Disease States Flashcards
What are some of the kidney’s function besides elimination?
Maintain fluid and ion homeostasis
Maintain blood pH balance
Maintain blood osmolarity
Produce erythropoietin for RBC production
Produce Renin for BP regulation
Produce calcitriol which helps maintain calcium and phosphate
CKD
Chronic kidney disease
GFR
ESRD
End stage renal disease
GFR
Creatinine is largely filtered. What is the implication for drugs removed by TS or TR?
?
Describe the Intact Nephron hypothesis
A nephron simply works or does not work. As other nephrons stop working the rest of the nephrons can increase their output up to a certain point. This can maintain GFR to a certain degree.
What are the two types of methods to calculate creatinine clearance?
Direct
Estimation (Cockroft and Gault)
If a drug was cleared by Tubular Secretion, what will their slope be on a clearance vs. GFR graph?
Greater than 1
If a drug was cleared by Tubular Reabsorption, what will its slope be on a clearance vs GFR graph?
Less than 1
What is the impact of CRD on a drug’s PK parameters if that drug is renally cleared?
Half-life increases
Clearance decreases
Volume does not vary much
Describe the general rule involving fe
If fe
How does renal failure affect protein binding?
In severe renal failure the total drug levels can change due to fu.
This is because Albumin levels will decrease, but AAG might increase.
How does renal failure affect hepatically cleared drugs?
Renal failure will only affect the hepatic elimination if the drug relies on transporters for removal or some metabolic processes.
How are plasma proteins and binding to plasma proteins affected by renal disease?
There is a decrease in plasma protein synthesis and accumulated waste products can displace drugs from plasma proteins. These two effects would lead to an increase in the fraction of unbound drug (fu).
If a drug is primarily eliminated by CYP2D6 and during renal disease the half-life is constant, but the AUC is increasing, what could be causing this?
An increase in [AAG] and the drug binds to this. This would lead to a higher bioavailability because the fraction unbound is less.
What is the affect of CRD on volume of distribution?
It is usually increased. This is due to a decrease in clearance and fluid accumulation.
Why are some enzymes and transporters down regulated during CRD?
High levels of PTH (parathyroid hormone), cytokines, and uremic toxins.
What is the impact of hemodialysis on PK?
HD can cause a rapid lose of drug during the dialysis session.
When might the impact of HD cause one to consider supplemental dosing?
When the peak and trough concentrations are too low.
When are the true troughs of a drug after dialysis?
1 hour post
How do you dose ESRD when someone is on HD?
Loading dose: 1.5-2mg/kg
Maintenance dose: 1mg/kg