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Pharmacology > Developmental Pharma > Flashcards

Developmental Pharma Flashcards

1
Q

What are the factors that affect drug absorption in children?

A

Blood flow at the site of administration
GIT function: Gastric acid secretion, Peristalsis, GI enzymes
Age after birth

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2
Q

What organs are vessel-rich therefore drugs can easily reach their receptors?

A

Brain
Kidney
Liver

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3
Q

What are the diff physiological conditions that reduce blood flow to the brain, liver, and kidneys?

A

CV shock
Vasoconstriction due to sympathomimetic agents
HF

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4
Q

What are the diff drugs that are affected by diminished peripheral perfusion at the IM route?

A

Cardiac glycosides
Aminoglycosides
Anticonvulsants

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5
Q

What route of admin has a greater skin to BSA ratio, approx 3x in adults?

A

Transdermal route

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6
Q

What drug agents when administred to children transdermally can cause dangerous AEs? What are these AEs?

A
  1. Hexachlorphene - bathing of infants -> neurotoxicity
  2. Povidone-iodine topical disinfectant -> neonatal thyroid dysf
  3. Hydrocortisone cream for diaper rash -> HPA axis suppression
  4. 4% Lidocaine -> Arrhythmias
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7
Q

What is the most useful and well-absorbed route of admin in children? Why?

A

Rectal route -> strong retal contractility in infants

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8
Q

What are the 4 important developmental alterations in pediatric clinical pharma?

A
  1. Diff in extravascular absorption rate & extent
  2. Altered body composition influences distribution
  3. Marked ontogeny of drug metabolizing enzymes
  4. Dynamic influence of devt on renal function
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9
Q

What are the 4 GIT factors that affect oral absorption?

A

GAstric pH
Gastric emptying time
Peristalsis
GI Enzymes

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10
Q

What are the 8 factors that affect extraoral absorption?

A

Barrier thickness
Regional blood flow
Temperature
Diffusional surface area
Hydration
Tissue binding sites
Local pH
Drug vehicle interaction

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11
Q

What oral drugs have a decreased oral absorption effect on neonates?

A

Acetaminophen
Phenobarbital
Phenytoin

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12
Q

What oral drugs have an increased oral absorption in neonates?

A

Ampicillin
Penicllin G

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13
Q

What oral drugs have a normal oral absorption in neonates?

A

Diazepam
Digoxin
Sulfonamides

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14
Q

What are the 5 factors that affect drug distribution in neonates/infants?

A

TBW
% fat content
Protein binding
Membrane permeability
Larger potential compartment
Larger potential compartment

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15
Q

What is the % TBW in neonates/infants?

A

% TBW
Neonates: 70-75%
Preterm: 85%
1 y/o: 6-65%

ECW: 40% body weight

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16
Q

WHat happens when neonates/infants have a larger TBW/ECW space?

A

There’s lower plasma concentration of the drug

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17
Q

What drugs have a greater distribution rate in neonates/infants?

A

Aminoglycosides (Amikacin)
Linezolid
Paracetamol

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18
Q

What drugs have a reducd capacity to accumulate in neonates/infants bcos they are lipid-soluble drugs?

A

Amphoteriicn
Benzodiazepines (Diazepam)
Digoxin
Amiodarone

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19
Q

What is the total body fat in preterm, full term, and 1 y/o?

A

Preterm: 1%
Full term: 10-15%
1 Y/o: 20-25%

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20
Q

At what age of infants can lipid-soluble drugs accumulate in small amts?

A

Premature infants (DEC fat content)

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21
Q

T/F Neonates & young infant have higher concentrations of most relevant plasma binding protein?

A

False
They have lower concentrations

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22
Q

What factors affect or influences the amount & type of circulating plasma proteins?

A

Drug disposition & drug action

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23
Q

T/F Protein binding is generally reduced in neonates?

A

True
THis leads to INC free/unbound levels of the drug

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24
Q

How come drug distribution in the CNS is hard for children?

A

Drug distribution to deep compartments is delayed & limited

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25
Q

How come infants are more susceptible to drug-induced neurotoxicity?

A

At this age, the brain is 10-12% of total body weight

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26
Q

what are the diff diseases that alter drug distribution in the brain?

A

Obesity
Protein malnutrition
PDA and Sepsis
Hypoalbuminemia
Environmental aspects
Binding characteristics
Meningitis
ECMO (Extracellular corporeal membrane oxygenation)

27
Q

What are the diff altered body composition influences distribution?

A
  1. Neonates w/ iNC TBW & ECW
  2. Neonates w/ DEC fat
  3. DEC protein-binding
  4. Competitive binding of bilirubin
  5. INC brain to body proportion
  6. Membrane permeability
28
Q

Why don’t we give Ceftriaxone to neonates?

A

Bcos this will displace binding of Bilirubin to Albumin —> INC level of free bilirubin —> goes to the brain —> Kernicterus

29
Q

What are maturational changes in hepatic biotranformation in the CYP system?

A
  1. CYP system is immature at birth
  2. CYP450 system
  3. HYP3A7
  4. CYP3A4/5
  5. Age from birth (not AOG)
30
Q

Are CYP2D6 poor metabolizers?

A

Yes

31
Q

What are the diff drug metab in neonates from adults?

A
  • slow clearance rates
  • prolonged elimination half-lives
  • DEC renal function —> DEC rate of elimination
32
Q

What drug can indice matureation of fetal hepatic enzymes when taken by a pregnantmother?

A

Phenobarbital

33
Q

At 12-36 mons (todderls), metab rate of drugs and elimination half-lives are?

A

Metab rate: exceed adult values
SHorter elimination half-lives than older children & adults

34
Q

What is the potentially lethal AE of a child’s exposure to Chloremphenicol?

A

Gray baby syndrome

35
Q

What is a dangerous AE of children if they take Valproate?

A

Hepatotoxicity

36
Q

What is a dangerous AE of Ifosfamide in children?

A

Renal tubular toxicity

37
Q

What happens if diseases/inflammation take effect on drug metab in children?

A

INC drug exposure, proinflam cytokines
Adverse drug rxns
DEC drug metab, CYP450

38
Q

Whta are the 3 processes responsible for elimination of drugs by the kidneys?

A

GFR
Tubular excretion
Tubular reabsorption

39
Q

At what age can GFR increase to 50% and 90% of adult value?

A

3rd wks AOG = INC to ~50% of adult
1 y/o = INC to ~90% of adult

40
Q

When does tubular secretion & tubular reabsorption mature in children?

A

Tubular reabsorption = 2yo
Tubular secretion = 15 mons

41
Q

What are the diff PK changes in puberty?

A

Hormonal fluctuations
Sexual maturation
INC in body fat
INC serum proteins
GFR -> exceeds ave adult values
Metabolic changes -> DEC drug clearance

42
Q

What drug can boys at the age of 12yo have a 37% greater clearance than girls?

A

Lopinavir

43
Q

Girls/Boys. Which one can have Caffeine metabolism DEC earlier during puberty?

A

Girls

44
Q

Are neonates more sensitive to the central depressant efefcts of opioids than older chldren & adults?

A

Yes

45
Q

T/F Infants are susceptible to the effects of B-adrenergic agonists like Dopamine?

A

False

46
Q

what topical agent has the potential to cause toxic epidermal necrolysis?

A

Lamotrigine

47
Q

What drug group can cause weight gain in adolescents?

A

Atypiacl antipsychotic agents

48
Q

What form of soln are evenly distributed with and without shaking?

A

Elixir: w/o shaking
Suspension: w/ shaking

49
Q

Drug dosage in pedia px depend on what ff factors?

A

Age, weight, & surface area

50
Q

What is the formula for pediatric dose if u only have the age of the px? WHat is this formula called?

A

Young’s Rule:

Dose = Adult dose x [(Age in yrs)/(Age +12)]

51
Q

What is the formula for pediatric dose if u only hgave the wt (kg & lbs) of the px? What is this formula called?

A

Clark’s rule:

Dose = Adult dose x [(weight in kg)/(70)]

Dose = Adult dose x [(Weight in lbs)/(150)]

52
Q

For breastfeeding mothers, at what time should drugs be taken?

A

30-60 minutes after nursing
3-4hrs before next feeding

53
Q

What is the side effect of Chloral hdyrate in breastfeeding mothers?

A

Drowsiness if infant is fed at peak conc of milk

54
Q

What is the side effect of Chloramphenicol in breastfeeding mothers?

A

BM suppression

55
Q

What is the side effect of Codeine in breastfeeding mothers?

A

Neonatal toxicity

56
Q

What is the side effect of large amts of consumed alcohol in breastfeeding mothers?

A

ALcohol effects in infants

57
Q

What is the side effect of Heroine in breastfeeding mothers?

A

Neonatal opioid dependence

58
Q

What is the side effect of Radioactive iodine in breastfeeding mothers?

A

Thyroid suppression in infants

59
Q

What is the side effect of Isoniazide in breastfeeding mothers?

A

Pyridozine def

60
Q

What is the side effect of oral contraceptives in breastfeeding mothers?

A

Suppress lactation in high doses

61
Q

What is the side effect of Phenobarbital in breastfeeding mothers?

A

Sedation in infants

62
Q

What is the side effect of Prednisone in breastfeeding mothers?

A

If dose is 2x the physiological amt (>15mg/day) —> IMmunosuppressant effect

63
Q

What is the side effect of Tetracycline in breastfeeding mothers?

A

Permanent staiing of the developing teeth of an infant

Pharmacology (19 decks)

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