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Flashcards in Final part 1 Deck (64):
1

Why TDM?

- maximize efficacy
- minimize toxicity
- PK changes
- monitor adherence

2

individualize

Use PK/PD parameters

3

maximize

best therapeutic response

4

minimize

watch for those adverse effects

5

context

treat the patient, not the number

6

narrow therapeutic drugs

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

7

PK

absorption
distribution
metabolism
elimination

8

PD

therapeutic effects
adverse effects

9

neonate

0-28 days

10

infant

1 month- 1 year

11

child

1 year- 12 years

12

adolescent

13- 18 years

13

elderly

>65

14

very elderly

>80

15

young old

65-74

16

old

75-84

17

old old

85-94

18

oldest old

>95

19

absorption- pediatrics

- 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

20

absorption- geriatrics

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

21

distribution- geri

- 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

22

Metabolism- Peds

- phase 1: variable rates; ~1 year to have adult rates
- phase II; variable rates; ~2 yrs to adult rates
- reduced glucuronidation
- reduced acetylation

23

metabollism- geri

- hepatic blood flow and liver size decr.
- phase I decreased
- phase II mostly unchaged
- decr clearance
- increased half life

24

elimination-peds

- GFR: sig. incr in 1st mon
- adult rates ~1 year

25

elimination- geri

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

26

acid production is greater in

men
- ph is lower

27

GI transit is faster in

men
- 1/2 of avg womens

28

blood volume is greater in

men
- inc hydrophilic Vd

29

fast % greater in

women
- incr lipophilic Vd

30

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

womein

31

kidney function generally less efficient in

women

32

estrogen is linked to

QT prolongation

33

opiate sensitivity is increased in

women

34

HLA-B*1502 & carbamazepine

- incr risk of developing SJS in Asians

35

CYP2C9 &/or VKORC1 & warfarin

- increased risk of bleeding for AA & whites
- lower doses needed

36

BSA formula

= sqrt(cm*kg/3600)

37

BSA for amputees

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

38

GFR deinition

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

39

exogenous markers of GFR

inulin, sinistrin, iothalamate, iohexol & radioisotopes
- most accurate

40

endogenous markers of GFR

creatinine, cystatic C

41

key points about creatinine

- breakdown product of creatine- directly dependent on mass
- dependent on age, gender, race and lean body mass

42

decreased renal function=

increased SCr

43

elderly creatinine

decreased

44

females creatinine

decreased

45

blacks creatinine

increased

46

cirrhotics/end stage liver disease

- lower than expected Scr secondary to:
- reduced muscle mass, protein poor diet, diminished hepatic synthesis of creatine, &/or fluid overload

47

pregnancy

- all eqns have been shown to be inaccurate; measure 24 hr urine creatinine excretion if need to determine clearance

48

critically ill patients

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

49

morbidly obese (BMI>40)

- controversy over which weight to use
- may need to calculate lean body weight

50

geriatrics

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

51

equations for measuring GFR are only accurate if

renal function is stable

52

MDRD equation indication

-recommended for use in pts with history of CKD risk factors and a GFR60
- age, SCr, female, black

53

chronic kidney disease epidemiology collaborative (CKD-EPI) equation

- more accurate than MDRD when GFR >60 & less bias in all GFR ranges
- Scr, age, female, black

54

schwartz equations

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

55

do not use cockcroft gault for

staging!!!
- use MDRD-4 or CKD-EPI

56

liver enzymes (AST, ALT, ALP) are

- helpful in identifying hepatic dysfunction, they do NOT help quantify function

57

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

- endogenous

58

child pugh score is used to

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

59

child pugh scores

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

60

model for end-stage liver disease (MELD)

- uses serum bilirubin, SCr, & INR to predict survival
- utilized by organ sharing network

61

hepatic dose adjustents for Low hepatic extraction ratio drugs

- maintenance dose: only component that needs to be reduced

62

hepatic dose adjustments for HIGH hepatic extraction ratio drugs

- loading & maintenance dose: may need to reduce

63

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

- clearance tends to be significantly impaired & thus dose adjustments are needed

64

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

- clearance NOT generally affected by liver disease