Lecture 4 (Part 2)-Pediatric Pharmacology Flashcards
Premature infant = an infant that was born at < ___ weeks post conception (gestational age)
< 37 weeks
Neonate/newborn = ___-___ weeks of age
0-4 weeks of age
Infant = ___ weeks to ___ months of age
4 weeks to 12 months of age
Pharmacological maturation occurs between ___-___ months of age
3-6 months of age
Drug absorption—there is no structural difference between infants, children, and adults that affect ___ absorption of drugs
GI
Drug absorption—there are differences in the neonate related to pH—___ (more/less) acidic; gastric ___; and gastric ___ time—markedly ___ (slower/faster)
pH—less acidic; gastric emptying; and gastric transit time—markedly slower
The amount of drug that reaches specific body compartments or tissues (the concentration of drug at the receptor site) is regulated by the ___ process
Distribution
Drug distribution—IV drugs are influenced by ___ binding, ___ binding, tissue ___, tissue ___ coefficients, tissue ___ flow
Protein binding, RBC binding, tissue volumes, tissue solubility coefficients, tissue blood flow
The neonate has a qualitative and quantitative ___ (increase/decrease) in protein binding
Decrease
There is a ___ (increase/decrease) in the number of plasma proteins, and a ___ (increase/decrease) in the affinity of proteins for drugs in the neonate
Decrease in the number of plasma proteins, and a decrease in the affinity of proteins for drugs in the neonate
The reduction in protein binding in neonates contributes to the apparent ___ (smaller/larger) volume of distribution in comparison to adult proportions
Larger volume of distribution
Neonates/infants have ___ (increased/decreased) total body water and extracellular fluid compared to adults
Increased
Neonates/infants have ___ (increased/decreased) blood volume, intracellular water, muscle mass, and fat compared to adults
Decreased
Full-term infants have greater ___ compared to adults
Blood volume
Infants go through a period of ___ following birth (3-6 months) with the destruction of fetal ___ and the concurrent but slow production of ___—this is referred to as the physiologic ___ of hemoglobin
A period of anemia following birth (3-6 months) with the destruction of fetal hemoglobin and the concurrent but slow production of RBCs—this is referred to as the physiologic nadir of hemoglobin
Total body ___, ___cellular fluid, and ___ volume are relatively larger when comparing the neonate with the child or adult on a per kg scale; this initial larger volume of distribution may explain why the neonate requires ___ (lower/higher) per kg doses of drugs to reach the desired effect
Total body water, extracellular fluid, and blood volume are relatively larger when comparing the neonate with the child or adult on a per kg scale; this initial larger volume of distribution may explain why the neonate requires higher per kg doses of drugs to reach the desired effect
The blood brain barrier is ___ (mature/immature)
Immature
Lipid soluble drugs diffuse ___
Easily
Rate of entry of drugs is based on blood ___
Flow
The infant’s brain receives a ___ (small/large) proportion of cardiac output in comparison to the adult, and the resultant brain concentration of many drugs is ___ (higher/lower) in the infant than in the adult
Large proportion of cardiac output, resultant brain concentration of many drugs is higher in the infant than in the adult
A high proportion of cardiac output is distributed to the vessel ___ (poor/rich) group, particularly the ___
Vessel rich group, particularly the brain
Smaller ___ mass and ___ stores (in relation to adults on a per kg basis) provide ___ (more/less) uptake to inactive sites and tend to keep plasma volumes ___ (lower/higher)
Smaller muscle mass and fat stores provide less uptake to inactive sites and tend to keep plasma volumes higher
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—T/F?
True
___ age, not gestational age, is more important in determining the maturity of drug metabolism
Postnatal age
Hepatic enzyme systems are ___ developed or ___ at birth
Incompletely developed or absent at birth
Phase I and II processes are limited but develop within ___ after birth
Develop within a few days after birth
Conjugation reactions are developed by ___ months
3
The ultimate elimination of most drugs or their metabolites is by ___ excretion
Renal
Drug clearance may be ___ (reduced/enhanced) in the neonate
Reduced
Clearance of most drugs reaches adult values by ___ months of age
3 months of age
The uptake of inhaled anesthetics is more ___ (slow/rapid) in infants and small children than in adults
Rapid
Tidal volume is relatively constant throughout life—___ml/kg
7 ml/kg
Infants have a ___ (lower/higher) alveolar ventilation in relation to FRC
Higher alveolar ventilation in relation to FRC
Va/FRC = ___:___ in infants; ___:___:___ in adults
5: 1 in infants
1: 4:1 in adults
Uptake and distribution—the infant has ___ (more/less) muscle mass on a per kg scale in relation to adults and a ___ (increase/decrease) in the proportion of cardiac output perfusing muscle in relation to adults
The infant has less muscle mass on a per kg scale in relation to adults and a decrease in the proportion of cardiac output perfusing muscle in relation to adults
Uptake and distribution—distribution of cardiac output is higher to the vessel ___ group (the ___) vs. adults
Higher to the vessel rich group (the brain) vs. adults
Shunting is more pronounced with insoluble agents such as ___ and ___
N2O and sevoflurane
Effects of shunting—___ to ___ shunt (as seen in patients with tetralogy of fallot, transposition of the great arteries, tricuspid atresia, and total anamolous pulmonary venous return) ___ (slows/speeds) uptake of agent; partial pressure of agent increases more ___ly; over-pressuring can be dangerous; ___ on means ___ off
R to L shunt slows uptake of agent; partial pressure of agent increases more slowly; over-pressuring can be dangerous; slow on means slow off
R to L shunt—deoxygenated blood on the right side of the heart shunts to the left side of the heart; slows uptake of agent because the blood on the right side of the heart isn’t going to the lungs to pick up agent
Over-pressuring can be dangerous because it takes a long time for the agent to come off, so the myocardial depressant effects will be long lasting
Effects of shunting—___ to ___ shunt (as seen in patients with ASD, VSD, PDA, BT shunt) uptake of agent is ___ (slower/faster); increase in uptake depends on ___ of shunt; large shunt (>80%) results in a ___ increase in agent partial pressure; small shunt (<50%) the change is ___
L to R shunt uptake of agent is faster; increase in uptake depends on size of shunt; large shunt results in a rapid increase in agent partial pressure; small shunt the change is negligible
L to R shunt—oxygenated blood from the left side of the heart is going to the right side of the heart (so body is not receiving the oxygen that it needs)
MAC—there is an ___ (direct/indirect) relationship between MAC of inhalation agents and age
Indirect relationship—the younger the child, the more agent needed (and vice versa)
Studies show that MAC of fetal lamb is ___ (lower/higher) than that of newborn lamb
Lower
MAC ___ (increases/decreases) during the first month of life
Increases
MAC starts to ___ (increase/decrease) after 6 months of life
Decrease
In the first week of life, the neonate’s response to pain is ___; the sensitivity and response to pain mature rapidly in the first few months of life
Diminished
Age-dependent differences in inhaled anesthetic requirements may be attributed to changes in ___ solubility, as well as the high ___ content of the neonatal brain
Changes in blood-gas solubility, as well as the high water content of the neonatal brain
Incidence of bradycardia, hypotension, and cardiac arrest during induction is ___ (lower/higher) in infants than in adults; this is due to the ___ (increased/decreased) amount of agent administered and ___ (increased/decreased) sensitivity of the cardiovascular system
Higher; this is d/t the increased amount of agent administered and increased sensitivity of the cardiovascular system
The baroreceptor reflexes of the neonate and premature infant are limited; anesthetic agents further blunt these reflexes and put the infant at a disadvantage during anesthesia with potent inhaled agents—T/F?
True
Halothane ___ the myocardium in direct proportion to the depth of anesthesia
Depresses
Halothane acts as a ___ blocker
Calcium channel blocker
Halothane causes a decrease in ___, ___ vascular resistance, and cardiac ___
Decrease in contractility, pulmonary vascular resistance, and cardiac slowing
___ heart tones, ___cardia, and ___tension are initial signs of halothane overdose
Muffled heart tones, bradycardia, and hypotension are initial signs of halothane overdose
Isoflurane has a direct negative ___tropic effect; causes a marked decrease in ___; has less depressant and fewer cardiovascular effects than ___
Direct negative inotropic effect; causes a marked decrease in PVR; has less depressant and fewer cardiovascular effects than halothane
Isoflurane is not used for inhalation induction d/t ___ smell and airway ___
Pungent smell and airway irritation
Sevoflurane is ___ (less/more) soluble than halothane or isoflurane and has a more ___ wash in
Less soluble and has a more rapid wash in
This agent maintains cardiovascular homeostasis and produces fewer dysrhythmias than halothane or isoflurane
Sevoflurane
The addition of ___ decreases the MAC of sevoflurane proportionately in adults
N2O
The addition of 60% N2O decreases the MAC of sevoflurane in children 1-3 years old by only ___%
25%
This inhalation agent has a strong pungent smell and is irritating to the airways
Desflurane
Desflurane is not used as an induction agent because of the high incidence of severe ___ in infants and children
Laryngospasm
Cardiac stability is maintained with desflurane, but ___ is decreased
SVR
Desflurane—high incidence of emergence ___ in pediatric population
Emergence delirium
MAC values in the neonate vs. adult—halo ___
Neonate halo = 0.87%
Adult halo = 0.75%
MAC values in the neonate vs. adult—iso ___
Neonate iso = 1.6%
Adult iso = 1.2%
MAC values in the neonate vs. adult—sevo ___
Neonate sevo = 3.3%
Adult sevo = 2.05%
MAC values in the neonate vs. adult—des ___
Neonate des = 9.2%
Adult des = 7%
Inhalation induction is often done in infants and children because they are usually uncooperative with ___ starts
IV
Inhalation induction—___ (increased/decreased) minute ventilation and ___ (small/large) body mass makes inhalation inductions safer and faster in children
Increased minute ventilation and small body mass
Inhalation induction—stage ___ is limited, therefore decreasing the chances of ___ during induction
Stage II is limited, therefore decreasing the changes of laryngospasm during induction
Inhalation induction—current method with sevoflurane—O2/N2O at ___L/___L; sevoflurane at ___% 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 ___ agent or ___ anesthetic
O2/N2O at 2L/4L; sevoflurane at 8%; continued administration of IV agent or inhalation anesthetic
Inhalation induction—old method with halothane—O2/N2O at ___L/___L; introduce halothane at ___% increments every 2-3 breaths until ___-___%; allow patient to deepen enough for IV to be started and decrease agent dose; decrease agent dose to prevent ___tension and ___cardia
O2/N2O at 2L/4L; introduce halothane at 0.5% increments every 2-3 breaths until 3-5%; allow patient to deepen enough for IV to be started and decrease agent dose; decrease agent dose to prevent hypotension and bradycardia
Induction with sevo—decrease agent as soon as the maximal point in ___ is reached; come down to ___-___%
Decrease agent as soon as the maximal point in heart rate is reached; come down to 3-5%
Midazolam—used as pre-operative ___lytic for kids ~___ months or older (when separation anxiety begins)
Pre-operative anxiolytic for kids ~9 months or older
Midazolam oral dose ___-___ mg/kg, onset ___-___ minutes
0.5-1.0 mg/kg, onset 15-30 minutes
Midazolam intranasal dose ___-___ mg/kg, onset ___ minute with peak in ___ minutes
0.2-0.3 mg/kg, onset 1 minute with peak in 10 minutes
Midazolam IV dose ___-___ mg/kg
0.1 mg/kg
Propofol—infants ___ mg/kg
3 mg/kg
Propofol—older children ___ mg/kg
2.4 mg/kg
Propofol induction dose is typically ___-___ mg/kg
2-5 mg/kg
Propofol—rapid redistribution and metabolism result in a ___ (long/short) duration of action
Short
Propofol can be used for ___ of general anesthesia and may be used as an ___ for maintenance of general anesthesia; propofol doses in pediatric patients are much ___ (lower/higher) than in adults
Can be used for induction of GA and may be used as an infusion for maintenance of GA; much higher
Ketamine—IV ___ mg/kg
2 mg/kg
Ketamine—IM ___ mg/kg
3-6 mg/kg
Ketamine can be given in intermittent ___ for sedation, as an ___, or as an IM ___ for uncooperative patient (usually given this way for autistic patients)
Intermittent blouses for sedation, as an infusion, or as an IM dart for uncooperative patient
Ketamine has potent analgesic properties for skin, muscle, and bone, but not for ___
Viscera
Ketamine causes increased ___, so give with an anti___
Increased salivation, so give with an antisialogogue
Ketamine causes ___ as well and should be co-administered with a ___
Hallucinations; administer with a benzo (i.e.: versed)
Neonates have an increased sensitivity to ___
Narcotics
Morphine IV dose ___-___ mg/kg
0.05-0.1 mg/kg
Morphine—there is a longer ___ time and ___ in the neonate; elimination half-life in neonates can be up to ___ hours
Longer elimination time and half-life in the neonate; elimination half-life in neonates can be up to 14 hours
Fentanyl IV dose—___-___ mcg/kg
1-5 mcg/kg
Clearance of fentanyl in neonates is similar to that of older children and adults—T/F?
True
Clearance of fentanyl in premature infants is markedly ___; half-life is ___-___ hours
Reduced; half-life is 6-32 hours
Remifentanil infusion rate = ___-___ mcg/kg/min
0.02-2 mcg/kg/min
Remifentanil onset = ___ minute
1
Half-life of remifentanil = ~ ___ minutes
~ 9 minutes
Remifentanil is metabolized by ___
Plasma esterases
Metabolism of remifentanil is relatively unchanged throughout life; initial studies in children show that clearance, volume of distribution, and half-life of remifentanil are similar to adult values—T/F?
True
Bolus IV dose of remifentanil can cause profound ___cardia and possibly ___
Profound bradycardia and possibly asystole
Primary purpose of anticholinergic agents in pediatrics is to protect against ___ challenge (prevent ___cardia)
Protect against cholinergic challenge (prevent bradycardia)
Neonates are born with a fully developed ___ nervous system
Parasympathetic
Sympathetic nervous system does not fully develop until ___-___ months of age
3-6 months of age
Another purpose of anticholinergic agents is to inhibit ___
Secretions
Anticholinergic agents are also used in combination with anticholinesterase drugs to prevent associated undesirable ___ effects
Muscarinic
Atropine IV dose ___-___ mcg/kg; onset ___ minute; duration ___-___ minutes; ___ (does/does not) cross BBB; has more profound ___ effects; is less effective as an anti___
10-20 mcg/kg; onset 1 minute; duration 30-60 minutes; does cross BBB; has more profound cardiac effects; is less effective as an antisialogogue
Glycopyrrolate IV dose ___-___ mcg/kg; onset ~___-___ minutes; duration ___-___ minutes; has moderate ___ effects; is better anti___ than atropine
10-20 mcg/kg; onset ~2-3 minutes; duration 30-60 minutes; has moderate cardiac effects; is better antisialogogue than atropine
Depolarizing NMB—succs—metabolized by plasma ___; dose infant ___ mg/kg (this is the ED95 dose required to give 95% blockade); may produce profound and sustained ___cardia in the infant and small child; doses are usually preceded by ___
Metabolized by plasma cholinesterase; dose infant 2.2 mg/kg; may produce profound and sustained bradycardia in the infant and small child; doses are usually preceded by atropine
Age related differences in succs dose requirements may be related to: cholinesterase activity—___ in infants up to 3 months of age; receptor sensitivity—the ACH receptor ___ with age; volume of distribution—small molecular size and ___ distributed to ECF
Cholinesterase activity—reduced in infants up to 3 months of age; receptor sensitivity—the ACH receptor matures with age; volume of distribution—small molecular size and rapidly distributed to ECF
Due to it’s large K+ release, succs is contraindicated in: ___ conditions (i.e.: paraplegia, stroke); ___ dystrophies (Duchenne’s); ___tonia; ___; ___ ___thermia
Neurologic conditions; muscular dystrophies; myotonia; burns; malignant hyperthermia
Because of the potential for life threatening side effects, succs use is usually restricted to ___ in the pediatric population (i.e.: ___ induction or ___spasm
Restricted to emergencies (i.e.: RSI or laryngospasm
Laryngospasm succs dose ___ mg/kg
0.4 mg/kg
Succs can be given ___ or ___ if no PIV is obtained
Sublingual or IM
Succs IM dose = ___ mg/kg
4 mg/kg
___ muscle relaxants are more commonly used in pediatrics; cardiovascular effects of these drugs are related to the degree of ___ release, ganglionic ___, and ___lysis
Non-depolarizing; degree of histamine release, ganglionic blockade, and vagolysis
Rocuronium ___ mg/kg; onset ___ minutes; duration—infants < 10 months = ~ ___ minutes; duration—children 1-5 years = ___ minutes; may be used as an alternative to succinylcholine in ___
0.6 mg/kg; onset 1.5 minutes; duration—infants < 10 months = ~ 45 minutes; duration—children 1-5 years = 26 minutes; may be used as an alternative to succinylcholine in RSI
Cisatracurium dose ___-___ mg/kg; onset ___-___ minutes (dose dependent); duration ___-___ minutes; metabolism = ___ elimination
0.1-0.2 mg/kg; onset 2-3 minutes; duration 30-45 minutes; metabolism = Hoffman elimination
Pancuronium dose ___ mg/kg; onset ___-___ minutes; duration ___-___ minutes; side effects = ___ effect resulting in ___ (increased/decreased) heart rate
0.1 mg/kg; onset 3-5 minutes; duration 60-100 minutes; side effects = vagolytic effect resulting in increased heart rate
Reversal agents—neostigmine and edrophonium—inhibit ___, increasing ___ which competes with the non-depolarizing agent
Inhibit acetylcholinesterase, increasing ACH which competes with the non-depolarizing agent
___ (neostigmine or edrophonium) has a stronger bond with true cholinesterase
Neostigmine
Neostigmine and edrophonium will work effectively with a high dose of NDNMB on board—T/F?
False—will NOT work effectively…patient must have 2/4 twitches
Neostigmine dose ___-___ mcg/kg; atropine ___-___ mcg/kg; glycopyrrolate ___-___ mcg/kg; neostigmine is more ___ as an anticholinesterase than edrophonium but has a ___ onset of action
35-70 mcg/kg; atropine 15-30 mcg/kg; glycopyrrolate 10-20 mcg/kg; neostigmine is more potent as an anticholinesterase than edrophonium but has a slower onset of action
Edrophonium dose ___ mg/kg; atropine ___-___ mcg/kg; has more ___ onset of action than neostigmine; must have minimum ___ out of 4 twitches, more appropriately ___ out of ___ twitches with little fade, to be able to use this as a reversal agent
0.5-1.0 mg/kg; atropine 10-20 mcg/kg; has more rapid onset of action than neostigmine; must have minimum 3 out of 4 twitches, more appropriately 4 out of 4 twitches with little fade, to be able to use this as a reversal agent
Sugammadex—efficacy and safety has been demonstrated for infants, children, and adolescents as a method for eliminating rocuronium—T/F?
True
Sugammadex adult dosing—___ mg/kg for shallow blockade (after appearance of T2); ___ mg/kg for deep blockade (1-2 post-tetanic counts but prior to appearance of T2); ___ mg/kg for rescue dose after administration of intubating dose
2 mg/kg for shallow blockade (3/4 twitches)
4 mg/kg for deep blockade (1/4 or 2/4 twitches)
16 mg/kg for rescue dose after administration of intubating dose
Local anesthetics—what (3) are usually used in children?
- Lidocaine
- Bupivacaine
- Ropivacaine
Local anesthetics are used for local and intra-___ infiltration, and in ___ blocks
Local and intra-tracheal infiltration, and in caudal blocks
Children are more resistant to LA toxicity than adults—T/F?
False! They are NOT more resistant to LA toxicity
The first signs of LA toxicity in infants and children may be ___ or ___ collapse
Dysrhythmias or CV collapse
Max local doses—lidocaine plain ___ mg/kg; with epi ___ mg/kg
Plain 5 mg/kg; with epi 7 mg/kg
Max local doses—bupivacaine plain ___ mg/kg
2.5 mg/kg
Max local doses—ropivacaine ___ ml/kg
0.5-1 ml/kg
The addition of epi to bupivacaine significantly increases the duration of action—T/F?
False—does NOT significantly increase the duration of action
Epi max dose ___-___ mcg/kg/dose, with re-injection of Epi possible after ___ minutes
2-3 mcg/kg/dose, with re-injection of epi possible after 30 minutes
Dexmedetomidine is an alpha-___ ___ similar to Clonidine
Alpha-2 agonist
Dexmedetomidine has a higher affinity for the ___ receptor
Alpha-2 receptor
Dexmedetomidine has ___, ___, and ___lytic effects
Sedative, analgesic, and sympatholytic effects
Dexmedetomidine ___ (increases/decreases) IV and inhalation anesthetic requirements
Decreases
Dexmedetomidine ___ (increases/decreases) post-operative analgesic requirements
Decreases
Dexmedetomidine ___ (does/does not) significantly depress respirations
Does not
Dexmedetomidine—initial ___ (increase/decrease) in BP with rapid administration; ___tension and ___cardia occur
Initial increase in BP; hypotension and bradycardia occur
Dexmedetomidine dose—bolus ___-___ mcg/kg; infusion ___-___ mcg/kg/hr
Bolus 0.25-1 mcg/kg; infusion 0.2-1 mcg/kg/hr
Tranexamic acid (TXA) is an anti___—reversibly blocks the ___ binding site on plasminogen, preventing binding of plasminogen to ___ and conversion to active ___; also improves hemostasis by preventing plasmin-induced ___ activation; anti-___ properties
Antifibrinolytic—reversibly blocks the lysine binding site on plasminogen, preventing the binding of plasminogen to fibrin and conversion to active plasmin; also improves hemostasis by preventing plasmin-induced platelet activation; anti-inflammatory properties
TXA is ___ times more potent as an inhibitor of fibrinolysis than aminocaproic acid
10 times
TXA loading dose—___ mg/kg; infusion dose—___ mg/kg/hr
Loading dose—30 mg/kg; infusion dose 10 mg/kg/hr
