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Neonatal Pharmacology > Basic Priniciples > Flashcards

Basic Priniciples Flashcards

1
Q

What is Pharmacokinetcis?

A

What the BODY does to the DRUG
(ADME=absorption, distribution, metabolism, elimination)
*remember BD (body-drug)-like BD syringes.

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2
Q

What is Pharmacodynamics?

A

What the DRUG does to the BODY

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3
Q

What is Absorption?

A

Translocation of drugs from the site of administration into the circulation

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4
Q

In Utero exposure to Medications does what?

A

Increases risk of adverse effects

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5
Q

What adverse reaction can Sulfonamides and Ceftriaxone cause?

A

Kernicterus

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6
Q

What adverse reaction can Chloramphenicol cause?

Chloramphenicaol is a wide-spectrum antimicrobial bacteriostatic agent

A

Grey baby syndrome

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7
Q

What additive used in many medications can cause gasping syndrome?

Give an example of a med w/this additive

A

Benzyl Alcohol

Ativan

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8
Q

Neonates have complex sources of Pharmacokinetic & Pharmacodynamic variability including?

A

Age
Size
Growth
Organ Function

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9
Q

Which is studied more in neonates, Pharmacokinetics or Pharmacodynamics?

A

Pharmacokinetics

Pharmacodynamic is not studied as much, harder to predict

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10
Q

What are the Routes of Absorption?

A 
IV (IV)
GI (PO, PT)
Rectal (PR)
Intramuscular (IM)
Percutaneous
Intraosseous (IO)
Intrapulmonary/Inhaled
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11
Q

What is Bioavailability?

A

How much drug enters the Systemic Circulation

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12
Q

For IV medications, if F=1, what does this mean?

A

It is 100% bioavailable

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13
Q

When is it important to consider the Bioavailability of a drug? (2 times)

A
  1. For ANY non-IV medication

2. When converting IV to PO (not all is absorbed, goes trhough many layers of metabolism 1st)

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14
Q

What 2 things affect Absorption?

A
  1. Physiochemical Factors

2. Patient Factors

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15
Q

Name 4 Physiochemical Factors that affect Absorption.

A
  1. Formulation of the Med
  2. Molecular Wt
  3. pKa (stability of the drug at different pH levels)
  4. Lipid Solubility
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16
Q

Name the 7 Patient Factors that affect Absorption.

A
  1. 1st Pass Metabolism
  2. Gastric Emptying Time
  3. Gastric pH
  4. Surface Area
  5. Size of Bile Salt Pool
  6. Bacterial Colonization
  7. Underlying Dz’s
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17
Q

Name the 7 Patient Factors that affect Absorption.

A
  1. 1st Pass Metabolism
  2. Gastric Emptying Time
  3. Gastric pH
  4. Surface Area
  5. Size of Bile Salt Pool
  6. Bacterial Colonization
  7. Underlying Dz’s
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18
Q

Name the 3 routes of Oral Administration

A
  1. PO
  2. Feeding tube (GT/NG/OG)
  3. Sublingual
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19
Q

What is important to know for Oral Admin. when a medication is given through a feeding tube?

Why?

A

Where the tube is located

  • Site may affect absorption (stomach vs. trans-pyloric)
  • Small-bore tubes & difficulty delivering some suspensions (crushed meds mixed-can get clogged)
  • Med may be incompatible w/tubing
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20
Q

What Oral Admin route is difficult in pediatric pts?

A

Sublingual :-)

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21
Q

Gastric emptying time is _________ in infants.

A

Erratic

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22
Q

Gastric emptying time is delayed/erratic until ___-___ months of life.

It is Faster/Slower in older infants/children.

It Increases/Decreases to adult timing around 3 y/o.

A

6-8 months

Faster

Decreases

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23
Q

Gastric emptying contributes to what symptom?

A

Reflux

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24
Q

Most drugs absorbed in the Small intestine rely on _____ _______ rate for absorption

A

Gastric Emptying rate

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25
Q

What are the 2 things that affect Gastric Motility?

A
  1. Gastric Emptying time (erratic/delayed)

2. Intestinal Motor activity Matures over time

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26
Q

Immature intestinal motor activity leads to?

A

Uncoordinated Peristalsis

Longer Transit Times (8-96 hrs Infant vs. 4-12 hrs Adult)

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27
Q

When is Intestinal Motor Activity Mature?

A

4 Months

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28
Q

When is Intestinal Motor Activity Mature?

A

4 Months

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29
Q

The Gastric pH in infants is ________.

Meaning Increased/Decreased Acid production.

A

Increased

Decreased

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30
Q

What is the Gastric pH of a Full Term infant?

Drops to ____ at 24 hrs.

A

pH 6-8 at birth

pH 2-3 at 24 hrs

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31
Q

Is the Gastric pH of a Preterm infant increased/decreased vs Term?
Due to what?

A

Increased (elevated)

Immature Acid Secretion

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32
Q

The pH of a Preterm infant takes Longer/Shorter to normalize vs. term?

A

Longer.

No specific age, is case by case.

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33
Q

Gastric acid production reaches Adult levels at ____ age.

A

2 y/o

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34
Q

Are H2 blockers effective in Preemies?

Why or why not?

A

No.

They have increased pH (which is the MOA of an H2 blocker-so doesn’t help much)

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35
Q

What are 3 reasons Gastric pH matters?

A
  1. Affects stability and degree of drug ionization.
  2. Increased absorption of acid-labile drugs.
  3. Decreased absorption of weak acids.
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36
Q

What are 3 reasons Gastric pH matters?

A
  1. Affects stability and degree of drug ionization.
  2. Increased absorption of acid-labile drugs.
  3. Decreased absorption of weak acids.
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37
Q

Enzymes and Efflux pumps, Oral Absorption is dependent on what?

A

Pancreatic and Biliary FunctionThe rate of enzyme synte

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38
Q

The rate of Enzyme synthesis and activity is Increased/Reduced?

A

Reduced

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39
Q

Enzymes and Efflux pumps, Oral Absorption is dependent on what?

A

Pancreatic and Biliary Function

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40
Q

What 2 enzymes important for PO absorption are 20% of adult levels?

Leading to what?

A

Amylase and Lypase

Leading to Delayed Pancreatic Function

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41
Q

Reduced Bile Acid Pool results in what?

A
  1. Decreased rate of synthesis and pool size

2. Decreased absorption of lipophilic drugs-(don’t have the bile salts to absorb them)

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42
Q

Absorption is dependent on _ ________ in the intestinal wall.

It takes ____ to develop after birth

A

p-glycoproteins

Time

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43
Q

P-glycoproteins do what?

A

Increase drug Distribution across membranes.

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44
Q

What 4 things affect Immature Gut Flora?

A
  1. Age
  2. Vaginal Delivery and Br. Fdg (increase gut flora)
  3. Feeding type
  4. Drug Therapy (i.e. acid suppression therapy)
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45
Q

Name an example of a medication dependent on gut flora for absorption.

A

Digoxin

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46
Q

What medication/s affect gut flora–>increased risk of NEC?

A

H2 Blockers/PPI’s

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47
Q

What medication/s affect gut flora–>increased risk of NEC?

A

H2 Blockers/PPI’s

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48
Q

Describe First Pass Metabolism

A

Drugs are absorbed through the Gut–>Hepatic Vein–>Liver

All before distribution to the rest of the Body.

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49
Q

First pass metabolism is Increased/Decreased in Infants vs. Adults?

Why?

A

Decreased

Due to Hepatic Immaturity

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50
Q

T/F: Some meds become Activated by the Liver and some become Inactivated by the liver?

A

True, so you need to know type of drug and how it is metabolized

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51
Q

Rectal Absorption is Increased/Decreased in neonates/young infants?

A

Increased (enhanced)

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52
Q

Where does Rectal Absorption take place?

Is absorption static?

A

Hemorrhoidal veins

No, may be erratic

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53
Q

True/False: Rectal absorption bypasses 1st-pass metabolism?

A

True (of the lower rectum)

Lower rectum: absorbed directly into circulatory system

54
Q

Does Upper rectal absorption by-pass 1st pass metabolism?

A

No, it is absorbed into the portal vein (has 1st pass)

55
Q

When is Rectal route an option?

A

When PO is not a good option and IV access is not available.

*emesis, seizures, aspiration, NPO

56
Q

What are 2 problems with Rectal route?

A
  1. High risk of expulsion of the med before absorption :-)

2. Doseage forms not commercially available for infants and small children (cut suppositories may not be accurate)

57
Q

IM absorption is dependent on what?

A

Blood flow to injection site
Muscle Mass
Muscle Activity

58
Q

Why is IM Absorption unpredictable in neonates/infants?

A

Less in neonates d/t:
Poor Muscle Perfusion
Decreased Muscle mass
Insufficient Muscle Contractions

59
Q

Is IM route recommended if an IV route is available?

A

No. IV is preferred

*exceptions: Immunizations and Vit K (Phytonadione)

60
Q

Why is Absorption substantially increased in NB’s?

A

Skin Hydration-(Increased perfusion and Hydration of Epidermis)

Thickness-(Thinner Stratum Corneum)

Total Surface Area-(Ratio of Total BSA: Body Mass is much higher than Adults)

61
Q

Infants have Increased/Decreased exposure to topical medications?

A

Increased

62
Q

Can topical medications lead to toxicity?

A

Yes

63
Q

Give an example of a topical med that can lead to toxicity.

A

Steroids.

NO occlusive dressings.

64
Q

What are the 2 methods of Intrapulmonary Absorption?

A
  1. Inhalation

2. Nasal delivery

65
Q

Intrapulmonary medications have predominantly what effect?

A

Local

66
Q

Can systemic exposure occur w/Intrapulonary absorption?

A

Yes

i.e. Tobramycin nebs (TOBI), Inhaled Corticosteroids

67
Q

Intrapulmonary Absorption is a Difficult/Easy delivery mechanism in small children?

A

Difficult–inhaled meds can adhere to tubing.

68
Q

True/False: Developmental changes and altered lung capacity alters the pattern of drug deposition?

A

True

69
Q

What is IO admin?

A

Administration of drugs/fluids into the bone marrow

70
Q

IO is an alternative to what?

A

IM/IV route

71
Q

Up to 5 y/o, the bone marrow is still very _______.

A

Vascular

72
Q

When is IO done?

A

Occasionally NICU, usually transport setting

73
Q

Distribution is determined by what 4 things?

A
  1. Body composition
  2. Hydrophylicity & Lipophylicity of meds
  3. Protein Binding
  4. Pathological Conditions
74
Q

What is meant by Body Composition?

A

Volume of Distribution

Total Body Water

75
Q

What is Volume of Distribution?

A

The volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration.

76
Q

Volume of Distribution depends on what?

A

The baby’s Fat vs. H2O content

77
Q

What is the Vd formula?

A

Vd= Xo (total drug in body)/Co (concentration in plasma)

*expressed as a unit of Volume

78
Q

What is the approximate % total body water in a preterm infant?

A

80% water

79
Q

The TBW to Fat ratio is Increased or Decreased?

A

Increased

more TBW to Fat

80
Q

The Body Composition of an infant leads to Increased volume of distribution for Hydorphilic OR Lipophilic drugs?

Why?

A

Hydrophilic

It takes larger loading doses to “Fill the Tank” to reach steady state

81
Q

Name 3 drugs discussed in lecture that are hydrophilic and need larger loads.

A

Gentamicin, Linezolid, Phenobarbital

82
Q

Adipose tissue in an infant has Higher/Lesser Water content (than other age groups)?

A

Higher water content in their Adipose tissue

83
Q

What happens to Lipophilic drugs in babies?

A

They don’t stay in the body-get excreted.

They have lower levels of lipophilic drugs.

84
Q

What is the Fat % of Preterm (<2kg)?
Full term (3.5kg)?
& 1 yr (10kg)?

A

6%

  1. 4%
  2. 4%
85
Q

What is the Water % of Preterm (<2kg)?
Full term (3.5kg)?
& 1 yr (10kg)?

A

80%
70%
61.2%

86
Q

As a baby develops, the dose will need to ______ with the Volume of Distribution change

A

Change.

87
Q

What does Protein binding affect?

A

Volume of Distribution
Half-Life
Clearance of Medications

88
Q

Neonates and young children have _______ quantities of plasma proteins and _______ affinity for binding medications

A

Decreased plasma proteins

Reduced affinity

89
Q

Name 2 main proteins in the body that carry drugs?

A

Alpha-1 acid glycoprotein

Albumin

90
Q

If a drug binds to a protein, it IS or IS NOT available to the body

A

Is Not

91
Q

What do we worry about in regards to protein binding?

A

The Free-Circulating amount of drug

Monitor “free” levels

92
Q

When the proteins bind with a drug, how are they released?

What is the unbound drug called?

A

A little at a time.

Free Fraction–free to distribute into tissues–>Increasing Vd

93
Q

T/F: Some drugs displace bilirubin from binding sites on Albumin?

A

True

Sulfonamides (Bactrium) & Ceftriaxone (can use after 42 wks CGA-liver more developed)

94
Q

If drugs displace bilirubin from binding sites on Albumin, what can result?

A

Kernicterus

95
Q

Infants have More/Less Protein binding than Adults.

Thus, they have More/Less of the Active form of the drug.

A

Less Binding

More Active form

96
Q

What Pathological Conditions can alter drug Distribution?

A

Cardiac Output and Regional Blood Flow

shunting of blood from different organ systems

97
Q

What 2 conditions cause Decreased Vd?

A
  1. Cardiac Conditions

2. Malnutrition

98
Q

What can cause Increased Vd?

A

Surgery

i.e. they need increased fluids and meds

99
Q

Most drugs are metabolized by the?

A

Liver

100
Q

Drugs are metabolized by the Liver into what 3 things?

A
  1. Inactive drug
  2. Active metabolites (weaker form)
  3. Pro-drug to active drug
101
Q

What are the Phase 1 Reactions of Metabolism?

A

Oxidation
Hydrolysis
Hydroxylation
Reduction

102
Q

What are the Phase 2 Reactions of Metabolism?

A

Conjugation
Glucuronidation
Sulfation

103
Q

In Phase 1 Metabolism, the CYP450 System has _______ that metabolize drugs in the liver.

A

Enzymes

104
Q

In Phase 1 Metabolism in Neonates, the _______ _____ of enzymes is decreased.

A

Absolute Mass

105
Q

T/F: In Neonates, different enzymes mature at different rates.

A

True

106
Q

T/F: Drugs are metabolized by different enzymes.

A

True

107
Q

Glucuronidation doesn’t mature until ___ y/o.

A

3

108
Q

Reduced glucuronidation =

A

Reduced conversion to metabolites

109
Q

T/F: Infants have Sulfation at adult levels at birth?

A

True (it’s one of the main pathways of metabolism used by infants)

110
Q

T/F: Infants are more susceptible to toxicity from overdose?

Why?

A

False-they are less susceptible

D/T reduced glucuronidation–>reduced ability to make the toxic metabolite NAPQI

111
Q

What Phase 2 reaction is present in Infants but NOT adults?

Give a med example.

A

Methylation

Theophylline–>Methylation–>Caffeine

112
Q

Elimination of drugs is done mostly by the _____.

A

Kidneys

113
Q

The kidneys are _________ in structure and function at birth.

A

Immature

114
Q

Renal blood flow Increases/Decreases over the 1st year of life.

A

Increases

115
Q

As GFR increase, drug clearance _______.

A

Increases

116
Q

What is the best indicator of renal function?

A

GFR

117
Q

What 2 equations (names) can be used to indicate GFR/renal function?

A

Schwartz

Bedside Schwartz

118
Q

GFR increases from birth w/age but is dependent on what 2 things?

A
  1. Blood Flow

2. Protein Binding

119
Q

Serum Cr is a reflection of _______ _____ in the first few days of life?

A

Maternal Creatinine

120
Q

What value can change Renal elimination?

A

Cardiac Output
(Increased Cardiac blood flow = Increased Renal blood flow = increased filtration)
*also works in the opposite direction.

121
Q

Why do we need an increased dose with increased interval with a Neonate vs. Older child?

A

They need increased dosing to reach Therapeutic concentration, But need increased interval for Renal Clearance

122
Q

How does Cooling affect metabolism and clearance?

A

Slows metabolism and clearance (slowing renal elimination)

123
Q

A PDA will Increase/Decrease the Vd?

A

Increase Vd

124
Q

A PDA results in Increased/Decreased blood flow to the kidneys?

PDA can/cannot be Tx’d w/ NSAID’S

A

Decreased

Can

125
Q

What do indomethacin/Ibuprofen do?

A

Decrease Prostaglandins = Decreased Vasodilatin = Decreased Renal Blood Flow

126
Q

With Indo/Ibuprofen use, infant’s will have short-lived increase in what due to decrease in what?

A

Serum Cr due to decreased GFR

127
Q

Tubular secretion is about ____% of adult at birth.

It matures by _____ age.

A

20%

1 year

128
Q

Neonates have _____ nephron function

A

Immature

129
Q

Furosemide has a potential _______ Diuretic effect due to _________ of secretion into the intraluminal space (can’t get to the site of action).

Increased/Decreased doses/Kg needed.
Increased/Decreased Interval spacing needed.
Why?

A

Blunted effect
Immaturity

Increased
Increased
d/t decreased clearance or increased 1/2L

130
Q

Secretion and Reabsorption mature within ____ wks Postnatal Age

A

30 wks PNA

131
Q

Name 4 prinicples of Pharmacodynamics

A
  1. Relationship between the drug and the body
  2. Reflected in receptor binding and post binding affects
  3. Difference can alter drug efficacy and safety
  4. Data has not been elucidated for neonates.
132
Q

Give a drug example with varying Pharmacodynamics

A

Milrinone. See different effects in different babies. It’s receptor-based but we don’t know/can’t predict it yet.

Neonatal Pharmacology (17 decks)

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