Pharm-Kidney toxity NSAIDs and Acute renal failure Flashcards
What are the causes of reduced drug elimination through the kidneys in the elderly?
- Reduced renal Blood Flow
2. Perturbations in GFR
Where are most drugs and their active metabolites eliminated?
Through the kidney
What must be adjusted in those with reduced renal function?
Drug Dosage in order to
- Avoid accumulation of their metabolites
- Adverse reactions
- Aggravation of renal involvement
What are the three processes that contribute to the renal clearance of a drug?
- GFR
- Tubular secretion
- Primarily in renal proximal tubule - Tubular reabsorption
What does it mean when a drug is perfusion rate limited?
The extraction rate (secretion) is not limited to the unbound fraction of drug.
What does it mean when a drug secretion is capacity rate limited?
The extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in red blood cells.
What sort of process is tubular reabsorption?
Passive process for the majority of drugs and drug metabolites
What drives the reabsorption process?
The extensive reabsorption of filtered water along the renal tubule
What are the features of a drug which may govern its reabsorption?
- Lipophilicity
- pKa
- Molecular weight
What are the peptide transporters responsible for the tubular reabsorption of peptide like drugs such as B-lactam antibiotics and ACE inhibitors.
- PEPT1
2. PEPT2
Where are the PEPT1, and PEPT2 transporters located?
Apical membrane of the renal epithelial cells
Are prostaglandins a primary regulator of renal function in healthy individuals?
NO.
What compounds modulate the effects of both systemic and locally produced vaso-constrictor hormones?
Eicosanoids
Which prostaglandins are the predominant mediators of physiologic activity.
- PGI2
2. PGE2
What are the actions of the prostaglandins in the kidney?
1.Induce vasodilation in interlobar arteries afferent and efferent arterioles and glomeruli
In what situations do prostaglandins become essential to the kidneys?
- Development of true intravascular volume depletion (vomitting diarrhea) PG synthesized to optimize renal blood flow.
- Effective decrease in renal blood flow as seen with CHF, cirrhosis
- PGI2 and PGE2 counteract Angiotensin II, endothelin, vasopressin and catecholamines that would normally maintain systemic BP at the expense of renal circulation
How do the eicosanoids conduct their function?
Prserve GFR by antagonizing arteriolar vasoconstriction and blunting mesangial and podocyte induced by these endogenous vasoressors
What induces PG synthesis in CKD?
Intrarenal mechanisms activated to increase perfusion of remnent nephrons
NSAID administration in a CKD patient would lead to?
acute reductions in renal blood flow and GFR
What are the roles of PGs in the loop of Henle?
- PGE2 decreases cellular transport of sodium chloride in TALH cells and collecting duct
- Increase renin secretion
- inhibit c-AMP synthesis and oppose the action of antidiuretic hormone
What is the Net effect of chronic NSAID consumption.
A mild dose dependent increase in BP
What other drugs mimic NSAID nephrotoxic effects?
COX-2
