L38 - Excretion 1

• Define elimination


  Irreversible loss of drug by excretion or metabolism
• Define excretion.

  
  

  Where does it mainly occur?

  Irreversible loss of chemically unchanged drug.

  
  

  Mainly in kidneys via urine. Or bile, sweat, saliva.
• Define metabolism. What is it also known as?

  
  

  Where does it occur?

  Conversion of a drug into a different chemical species.

  
  

  Aka biotransformation.

  
  

  - Mainly in liver, also GI wall, blood etc
• Define renal clearance.


  volume of fluid (blood/plasma) completely cleared of a drug by the kidneys per unit time.

  
  

  OR

  
  

  The proportionality factor that relates renal elimination rate of a dru.g
• Give the eqn for renal elimination rate.

  
  

  What's the proportionality constant?

  Renal Elimination Rate = Renal Clearance x [drug].

  
  

  Proportionality constant = Renal Clearance.

  
• Give the equation for total clearance.

  Total Clearance = Renal + Hepatic clearance.

  
• How can we find Renal Clearance from a graph?

  Plots rate of Renal Excretion vs Plasma [drug].

  
  

  Find gradient.

  
  

  The steeper the slope, the greater the renal clearance.

  
• Give the eqn for elimination rate.

  Elimination rate = Blood Flow x (Centering - Cleaving).

  
• Give the eqn for rate of presentation.

  Rate of presentation = blood flow x Centering

  
• Define the renal rate of presentation.


  The amount of drug that arrives to the kidneys per unit time.

  
• Define Renal Extraction Ratio


  - Measure of efficiency of the kidneys in eliminating drug from systematic circulation via a single pass through the organ.

  
  

  OR

  
  

  - Ratio between renal elimination rate and rate of drug presentation to the kidneys.

  
  

  OR

  
  

  - Fraction of drug passing by the kidneys which gets eliminated by them.

  
• Give the eqn for renal extraction ratio.

  Extraction Ratio = Elimination Rate / Presentation Rate.

  
  

  = Blood flow x (Centering - Cleaving) / blood flow = Centering

  
• Define Renal Clearance


  = The blood volume entering the kidney from which all drug is removed per unit time.

  
  

  OR the ratio between elimination rate by the kidney and incoming [drug]

  
• Give the equation for Renal Clearance.

  Renal Clearance = Renal Blood Flow x Renal Extraction Ratio.

  
  

  = Elimination rate / Centering.

  
  

  = blood flow x (Centering-Cleaving) / Centering.

  
• What happens if renal clearance

  a) is 0

  b) is approaching 1/ at 1

  c) is 0.25

  a) the drug is NOT excreted by the kidney.

  
  

  b) Renal Clearance value approaches that of blood flow. At 1, the drug is competely eliminated.

  
  

  c) 25% of the drug is eliminated.
• Which 3 processes contribute to excretion?

  - Glomerular filtration.

  
  

  - Tubular secretion (Active).

  
  

  - Tubular reabsorption (active and passive).
• Why would renal excretion vary?

  - Renal disease.

  
  

  - Age (decreased renal function).

  
  

  - Drug interactions.
• Give the crucial eqn for Amount Excreted from the kidney.

  Amount Excreted = Amount filtered + Amount Secreted - Amount Reabsorbed.

  
• List the main roles of the kidney.

  - Water and electrolyte balance. Regulates water loss.

  
  

  - Hormone secretion.

  
  

  - Blood pressure control.

  
  

  - Removal of metabolic waste, endogenous substances.

  
  

  - Filter and conserve useful products.

  
• Describe Glomerular Filtration.

  
  

  Does it increase/decrease renal clearance?

  DECREASES Renal Clearance.

  
  

  - Unidirectional.

  
  

  - Aided by hydraulic pressure exerted by arterial blood.

  
  

  - 10% of blood is filtered (120mL/min) (GFR).

  
  

  - Ionised and unionised molecules are filtered.

  
  

  - No albumin found in ultrafiltrate. Only unbound drugs are filtered, unless diminished renal function/renal insufficiency.
• How much blood to kidneys receive on average?

  1.2L/min
• Describe Tubular Reabsorption.

  
  

  Does it increase/decrease renal clearance?

  DECREASES Renal Clearance.

  
  

  - Passive reabsorption occurs along nephron.

  
  

  - 99% of filtered water reabsorbed.

  
  

  - Active reabsorption is mediated by transporters, ONLY at PCT.

  Eg vit B, C, glucose.

  
• Describe Tubular Secretion.

  
  

  Does it increase/decrease renal clearance?

  
  

  Active or passive?

  
  

  What's it dependent on?

  
  

  Is extraction ratio high or low?

  INCREASES Renal Clearance.

  
  

  - Always active; mediate by non-specific carriers at PCT.

  
  

  - Transporters carry anion secreting systems (acids) and cation secreting systems (bases).

  
  

  - Dependent on renal blood flow (Qr).

  
  

  - Efficient for good substrates so high extraction ratio.