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IPFC 2 Final > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

What dosing strategies almost double when use?
What would these methods do for neonates overestimate/underestimate?
What would these methods do for infants and children under 5 overestimate/underestimate?

A

Clarks rule and BSA-based dosing

Neonates: Overestimate
Infants, children under 5: under/over or appropriately-estimate dose

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2
Q

What factors INCREASE drug absorption in children relative to adults (4)

A
  • inc AMOUNT of Gastric emptying (kids eat more)
  • inc GI pH (more basic) (eg. penicillin absorption increased)
  • small intestinal length in proportion to body weight (quicker absorption)
  • Higher absorption of topical drugs
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3
Q

What factors DECREASE drug absorption in children relative to adults (4)

A
  • intestinal surface area
  • biliary flow and acid secretion
  • transporter expression and activity
  • metabolic enzyme expression and activity
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4
Q

What factors are consistent between adults and children for drug absorption (2)

A
  1. Small intestinal transit TIME
  2. Gastric emptying TIME
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5
Q

Describe the drug distribution in child (1 year0 vs adults.
Water vs. fat

A

Child (1 year)
- more water
- less fat
**inc V for hydrophilic drugs
**dec V for hydrophobic drugs

Adult
- more fat
- less water
**inc V for hydroPHOBIC drug
**dec V for hydrophilic drug

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6
Q

What is the drug distribution in children regarding protein binding (higher unbound or bound drugs)

A

Higher unbound protein drugs
- less conc of proteins
- lower affinity for protein

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7
Q

In drug metabolism in children, what is AUC greatly dependent on for moderate extraction ratio drugs?

A

CLint

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8
Q

Is total absolute clearance higher/lower in children compared to adults

A

Always lower
- lower mg dose than adults

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9
Q

is total weight normalized clearance higher/lower in children than adults

A

Can be higher/lower than adults
eg. 3 weeks old at same mg/kg has way HIGHEST plasma conc

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10
Q

When dosing mg/kg, how will the AUC factors change in adult levels
at birth
early life
adult (at what age is the same)

A

AUC:
at birth: higher at birth (low CL)
early life: lower (high CL)
adult: same levels at 6+

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11
Q

When dosing mg how will the AUC factors change in children levels?

A

AUC will always be higher in adults (higher plasma conc, lower clearance)
- dose will never exceed in adults

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12
Q

Clearance per Kg (higher/lower)
1 year
Adult

A

1 year: higher Cl
Adult: lower Cl

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13
Q

Clearance overall (higher/lower)
1 year
Adult

A

1 year: lower Cl
Adult: higher Cl

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14
Q

Compare GFR/kg in children vs adults. Compare GFR to tubular secretion

A

inc GFR/kg in children than adults

Tubular secretion doesn’t have the same sharp rise that renal clearance does

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15
Q

What happens to INR when you give a low warfarin dose to children vs adults

A

INR increases with low dose in children
- thinner blood

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16
Q

In large molecules for pediatrics, what is changed (5)

A
  1. Inc capillary surface area
  2. Inc leaky tight capillary ratio
  3. Inc lymph flow rate
  4. Inc hematopoietic cells
  5. DEC FcRN (EcF) expression –> inc in drug clearance
17
Q

mg/kg dosing for biologics children vs adults. Lower/higher exposure?

A

Lower exposure
- children are sub-therapeutic

18
Q

What is the minimum are for Clark’s rule? Young’s rule

A

Clark: 2-12
Young: 1-12

19
Q

Filtration
Passive/active
What gets filtered?

A

Passive

  • unbound drug gets filtered
20
Q

Tubular SECRETION
active/passive
What gets transported?

A

Active
- transport drug from blood to urine

21
Q

Tubular reabsorption
passive/active

A

Both

22
Q

Using CL, fu, GFR
What indicates more reabsorption is occurring
What indicates more secretion is occurring

A

Reabsorption
- CL < fu x GFR

Secretion
- CL > fu x GFR

23
Q

What happens to the following factors with a renal impairment patient
Half-life
k
V of D
CL
Time to steady state
Concentration at steady state

A

Half-life: increased

k: decreased

CL: decreased

V of D: the same

Time to steady state: increased

Concentration at steady state: increased

24
Q

Effect on peak and trough when you change:
Dosing interval
Change the dose

A

Dosing interval
- maintain same peak and trough

Change the dose
- decrease difference between peak & trough

25
Q

What is the goal of therapeutic drug monitoring?

A

Optimize the time within the therapeutic window

26
Q

When is a good time to take a sample for therapeutic drug monitoring.

  1. What type of conc do you get if you take a sample right before the next dose is administered (trough/peak)
  2. What type of conc do you get if you take a sample right after the maintenance dose is administered (trough/peak)
A

WHEN STEADY STATE IS REACHED
- after 3-5 half lives

  1. Trough conc
  2. Peak conc
27
Q

Does using a loading dose make patient reach steady state faster?

A

No

28
Q

Do you achieve steady state concentrations quicker?

A

Yes
- close to steady state almost immediately
(not actually at steady state)

29
Q

What is the VofD across groups of patients

A

0.5L/kg

30
Q

When would you perform therapeutic drug monitoring (3)

A
  1. If you’re using medications known to interact with the drug
  2. If there is is a therapeutic failure (eg. exacerbation of lung disease)
  3. Following the development of potential signs/symptoms of toxicity
31
Q

What happens to half life with the following diseases
Smoking -> induces enzymes
Hepatic disease –> inhibits enzymes
Obesity –> larger V

A

Smoking -> induces enzymes
- dec half-life

Hepatic disease –> inhibits enzymes
- inc half-life

Obesity –> larger V
- inc half-life

IPFC 2 Final (6 decks)

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