Peds Pharm: Lecture 1

Front 1

What is meant by gestational age?

Back 1

time from conception to the date of birth

Front 2

What is the definition of postnatal age?

Back 2

from birth to the present time

Front 3

What age is being discussed if the range is from conception to the present time?

Back 3

postconceptional age

Front 4

If a child is called premature, what age are they?

Back 4

<37 weeks

Front 5

For a child to be full term, what must their gestational age be?

Back 5

>37 weeks

Front 6

What is the age range of the neonate?

Back 6

postnatal age 1 day to 1 month

Front 7

what is the age range for an infant?

Back 7

1 to 12 months

Front 8

To be considered a "child", what is the age range?

Back 8

1 year-12 years

Front 9

what is the proper age group name for children 12-18 years of age?

Back 9

pubescent or adolecent

Front 10

To be considered an adult, a child must be ___ years old.

Back 10

18

Front 11

Define pharmacokinetics.

Back 11

the study of the bodily absorption, distribution, metabolism and excretion of drugs

Front 12

Other than ADME, what are the 6 major topics to consider for pharmacokinetics?

Back 12

1. Volume of distribution
2. half-life
3. elimination constant
4. clearance
5 linear pharmacokinetics
6. non-linear pharmacokinetics

Front 13

What is the volume of distribution?

Back 13

hypothetical volume that is the proportionality constant that relate3s amount of drug in the body to the serum concentration.

Front 14

Hos is Vd expressed?

Back 14

Liters or Liter/kg

Front 15

What is Vd useful for?

Back 15

calculating the loading dose
LD=Vd*C

Front 16

Which drug is the prime example of fat soluble?

Back 16

vancomycin

Front 17

Define half-life.

Back 17

Elimination half-life is the time required for serum concentration to decrease by 1/2 after absorption and distribution phase

Front 18

T of F: the half life can be calculated right away after being given to a patient?

Back 18

FALSE: it is calculated after the absorption and distribution phase have been completed

Front 19

How is half-life expressed?

Back 19

hours or minutes: sometimes days

Front 20

It takes __ to ___ half-lives to reach steady state.

Back 20

3-5

Front 21

What is the HALF-LIFE DEPENDENT on?

Back 21

Clearance and volume of distribution

Front 22

When the amount of drug coming into the patient is at a constant level to its elimination, the patient is said to be in __ __

Back 22

steady state

Front 23

The elimination rate constant is the ___

Back 23

fraction of the drug in the body eliminated over time

Front 24

The ___ represents the volume of plasma (or blood) from which drug is removed in a given time period

Back 24

clearance

Front 25

the pharmacokinetic value expressed as volume/time is the __ rate

Back 25

clearance

Front 26

ToF: clearance is a model dependent parameter and used to estimate average steady state concentrations and adjust maintenance dose.

Back 26

FALSE: independent!!

Front 27

If the serum concentration of a drug changes proportionally with an increase in dose, this drug has ___ pharmacokinetics.

Back 27

linear

Front 28

non-linear pharmacokinetics describes the situation where as the dose given increases, the plasma concentration increases ____ to the dose.

Back 28

disproportionally

Front 29

what is the prime example of non-linear drug?

Back 29

phenytoin

Front 30

What is the other name for non-linear pharmacokinetics?

Back 30

Michaelis-Menten

Front 31

___ is the study of the action of a drug in the body over a period of time, including the processes of of absorption, distribution, localization in the tissues, ____, and excretion

Back 31

pharmacodynamics, biotrasnformation

Front 32

Define Emax?

Back 32

maximum response of the system to the drug

Front 33

Describe EC50.

Back 33

the concentration of drug that produces a response 1/2 of the maximum

-the dose at which 50% of individuals exhibit the specified effect

Front 34

What is effiay?

Back 34

the maximum effect (Emax) of a drug

Front 35

Describe potency

Back 35

a comparative measure referring to the different doses of 2 drugs needed to produce the same effect

Front 36

give an example of potency issues.

Back 36

Corticosteroids: prednisone and dexamthasone are not the same mg for the same dose of drug

Front 37

List the physiologic differences of neonates to older children that must be considered when administering ORALLY absorbed drugs

Back 37

Neonates have...
1. decreased acid secretion; increased gastric pH
2. Prolonged gastric emptying
3. reduced bile acids and pancreatic enzymes
4. reduced bilirubin excretion (unconjugated)
5. immature or altered permeability of intestinal mucosa

Front 38

What pH are neonates born with? when and how does it change?

Back 38

Born with gastric pH of 6-8. It decreases to 1-3 within 24 hours and then increases.

Front 39

ToF premature infants have lower gastric pH?

Back 39

FALSE: higher

Front 40

Which 2 drugs have difficulty with absorption at high pH?

Back 40

penicillin and ampicillin

Front 41

If a neonate is given an oral drug that has a target tissue in the small intestine, why might the drug take longer to have an effect?

Back 41

Neonates and infants have delayed gastric emptying so the drug will take longer to reach the small intestine

Front 42

Due to the redeuced ability for bilirubin excretion, which 2 drugs are discouraged in the first 30 days of life?

Back 42

cephtriaxone and sulfonamides

Front 43

higher stomach pH (decreases/increases) absorption of acid-labile drugs in premature infants?

Back 43

INCREASES

Front 44

Give 2 reasons in neonates that would cause a decrease in absorption of lipid soluble drugs.

Back 44

1. decrease pancreatic enzyme
2. decrease in biliary activity

Front 45

ToF: IM is considered a consistent absorption location?

Back 45

FALSE: erratic route

Front 46

What are the patient characteristics that determine the rate and extent of absorption of a drug administered IM?

Back 46

1. Low blood flow to injection site
2. decreased muscle mass
3. decreased quantity of adipose tissue
4. low muscle activity (insufficient contractions in preemies)

Front 47

Which 2 drugs should never be given IM?

Back 47

phenytoin and diazepam

Front 48

Why are IM drugs most disliked?

Back 48

Pain and tissue irritation

Front 49

MUSCLE absorption is ___ and ___ in the young infant and Premature infants.

Back 49

unpredictable and erratic

Front 50

ToF: rectal absorption is increased?

Back 50

FALSE decreased

Front 51

Describe rectal absorption.

Back 51

-typically erratic and incoplete
-reduced bioavailability

Front 52

which groups of children should NEVER receive rectal meds?

Back 52

Those with low platelets and cancer patients

Front 53

Describe the 3 reasons why percutaneous drugs are absorbed more in babies.

Back 53

1. They have a thinner stratum corneum
2. higher water content in dermis
3. Greater body surface area to the body weight ratio

Front 54

Which types of percutaneous drugs are greatly absorbed in infants and should be monitored?

Back 54

topical steroids

Front 55

Percutaneous absorption ___ in newborns

Back 55

INCREASES

Front 56

WHat are 3 examples of percutaneous drugs/solutions that are increases in absorption in newborns?

Back 56

1. hydrocortisone
2. salicylic acid
3. rubbing alcohol

Front 57

What are the 3 factor effect drug distribution?

Back 57

1. concentration gradient
2. blood flow
3. molecular weight

Front 58

which barrier in the body is the most difficult to get drugs into?

Back 58

Blood brain barrier

Front 59

When ___ is used to treat meningitis, its large size must be considered when dosing to make it effect in its target organ the ___.

Back 59

Vancomycin; CNS

Front 60

What is meant by the drug distribution?

Back 60

Where it starts and where it ends

Front 61

Drugs bound to plasma proteins are ___ ___

Back 61

pharmacologically inert

Front 62

What is the protein in the body that most greatly effect the distribution of protein bound drugs?

Back 62

albumin

Front 63

ToF: only unbound drugs exert phamacologic effects?

Back 63

TRUE

Front 64

ToF: displacement of drugs bound to proteins may alter pharmacologic and toxic effects of the drug?

Back 64

TRUE

Front 65

What is an example of drug displacement in babies that can cause toxic effects?

Back 65

sulfonamides/cephs that cause displacement of bilirubin and jaundice

Front 66

What is the blood brain barrier?

Back 66

cerebral endothelial cells that have tight junctions between them and is a lIpid barrier without pores

Front 67

the Blood brain barrier is a ___ barrier without ___

Back 67

lipid; pores

Front 68

Which 2 groups of drugs are unable to cross the BBB?

Back 68

low lipid solubility and ionized forms of drugs

Front 69

What is the characteristics of drugs that CAN cross the BBB

Back 69

highly lipid soluble

Front 70

The total body water composition of neonates and infants is ___ proportional to age

Back 70

inversely

Front 71

List the age and water concentrations of neonates by gestational age with lowest concentration of water at the left.

Back 71

neonates (78%) < premature infant (85%) < fetus (94%)

Front 72

What are common hydrophilic drugs

Back 72

aminoglycosides

Front 73

ToF: in order for a water soluble drug to reach its target organ, the dose will have to be higher

Back 73

True, because infants have a higher volume of distribution of water and thus more drug is needed to fill the water space first

Front 74

ToF: neonates have a high body fat level that increases with age

Back 74

FALSE: low body fat level

Front 75

Plasma protein binding is generally (decreased/increased) in young infants.WHat does this cause?

Back 75

decreased; have an increase in free drug and thus increased effects or toxicity of the drug

Front 76

Describe how kernicterus can occur in infants.

Back 76

Drugs that are highly protein bound may potentially displace bilirubin from protein binding sites

Front 77

which drugs have decreased binding affinity with fetal albumin?

Back 77

acidic drugs: phenytoin

Front 78

ToF: neonates and infants by nature have fewer plasma proteins

Back 78

True

Front 79

What 3 things compete for binding sites on albumin?

Back 79

bilirubin, free fatty acids and drugs (sulfisoxazole)

Front 80

Which drug has greater TISSUE binding in infants and children?

Back 80

digoxin= less free drug available

Front 81

What enzymes in the liver is most notorious for metabolism?

Back 81

CYP P450

Front 82

What are the characteristics of Phase I metabolism?

Back 82

1. Mixed-function oxidase enzyme system
2. increase hydrophilicity of drugs and thus facilitate elimination of durgs by the kidney
3. Factors regulating mixed-function oxidase

Front 83

What must be done to get a drug excreted by the kidneys?

Back 83

Must be made water soluble: an OH group is added

Front 84

ToF: drugs that have active metabolites do not cause toxicity?

Back 84

FALSE: they do when the metabolites are active

Front 85

What are the PHase II reactions?

Back 85

1. Conjugation reactions
2. Enzymes which catalyze the formation of conjugates with the oxidized drug or the parent compound

Front 86

What is a prodrug?

Back 86

a drug that is inactive until a portion is cleaved to make it active

Front 87

ToF: Phase I reactions are increased in neonates?

Back 87

FALSE!: must give the drug less often because the kidneys are not mature enough to excrete the drugs

Front 88

How is methylation different in the neonate? is this phase I or II?

Back 88

it is increased. Phase II

Front 89

In the phase II reaction of glucuronidation, the neonate has a ___ reaction.

Back 89

decreased

Front 90

Which form of clearance is known to increase rapidly in the first 3 months of life?

Back 90

hepatic

Front 91

The hepatic clearance of preschoolers significantly ___ adult clearance rate

Back 91

exceed

Front 92

The hepatic clearance level in the adolescent years (increases/decreases) from its rate during the preschool years?

Back 92

decreases: becomes more like adult rate

Front 93

Which drug has been found to have altered clearance rate in neonates? What is the metabolite formed from the breakdown of this drug?

Back 93

Theophylline--caffeine

Front 94

What is the major route by which drugs leave the body?

Back 94

renal excretion

Front 95

What is the rate of renal excretion dependent on?

Back 95

1. Pharmacologic properties of the drug
2. concentration of drug in blood
3. rate of urine production

Front 96

What are the characteristics of biliary excretion?

Back 96

1. drugs present in the liver may be secreted along with bile into the duodenum
2. drugs may also be reabsorbed! babies have short guts and can cause toxicity

Front 97

why do neonates and infants have alterations in renal excretion?

Back 97

1. they have decreased GFR and tubular secretion at birth, especially during the first week of life
2. at 6 months of age, they reach relative adult function

Front 98

at what age do children's renal excretion function match that of adults?

Back 98

6 months

Front 99

First order kinetics are (linear or non-linear)

Back 99

linear

Front 100

ToF: first order kinetics describe drugs that are saturable and capacity limited?

Back 100

FALSE: non-saturable and capacity limited

Front 101

In first order kinetics, as the drug serum concentration rises, more drug is available to the ___ ___

Back 101

eliminating organ

Front 102

Describe clearance in first order kinetics

Back 102

1. a measure of efficiency of drug elimination
2. defined as the volume of plasma that is totally cleared of drug per unit time
3. constant and independent of drug concentration
4. Principle determinant of average steady-state drug concentration during a dosing interval at a constant dose rate

Front 103

What is zero order kinetics

Back 103

1. a process that occurs at a constant rate, independent of serum concentration
2. non-linear kinetic

Front 104

list the 3 characteristics of dose (concentration) dependent kinetics

Back 104

1. the change in certain pharmcokinetic paraemeters (which are usually constant) as a function of administered dose or serum concentration
2. physiologic processes that influence dose dependent parameters are generally capacity-limited

Front 105

What is meant by capacity limited?

Back 105

characteristic of pharmacokinetic or physiologic processes that involves interaction of drug molecules with a limited number of sites

Front 106

Which drug is known to react with multiple drugs due to the cyp 450 pathway?

Back 106

coumadin

Front 107

the CYP P 450 are ___ containing membrane proteins located in the __ ___ __ of the liver, kidneys, skin, ___ and lungs

Back 107

Heme; smooth endoplasmic reticulum; GI tract

Front 108

What are the CYP P450 isoenzymes responsible for?

Back 108

biotransformations of drugs via oxidation

Front 109

Which drugs are known to act on the CYP 3A4 pathway?

Back 109

azoles

Front 110

What is a substrate?

Back 110

the substance that is acted upon by an enzyme

Front 111

When a drug stimulates the synthesis of more enzyme protein enhancing the enzyme's metabolizing capacity the drug is thought to be an ___

Back 111

inducer

Front 112

Why is it difficult to determine the time course of enzyme induction?

Back 112

1. drug half-lives and enzyme turn over

Front 113

What are inhibitors?

Back 113

drugs that compete with another drug for the enzyme binding site

Front 114

when does inhibition usually occur?

Back 114

begins with the fist dose of the inhibitor and onset and offset of inhibition correlate with the half-lives of the drugs involved

Front 115

ToF: if a drug is an inducer, a smaller dose is needed because the drug has a greater capacity to bring about physiologic effect?

Back 115

FALSE! it needs a higher dose, because the drug is metabolized faster by the induced enzyme than the time needed for the drug to act

Front 116

what is the one drug that is considered an auto-inducer?

Back 116

carbamazapine

Front 117

What are the 4 genetic factors relating to the patient that can effect the occurrence of drug interactions?

Back 117

1. poor metabolizers v extensive metabolizers
2. age
3. underlying liver disease
4. nutrition

Front 118

which juice is stronger discouraged for patients on medication?

Back 118

grapefruit

Front 119

What was the example of a drug that had the possibility of acting on poor metabolizers and extensive metabolizers?

Back 119

Tylenol # 3 given to mothers and then excreted in breastmilk. the baby could not metabolize the metabolite (morphine) and thus became toxic = respiratory distress and death

Front 120

ToF acute alcoholism can cause the liver enzymes to act as inducers?

Back 120

TRUE. chronic can make them inhibitors

Front 121

What are the consequences of increased exposure to toxic drugs in children?

Back 121

1. impedes linear growth: steroids
2. acute dystonic reactions
3. respiratory depression from opioid drugs
4. paradoxical hyperactivity
5. effects on learning abilities: topomax
6. kernicterus

Front 122

which antibiotic was linked to gray baby syndrome?

Back 122

chloramphenicol

Front 123

what is kernicterus?

Back 123

bilirubin encephalopathy

Front 124

which drug if given to children under 8 years old can cause permanent teeth staining>?

Back 124

tetracyline

Front 125

What adverse reaction has been found associated with floroquinolones?

Back 125

joint arthropathy in beagles; permanent lesions of the cartilage

Front 126

what are the 3 drugs associated with acute dystonic reactions or seizures?

Back 126

Metoclopramide
prochlorperazine
haloperidol

Front 127

Which drug has caused acute cardiac arrest in infants < 1year

Back 127

verapamil

Front 128

What has Dextromethorphan and codeine in infants <1 years old often lead to?

Back 128

respiratory depression

Front 129

Name the preservative responsible for gasping baby syndrome

Back 129

Benzyl alcohol

Front 130

A toxic level of popylene glycol can lead to ___

Back 130

hyperosmolarity

Front 131

Name the drug that forced the FDA to make safety regulations on drugs given during pregnancy?

Back 131

Thalidomide

Front 132

Which 2 forms of drugs have a DECREASED risk of adverse effects in infants and neonates and why?

Back 132

1. Aminoglycosides: reduced intracellular resulting in multiple congenital fetal abnormalities
2. Acetaminophen overdose: mild liver toxicity (children can tolerate an overdose more than adults)

Front 133

What are the 3 methods for determining pediatric dosing for medications?

Back 133

1. weights
2. BSA
3. age

Front 134

ToF: as long as a child's creatinine clearance stays within normal limits an increase as high as doubling is ok.

Back 134

FALSE if the clearance doubles then there is usually a problem

Front 135

What is the Traub-Johnson Equation for creatinine clearance?

Back 135

CLcr=0.48 x H/Scr

H=height in cm
Scr = serum creatinine concentration in mg/dL

Front 136

What is the Schwartz Equation for creatinine clearance?

Back 136

CLcr = K x L/Scr

K = constant of proportionality that is age specific
L = Length (height) in cm
Scr = serum creatinine concentration in mg/dL

Front 137

What are the 5 factors to consider for overall medication administration?

Back 137

• Method of drug infusion influences peak concentrations and time to attain peaks
• Flow rate and injection site may delay delivery of medications
• Drugs with lower specific gravity than maintenance fluid will layer at top of tubing
• Injection into filter chamber or Y-site with dead space delays delivery
• Infusion systems vary from institution to institution

Front 138

If a drug is considered Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters), what is its grading?

Back 138

Category A

Front 139

What pregnancy grading is most often seen for drugs? Why?

Back 139

B or C: because the US does not do drug testing on pregnant women

Front 140

What are 3 classes of drugs that are category X?

Back 140

Thalidomides, statins and faromax

Front 141

What are the indications for therapeutic drug monitoring?

Back 141

• Inadequate response
• Higher than standard dose required
• Serious or persistent side effects
• Suspected toxicity
• Suspected noncompliance
• Suspected drug-drug interactions
• New preparation, changing brands
• Other illnesses, e.g. hepatic/renal problems, inflammatory diseases

Front 142

ToF: all drugs have target concentrations?

Back 142

False: most have very wide levels of concentrations that can work

Front 143

What are some example of drugs that have benefited from therapeutic drug monitoring?

Back 143

• Aminoglycosides
• Vancomycin
• Antiepileptic drugs
• Immunosuppressants
• Aminophylline
• Anticoagulants