Final part 1 Flashcards
Why TDM?
- maximize efficacy
- minimize toxicity
- PK changes
- monitor adherence
individualize
Use PK/PD parameters
maximize
best therapeutic response
minimize
watch for those adverse effects
context
treat the patient, not the number
narrow therapeutic drugs
- AGs
- Vanc
- Anti-epileptics (carbamazepine/ phenytoin/ valproic acid)
- anticoags
- anti-arrhythmics (digoxin/procainamide)
- immunosuppressants (cyclosporine)
- methylxanthines (theophylline/caffeine)
- anidepressanets (lithium)
PK
absorption
distribution
metabolism
elimination
PD
therapeutic effects
adverse effects
neonate
0-28 days
infant
1 month- 1 year
child
1 year- 12 years
adolescent
13- 18 years
elderly
> 65
very elderly
> 80
young old
65-74
old
75-84
old old
85-94
oldest old
> 95
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
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
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
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
metabollism- geri
- hepatic blood flow and liver size decr.
- phase I decreased
- phase II mostly unchaged
- decr clearance
- increased half life
elimination-peds
- GFR: sig. incr in 1st mon
- adult rates ~1 year
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
acid production is greater in
men
- ph is lower
GI transit is faster in
men
- 1/2 of avg womens
blood volume is greater in
men
- inc hydrophilic Vd
fast % greater in
women
- incr lipophilic Vd
more efficient 3A4 & less efficient 1A2 & 2E1
womein
kidney function generally less efficient in
women
estrogen is linked to
QT prolongation
opiate sensitivity is increased in
women
HLA-B*1502 & carbamazepine
- incr risk of developing SJS in Asians
CYP2C9 &/or VKORC1 & warfarin
- increased risk of bleeding for AA & whites
- lower doses needed
BSA formula
= sqrt(cm*kg/3600)
BSA for amputees
- determine non-amputated wt= act wt/(1-fw)
- BSA for non amp wt
- corrected BSA= BSA non amp* (1-fBSA)
GFR deinition
the amount of plasma that is filtered by all nephrons per unit of time
exogenous markers of GFR
inulin, sinistrin, iothalamate, iohexol & radioisotopes
- most accurate
endogenous markers of GFR
creatinine, cystatic C
key points about creatinine
- breakdown product of creatine- directly dependent on mass
- dependent on age, gender, race and lean body mass
decreased renal function=
increased SCr
elderly creatinine
decreased
females creatinine
decreased
blacks creatinine
increased
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
pregnancy
- all eqns have been shown to be inaccurate; measure 24 hr urine creatinine excretion if need to determine clearance
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.
morbidly obese (BMI>40)
- controversy over which weight to use
- may need to calculate lean body weight
geriatrics
- controversy over whether or not to round Scr to 1mg/dL to account for reduced muscle mass
- Should be AVOIDED- dont round
equations for measuring GFR are only accurate if
renal function is stable
MDRD equation indication
- recommended for use in pts with history of CKD risk factors and a GFR60
- age, SCr, female, black
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
schwartz equations
- neither of these equations provide an accurate GFR estimation in pts with:
- normal renal function >75
- advanced renal failure
do not use cockcroft gault for
staging!!!
- use MDRD-4 or CKD-EPI
liver enzymes (AST, ALT, ALP) are
- helpful in identifying hepatic dysfunction, they do NOT help quantify function
there are no ___ markers to determin hepatic clearance to use for drug dosing
- endogenous
child pugh score is used to
define severity of liver dysfunction/ assisting in drug adjustments
- bilirubin, serum albumin, INR, ascites, hepatic encephalopathy
child pugh scores
- mild (A): 5-6; live 15-20yrs
- mod (B): 7-9; candidate for transplant
- severe (C): 10-15; live 1-3yrs
model for end-stage liver disease (MELD)
- uses serum bilirubin, SCr, & INR to predict survival
- utilized by organ sharing network
hepatic dose adjustents for Low hepatic extraction ratio drugs
- maintenance dose: only component that needs to be reduced
hepatic dose adjustments for HIGH hepatic extraction ratio drugs
- loading & maintenance dose: may need to reduce
hepatic dose adjustment for drugs that undergo metabolism via P450 (phase I)
- clearance tends to be significantly impaired & thus dose adjustments are needed
hepatic dose adjustments for drugs that undergo conjugation (phase II)
- clearance NOT generally affected by liver disease
