Pharmacology Issues in Renal Failure Flashcards
At what GFR do you need to begin to reduce dosage of renally excreted drugs?
- <59
For patients with CKD
- Would you raise or lower the dose of a drug that has a low volume of distribution (Vd)?
- Would you raise or lower the dose of a drug that has a high volume of distribution (Vd)?
- Lower: CKD decreases the Vd even further, and thus will increase your plasma concentration i.e - same amount of drug in less volume
- Lower: CKD often results in hypoalbuminemia resulting in less drug to binding proteins.
- Greater levels of free drug and greater ability to distribute outside of the plasma and greater potential for toxicity
What is a maintenence dose (MD)?
- Represents the dose that is designed to equal the amount of drug that has been eliminated by the body in the preceding dosage interval
MD / tau [mg/hr] = Cpss (avg) [mg/L] x CL [L/hr]
Cpss = Plasma Concentration @ steady state
CL = drug clearance from plasma
T/F: Renal metabolism is responsible for the amount of 30% of a normal insulin dose, and therefore insulin should be reduced in patients with CKD.
- True, insulin needs to be reduced in patients with CKD 3 or higher
T/F: Hepatic metabolism can result in active metabolites that are renally excreted that can result in toxcicity in patients with CKD
- True
What 3 factors influence the kidney’s capacity to excrete (clear) drugs?
- Glomerular filtration rate
- Tubular secretion
- Tubular reabsorption
What stages of CKD generally require “renal dosing”?
- CKD 3-5
- CKD 1 &2 have a GFR >60 and do not usually reuqire special dosing.
What drugs dilate afferent arterioles (dec. arteriolar resistance) and increase GFR?
- Dopamine
- Caffeine => Adenosine antagonist
- Nitric Oxide, Prostaglandins
What drugs constrict afferent arterioles (increase in arteriolar resistanc) and reduce GFR?
- NSAIDS => decreased prostaglandins
- Ang II, NE, Adenosine
What drugs constrict efferent artiorles (increased arteriolar resistance) and increase GFR?
- Ang II, NE
What drugs dilate efferent arterioles (decreased arteriolar resistance) and decrease GFR?
-
ACE-I, ARBs => decreaeed Ang II
- Why: If you vasodilate the efferent arteriole, you increase renal blood flow, but induce renal failure because now you do not have the “squeeze” to push blood through the glomerulus (reduced GFR) because there is less resistance to just go through the efferent arteriole
What class of diuretics is considered first line treatment for HTN?
-
Thiazides
- However as GFR falls, diuretic efficacy decreases and a more potent loop diuretic (furosemide) is necessary to maintian the antiHTN effect
How do you overcome diuretic resistance in patients with CKD?
- Synergistic combination of diuretics that act at different sites in the nephron
For a patient with CKD 3-4 and state the necessary adjustments for the following Diabetes medications
- Glyburide
- Glipizide
- Metformin
- Insulin
- Glyburide: Half-life pronlonged
- Glipizide: No adjustments necessary
- Metformin: Use NOT recommended if SCr (serum Cr) > 1.5
- Insulin: Half-life prolonged
For a patient with CKD 3-4 and state the necessary adjustments for the following HTN medications
- Diuretics
- ACE-i & ARBs
- B-Blockers
- Ca-channel blockers
- Alpha blockers
- Vasodilators
- Thiazides may lose effectiveness; avoid potassium-sparing diuretics
- Monitor for hyperkalemia; May cause ARF in hypovolemic pts
- Atenolol: Half-life prolonged; metoprolol/carvedilol no adjusment
- No adjustment
- No adjustment
- No adjustment
For a patient with CKD 3-4 and state the necessary adjustments for the following hyperlipidemia medications
- HMG CoA reductase inhibitors
- Fibrates
- Niacin
- Ezetimibe
- No adjustment
- Gemfirbozil recommended fibrate in CKD Stage 5
- No adjustment
- No adjustment
- Why is anemia a common comorbidity of CKD?
- At what stage of CKD does anemia have increased prevalence?
- What is the treatment?
- Kidney produces 90% of body’s EPO. Dec in kidney function = decreased serum EPO => anemia
- CKD stage 3-5
-
Epoetin Alfa & Darbapoetin
- Fe supplenets
How does CKD lead to Renal Osteodystrophy?
Dec GFR => elevated serum phosphate levels => lowers serum calcium => stimulates release of PTH
-
PTH initially normalizes serum calcium and phosphate concentrations
- Long-term elevated PTH leads to osteodystrophy
- Problem is compounded by failing kidneys decreased ability to convert Vit. D to its most active form => Vit. D deficiency (reduces serum calcium and increases PTH more
What is the the treatment for Renal Osteodystrophy?
-
Phosphate binding agents (Calcium acetate or sevelamer bicarb)
- Usually these are calcium compounts or non-elemtal agents
-
Vitamin D compounds (Calcitrol)
- Best choice is agent that does not req. renal conversion to the most biologically active form
-
Calcimimetics (Cinacalcet)
- Alt to Vit. D in pts developing hypercalcemia
- Increases sensitivity to plasma Ca2+ => reduces release of PTH
What is the treatment for Hyperkalemia?
-
Treatment
- Acute: Hemodialysis, IV calcium gluconate, insulin & glucose, sodium bicarb, & nebulized albuterol
- Shift K+ into intracellular compartment, antagonism of cardiac cunduction abnormalities
- Chronic (asymptomatic): Sodium polystyrene sulfonate (Kayexalate)
- Acute: Hemodialysis, IV calcium gluconate, insulin & glucose, sodium bicarb, & nebulized albuterol
What drugs can cause hyperkalemia in patients with severe CKD?
Drugs that can cause Hyperkalemia
-
Potassium sparing diuretics
- Aldo antagonists
- Spironolactone/Eplerenone =
- Collecting Duct Na+ channel blockers
- Triamterene/Amiloride
- Aldo antagonists
- ACE-i/ARB
- Digoxin (toxic does)
