Non-diuretic Drugs and Renal Function Flashcards
What are the 3 processes that contribute to the renal elimination of a drug?
1- Glomerular Filtration 2. Tubular Secretion 3. Tubular Reabsorption
Which of these 3 processes is dependent on ionization status of the drug, as well as concentration gradient?
Tubular Reabsorption. It is a passive diffusion process, and water reabsorption is the driving force. Amount reabsorbed depends on the physical/chemical properties of the drug: pH, molecular weight, esp. lipophilicity. Some protein like drugs (B-lactams and ACE inhibitors) utilize peptide transporters on the apical membrane of the tubular epithelium. (PEPT1, PEPT2)
How effective is drug elimination by glomerular filtration? Why?
Not very. It is a low clearance process, entirely dependent on perfusion pressure of the kidney. Also: ONLY UNBOUDN DRUG in plasma can be excreted by glomerular filtration.
The potential for drug/drug interactions occurs with which of the 3 renal elimination routes? Explain.
Tubular secretion. This process is based on transporters in the basolateral and luminal side of the tubular membrane. (from blood to tubule) Drugs may be secreted by the same transporter (compete), thereby decreasing their respective clearances.
Why is drug elimination reduced in the elderly?
As we age, our kidney function declines, and so does our GFR.
The Crockroft-Gault equation gives a value of GFR that take what into account?
What extra factor does the MDRD1 equation account for?
GFR varies by individual, age, muscle mass, and sex. Cockroft-Gault equation gives a standardized measurement of GFR, taking 2 of these factors into account: Age and Sex.
MDRD1 equation also factors in RACE (whether or not you’re black)
To tell if kidney disease is acute or chronic, what would you do?
Compare current and previous Creatinine levels.
Why are the elderly at increased risk for NSAID adverse effects?
-Use them more often - Increased prevalence of conditions exacerbated by NSAIDs -More comorbid conditions -More concurrent medications
What conditions are exacerbated by NSAIDs?
HTN CHF Renal Insufficiency
How do NSAIDs increase Hypertension?
NSAIDs block prostaglandin synthesis. Decreased bloodflow to the kidney because PGs aren’t there to vasodilate the afferent arterioles. Decreased GFR. Increased RAAS –> increased vascular resistance/ Na+ and H2O retention.
What effects do NSAIDs elicit in a healthy person?
Beneficial effects of pain relief. There is no need to worry about renal NSAID adverse effects in a healthy individual, because their volume status is normal, and PG production is LOW in healthy people.
T/F: Prostaglandins are primary regulators of renal function.
FALSE! They are secondary auto regulators of bloodflow and vascular resistance.
What are the renal functions of PGE2 and PGI2?
Induce VASODILATION of the inter lobar arteries, afferent and efferent arterioles, and glomeruli.
Why is PG production low in healthy people and high in people with renal disease?
Pre-renal kidney disease involves decreased ECV, thereby activating local mediators of GFR by the kidney. The RAAS system is activated (Ang II constricts the efferent arteriole), and PGs are synthesized to maintain GFR (dilate the afferent arteriole). PGs are only used by the kidney when there is something wrong, and GFR needs to be supplemented.
Give a person with Bilateral Renal Artery Stenosis an NSAID. What happens?
The person develops Acute Kidney Failure: Acute reduction in renal bloodflow and GFR. RAS already causes a decrease in GFR, and PGs are compensating for that, trying to maintain a healthy renal bloodflow. NSAIDs take away this auto regulatory mechanism. GFR decreases further.
