Pharm Considerations in Kidney Disease Flashcards
What is pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Elimination
ADME of a drug
What do you know about absorption if you give a drug parenterally?
All of it will enter circulation
PO drugs, on the other hand, must be absorbed in the GI tract. What are the fates once absorbed?
The drug can either be bound (by proteins) or unbound. The unbound percentage is then free to distribute
What is fe?
fraction of drug RENALLY eliminated
What is the equation for Css of a drug?
If you give an infusion, Css will be equal to Dose/Clearance
How could you estimate how long it would take a drug to reach Css?
if giving an infusion, it usually takes about 4-5 half lives (it also takes about 4-5 half lives for the drug to be eliminated)
What do you do if you want to reach steady state more quickly?
give a loading dose
A 40 year old white male with CKD stage 3b is admitted to the hospital for sepsis and is started on empiric antibiotic therapy that includes gentamicin (an aminoglycoside which has concentration-dependent activity). His serum creatinine on admission is 2.5 mg/dL (estimated GFR 31 mL/min/1.73 m2). The dose of gentamicin for normal kidney function is 1.7 mg/kg every 8 hours with a target trough concentration of
Prolong the dosing interval (see similar peaks and troughs)
What happens if you reduce the dose?
Takes longer to reach steady state and you see lower peaks (less effective) and high troughs (more side effects)
So what is the best option for someone with kidney dysfunction and taking aminoglycosides to limit AEs?
prolong the dosing interval
What would be the best change if you needed to shorten the drug therapeutic window?
lower the dose (digoxin does this)
Why would kidney disease change drug absorption?
in many of the primary diseases that cause CKD (diabetic nephropathy) you see gastroparesis (delayed gastric emptying) or uremic gastritis or the gastric pH may change
What are some common drug interactions of someone with CKD?
patients are frequently on calcium-containing phosphate binders (aka antacids) and iron supplements (flouroquinolones!!)
Case. 47-year-old type I diabetic with end-stage renal disease has severe autonomic neuropathy, including severe gastroparesis with delayed gastric emptying and almost daily episodes of nausea and vomiting. She received a living related donor kidney transplant with excellent function. Postoperative day 4 serum creatinine is 1.0 mg/dL, however, tacrolimus level is subtherapeutic, leading to an increase in the daily dosage. Over the next 3-4 weeks nausea and vomiting significantly improved and tacrolimus level is supra-therapeutic, requiring a reduction in dosage. What’s happening?
The N/V and gastropheresis likely made it so that much of the drug wasn’t being absorbed and when it subsided, levels became too high
What are some drugs that see decreases protein or tissue binding in uremic pts.?
- Phenytoin
- Diazepan
- Salicylate
- Valproic Acid
- Pentobarbital
- Warfarin
so effective dose goes up!
Describe the protein binding of phenytoin.
Phenytoin is about 90% protein bound typically. It is an acidic drug so it binds to albumin
In kidney disease albumin levels may not be decreased but you still see increased unbound phenytoin levels. Why?
Albumin is displaced from normal binding sites
What is the overall effect of this change?
The effect of this change in phenytoin’s protein binding is that the measured total concentration could be low, but still therapeutic because the ratio between the free and total concentration has increased.
Example of slide 18.
Thus, at a normal protein binding level of 90%, a total phenytoin concentration of 7 mg/L is subtherapeutic (free concentration = 0.1 x 7 mg/L = 0. 7 mg/L), but if protein binding is decreased to 85%, then a measured total concentration of 7 mg/L would be therapeutic (free concentration = 0.15 x 7 = 1.05 mg/L).
