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Therapeutic Dosing > Final part 1 > Flashcards

Final part 1 Flashcards

1
Q

Why TDM?

A
  • maximize efficacy
  • minimize toxicity
  • PK changes
  • monitor adherence
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2
Q

individualize

A

Use PK/PD parameters

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3
Q

maximize

A

best therapeutic response

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4
Q

minimize

A

watch for those adverse effects

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5
Q

context

A

treat the patient, not the number

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6
Q

narrow therapeutic drugs

A
  • AGs
  • Vanc
  • Anti-epileptics (carbamazepine/ phenytoin/ valproic acid)
  • anticoags
  • anti-arrhythmics (digoxin/procainamide)
  • immunosuppressants (cyclosporine)
  • methylxanthines (theophylline/caffeine)
  • anidepressanets (lithium)
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7
Q

PK

A

absorption
distribution
metabolism
elimination

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8
Q

PD

A

therapeutic effects

adverse effects

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9
Q

neonate

A

0-28 days

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10
Q

infant

A

1 month- 1 year

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11
Q

child

A

1 year- 12 years

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12
Q

adolescent

A

13- 18 years

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13
Q

elderly

A

> 65

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14
Q

very elderly

A

> 80

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15
Q

young old

A

65-74

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16
Q

old

A

75-84

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17
Q

old old

A

85-94

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18
Q

oldest old

A

> 95

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19
Q

absorption- pediatrics

A
  • relative achlorhydria in newborns
  • acid production fluctuates widely
  • per kg production at adult liver by ~2yrs
  • delayed gastric emptying in newborns
  • increases quickly; adult rates by 6-8 months
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20
Q

absorption- geriatrics

A
  • increased PH/ decreased acidity (similar to infants)
  • delayed GI transit
  • incr. T max
  • AUC unchaged
  • drugs using active transport can have decr. F
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21
Q

distribution- geri

A
  • decreased body water
  • decr. Vd of hydrophilic drugs; incr concentration
  • increased fat content; incr Vd lipo drug; & terminal half-life
  • albumin/alpha-1 acid decreased
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22
Q

Metabolism- Peds

A
  • phase 1: variable rates; ~1 year to have adult rates
  • phase II; variable rates; ~2 yrs to adult rates
  • reduced glucuronidation
  • reduced acetylation
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23
Q

metabollism- geri

A
  • hepatic blood flow and liver size decr.
  • phase I decreased
  • phase II mostly unchaged
  • decr clearance
  • increased half life
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24
Q

elimination-peds

A
  • GFR: sig. incr in 1st mon

- adult rates ~1 year

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25
Q

elimination- geri

A
  • decr nephron function & kidney mass
  • decr. GFR & renal blood flow
  • incr T1/2 of drugs removed by kidney
  • incr. exposure to toxic metabolites
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26
Q

acid production is greater in

A

men

- ph is lower

27
Q

GI transit is faster in

A

men

- 1/2 of avg womens

28
Q

blood volume is greater in

A

men

- inc hydrophilic Vd

29
Q

fast % greater in

A

women

- incr lipophilic Vd

30
Q

more efficient 3A4 & less efficient 1A2 & 2E1

A

womein

31
Q

kidney function generally less efficient in

A

women

32
Q

estrogen is linked to

A

QT prolongation

33
Q

opiate sensitivity is increased in

A

women

34
Q

HLA-B*1502 & carbamazepine

A
  • incr risk of developing SJS in Asians
35
Q

CYP2C9 &/or VKORC1 & warfarin

A
  • increased risk of bleeding for AA & whites

- lower doses needed

36
Q

BSA formula

A

= sqrt(cm*kg/3600)

37
Q

BSA for amputees

A
  1. determine non-amputated wt= act wt/(1-fw)
  2. BSA for non amp wt
  3. corrected BSA= BSA non amp* (1-fBSA)
38
Q

GFR deinition

A

the amount of plasma that is filtered by all nephrons per unit of time

39
Q

exogenous markers of GFR

A

inulin, sinistrin, iothalamate, iohexol & radioisotopes

- most accurate

40
Q

endogenous markers of GFR

A

creatinine, cystatic C

41
Q

key points about creatinine

A
  • breakdown product of creatine- directly dependent on mass

- dependent on age, gender, race and lean body mass

42
Q

decreased renal function=

A

increased SCr

43
Q

elderly creatinine

A

decreased

44
Q

females creatinine

A

decreased

45
Q

blacks creatinine

A

increased

46
Q

cirrhotics/end stage liver disease

A
  • lower than expected Scr secondary to:

- reduced muscle mass, protein poor diet, diminished hepatic synthesis of creatine, &/or fluid overload

47
Q

pregnancy

A
  • all eqns have been shown to be inaccurate; measure 24 hr urine creatinine excretion if need to determine clearance
48
Q

critically ill patients

A
  • creatinine may be increased or decreased

- all eqns have been shown to be inaccurate, as well as the 24 hr creatinine collection.

49
Q

morbidly obese (BMI>40)

A
  • controversy over which weight to use

- may need to calculate lean body weight

50
Q

geriatrics

A
  • controversy over whether or not to round Scr to 1mg/dL to account for reduced muscle mass
  • Should be AVOIDED- dont round
51
Q

equations for measuring GFR are only accurate if

A

renal function is stable

52
Q

MDRD equation indication

A
  • recommended for use in pts with history of CKD risk factors and a GFR60
  • age, SCr, female, black
53
Q

chronic kidney disease epidemiology collaborative (CKD-EPI) equation

A
  • more accurate than MDRD when GFR >60 & less bias in all GFR ranges
  • Scr, age, female, black
54
Q

schwartz equations

A
  • neither of these equations provide an accurate GFR estimation in pts with:
  • normal renal function >75
  • advanced renal failure
55
Q

do not use cockcroft gault for

A

staging!!!

- use MDRD-4 or CKD-EPI

56
Q

liver enzymes (AST, ALT, ALP) are

A
  • helpful in identifying hepatic dysfunction, they do NOT help quantify function
57
Q

there are no ___ markers to determin hepatic clearance to use for drug dosing

A
  • endogenous
58
Q

child pugh score is used to

A

define severity of liver dysfunction/ assisting in drug adjustments
- bilirubin, serum albumin, INR, ascites, hepatic encephalopathy

59
Q

child pugh scores

A
  • mild (A): 5-6; live 15-20yrs
  • mod (B): 7-9; candidate for transplant
  • severe (C): 10-15; live 1-3yrs
60
Q

model for end-stage liver disease (MELD)

A
  • uses serum bilirubin, SCr, & INR to predict survival

- utilized by organ sharing network

61
Q

hepatic dose adjustents for Low hepatic extraction ratio drugs

A
  • maintenance dose: only component that needs to be reduced
62
Q

hepatic dose adjustments for HIGH hepatic extraction ratio drugs

A
  • loading & maintenance dose: may need to reduce
63
Q

hepatic dose adjustment for drugs that undergo metabolism via P450 (phase I)

A
  • clearance tends to be significantly impaired & thus dose adjustments are needed
64
Q

hepatic dose adjustments for drugs that undergo conjugation (phase II)

A
  • clearance NOT generally affected by liver disease

Therapeutic Dosing (3 decks)

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