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Anesthesia Pharm Exam 3 > Pediatric Pharm > Flashcards

Pediatric Pharm Flashcards

1
Q

Neonate

A

< 4 weeks old

  • premature: born before 37 weeks gestation
  • term: born after 37 weeks
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2
Q

Infant

A

4 weeks - 1 year

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3
Q

Child

A

> 1 year but < 18 years

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4
Q

What two things affect drug mvmt from plasma to tissues?

A

CO and VRG

  • peds have a higher CO going to VRG plus higher surface area
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5
Q

What organ is the primary determinant of biotransformation?

A

Liver

  • high extraction ratio if drugs are flow dependent clearance (ie: propofol… if liver enzymes aren’t fully developed, drugs can accumulate)
  • low extraction ratio drugs are enzyme activity dependent clearance (alfentanil and methadone)
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6
Q

What is the primary excretion organ?

A
  • kidneys (renal CO x extraction ratio)

– Small, unbound drugs pass from plasma to GF

– Nonionized (uncharged) drug reabsorbed in tubules

– Ionized (charged) drug is excreted.

– GFR 30-40% adult for 34+weekers; 60% by 3rd week nml @6 mos.

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7
Q

t1/2 life elimination

A
  • time for [] to fall 50%
  • anesthesia drugs have multiple t1/2 b/c multiple compartments model
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8
Q

Oral Absorption

A

• Principle site of absorption is 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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9
Q

Rectal Absorption

A
  • Absorption of drugs administered rectally is erratic and variable.
  • Bioavailability of rectal acetaminophen in premature neonates and infants is variable.

– It is approximately 80% of oral dose and the rate of absorption is slower.

– Rectal bioavailability is formulation dependent and

decreases with age.

– Peak blood levels achieved at 60 to 180 minutes.

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10
Q

Intranasal

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 IN medications the rates of absorption and plasma concentrations are comparable to intravenous administration, and are typically better than subcutaneous or intramuscular routes.
  • Poor patient cooperation can be a factor in absorption
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11
Q

Transdermal/IM

A

• Increased cutaneous perfusion, thinner skin in neonates increases absorption of topically applied drugs in neonates.

– More tendency to form methemoglobin so use of EMLA in neonates need to be done cautiously.

  • Skin thickness, perfusion, and hydration in infancy increases percutaneous absorption.
  • IM in neonates/children is not altered.
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12
Q

Pulmonary Absorption

A

• Pulmonary absorption is more rapid in infants and children than adults.

• Increased respiratory rate and cardiac index.

• Greater proportional distribution of cardiac output 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 inhalational anesthetics.

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13
Q

Distribution

A

• Children exhibit different drug distributions from adults due to

– different body composition

– altered protein binding

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14
Q

Baby Fat/H2O and distribution: implications for anesthesia drugs

A
  • Water soluble drugs are more diluted and have lower receptor concentrations
  • The loading dose must be increased in younger children to achieve effect
  • Succinylcholine dose in infants up to 4mg/kg
  • Less pronounced with lipid soluble drugs
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15
Q

Peds Drug Distribution

A

• Total body water is:

– 80-85% for premature infant

– 70-75% for term infants

– 50-60% adults

– 40% infants body weight is in ECF

– 20% adults body weight is ECF

– Vd H20 soluble drugs is >> in peds than adults

– Vd lipid soluble drugs is ??? In peds than adults

• Lower amounts of body muscle prolongs action of the drugs because?

– They can’t redistribute from site of action (Contact sensitive T 1/2 )

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16
Q

Compartments

A
  • Reduction in total body water is due to a gradual decline in ECF.
  • Increased Vd for water soluble drugs

– NMBDs distribute rapidly to the ECF but into cells more slowly.

– Initial dose is higher in neonates and infants.

17
Q

Protein Binding

A

• Degree of protein binding is less in the pre-term and term infants than in older children and adults.

– Lower concentrations of total body proteins and albumin

– Many drugs that are highly protein bound in adults have less of an affinity for protein in neonates

– Bilirubin can displace protein bound drugs and vice versa

– Affects weakly bound drugs more than highly bound

18
Q

Implications of lower protein binding in infants than in children/adults

A

– Lower concentrations of total body proteins and albumin

– Many drugs that are highly protein bound in adults have less of an affinity for protein in neonates

– Bilirubin can displace protein bound drugs and vice versa

– Affects weakly bound drugs more than highly bound

– What does this mean for anesthetic drugs?

• Lower protein binding means more free medication and a greater pharmacological effect for drugs that are highly protein bound

– What are the implication for anesthesia?

  • Albumin binds Benzodiazepines, Barbiturates, and ASA
  • α 1 AAG binds Amide local anesthetics, α-blockers, opioids, NMBs
19
Q

Drug Metabolism

A
  • Majority of drug metabolism happens in the liver, GI tract, gastric mucosa, and lungs
  • Neonates have

– decreased Hepatic BF

– immature hepatic enzymes

—decreased biotransformation

– decreased GFR &

– decreased renal tubular fxn

– Lipid soluble compounds are converted to more water- soluble compounds.

• Water soluble drugs may be excreted unchanged in the kidneys.

20
Q

What are drug metabolism implications for peds?

A

• Drug doses need to be adjusted accordingly and should be reduced until liver enzymes and renal function approaches adult levels.

– GFR ~ 3 months

– Tubular fxn ~ 8-12 months

21
Q

Drugs w Prolonged t1/2 at Birth

A

– Bupivacaine-25hrs

– Meperidine-22hrs

  • Diazepam-100hrs
  • Phenytoin-21hrs
22
Q

Hepatic Metabolism - Maturation

A
  • Hepatic blood flow also increases as infants mature.
  • Phase I metabolism (oxidation, reduction, hydrolysis)
  • The cytochrome P450 enzyme system is also immature in the neonate.

– Ondansetron, acetaminophen, fentanyl, ibuprofen, codeine

– Immature system decreases the formation of some toxic metabolites, like those with acetaminophen.

• Phase II metabolism processes are immature in neonates and mature within the first year of life.

– Issues with conjugation (bilirubin)

– Beware acetaminophen, sulfonamides, chloramphenicol

23
Q

Extrahepatic Elimination Implications

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 in adults (2.1 L/hr/kg) meaning what? keep remi infusions running when transporting pts!!!
24
Q

What is the implication of decreased plasma pseudocholinesterases in neonates?

A
  • ester LA may have a prolonged effect!
  • decrease doses
  • avoid sux for undiagnosed DMD
25
Q

Renal Elimination

A
  • Drug are excreted by either glomerular filtration or tubular excretion.
  • GFR is ≈ 30% that of adults at birth in term neonates and is 90% at one year.
26
Q

Decreased Renal Clearance

A
  • Drugs such as aminogylcoside antibiotics (micin’s and some “mycins”) that are excreted primarily through glomerular filtration or tubular secretion have prolonged elimination half-life.
  • Whenever administering a drug to a preterm or term infant, one must consider the contribution of renal function in the termination of its action.
27
Q

Developmental Pharmacodynamics: Opioid Receptors

A

– Not fully developed in the newborn rat and mature

through adulthood.

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

28
Q

Developmental Pharmacodynamics: Nicotinic Receptors

A

– Neonates have an increased sensitivity to the effects of neuromuscular blocking drugs (NMBs).

– Unknown why, but there is a three fold reduction in the release of Ach from the infant rat phrenic nerve

29
Q

Other Pediatric Issues Impacting Anesthesia

A

• Reduced FRC and O 2 reserves

– Reduced lung compliance d/t fewer & smaller alveoli.

– Compliant chest wall—collapses easily

  • May have profound Bradycardia and asystole with 1 st dose of Succinylcholine if not given atropine pretreatment.
  • Fluid management more critical
30
Q

Inhalation Agent Issues

A
  • decreased alveolar ventilation relative to adults
  • decreased FRC relative to adults AND decreased oxygen consumption
  • Large VRG
  • MAC is higher than adults
  • B/P is sensitive to CV effects d/t less well developed compensatory mechanisms

– Vasoconstriction; tachycardia

– Very sensitive to myocardial depression

31
Q

GABA

A

– At birth the cerebellum only contains 1/3 of the number of GABAA receptors found in the adult.

– Changes in receptor binding occur during postnatal development.

– The GABAA receptor complex becomes more prevalent from birth to 2 years and then decrease to 50% of peak values by 17 years.

– This is consistent with age related MAC changes and higher doses of oral midazolam.

less GABA receptors = less anesthetic

32
Q

Propofol

A
  • Larger Vd—why? What effect on induction?
  • Shorter T 1/2 E—why?
  • This does not really effect a single induction dose but does increase recovery rate from infusion
  • Induction dose 2-3mg/kg vs. 1.5-2.5mg/kg adults
  • Infusion rates 250 mcg/kg/min with rapid emergence
  • Remember Propofol infusion syndrome

– Rhabdo; Metabolic acidosis; hemodynamic instability; hepatomagaly; multiorgan system failure

33
Q

ED95 of NMBs in Peds Table

A
34
Q

Dosing Calculations

A

Anesthesia Pharm Exam 3 (6 decks)

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