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Anesthesia Pharm > Week 10 - Pediatric Pharmacology > Flashcards

Week 10 - Pediatric Pharmacology Flashcards

1
Q

What are the different pediatric age groups?

A

Neonate - up to 30 days old (premature - born before 37 weeks; term - born after 27 weeks; postmenstural age -gestational age + chronological age in weeks)

Infant - between 30 days to 1 year

Toddler - 1-3 years old

Preschool - 4-6 years old

School Age - 6-13 years old

Adolescents - 13-18 years old

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2
Q

What are physiologic considerations in pediatrics?

A
  • Total body water (greater)
  • Immature drug metabolism
  • Decreased protein binding
  • Immature BBB
  • Increased VRG (greater proportion of blood flow to brain, heart, liver, and lungs)
  • Decreased GFR (30% that of adults at birth in term neonates – 90% at 1 year – reaches normal by 6-12 months)
  • Reduced FRC and O2 reserves (reduced lung compliance due to fewer/smaller alveoli)
  • Compliant chest wall collapses easily
  • Increased minute ventilation
  • Immature receptors
  • Less developed compensatory mechanisms (BP is sensitive to CV effects)
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3
Q

What is the body composition of a newborn (1.5kg) and full term newborn (3.5kg)?

A

Muscle Mass (% of BW): Newborn = 15% — Full Term = 20% (adult = 50%)

Fat (% of BW): Newborn = 3% — Full Term = 12% (adult = 18%)

Total Body Water: Newborn = 90% — Full Term = 80% (adult = 60%)

Extracellular Fluid: Newborn = 50% — Full Term = 40% (adult = 20%)

Intracellular Fluid: Newborn = 40% — Full Term = 40% (adult = 40%)

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4
Q

What are the extravascular routes of administration in pediatrics?

A 
Oral
Nasal
Rectal
IM
Transdermal
Pulmonary (inhalation)
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5
Q

How is oral absorption different in pediatrics?

A

Principle site of absorption is the small intestine (rate at which drug leaves the stomach determines speed of absorption)

Rate of absorption is SLOWER in neonates and young infants than in older children due to delayed gastric emptying
*matures through infancy and doesn’t reach adult rates until 6-8 months

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6
Q

How is rectal absorption different in pediatrics?

A

Absorption of drugs administered rectally is erratic and variable
-directly affected by drug formulation and rectal blood flow

Bioavailability of rectal acetaminophen in premature neonates and infants is variable (approx 80% of PO dose and rate of absorption is slower)

  • rectal bioavailability is formulation dependent and decreases with age
  • peak blood levels achieved at 60-180 minutes
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7
Q

Why is intra-nasal absorption beneficial in pediatrics?

A
  • Rich vascular plexus of the nasal cavity provides a direct route into the blood stream for medications that easily cross mucous membranes
  • For many intra-nasal medications the rates of absorption and plasma concentrations are comparable to IV admin, and are typically better than SubQ or IM routes
  • Intra-nasal medication achieves therapeutic threshold without reaching respiratory depression threshold compared to IV admin (still need to monitor for respiratory depression)

*poor patient cooperation can be a factor in absorption

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8
Q

What drugs are typically used intranasally in pediatrics?

A

Dexmedetomidine: 1-2 mcg/kg with onset in 15-30 min and duration of 55-100 minutes
*may be preferred when more than mild sedation is desired; monitor for HoTN and bradycardia

Fentanyl: 1.5-2 mcg/kg; onset 10-20 min; duration 30 min
*monitor for hypoxia

Ketamine: 5-8 mg/kg; onset 5-10 min; duration up to 60 min
*monitor for hypoxia

Midazolam: 0.4-0.5 mg/kg; onset 10-20 min; duration 20-40 min
*may cause nasal burning for 30-45 seconds

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9
Q

How are transdermal and IM absorption different in pediatrics?

A
  • Increased cutaneous perfusion, thinner skin in neonates increases absorption of topically applied drugs than younger children(more tendency to form methemoglobin)
  • IM in neonates and infants is greater than children due to higher density of skeletal muscle capillaries
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10
Q

What in infancy increases percutaneous absorption?

A

Skin Thickness

Perfusion

Hydration

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11
Q

What can occur with the 1st dose of Succinylcholine administered to a pediatric patient?

A

May have profound bradycardia and asystole with 1st dose of SUX if not given atropine pretreatment

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12
Q

Management of what is more critical in pediatric anesthesia? What are considerations to manage it?

A

Fluid management is more critical

Considerations in planning fluid management in a neonate:

  • degree of dehydration present before pre-op
  • fluid deficit due to NPO guidelines
  • maintenance requirements during aneshesia/surgery
  • estimated 3rd space loss
  • alterations in body temp
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13
Q

How is pulmonary (inhalation) absorption different in pediatrics?

A
  • It is more rapid in infants and children than adults
  • Increased respiratory rate and cardiac index
  • Greater proportional distribution of CO to vessel rich organs
  • **Anesthetic levels can become toxic more quickly than adults
  • Congenital anomalies with right to left shunting can delay the FA/FI of inhalation anesthetics
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14
Q

Why is inhalation induction faster in children?

A

Differences in lung physiology:

  • Increased alveolar ventilation relative to adults
  • Decreased FRC relative to adults
  • Increased oxygen consumption
  • *-Increased minute ventilation and increased ratio of tidal volume to FRC

**Large VRG (% of blood to VRG is greater) – increased CO

Blood gas partition coefficient is lower in children – reduced solubility of inhaled anesthetics in blood (also have less fat and muscle)

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15
Q

How is MAC changed with pediatrics?

A

MAC is lower in neonates

MAC is higher age 1 month to 6 months

After 6 months, MAC decreases with increasing age

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16
Q

What is the MAC of Sevo, Iso, and Des for neonates <6 months and 6 months to 1 year?

A

SEVO:

  • MAC < 6 months = 3%
  • MAC > 6 months - 1 year = 2.5-2.8%
  • adults = 2%

ISO:

  • MAC < 6 months = 1.6%
  • MAC > 6 months - 1 year = 1.6%
  • adults = 1.15%

DES:

  • MAC < 6 months = 9%
  • MAC > 6 months - 1 year = 6-10%
  • adults = 6%
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17
Q

What is the best inhalation agent for children?

A

Sevoflurane because it is NOT irritating to the airway
-rapid induction and emergence

  • Iso will cause them to have breath holding
  • Des will cause them to cough and sputter
  • *both have more incidences of laryngospasm with copious secretions than sevo
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18
Q

Why do children exhibit different drug distributions from adults?

A

Due to different body composition and altered protein binding

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19
Q

How does the increased total body water in pediatrics affect anesthesia drugs?

A
  • Water soluble drugs are more diluted and have lower receptor concentrations
  • Loading dose must be increased in younger children to achieve effect
  • SUX dose in infants up to 4 mg/kg
  • Increased Vd for water soluble drugs (NMDBs distribute rapidly to the ECF but into cells more slowly)
  • Less pronounced with lipid soluble drugs
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20
Q

What is the reduction in total body water as we age due to?

A

A gradual decline in extracellular fluid

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21
Q

How is protein binding different in pediatrics? How does this affects anesthetic drugs?

A

Degree of protein binding and function is less in the pre-term and term infants
-lower concentrations of total body proteins and albumin (until 6 months – albumin binding capacity fully functional at 1 year old)

Many drugs that are highly protein bound in adults have less of an affinity for protein in neonates – more free drug available (greater pharmacologic effect)

Bilirubin can displace protein bound drugs and vice versa
*affects weakly bound drugs more than highly bound

Need to consider lowering drug dose
Drugs will have a longer duration of action

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22
Q

How is drug metabolism different in neonates?

A
  • Decreased hepatic blood flow
  • Immature hepatic enzymes – decreased biotransformation
  • Decreased GFR and renal tubular function
  • Lipid soluble compounds are converted to more water soluble compounds
  • Water soluble drugs may be excreted unchanged in the kidneys

*lipid soluble drugs may not converted as quickly than in the adult population

23
Q

When does hepatic metabolism mature?

A

Phase I Metabolism (oxidation, reduction, hydrolysis) – CYP450 enzyme system is not fully developed during neonatal and early infancy periods – begins to mature within the first week of life and continue to increase during the first 3 months of life

Phase II Metabolism (conjugation reactions) – underdeveloped in neonates
*neonate lacks capacity of effectively conjugate bilirubin and metabolize metabolize medications such as acetaminophen, cloramphenicol, and sulfonamides

**Necessary enzyme systems are present at birth but enzyme activity is reduced increasing drug elimination half lives

24
Q

How are extrahepatic elimination pathways different in pediatrics?

A

Non specific esterase activity may be increased
-Remifentanil clearance is greater in neonates (4.5 L/hr/kg) than in infants (3.7 L/hr/kg) or adults (2.1 L/hr/kg)

Plasma pseudocholinesterase are decreased in neonates
*ester LA may have prolonged effect

25
Q

What is the major factor affecting drug action in pediatrics?

A

Reduced clearance

  • when administering a drug to a preterm or term infant, one must consider the contribution of renal function in the termination of its action
  • drugs such as aminoglycoside antibiotics (micin’s and some mycins) that are excreted primarily through glomerular filtration of tubular secretion have prolonged elimination half-life
26
Q

How are opioid receptors different in pediatrics?

A

Increased human neonatal sensitivity to morphine is attributed to pharmacokinetic rather than pharmacodynamic differences

In neonates, changes in the number and affinity of the mu and kappa receptors may account for the increased respiratory depression that results when opioids are used

27
Q

How are nicotinic receptors different in pediatrics?

A

There is a reduction in ACh release in the neuromuscular junction in the neonate – could account for the increased sensitivity to NDMRs

Immature ACh receptors have prolonged opening of the ionic channels – this allows immature muscles to be more easily depolarized
*have greater affinity for depolarizing agents and lower affinity for NDMRs

**these maturational changes cause greater variability in response to NDMRs in neonates

28
Q

How are GABA receptors different in pediatrics?

A

Number of GABA receptors in neonate are only 1/3 that of the adult
-1/2 of these receptors have a high affinity for binding with benzos and other anesthetics

GABA receptor complex becomes more prevalent from birth to 2 years and then decreases to 50% of peak values by 17 years old
-this is consistent with age related MAC changes and higher doses of oral midazolam

29
Q

How is propofol different in infants?

A

Has a larger Vd – need larger dose

Shorter time of onset – higher % of CO goes to the VRG so it distributes quicker

Propofol Infusion Syndrome

  • kids with mitochondrial defects are more susceptible
  • Causes rhabdo, metabolic acidosis, hemodynamic instability, hepatomegaly, multiorgan system failure
30
Q

What is the induction dose of Propofol in pediatrics?

A

2-3 mg/kg

*compared to 1.5-2.5 mg/kg in adults

31
Q

What is the induction dose of etomidate in pediatrics?

A
  1. 3-0.4 mg/kg

* compared to 0.2-0.4 mg/kg in adults

32
Q

What is the induction dose of ketamine in pediatrics (IV and IM)?

A

IV: 2 mg/kg

IM: 5-6 mg/kg

*compared to 1-3 mg/kg IV and 4-8 mg/kg IM

33
Q

What is the dose of benzodiazepines in pediatrics (IV, IN, PO)?

A

IV: 0.01-0.02 mg/kg IV

Intra-Nasal: 0.2-0.3 mg/kg

PO: 0.3-0.5 mg/kg

34
Q

Why are neonates especially vulnerable to drug toxicity?

A

Due to increased Vd and immature metabolism and excretion of drugs

*increase in ECF concentration leads to increased initial dosages of polar drugs (NMBs) but have slower entry into cells

35
Q

At what age are metabolism and excretion systems fully mature?

A

not fully mature until around 1 year of age

36
Q

What differences in the neonate cause an increase in absorption and distribution?

A

Increased CO per kg of body weight – circulation time in neonates is faster than in adults, increasing rate of drug delivery to site of action

Protein concentration and binding capabilities – decreased binding = more free drug = greater pharmacologic effect

Body composition – affects Vd of drugs

Immaturity of the BBB – small molecules access brain more easily than in the adult
*unbound lipophilic drugs passively diffuse across – contributes to the tendency of drugs such as LA to produce seizures in neonates

37
Q

What differences in the neonate cause a decrease in elimination?

A

Immature metabolic pathways

Renal immaturity

38
Q

How does a right-to-left intracardiac shunt in a neonate affect inhalation induction?

A

Inhalation induction can require more time prior to loss of consciousness

-slowing of the rate of rise of alveolar concentration is due to the decrease in the anesthetic concentration in arterial blood

39
Q

Why do IV administered drugs have a prolonged duration of action in neonates and infants?

A

They have decreased percentages of muscle and fat

Decreased hepatic degradation and renal excretion

*IV anesthetic agents are readily taken up by the VRG tissues and are subsequently redistributed to tissues less well perfuse (muscle/fat)

40
Q

What is the ED95 of succinylcholine for a neonate, infant, and child?

A

Neonate: 0.62 mg/kg (620 mcg/kg)

Infant: 0.73 mg/kg (729 mcg/kg)

Child: 0.42 mg/kg (423 mcg/kg)

**should only be used for emergency airway stabilization in children younger than 8 years old – not for routine intubation

Adult: 0.3 mg/kg

41
Q

What is the ED95 of rocuronium for a neonate, infant, and child?

A

Neonate: 0.6 mg/kg

Infant: 0.6 mg/kg

Child: 0.6 mg/kg

*adult: 0.3 mg/kg

42
Q

What is the ED95 of vecuronium for a neonate, infant, and child?

A

Neonate: 0.047 mg/kg (47 mcg/kg)

Infant: 0.042-0.047 mg/kg (42-47 mcg/kg)

Child: 0.056-0.08 mg/kg (56-80 mcg/kg)

*adult: 0.027-0.056 mg/kg (27-56 mcg/kg)

43
Q

What is the ED95 of atracurium for a neonate, infant, and child?

A

Neonate: 0.12 mg/kg (120 mcg/kg)

Infant: 0.15-0.17 mg/kg (156-175 mcg/kg)

Child: 0.17-0.35 mg/kg (170-350 mcg/kg)

*adult: 0.11-0.28 mg/kg

44
Q

Why is myocardial depression exaggerated when inhalation anesthetics are administered to pediatric patients?

A

More rapid rise in the FA/FI ratio

Greater % of blood flow to VRG

Higher administered anesthetic concentrations

*incidence of hemodynamically compromising myocardial depression is greater than in an adult due to the structural and functional immaturity of the pediatric heart

45
Q

What is emergence delirium in the pediatric population?

A

Altered behavior in the immediate post-op period

  • manifests as restlessness, crying, moaning, incoherence, and disorientation
  • can last as long as 45 minutes
46
Q

What is the common premedication pediatric doses of morphine?

A

IM: 0.1-0.3 mg/kg

IV: 0.05-0.1 mg/kg

47
Q

What is the common premedication pediatric doses of fentanyl?

A

IV: 0.5-1.0 mcg/kg

Oral Transmucosal: 10 mcg/kg

48
Q

What is the common premedication pediatric doses of midazolam?

A

IM: 0.05-0.1 mg/kg

Nasally: 0.2 mg/kg

IV: 0.025-0.05 mg/kg

PO: 0.25-1.0 mg/kg

Rectally: 0.5-1 mg/kg

49
Q

What is the common premedication pediatric doses of ketamine?

A

PO: 5-10 mg/kg

IM: 2-10 mg/kg

IV: 1-2 mg/kg

50
Q

What is the common premedication pediatric doses of clonidine?

A

PO: 2.5-5 mcg/kg

IV: 1-2 mcg/kg

51
Q

What is the common premedication pediatric doses of dexmedetomidine?

A

Intra-Nasally: 0.5-1 mcg/kg

PO: 2-5 mcg/kg

IV infusion: 0.4-0.6 mcg/kg in 100mL saline

52
Q

What is the common premedication pediatric dose of atropine?

A
  1. 02 mg/kg

* PO, IV, and IM

53
Q

What is the common premedication pediatric dose of glycopyrrolate?

A

0.01 mg IV

Anesthesia Pharm (18 decks)

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