Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PDAT3 > 19 - Drug use in Renal Failure > Flashcards

19 - Drug use in Renal Failure Flashcards

1
Q

Glomerular Filtration

  • *Excretion =**
  • *Filtraton + Secretion - ReAbsorption**
A

Water + Small MW ions or molecules
PASSIVELY diffuse across glomerular capillary membrane
VVV
Bowman Capsule –> Proximal Tubule

Proteins / protein-bound compounds are TOO LARGE

Amount of soute filtured is related to:
GFR & Extent of Plasma Protein Binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

SECRETION

  • *Excretion =**
  • *Filtraton + Secretion - ReAbsorption**
A

ACTIVE TRANSPORT
from renal circulation –> tubular lumen
Renal clearance via secretion can be >GFR (1000mL/min)

Anionic / Cationic Transport Systems
for wide range of endo/exogenous substances

Efflux Proteins (P-gp)
contribute to renal elimination of many drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

REABSORPTION

  • *Excretion =**
  • *Filtraton + Secretion - ReAbsorption**
A

Water + Solutes
reabsorbed throughout nephron

Most Drugs Reabsorbed in
DISTAL Tubule + COLLECTING DUCT

Affects Reabsorption:
Urine Flow Rates
Physicochemical Characteristics
highly IONIZED molecules WONT be reabsorbed
unless urine pH changes –> unionized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the Principle Marker of KIDNEY DAMAGE?

A

Urine Protein / Albumin

Characterizes the Severity of CKD
&
Monitors Disease Progression/regression

most protein is NOT excreted into urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Urine Dipstick Test

A

Semi-Quantitative
Detection of Protein in Urine

  • *False Positives**
  • *Concentrated urine** samples may be considered proteinuria

False negatives
protein may be undetected until excretion gets to HIGH level

Many other reasons for FALSELY Elevated Protein in the urine on a “Spot Check”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Many other reasons for FALSELY Elevated Protein in the urine on a “Spot Check”​

Urine Dipstick Tests

A

EXERCISE within 24 hours

UTI

CHF / HTN

HYPERglycemia

Pregnancy

Hematuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
  • *Clinical Proteinuria**
  • *Quantitative Diagnosis**
A

24 hour collection = Spot Protein/Albumin : Cr Ratio
in terms of efficacy

24 Hour Collection
> 300mg/day
albumin or protein

Spot Protein:Cr
> 200 mg/g (> 0.2 mg/mg)

Spot Albumin
> 300 mcg/mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

MicroAlbuminuria
​Quantitative Diagnosis

Earliest marker for Diabetic Nephropathy / CV risk

A

24 hour collection = Spot Protein/Albumin : Cr Ratio
in terms of efficacy

24 Hour Collection
30 - 299 mg/day albumin

Spot Protein:Cr
n/a

Spot Albumin
30 -299 mcg/mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Qualitative Diagnosis of Kidney Disease

Purpose / Types

A

To evaluate the ETIOLOGY of the kidney disease

Renal Ultrasound
can detect structural abnormalities (obstruction)

Biopsy
to fascilitate diagnosis when clinical/lab/imaging is inconclusive
evaluate renal parenchymal disease
complications for bleeding risk ( peri-renal hematoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Normal GFR
Men / Women

A

Males
127+20
ml/min/1.73m2

  • *Females**
  • *118** + 20
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Best Exogenous Compound

for Measuring GFR

A

INULIN

low availability / HIGH COST
assay variability / sample prep

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Exogenous Compounds

Measurement of GFR

A

Markers have to be:

  • *FREELY FILTERED**
  • NOT - secreted / reabsorbed / metabolized*
  • minimally protein bound + minimal non-renal clearance*

INULIN
Iothalamate / Iohexol / RadioIsotopes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Serum Creatinine

Measurement of GFR

Metabolic product of:
Creatine + Phosphocreatine
found almost exclusively in the MUSCLE

A
  • *Endogenous Compound**
  • less technical /* MORE variable results

does NOT bind to plasma proteins // freely filtered by glomerulus

Cr undergous VARIABLE TUBULAR SECRETION
VV
OVERestimation of kidney fxn
as renal fxn declines –> tubular secretion of SCr INCREASES

Medications can inhibit tubular secretion:
Trimethoprim / dronedarone / H2blockers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cockcroft Gault Equation

A

Most commonly used equation to:
DETERMINE DRUG DOSES
for patients with impaired kidney fxn

  • *CrCl** = (140 - AGE) x Weight
  • *(SCr x 72)**

*x0.85 for females

Variables:
SCr - Age - Weight

Weight varies on the patient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What Weight to use if
Normal Weight = BMI 18.5-24.9 ?

for CG Equation

A

IDEAL BODY WEIGHT

IBW Male = 50kg + ( 2.3kg x each inch >5ft )

IBW Female = 45.5kg + ( 2.3kg x each inch >5ft )

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  • *What Weight to use if
  • UNDERweight* = BMI <18.5 ?**

for CG Equation

A

ACTUAL BODY WEIGHT

ABW for underweight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What Weight to use if
OBESE/OVERWEIGHT = BMI >25 ?

for CG Equation

A

ADJUSTED BODY WEIGHT

Adjusted BW = IBW + 0.4 (ABW - IBW)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Liver Disease / Renal Transplant / HIV

Special Populations - CG equation

A

CG tends to OVERESTIMATE measured 24 hr CrCl

Liver Disease
↓SCrfromreduced muscle mass & many other factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Pregnancy / Elderly

Special Populations - CG equation

A

CORRELATES WELL
with 24hr CrCl

  • *Elderly**
  • reduced muscle mass = reduced Scr
  • do NOT round SCr up to 1**
20
Q

Children

Special Populations - CG equation​

A

Use the:
Children SCHWARTZ Equation

CrCl is more dependent on:

  • *Child’s AGE & LENGTH**
  • rather than weight*
21
Q

Which Equation do is the MOST ACCURATE for estimating GFR in

PATIENTS WITH CKD?

A
  • *MDRD4**
  • CKD-EPI is just AS accurate for GFR <60*

Variables:
SCr / Age / Gender / Race
MDRD6 has SUN & Albumin

LESS ACURATE with pts with GFR > 60

use in caution in:
children / elderly / pregnant / women / critically ill

22
Q

Which Equation BEST ESTIMATES GFR in the

NON-CKD Population?

A

CKD-EPI

MORE ACCURATE than MDRD
for GFR > 60

Equal Accuracy as MDRD for GFR <60

Factors:
SCr / Race / Gender / Age

23
Q

Limitations of SCr-Based Estimation Equations

A

Use of SCr as filtration marker
affected by age/gender/race/muscle mass
undergoes VARIABLE tubular secretion
affected by unusual dietary habits

CG / MDRD Studies did NOT include this population
pregnant / obese / vegetarian / amputees / liver disease
Transplant / HIV / children / elderly / unstable renal fxn

MDRD ONLY studied CKD patients

24
Q

IDMS-SCr Assay

A

Used to STANDARDIZE SCr across institutions

5-20% underestimation of SCr –> overestimates GFR

MDRD-IDMS Equation

CKD-EPI
is ALREADY SET to use IDMS-SCr

25
Q

What Effect on Drug ADME?

Increased Gastric pH
seen in many CKD patients
Ammonia in gut
Phos Binders / Antacids / H2RA / PPI are often used in CKD’s

A

↓DRUG ABSORPTION

26
Q

What Effect on Drug ADME?

  • *Gastroparesis**
  • delayed GI transit time*
A

↓DRUG ABSORPTION

Gastroparesis
prolongs the TIME to reach MAX drug concentration

27
Q

What Effect on Drug ADME?

Vomiting & Diarrhea

A

↓DRUG ABSORPTION

28
Q

What Effect on Drug ADME?

CHELATE FORMATION
Many CKD drugs are suceptable:
Mg / Ca / Al-OH / Ferrous SUlfate / SPS
+
TetraCyclines / Fluoroquinolones

A

↓DRUG ABSORPTION

Chelate formation –> Reduced Absorption

29
Q

What Effect on Drug ADME?

Bowel Wall Edema

A

↓DRUG ABSORPTION

30
Q

What Effect on Drug ADME?

Magnesium Hydroxide + Sodium Bicarbonate

A

↑DRUG ABSORPTION

Mag-OH + NaBicarb
can INCREASE absorption of weakly acidic drugs
(ibuprofen / glipizide / glyburide)
by increasing their water solubility

31
Q

What Effect on Drug ADME?

↓INTESTINAL METABOLISM
CKD patients have:
↓intestinal metabolism & ↓p-gp drug transport
↓CYP450 intestinal activity

A

↑DRUG ABSORPTION

INCREASED BIOAVAILABILITY OF CERTAIN DRUGS

—Drugs with increased bioavailability in CKD due to decreased intestinal or liver metabolism:
dextropropoxyphene, dihydrocodeine, propranolol, felodipine, sertraline, cyclosporine

32
Q

What Effect on Drug ADME?

P-Gp Transport
↓P-Gp activity in CKD

A

↑DRUG ABSORPTION

33
Q

What Effect on ​Drug ADME?

FIRST PASS METABOLISM in LIVER

A

AFFECTS ABSORPTION IN BOTH WAYS

↓intestinal absorption & ↓p-gp transport = ↓absorption

↓less protein bound drug = ↓absorption

  • Drugs with reduction in 1st pass metabolism*
  • *= INCREASED absorption**
34
Q

What Effect on ​Drug ADME?

  • *ALBUMINURIA**
  • less albumin available to bind in CKD*
A

↑DISTRUBUTION

Since less albumin binding –> MORE FREE DRUG

35
Q

What Effect on ​Drug ADME?

ACIDIC DRUGS
especially those bound to albumin

Cephalosporins / PCN
Phenytoin / Furosemide / Salicylates
Barbituates / Valproate / Warfarin

A

↑DISTRUBUTION

36
Q

What Effect on ​Drug ADME?

ALKALINE DRUGS
bind mostly to NON-albumin proteins
like a-1 acid glycoprotein (high in renal dysfunction)

Propranolol / Morphine
Oxazepam / Vancomycin

A

↓DISTRUBUTION
likely unchanged

Alkaline Drugs bind to a-1 acid glycoprotein
which is ELEVATED in renal dysfunction

37
Q

What Effect on ​Drug ADME?

  • *TISSUE BINDING**
  • usually irrelevant but…*

DIGOXIN
is primarily bound to tissues

A

↓DISTRUBUTION

Vd is reduced by 50% in CKD stage V

DIGOXIN –> need to REDUCE LOADING DOSE
since digoxin is primarily bond to tissues, not plasma

38
Q

CKD’s Effect on Drug METABOLISM in LIVER
ADME

A
  • *PHASE 1_ & _PHASE 2** metabolism
  • *BOTH SLOWED** in CKD

Phase 1 = Hydrolysis / Reduction / CYP450 oxidation

Phase 2 = Acetylation / Glucuronidaition / Sulfation / Methylaition

INCREASED DRUG CONCENTRATION

39
Q

CKD’s Effect on Drug METABOLISM in KIDNEY
​ADME

A

REDUCED Kidney Metabolism in CKD
VVV
INCREASED DRUG CONCENTRATION

APAP / Salicylate / Insulin
Oxytocin / Morphine
Somatostatin / Vasopressin

40
Q

What Effect on Drug ADME?

  • *Drugs Metabolized by CYP3A4**
  • *Presence of Uremia –> decreased CYP activity**
  • *Uremic toxins –> endogenous inhibitors**
  • *CKD also alters NON-RENAL clearance of many meds**
  • due to uptake / efflux transporters*
A

REDUCTION IN METABOLISM
VVV
INCREASED DRUG CONCENTRATION

41
Q

CKD Effects on EXCRETION

Glomerular Filtration

A

Drugs with:
LOWER Molecular weight** & **LESS Protein-Bound
VVV
MORE LIKELY to be FILTERED
↓filtration rate in CKD
VVV
↓Elmination of filtered drugs
VVV
PROLONGED FREE-DRUG

42
Q

CKD Effects on EXCRETION

SECRETION

A

INCREASED DRUG + METABOLITES

Highly Protein-Bound Drugs = less likely to be filtered

CKD: Active transport system of secretion is REDUCED
less so vs filtration
VVV
INCREASED HALF LIFE

—Ampicillin, furosemide, salicylic acid, cimetidine, dopamine, neostigmine, procainamide, trimethoprim, quinidine

43
Q

CKD Effect on EXCRETION

REABSORPTION

A

Healthy Kidneys:
substantial reabsorption in distal nephron

CKD:
REDUCED reabsorption
VVV
INCREASED URINARY CONCENTRATION of DRUGS

Aspirin / Lithium

44
Q

Loading Dose Considerations for CKD

A
  • *Normal LD for CKD patients**
  • except for DIGOXIN*, –> reduced due to altered tissue binding

Patients with edema –>
fluid overload requires higher LD for increased LD

45
Q
  • *Maintanence Dose**
  • *Considerations for CKD**
A

REDUCED DOSE
lower peak / HIGHER troughs
associated with higher risk of ADR

  • *EXTENDED INTERVAL**
  • reduced toxicities*, BUT potential for sub-therapeutic periods

BOTH:
Optomizes efficacy / minimize toxicity

PDAT3 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions