Drug Dosing in Chronic Kidney Disease

Question 1

What is the definintion of glomular filtration rate?

Why is it important?

Answer 1

the volume of fluid filtered from the renal glomerular capillaries into the Bowman’s capsule per unit time.

Determines renal function

Question 2

What should we remember about Sr Cr levels?

2

Answer 2

1. dont use it as the true marker of kidney function

2. slight bump in creatinine in an acute setting is a big problem! Red flag

Question 3

What specific sign would clue us in to kidney disease?

Answer 3

Be thinking about kidney disease when they are HTN. abnormalitites on the UA with this would help.

Question 4

What is GFR estimated by?

Answer 4

Estimated by creatinine clearance (CrCl)

Question 5

What are two ways to acquire CrCl?

Answer 5

1. The least common is through direct collection – measurement of the creatinine in a twenty four hour sample of urine
2. The more common and practical way is to calculate creatinine clearance using serum creatinine (SCr)
   Why is this? Easy to get a simple blood test

Question 6

What’s the problem with a 24 hour collection?

2

Answer 6

1. Compliance issues

2. Requires proper collection technique for accuracy

Question 7

What is creatinine?

Answer 7

The decomposition product of the metabolism of phosphocreatine, a source of energy for muscle contraction.

meat that we eat too. (sr cr will be higher)

Question 8

The higher the CrCl the 1.______ the kidney function, the higher the serum SCr the 2.______ the kidney function

Answer 8

1. better

2. worse

Question 9

What is a normal SCr?

Answer 9

About 0.6-1.3mg/dL (depends on the lab)

Question 10

The Cockcroft-Gault Equation?

How do we calculate ideal body weight?

What would happen if…
You increased the age?

Increased the weight?

Answer 10

CrCl (male) = (140-age) x weight (kg)/72 x SCr (mg/dL)
CrCl (female) = 0.85 x male CrCl

Male 50.0 kg + 2.3kg per inch over 5 feet
Female 45.5kg + 2.3kg per inch over 5 feet

CrCl would be lower (older=lower)
CrCl would be higher (accounting for more muscle mass-ideal body weight)

Question 11

In pts that are over 18 and have a SCr of less than 1 what number should we use?

How is CrCl expressed?

Answer 11

1

mL/min

Question 12

Who should we always check GFR on? 2

Answer 12

65 and older

SrCr less than 1.5

Question 13

Causes of Chronic Kidney Disease
Nephrotoxic agents:
5

Answer 13

1. NSAIDs
2. Aminoglycosides
3. Heavy metals (lead, gold compounds, mercury)
4. Radiocontrast (iodide compounds)
5. Ethylene glycol (antifreeze)- occurs 24-72 hours post injection. direct cytotoxic affect.

Question 14

1. How do NSAIDS affect kidney function?

2. Why would we not want to biopsy a kidney issue caused by radiocontrast?

Answer 14

1. blocks prostagladin activity, kidney vessels constrict and limit blood blood
2. dont biopsy them because it usually goes away after/refuses right away

Question 15

How would uremia affect the plasma protein binding of a drug?

Answer 15

Uremia may inhibit or enhance protein binding, therefore more active drug is in the system.

Question 16

Elimination-renal clearance:

1. Dependent on the processes of _______ _______ and ______ _______
2. Some drugs are converted to _________ that maintain pharmacologic activity when they accumulate in a patient with renal dysfunction.
3. When renal disease reduces _______ ________, the kidney’s ability to eliminate drugs declines in proportion to the decline in GFR.
4. What happens to the drugs that are usually filtered in kidney failure and what does this cause?

Answer 16

1. glomerular filtration and tubule transport
2. metabolites
3. nephron number
4. Drugs usually filtered and excreted accumulate, which produces a high prevalence of adverse reactions.

Question 17

1. Some drugs have toxic effects with high peak concentrations. Whats an example?
2. Other drugs have toxic effects with prolonged trough concentrations. Whats an example?

Answer 17

1. Imipenem can induce seizures at high concentrations
2. Aminoglycosides can cause nephrotoxicity (adding insult to injury) or ototoxicity with sustained trough levels above 2mcg/mL

Question 18

Drug Dosing in Chronic Kidney Disease: Two methods of dose adjustment?

Answer 18

1. Smaller dose

2. Longer interval between doses

Question 19

1. If GFR is less than ___ ml per min they will not eliminate that drug.
2. Be careful with drugs with pretty long half lives because why?

Answer 19

1. 50

2. it will be unpredictable for how long they will stick around or what the effect will be

Question 20

1. WHat is the purpose of a loading dose?

2. How is this affected in renal failure?

Answer 20

1. Are intended to generate a therapeutic steady-state drug level within a short period.
2. Despite renal failure, the loading dose is usually not different from normal.

Question 21

How long after should we check digitalis after we’ve given it for toxicity?

Answer 21

check a dig 6-12 hours after you’ve given drug. then lower their maintenance dose if you’ve given too much loading dose

Question 22

1. WHat is the purpose of a maintenance dose?

2. In the absence of a loading dose, maintenance doses will achieve 90% of their steady-state level in ___ half lives

Answer 22

1. Are used to sustain a therapeutic level when they are administered subsequent to a loading dose.
2. 3.3

Question 23

What are the maintenance methods for dealing with kidney failure pts?

Answer 23

1. Dosage reduction method

2. Interval extension method

Question 24

Describe each of the following methods of maintenance dosing in pts with renal failure and the benefit of each?

Answer 24

1. • Reduce amount of each dose, but interval time remains the same
   • Sustains a more constant blood level

2.

• Q 24 hours instead of q 12 hours, dose remains the same
• This method is practical for dugs with long half lives.

Question 25

What about patients who are receiving dialysis, how and when should we dose their meds?

Answer 25

1. Supplemental doses may be required
2. Dose can be given after dialysis

pain meds and blood pressure meds- usually give after dialysis. make sure to talk to the nephrologists

Question 26

Specific dosing guidelines based on patients renal function

GFR

Answer 26

Unless otherwise noted, one can assume that dose modification is not necessary for patients with GFR’s >50.

Question 27

Drug Dosing in Chronic Kidney Disease: monitoring is done how?

What drugs should we monitor? 6

Answer 27

Monitoring drugs by serum level
Wide variations in elimination in CKD (you have to look it up!)

1. Aminoglycosides
2. Digoxin (MAKE sure you know what time they took it)
3. Antiarrhythmic drugs
4. Vancomycin
5. Lithium
6. Anticonvulsants

Question 28

WHat are the Antiarrhythmic drugs we should be monitoring in CKD pts?
6

What are the anticonvulsants we should monitor?
4

Answer 28

1. disopyramide
2. flecainide (if not at therapuetic levels it can cause arrythmias)
3. lidocaine
4. procainamide
5. quinidine
6. tocainide
7. Carbamazepine
8. Phenobarbital
9. Phenytoin
10. Valproic Acid

Question 29

Drug supplementation with dialysis:

1. How should we deal with drugs that are dialyzed off?
2. not dialyzed off?

Answer 29

1. Most or all of drug is removed from blood stream during dialysis
   Give dose after dialysis
2. no supplemental dose needed

Question 30

Some antibiotic pearls to remember for CKD:
Examples of a few drugs where no dosage adjustment is required with chronic kidney disease:
4

Answer 30

1. Azithromycin (Zithromax)- protein synthesis inhibitor
2. Ceftriaxone (Rocephin)- beta lactam- interferes with cell wall synthesis.
3. Moxifloxacin (Avelox)- tendon rupture.
4. Doxycycline (Vibramycin)- tetracycline group. no prgnant or kids under 8

Question 31

Some things to remember:

1. Must always adjust for who?
2. In general, 50% decrease in renal function will result in ______ of SCr

Answer 31

1. African Americans (approximately 20% increased CrCl versus other ethnicities)
2. doubling

Question 32

Creatinine Clearance is an indicator of renal function and can be based off the _____ ___?

Answer 32

serum Cr

Question 33

If creatinine comes from phosphocreatine, which comes from muscle contraction, then creatinine will vary based on what?

Answer 33

muscle mass

Question 34

1. There are two ways you can adjust dosing for the patient with CKD. What are they?
2. Never associate an entire class of drugs with being eliminated by the kidneys. In other words….?

Answer 34

1. smaller dosing or longer interval between dose (or both)

2. several drugs within the same class may be eliminated in different ways