Renal Pharmacology & The Urinary System, Pt. 3 Flashcards
What are the most common causes of acute renal failure?
nephrotoxicity and infectious disease
- ethylene glycol
- lilies (cats)
- grapes and raisins (dogs)
- aminoglycosides
- amphotericin B
- cisplatin
- contrast agents
- NSAIDs
- ACE inhibitors
What is the most common cause of renal ischemic injury?
reperfusion injury following dehydration, shock, hypotension, cardiac output failure, or thrombosis
Renal ischemic reperfusion injury:
What is renal ischemia? Reperfusion? How do each cause injury?
ISCHEMIA = interruption of blood supply to the tissue that the cells may adapt to
REPERFUSION = re-establishments of blood flow that tends to cause injury due to the overwhelming oxygen supply
Significant changes following reperfusion:
What are the 5 key events in acute renal failure resulting in ischemic reperfusion injury? What does this result in?
- inflammatory cells infiltrate the injured tubular cells resulting in the release of cytokines
- generation of ROS, like NO, ONOO-, OH, superoxide
- disruption of cytoskeleton
- translocation of carriers causing loss of function
- damaged cells activate apoptotic pathways via caspases and MAP kinase
impaired renal function
What are the major ROS and RNS produced by acute renal failure?
ROS: superoxide, peroxynitrite, hydrogen peroxide, hydroxyl radical
RNS: NO from arginine and nitric oxide synthase
What ROS causes the most damage?
hydroxyl radical generated from fenton reactions converting hydrogen peroxide, resulting in the oxidation of DNA, proteins, and lipid membranes
What are the 2 major generators of ROS?
- mitochondrial complexes
- hypoxanthine
What is the proposed mechanism for the formation of ROS during ischemic reperfusion injury with hypoxanthine?
- as ischemia prolongs ATP is converted into AMP, adenosine, inosine, then hypoxanthine
- as reperfusion and reoxygenation occurs, released Ca and proteases convert xanthine dehydrogenase into xanthine hydrogenase
- xanthine hydrogenase converts hypoxanthine into superoxide, hydrogen peroxide, and hydroxyl radical
What are the 5 main steps to the pharmacological management of acute renal failure?
- treat or minimize underlying disease
- manage systemic complications (other organs affected)
- correct fluid, electrolyte, and acid-base balance
- initiate diuresis
- establish a prognosis depending on recovery, chronic disease, and permanent damage
How is the fluid deficit measured to properly relace it?
% dehydration x BW = liters required (volume)
What fluids are recommended for acute renal failure fluid therapy? In what situation should this be altered?
0.9% NaCl - physiological level will not alter osmolality
HYPERNATREMIA/CARDIAC INSUFFICIENCY - use low sodium fluids, like 0.45% NaCl in 2.5% dextrose or LRS in 2.5% dextrose
What should be measured during fluid therapy treatment for acute kidney failure?
- urine output via catheter (1-2 mL/kg/hr)
- BW
- hematocrit
- plasma protein concentration
- sodium concentration
What 4 treatments are preferred for urine production enhancement during acute kidney failure?
- Furosemide*
- Dopamine
- 10-20% Mannitol**
- 10-20% Dextrose
What can Furosemide exacerbate during treatment?
gentamicin toxicity