Lecture 4: Excretion Flashcards
major routes of excretion
-renal (primary)
-bile to feces
other routes of excretion
-pulmonary
-salivary
-mammary
Nephron
-primary functional unit of kidney
-compact
mechanisms of renal excretion
-filtration
-active tubular secretion
-tubular reabsorption
-biotransformation
Filtration location
-glomerulus
tubular secretion location
-proximal convuluted tubule
tubular reabsorption location
-distal convuluted tubule
-collecting duct
Glomerular filtration
Determinants of Filtration
-number of functional nephrons
-size (<5000)
-protein binding (permeability)
-renal blood flow (delivers drug to kidney)
Old people have less nephrons
-reduce dose
-less excretion
Renal Clearance vs weight graph
-negative slope
-increase weight decreases clearance rate
Renal clearance vs Creatinine Clearance
-positive slope
-increase together
Decrease creatinine clearance
-decrease renal clearance by filtration
= lower dose
Active Tubular Secretion
-carrier-mediated transport
-some filtration still
-susceptible to competitive interactions
-stereoselective excretion
carrier-mediated reactions (ATS)
- saturable
- competitive interactions (only certain amount of carriers available = drug interactions)
dose vs excretion rate
-positive slope for filtration
-positive slope that levels off for ATS
Tubular Reabsorption
-most passive
-some carrier-mediated
passive tubular reabsorption
-driven by concentration gradient
-determined by lipophilicity and pKa
-influenced by urine flow and pH
carrier-mediated (ACTIVE) reabsorption
-saturable (capacity-limited)
-ascorbic acid and glucose
-what shows up in urine is reabsorbed back into blood
saturable
-increase concentration saturates reabsorption
Urine vs blood drug concentration
-blood more accurate
-urine reabsorption leads to higher concentration
-why we use blood glucose for diabetes
tubular/plasma concentration
1=same
>1: higher in tubule (creatinine)
<1: higher in blood (glucose)
What happens to reabsorption as urine flow is INcreased?
-DEcrease reabsorption
Why do some meds require u to drink lot of water
-drug can precipitate out if drug concentration is too high
-kidney stones
Ascorbic acid
-undergoes REabsorption
-massive increase in dose barely increases plasma level
-bc ur saturating = spills out into the urine
Biotransformation of drugs
-mostly liver but some in kidney (vitamin D)
Vitamin D
-must be bioactivated to active form
-liver makes active form
What is the most important determinant of filtration of a drug?
molecular weight
How do passive and active tubular reabsorption differ?
-saturability
-need to look at variety of doses to see effect ?
What occurs to secretion as blood concentration increases
-reach maximum secretion (saturation)
Which types of drugs will have more drug interactions? (filtered or secreted?)
-secretion because of carriers
-carriers=competition
