Pharmacology Issues in Renal Failure Flashcards
What causes vasodilation of the afferent arterioles? (4)
- NO
- PGE2/PGI2
- Dopamine
- Caffeine
What causes vasoconstriction of the efferent arterioles? (2)
- Angiotensin II
- Norepinephrine
What causes vasoconstriction of the afferent arteriole? (4)
- Norepinephrine
- Adenosine
- NSAIDs (blocks the beneficial vasodilation of PGs at afferent arteriole)
- Angiotensin II (only a little. Acts mainly on efferent arteriole)
What happens to RBF and GFR in the following:
- Dilate afferent
- Dilate efferent
- Constrict afferent
- Constrict efferent
- Dilate afferent
- RBF goes up
- GFR goes up
- Dilate efferent
- RBF goes up
- GFR goes down
- Constrict afferent
- RBF goes down
- GFR goes down
- Constrict efferent
- RBF goes down
- GFR goes up
For CKD, as GFR goes down, you have to adjust (decrease) drug dosing for renally eliminated drugs to avoid toxicity. Explain the stages of chronic kidney disease and when decreasing dosage of renally eliminated drugs begins.
What are the mosti mportant management principles for CKD? (4)
- Delay CKD progression
- Treat complications of CKD
- Screen for and treat cardiovascular risk factors
- Prepare for dialysis
How do we slow the progression of CKD?
Blood pressure control
- ACE-I, ARBs (patient must have potassium below 5 and GFR over 30. This is because ACE-I and ARBs are potassium sparing and will decrease GFR by opposing the efferent arteriole vasoconstriction of ATII)
- Thiazides (may lose effectiveness when GFR is under 30 and addition of loop diuretics may be necessary)
- Avoid potassium-sparing diuretics like spironolactone, eplerenone, and amiloride because as GFR goes down, elimination of potassium goes down.
- Beta blockers: metoprolol is preferred. Atenolol if longer half-life is desired.
How can CKD cause renal osteodystrophy and how do we treat this?
Declining kidney function results in decreased phosphate elimination resulting in elevated serum phosphate levels. These elevated phosphate levels lower serum calcium which stimulates the release of PTH. PTH initially normalizes serum calcium and phosphate concentrations by increasing renal calcium reabsorption and decreasing renal phosphate reabsorption but long term elevation of PTH leads to osteodystrophy. This problem is compounded by the failing kidney’s decreased ability to convert 25-hydroxy vitamin D to the most active 1,25-dihydroxy vitamin D resulting in a vitamin D deficiency and a further reduction in serum calcium levels and increased release of PTH.
This is treated by implementing a low phosphorus diet and giving phosphate binders. Calcium acetate is a great binder of phosphate and used to be used but it’s not really used anymore due to risk of hypercalcemia. A non-elemental binder like sevelamer is preferred.
What about giving vitamin D to decrease PTH release? Giving 1,25-dihydroxy vitamin D decreases PTH levels but also has the risk of causing hypercalcemia. So, you can give paracalcitol which acts selectively at D3 receptors in the PT gland but not at the intestines. This will reduce PTH levels without causing hypercalcemia.
What drugs can cause hyperkalemia? (5)
- Aldosterone antagonists (spironolactone, eplerenone)
- Collecting duct sodium channel blockers (triamterene, amiloride)
- ACE inhibitors (lisinopril, enalapril, captopril)
- Angiotensin receptor blockers (losartan, valsartan)
- Digoxin (only at toxic doses. potassium neutral at therapeutic levels)
What does patiromer (veltassa) do?
It exchanges Ca-sorbitol counterion for K+ in the gut (eliminating K). It is an oral drug that is taken once daily that is used to treat non-life threatening hyperkalemia. This allows patients with comorbid conditions (CKD, HF, diabetes) to continue taking potassium sparing agents (like ACEI-ARB, spironolactone).
