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Kinetics Final > 19 - PK of RENAL DISEASE > Flashcards

19 - PK of RENAL DISEASE Flashcards

1
Q

Age & CKD

A
  • Renal plasma flow declines with age
    • 600ml/min –> 350-450 ml/min
  • ​Linear Decrease in GFR 0.4-1.02 ml/min
    • ​PER YEAR
  • Elderly have a Falsely Elevated GFR
    • ​if have a lack of muscle mass
    • due to creatinine
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2
Q

Falsely Elevated GFR

for Elderly

A

Creatinine decreases due to lower muslce mass

Low Serum creatinine (SCr) shows

a greater creatinine clearance (CrCl)

–> Falsely Elevated GFR

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3
Q

Uremia

A
  • GFR is impaired due to:
    • Increased Fluid
      • ​–> INCREASED Vd
    • Accumalation of TOXINS
  • ​Reduced GFR & Reduced Active Secretion
  • Uremic patients must have dosage adjustment
    • ​F / Vd / CL are affected
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4
Q

Methods of Renal Excretion

A

Drug Filtration Rate =

GFR x free fraction of drug x drug concentration

  • Glomerular Filtration
    • All drugs + metabolites
    • PROTEIN BINDING
  • Renal tubular secretion
    • ​No protein binding influence
    • COMPETITION w/ other drugs
  • Reabsorption
    • AFFECTS IONS
      • affects acids/bases
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5
Q

CKD Stages

A

<60 GFR

(mL/min/1.73m2)

Diagnosed with CKD

  • There is G1-G5
    • G3 has a split = G3a &G3b
      • ​this is where u are diagnosed with CKD
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6
Q

Normal GFR

mL/min/m2

A

120-130 mL/min/m2

Declines with age

70+ years old avg GFR = 75

  • 1.1/min of blood flows through kidney
    • 20% of cardiac output
    • 10% if filtered thru glomerulus
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7
Q

Inulin

A
  • More exact measurement of GFR vs CrCl
    • but is more expensive
    • is std of practice but not used that often.
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8
Q

Creatinine Clearance

ml/min

A

NOT EQUAL TO GFR

OVERESTIMATES ACTUAL GFR

small amount creatinine eliminated by secretion/non-renally

  • Most often used as a measurement of GFR
    • but Varies w/ age/gender/weight
  • ​Best to measure 24-hour urine collection
  • Based on Cockcroft-Gault Equation
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9
Q

CrCl

Used Carefully in which populations?

A
  • Elderly / Malnourished
    • ​low muscle mass -> low SCr
      • –> Falsely Increased CrCl
  • ​​​​Obese
  • Body Builders
    • ​HIGH muscle mass -> HIGH SCr
      • –> Falsely low CrCl
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10
Q

IBW for males

A

50 + 2.3 (#inches over 5 feet)

IN KILOGRAMS

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11
Q

IBW for Females

A

45.5 + 2.3 (#inches over 5 feet)

IN KILOGRAMS

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12
Q

Cockcroft Gault Equation

CrCl

A

ClCr = (140-age) x IBW(kg)

72 x SCr

Multiply by 0.85 if female

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13
Q

Problems with Cockcroft-Gault

A
  • Study was mainly with caucasian males
    • NOT GOOD for very small or Very obese patients
  • OVERESTIMATES GFR by 10-20%
  • Does NOT account for BSA
    *
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14
Q

MDRD Equation

Modification of Diet in Renal Disease

A

eGFR (estimated GFR, also in mL/min/m2)

More accurate than Cockcroft Gault (CrCl)

Can calculate BSA for very small/obese patients

  • Larger and more diverse study
  • Limitations:
    • Can not be used when SCr is NOT stable
    • UNDERESTIMATES eGFR @ normal levels
    • OVERestimates eGFR when <20
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15
Q

CKD-EPI Equation

A

Most Accurate Estimator of eGFR

  • More accurate than MDRD
    • but limited # of elderly & ethnic minorities
  • ​Better for patients with HIGHER GFR than MDRD
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16
Q

Adjusted Body Weight

Adj BW

A

Adj BW = IBW + 0.4(Actual BW - IBW)

Used if Actual BW >30% of IBW

17
Q

CKD’s Affect on Kinetic Parameters

ORAL BIOAVAILABILITY

A
  • Reduce Bioavailabilty (F)
    • Reduced by altered GI motility
    • Altered pH
      • Increase in Acidity
    • Decreased Liver Function
18
Q

CKD’s Affect on Kinetic Parameters

Volume of Distribution

Vd

A
  • INCREASE in fluid/ Vd
    • Depends on drug-protein binding
    • High Uremic patients hold onto more water as kidney loses function
      • –> Increase Vd
    • Lower levels of Albumin
  • ​​MAY Need to Increase loading dose for CKD patients
19
Q

Small Vd Drugs

<0.7 L/kg

A

HIGHLY DIALYZABLE

Highly Water Soluble Drugs

Aminoglycosides / beta lactam antibiotics

20
Q

Large Vd Drugs

>0.7 L/kg

A

NOT READILY DIALYZED

  • Lipid-Soluble Drugs
    • ​Fluoroquinolones / macrolides
  • ​Highly Tissue Bound drugs
  • Highly Protein bound drugs
    • ​Phenytoin / Warfarin
21
Q

Protein Binding & Vd

for CKD patients

A

CKD Patients may eliminate Albumin in urine

  • DECREASE protein synthesis (protein spill)
    • Due to decreased protein intake
    • Poor apititite –> lower albumin
      • ​–> Increase in free drug
        • –> possible toxicity
  • Alterations @ tissue binding sites
    • Uremic toxins –> bind to receptor sites
      • –> Increase in nitrogen metabolites​
22
Q

Modified Loading Dose

Vd of CKD patient

A

Modified LD = (Pt’s Vd / Normal Vd) x Ld x weight

Pt’s Vd = Vd of CKD Patient = 0.3-0.35 L/kg

23
Q

Bioavailability in CKD Patients

A
  • REDUCED Bioavailability
    • Slowed absorption
      • -edema
    • Concurrant medications
      • Binders for dialysis patients
    • ALKALINE ENVIRONMENT
      • Basic due to PPI’s -/-> blocking acidity
24
Q

Protein Binding in CKD

A
  • Decreased Protein Binding
    • ​Less albumin –> MORE free drug
      • –> posible toxicity
    • HIGHLY protein bound drugs
      • have a low Vd
      • because not much protein to bind
25
Q

Metabolism in CKD patients

A
  • Elimination may be IMPAIRED
    • CYP 3A4 / 2C9
      • REDUCED by up to 50%
    • Glucoronidation reduced
      • polar metabolites
      • conjugates can accumalate –> adverse drug events
  • Kidney metabolizes some drugs
  • IF On Helodialysis
    • ​–> INCREASE clearance of meds that are NOT renally cleared
26
Q

Clearance in CKD patients

A
  • Decreased:
    • ​GFR
    • Active tubular Secretion
    • Hepatic Clearance
  • Lead to Prolonged Elimination HALF LIVES
    • ​Toxic metabolite accumalation can occur
27
Q

Elimination in CKD

A
  • Stage of CKD matters (shows degree of renal insufficiency)
    • Beware of drugs w MOA in renal
      • ​HCTZ
    • _​_Toxicity due to electrolytes retained
      • K+ sparing diuretics
  • ​​​ACUTE RENAL FAILURE
    • ​Always need to adjust dose
    • Dosing guidelines are based on CHRONIC renal failure
28
Q

Residual Renal Function

A

MISCONCENPTION

There is still renal fxn in patients with CKD

we want to preserve it!

avoid using nephrotoxic agents (NSAIDS/aminoglycosides)

29
Q

How to Dose Adjust for Patients w/ CKD

A

Decrease maintanence dose

INREASE dosing interval

OR BOTH!

Loading Dose is based on Vd

Maintanence dose is based on clearance

30
Q

CKD Dose Adjustment Goal

A

Attain same drug concentration found in

NORMAL RENAL FXN PATIENTS

31
Q

Fraction of Drug Excreted (fe)

&

Half Life

A

Assume that non-renal elimnation remains UNCHANGED

all other factors (like liver and GI ) are the same

  • When fe is known
    • You can estimate a dosage regimen in CKD patient
  • Half life changes when
    • clearance or Vd is modified
32
Q

Dialysis

A
  • Hemodialysis / Peritoneal Dialysis
    • ​can be outpatient/home
  • CVVH/CVVHD/SLEDD/EDD
    • ​in patient ONLY
  • Most machines are HIGH FLUX
    • high permeability, dialyze drugs
      • w/ Large MW
        • ​30k-40k
    • Low flux exist but not usually used
33
Q

Hemodialysis

DIALYSANCE

A

Dialysance = Drug cleared by dialysis

Medications still get cleared by dialysis

  • Blood filtered through artifical membrane
    • need artery/vein to allow blood to flow back to body
  • 400-600ml/min
    • done for 4 hours three times a week
34
Q

Hemodialysis on

Drugs With Small Vd

< 1 L/kg

A

DIALYZED THE MOST

large amounts are in the PLASMA

small amounts in the tissue

Water soluble

  • large Vd drugs are the opposite*
  • >2 L/kg*

Kinetics Final (3 decks)

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