Renal Pharm Flashcards
How much of a bump in serum creatinine is concerning?
- 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
What is a GFR?
- 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
How is the GFR estimated?
- 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
What is creatinine?
- 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
What is the cockcroft gault equation?
- 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
What happens if you increase the age in the CCG formula?
- CrCl will decrease (the older, the lower it gets)
What happens if you increase teh wt in the CCG formula?
- CrCl will increase (accounting for more muscle mass)
2 criteria when you don’t have to check kidney fxn?
- less than 65
- Serum Cr is less than 1.5
Nephrotoxic agents?
- 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
What is impt to remember in drug dosing in chronic kidney disease?
- Pharmacokinetic principles:
absorption
distribution of drugs into tissues
elimination of drugs (metabolized or excreted)
Distribution of drugs?
- 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
elimination - renal clearnance is dependent on? How is it effected in renal disease?
- 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
Drug dosing in CKD? Peaks and troughs?
- 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
dose adjustment in CKD?
- 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
Why use a loading dose?
- 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
use of maintenance doses?
- 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
How should maintenance doses be modified in CKD?
- 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
How should maintenance doses be handled when pts on dialysis?
- supplemental doses may be required
- dose can be given after dialysis (pain meds, and BP meds)
What are the specific dosing guidelines based on pts renal fxn?
- 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.
What drugs should be monitored by serum level in CKD?
- aminoglycosides
- digoxin
- vancomycin
- lithium
- antiarrhythmic drugs (super impt - cause dysrhythmias)
-disopyramide
flecainide
lidocaine
procainamide
quinidine
tocainide - anticonvulsants:
carbamazepine
phenobarbital
phenytoin
valproic acid
What drugs are primarily elim by the kidney?
- methotrexate
- metoclopramide
- metolazone
- misoprostol
- nadolol
- norfloxacin
- ofloxacin
- PCNs
- procainamide
- ranitidine
- spironolactone
- tetracycline
- thiazides
- ticarcillin
- tobramycin
- vancomycin
Drugs with metabolites that accum in renal failure?
- acebutolol
- acetohexamide
- azathioprine
- chlorpropamide
- clofibrate
- daunorubicin
- diazepam
- digoxin
- doxorubicin
- meperidine
- methyldopa
- primidone
- procainamide
- propoxyphene
- rifampin
- sulfonamides
What drugs should be avoided in severe kidney disease?
- 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
What drugs cause serious adverse effects if not appropriately dosed in CKD?
- imipenem (primaxin): seizures
- aminoglycosides: nephro and ototoxicity
- vanco: nephro and ototoxicity
- amphotericin B: may decrease GFR by 20-60%
- meperidine: seizures
Drug dosing during dialysis?
- 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
What are some key drugs that don’t need dosage adjustment in CKD?
- azithro
- ceftriaxone
- moxifloxacin
- Doxycycline
What do you have to remember for Crcl adjustment in African americans?
- have to adjust, approx 20% increased CrCl versus other ethnicities
What will happen in a 50% decrease in renal fxn?
- result in doubling of Scr
If one drug of a class is eliminated by the kidneys, are they all?
- no, never assoc an entire class of drugs with being assoc by the kidneys.
