Renal Pharm

Question 1

How much of a bump in serum creatinine is concerning?

Answer 1

• only a slight bump should raise alarm (from 1.1-1.4)
• don’t just use serum creatinine for testing for kidney disease (not reliable in pts over 65)
• need a true est of GFR

Question 2

What is a GFR?

Answer 2

• vol of fluid filtered fro renal glomerular capillaries into bowman’s capsule per unit time
• male norm: 130
• female norm: 120
• depends on race, age, body mass, sex

Question 3

How is the GFR estimated?

Answer 3

• CrCl
• least common: is through direct collection, measuring over 24hr time period, COMPLIANCE issues, and it requires proper collection technique for accuracy
• or most common way: most practical as well - is to calculate creatinine clearance using SCr - easy to get blood test
• gold std: inulin, freely filtered, but very expensive and difficult to assay, it’s high maintenance

Question 4

What is creatinine?

Answer 4

• decomposition product of metabolism of phosphocreatinine, a source of energy for muscle contraction (dependent on muscle breakdown and protein intake)
• the higher the CrCl the better thenkidney function, the higher the serum Cr the worse the kidney fxn is
• normal SCr is about 0.6-1.3 mg/dl
• *** SCr alone isn’t an accurate measure of renal fxn

Question 5

What is the cockcroft gault equation?

Answer 5

• CrCl (male) = (140-age)x wt (kg)/ (72x SCr)
• CrCl (female) - 0.85x male CrCl
• wt is ibw unless actual is less:
  male 50 kg + 2.3 kg/inch over 5 ft
  female 45.5 kg+2.3 kg/inch over 5 ft
• in pts over 18: if SCr is less than 1 use 1

Question 6

What happens if you increase the age in the CCG formula?

Answer 6

• CrCl will decrease (the older, the lower it gets)

Question 7

What happens if you increase teh wt in the CCG formula?

Answer 7

• CrCl will increase (accounting for more muscle mass)

Question 8

2 criteria when you don’t have to check kidney fxn?

Answer 8

• less than 65

- Serum Cr is less than 1.5

Question 9

Nephrotoxic agents?

Answer 9

• NSAIDs: moa - block prostaglandins which causes prolonged vasoconstriction of afferent arteriole leading to kidney disease
• aminoglycosides: (tobra and gentamycin), only systemic: effect epithelial cells lining PCTs
• heavy metals: lead, gold compounds, and mercury, (tissues become fibrotic)
• radiocontrast: iodide compounds ( MAC, hydration, dialyze, get acute kidney injury)
• ehtylene glycol (antifreeze): 24-72 hrs post ingestion, direct cytotoxic ingestion, direct cytotoxic effect, binds to calcium - turn into crystals and gets deposited in the kidneys, leads to damage and acute renal failure

Question 10

What is impt to remember in drug dosing in chronic kidney disease?

Answer 10

• Pharmacokinetic principles:
  absorption
  distribution of drugs into tissues
  elimination of drugs (metabolized or excreted)

Question 11

Distribution of drugs?

Answer 11

• plasma protein binding drugs:
  drug isn’t active when bound to protein
  uremia may inhibit or enhance protein binding, therefore more active drug is in the system

Question 12

elimination - renal clearnance is dependent on? How is it effected in renal disease?

Answer 12

• dependent on processes of glomerular filtration and tubular transport
• some drugs are converted to metabolites that maintain pharm activity when they accum in pt with renal dysfxn
• when renal disease reduces nephron number, kidney’s ability to eliminate drugs declines in proportion to decline in GFR
• drugs usually filtered and excreted accumulate which produces high prevalence of adverse reactions

Question 13

Drug dosing in CKD? Peaks and troughs?

Answer 13

• some drugs have toxic effects with high peak concentrations (ex: imipenem can induce seizures at high concentrations - when used in renally impaired)
• other drugs have toxic effects with prolonged trough concentrations - aminoglycosides can cause nephrotoxicity (adding insult to injury) or ototoxicity with sustained trough levels about 2 mcg/mL

Question 14

dose adjustment in CKD?

Answer 14

• smaller dose
• longer interval b/t doses (go from TID to BID)
• drugs or their metabolites that are norm excreted by kidney require major dose adjustments in renal failure
• these adjustments involve either interval extension b/t doses or dose size reduction at usual intervals

Question 15

Why use a loading dose?

Answer 15

• are intended to generate a therapeutic steady state drug level within a short period
• depsite renal failure loading dose is usually not diff from normal
• have to check drug concentration within 6-12 hours

Question 16

use of maintenance doses?

Answer 16

• used to sustain a therapeautic level when they are administered subsequent to a loading dose
• in the absence of a loading dose, maintenance doses will achieve 90% of their steady state level in 3.3 half lives

Question 17

How should maintenance doses be modified in CKD?

Answer 17

• dosage reduction method: reduce amt of each dose, but interval time remains the same, sustain a more constant blood level
• interval extension method: q 24 hrs instead of q 12 hrs. dose remains the same: this method is practical for drugs with long half lives

Question 18

How should maintenance doses be handled when pts on dialysis?

Answer 18

• supplemental doses may be required

- dose can be given after dialysis (pain meds, and BP meds)

Question 19

What are the specific dosing guidelines based on pts renal fxn?

Answer 19

• GFR less than 10
• GFR b/t 10-50

= unless otherwise noted, one can assume that dose modification isn’t necessary for pts with GFRs greater than 50.

Question 20

What drugs should be monitored by serum level in CKD?

Answer 20

• aminoglycosides
• digoxin
• vancomycin
• lithium
• antiarrhythmic drugs (super impt - cause dysrhythmias)
  -disopyramide
  flecainide
  lidocaine
  procainamide
  quinidine
  tocainide
• anticonvulsants:
  carbamazepine
  phenobarbital
  phenytoin
  valproic acid

Question 21

What drugs are primarily elim by the kidney?

Answer 21

• methotrexate
• metoclopramide
• metolazone
• misoprostol
• nadolol
• norfloxacin
• ofloxacin
• PCNs
• procainamide
• ranitidine
• spironolactone
• tetracycline
• thiazides
• ticarcillin
• tobramycin
• vancomycin

Question 22

Drugs with metabolites that accum in renal failure?

Answer 22

• acebutolol
• acetohexamide
• azathioprine
• chlorpropamide
• clofibrate
• daunorubicin
• diazepam
• digoxin
• doxorubicin
• meperidine
• methyldopa
• primidone
• procainamide
• propoxyphene
• rifampin
• sulfonamides

Question 23

What drugs should be avoided in severe kidney disease?

Answer 23

• metformin: high risk of lactic acidosis
• aspirin, NSAIDs: may worsen or decrease GFR
• acetazolamide: decreases GFR
• spironolactone: K+ accum
• thiazide diuretics: not effective
• bretylium: may induce arrhythmias
• chlorpopamide and acetohexamide: prolonged hypoglycemia
• K+ supplements: hyperkalemia
• sodium: hypernatremic
• phosphates: hyperphosphatemia usually present
• excess fluids

Question 24

What drugs cause serious adverse effects if not appropriately dosed in CKD?

Answer 24

• imipenem (primaxin): seizures
• aminoglycosides: nephro and ototoxicity
• vanco: nephro and ototoxicity
• amphotericin B: may decrease GFR by 20-60%
• meperidine: seizures

Question 25

Drug dosing during dialysis?

Answer 25

• drugs that are dialyzed off: most or all of drug is removed from blood stream during dialysis, give dose after dialysis
• drugs that are not dialyzed off: no supp dose needed

Question 26

What are some key drugs that don’t need dosage adjustment in CKD?

Answer 26

• azithro
• ceftriaxone
• moxifloxacin
• Doxycycline

Question 27

What do you have to remember for Crcl adjustment in African americans?

Answer 27

• have to adjust, approx 20% increased CrCl versus other ethnicities

Question 28

What will happen in a 50% decrease in renal fxn?

Answer 28

• result in doubling of Scr

Question 29

If one drug of a class is eliminated by the kidneys, are they all?

Answer 29

• no, never assoc an entire class of drugs with being assoc by the kidneys.