor reflexes of the neonate and premature infant are _____
limited
Halothane ______ the myocardium in direct proportion to depth of anesthesia and acts as ____ _____ _____
depresses, calcium channel blocker
Isoflurane has a direct ____ ____ _____
negative inotropic effect
Not used for inhalation induction due to pungent smell and airway irritation
Sevoflurane
Less soluble agent with more rapid wash in than halothane or isoflurane
Maintains cardiovascular homeostasis and produces fewer dysrhythmias than halothane or isoflurane
What does adding N20 to sevo do?
decreases the MAC of sevoflurane proportionately in adults
The addition of 60% N2O decreases the MAC of sevoflurane in children 1-3 years old by only 25%
Desflurane
Not used as an induction agent because of the high incidence of severe laryngospasm in infants and children
Cardiac stability is maintained but SVR is decreased
High incidence of emergence delirium in pediatric population
Pediatric MAC values
Halothane 0.87
Isoflurane 1.6
Desflurane 9.2
Sevoflurane 3.3
Why inhalation induction?
Infants and children are often uncooperative with IV starts
Increased minute ventilation and small body mass makes inhalation inductions safer and faster in children
Stage II is limited therefore decreasing chances of laryngospasm during induction
How to do the inhalation method
O2/N20 at 2L/4L
Sevoflurane at 8% until patient is deep enough for IV start*
This produces rapid stun effect for an anxious or uncooperative child but must be followed with continued administration of IV agent or inhalation anesthetic
Pay close attention to heart rate – always in tune with the rate on the pulse ox, need to decrease agent once maximal point in reached to prevent bradycardia and cardiovascular effects
Midazolam
~ 9 months and older
IV: 0.1 mg/kg
Propofol
Induction dose from 2-5 mg/kg
ED50 infants: 3.0 mg/kg
ED50 older children: 2.4mg/kg
Ketamine
IV: 2mg/kg
IM: 3-6mg/kg
Has potent analgesic properties for skin, muscle and bone (not for viscera)
Causes increased salivation (give with antisialogogue)
Causes hallucinations as well and should be co-administered with a benzodiazepine (i.e. Midazolam)
Narcotics
Fentanyl
Neonates have an increased sensitivity to narcotics
Dose: 1-5 mcg/kg
Anticholinergic Agents
Primary purpose in pediatrics is to protect against cholinergic challenge (prevent bradycardia)
Another purpose is to inhibit secretions
Treu/False: Neonates are born with a fully developed parasympathetic nervous system
Sympathetic nervous system does not fully develop until 3-6 months of age
True
Atropine
Dose: 10-20 mcg/kg
Glycopyrrolate: 10-20 mcg/kg
Succinylcholine
Metabolized by plasma cholinesterase
Dose: Infant 2.2 mg/kg (the ED 95 required to give 95%
blockade)
May produce profound and sustained bradycardia in the infant and small child
Doses are usually preceded by atropine
Because of the potential for life threatening side effects, Succinylcholine use is usually restricted to emergencies in the pediatric population (ie. RSI or Laryngospasm)
Due to its large K+ release, Succinylcholine is contraindicated in:
Neurologic conditions: paraplegia & stroke
Muscular Dystrophies- Duchenne’s
Myotonia
Burns
Malignant hyperthermia
Laryngospasm dose of succs
0.3-0.5 mg/kg range IV and 4 mg/kg IM
Rocuronium
Similar dose to adult
Neostigmine
Dose: 35-70 mcg/kg
More potent as an anticholinesterase than Edrophonium but slower onset of action
Edrophonium
Dose: 0.5-1.0 mg/kg
Has more rapid onset of action than neostigmine
Must have minimum of ¾ twitches, more appropriately 4/4 with little fade, to be able use as a reversal
Children are ___ more resistant to LA toxicity than adults!
NOT
The first signs of LA toxicity in infants and children may be:
dysrhythmias or cardiovascular collapse
Max local doses of lido, bupivcacaine, ropivacaine
lido: 5 mg/kg
bupiv: 2.5 mg/kg
ropiv: 0.5-1 ml/lg
Precedex for SVT
2 mcg/kg rapid bolus and followed with an infusion
Precedex
Initial increase in BP with rapid administration
Hypotension and bradycardia occur
Dose:
Bolus 0.25-1 mcg/kg
Infusion 0.2-1 mcg/kg/hr
Has sedative, analgesic, and sympatholytic effects
Reduces IV and inhalation anesthetic requirements
Decreases post operative analgesic requirements
Tranexamic Acid
Antifibrinolytic
Reversibly blocks the lysine binding site on plasminogen, preventing binding to fibrin and conversion to active plasmin
Also improves hemostasis by preventing plasmin-induced platelet activation
Anti-inflammatory properties
Tranexamic acid is 10 times more potent as an inhibitor of fibrinolysis than Aminocaproic Acid
Dose
Loading dose at CHP: 30 mg/kg
Infusion dose at CHP: 10 mg/kg/hr
