Nephrology and dosing-final Flashcards
What are the excretory fxns of the kidney?
- making urine
- regulating electrolytes
- regulating osmolarity and water balance
- acid-base balance
- metabolite and waste elimination
What are the endocrine actions of the kidney?
- Secretion of renin
- Production and secretion of eythropoietin
- Production and metabolism of prostaglandins and kinins
What does RAAS do?
- Maintains intraglomerular pressure
- Maintains systemic blood pressure
- Regulates sodium excretion
What are the metabolic fxns of the kidney?
- Activation of Vitamin D
- Gluconeogensis
- Metabolism
* Insulin
* Steroids
* Xenobiotics
True or false; the kidneys have an effect on blood pressure, RBC production, and bone health?
True
What is the best overall index of kidney fxn?
GFR
What is GRF?
The volume of plasma filtered across the glomerulus per unit time
Represents sum total filtration rates of all functional nephrons in both kidneys
What is normal GFR in an adult?
> 90ml/min
What is the criteria for an ideal marker for GFR estimation?
•Stable plasma concentration
•Freely filtered = freely diffuses across the glomerulus and into Bowman’s capsule
•Not reabsorbed, secreted, synthesized, or metabolized by the kidney
Does not alter renal function
What is clearance?
volume of plasma “cleared” of a marker per unit time (mL/min)
What is the GOLD STANDARD for measuring GFR?
Inulin clearance ….inulin is a substance that is a small, inert polysaccharide molecule that readily passes through the glomeruli into the urine without being reabsorbed by the renal tubules.
Why is inulin gold standard?
•Distributed only in extracellular fluid
•Not bound to plasma proteins or tissues
•Easily passes through glomerular pores (freely filtered)
•Not secreted, reabsorbed, or metabolized in renal tubules
•No nonrenal elimination
HIGHLY ACCURATE
Why is inulin clearance not used often?
•Procedure highly complicated
Requires continuous IV infusion
Collection of series of blood and urine samples
Need reliable assay to measure inulin in samples
•$$$$
•→ NOT convenient for clinical practice
What is an accepted alternative to inulin clearance?
CrCl
What is normal CrCL?
100-120 ml/min
What is creatinine?
Product of creatine metabolism from muscle and dietary meat intake (endogenous molecule)
What is production and release of creatinine related to?
- Production and release related to age, sex, & muscle mass
* Released at relatively constant rate
Where is creatinine filtered?
Freely filtered at the glomerulus and not reabsorbed or metabolized by the kidneys
What is the relationship of creatning to GFR?
Creatinine concentration increases proportionally to GFR decrease
What are some limitations of using SrCr as GFR marker?
- Delayed SCr increase in early renal disease and acute renal failure
- Compounds can interfere with SCr secretion (cimetidine (OTC), trimethoprim)
- Compounds can interfere with SCr plasma assay (cephalosporins
- variability with fluid status, age, gender, muscle mass, and diet
What is the Cockcroft gault equation used for?
- Estimate renal function in adults… used to dose adjust drugs
- Uses SCr to estimate CrCl (approximates GFR)
- Accounts for ↑SCr with ↑weight, and ↓SCr with ↑age
What is the Cockcroft gault equation?
CrCl = (140-age)ABW / 72xSrCr X 0.85 if female
What body weight should be used for obese pts?
Ideal body weight if actual is >30% above ideal
What wt should be used in underwt patients?
If actual body wt is
What are limitations of 24hr CrCl?
•Inconvenient
•↓ accuracy with incorrect sample collection and storage
Shorter collection times tend to be less accurate
What is the normal range for BUN?
10-20 mg/dl
Why is BUN less useful than SCR?
BUN changes independently of GFR
What factors affect BUN but NOT renal fxn?
- Dehydration/hypovolemia (↑)
- Hypervolemia (↓)
- High protein diet (↑)
- Catabolism (↓)
* Febrile illness
* Steroids - Liver disease (↓)
- Decreased cardiac output (↑)
What are causes of red-brown urine?
- Hematuria, myoglobinuria, hemoglobinuria
- Drugs: nitrofurantoin, metronidazole
- Food: beets, rhubarb
What are causes of orange urine?
- Drugs: phenazopyridine, rifampin
* Food: Carrots
What are causes of blue green urine?
Drugs: methylene blue, propofol, amitriptyline
If RBC are found in microscopic UA, what could it indicate?
Glomerular damage, kidney trauma, UTI
If WBC are found in microscopic UA, what could it indicate?
- UTI, pyelonephritis
* Acute interstitial nephritis (eosinophiluria)
If renal tubular or epithelial cells are found in microscopic UA, what could they indicate?
Tubular damage
If squamous cells are found in microscopic UA, what could they indicate?
Lower genital tract
skin contamination
If casts are found in microscopic UA, what could they indicate?
•cylindrical bodies composed of proteins and/or cells
•Indicates various types renal injury
Types: hyaline, RBC, WBC, granular, waxy
If crystals are found in microscopic UA, what could they indicate?
- Oxalate, phosphate
* Drugs: indinavir, acyclovir
What are some reasons the pH of urine would be >8?
Aged urine, systemic alkalosis, UTI
What are some reasons the pH of urine would be
Metabolic acidosis
Large amount of dietary meat intake
What does specific gravity measure?
Urine concentrating ability of the kidneys
What is protein in the urine?
Marker of kidney damage
Why might there be glucose in the kidneys?
Uncontrolled DM
What do ketones in the urine indicate?
Diabetic ketoacidosis
Fasting or starvation
What are the pharmacokinetic changes in CKD?
Absorption
Distribution
Metabolism
Elimination
What are changes in distribution related too?
Protein and tissue binding alterations
Vd changes
What is elimination dependent on?
Amount of drug normally excreted unchanged in urine
Degree of renal impairment
What drugs have accumulation d/t there renally excreted metabolites? What are there toxic or therapeutic effects?
Morphine → morphine-6-glucuronide
Prolonged analgesia, sedation, respiratory depression
Meperidine → normeperidine
Seizures
Propoxyphene → norpropoxyphene
Cardiotoxicity
Sulfadiazine → acetylsulfadiazine
Crystaluria, nephrolithiasisWhat is likely to develop in a pt with renal impairment if they receive lorazepam IV?
Propylene glycol toxicity
lactic acidosis, hyperosmolality, hypotension during administration of higher than recommended doses
What is Cockcroft-Gault equation used for?
To estimate CrCl
When is the MDRD equation used?
To estimate GFR- used to ID and stage chronic kidney dz
What are advantages of reducing each dose while maintaining normal dosing intervals?
Provides sustained serum concentrations
Desirable for antibiotics with time dependent bactericidal activity
What are disadvantages of reducing each dose while maintaining normal dosing intervals?
Lower peaks
Higher troughs
May require unusual dosages
Associated with a higher risk of toxicities if the dosing interval is inadequate to allow for drug elimination
What is an extended interval?
Normal doses are maintained, but the dosing interval is lengthened to allow time for drug elimination before re- dosing.
What are advantages to extended interval dosing?
Similar peak and trough concentrations to those achieved in normal renal function
Ideal for antibiotics with concentration dependent bactericidal activity
Less pharmacy/nursing time
What are disadvantages to extended interval dosing?
Interval may be “impractical” (every 90 hours)
Associated with a lower risk of toxicities but a higher risk of subtherapeutic drug concentrations, especially toward the end of the dosing interval.
What are exceptions to the general hemodialysis dosing rule? Why are they exceptions?
Erythropoetin
Darbepoetin
These drugs too large to fit through dialyzer
