Elimination

Question 1

When does elimination occur?

Answer 1

Once drug has been broken down into something more hydrophilic

Question 2

What is elimination?

Answer 2

Removal of drug from body

Question 3

How does blood flow to kidney affect excretion rate?

Answer 3

Influences rate of delivery of drug to kidney

Question 4

What 3 stages does renal excretion involve?

Answer 4

1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption

The sum of these determines the net renal drug excretion

Question 5

What will glomerular filtration remove?

Answer 5

Passive process - only removes small molecules (water soluble and unbound)

Question 6

What is tubular secretion important for?

Answer 6

Active secretion of drugs into kidney tubule

Important for drugs that are highly plasma protein bound as these are not excreted effectively by glomerular filtration (not effected by degree to which drug is bound)

Question 7

What happens during tubular reabsorption?

Answer 7

In renal tube, nonionised form of drug can diffuse across tubular membrane and re-enter plasma

As water is reabsorbed along renal tube –> tubular drug conc increases –> providing conc gradient favouring drug reabsorption

Question 8

What is clearance?

Answer 8

Volume of blood/plasma cleared of drug per unit time

Question 9

What does clearance indicate?

Answer 9

The volume of plasma from which drug is completely removed in a given time period

NOT the amount being removed

Question 10

What is half-life?

Answer 10

Time taken for conc to deduce 50%

Assume at point of ingestion that there’s 100%

Question 11

If drug undergoes 5 half-lives, what can you assume?

Answer 11

Less than 3% in system

Question 12

What is half life increased by?

Answer 12

1. Diminished renal plasma flow
2. Addition of 2nd drug that displaces first from albumin
3. Decreased extraction ratio (renal disease)
4. Decreased metabolism (liver disease)

Question 13

How can you evaluate renal function?

Answer 13

Looking at creatine

Estimation of creatine clearance - estimates clearance of drugs filtered at glomerulus

Question 14

What is creatine?

Answer 14

Produced in skeletal muscle which is excreted through kidneys

It is neither passively reabsorbed nor actively secreted

Question 15

What is eGFR?

Answer 15

Estimating Glomerular Filtration Rate

Question 16

What is Cockcroft Gault Equation?

Answer 16

Estimated creatine clearance in mL/min

Question 17

What is eGFR in relation to?

Answer 17

Muscle mass not actual weight - rugby player with large muscle mass would appear to have poor creatine clearance

Not good indicator but can show renal impairment

Question 18

What is Cockcroft Gault equation good indicator of?

Answer 18

How well someone’s kidneys are functioning - important to use during renal dosing

Question 19

What does elimination via the liver depend on?

Answer 19

Blood flow to liver and activity of enzymes in liver

Question 20

What do liver enzymes alter the drug to form?

Answer 20

Metabolites which are inactive or equally or more active than parent drug

Question 21

To be efficiently excreted in urine, what must drug be?

Answer 21

Water soluble and not too tightly bound to proteins in bloodstream

Question 22

What is the glomerular filtration rate affected by?

Answer 22

Disease/age

Question 23

How does excretion differ in children and elderly?

Answer 23

Children –> reduce capacity due to immature kidneys

Adults –> reduction due to impaired glomerular filtration rate

Question 24

What is glomerular filtration?

Answer 24

Kidneys filter excess fluid and waste products out of the blood to form the glomerular filtrate

Question 25

What are the main products excreted in urine?

Answer 25

- Metabolic waste products - e.g., urea and creatinine - Electrolytes (including sodium, potassium, calcium, chloride and bicarbonate) - Water

Question 26

What is glomerular filtration caused by?

Answer 26

The force of the difference between the outward and inward pressure (pressure gradient in the glomerulus)

Question 27

What is the outward pressure?

Answer 27

The force of the pressure exerted from the pressure of the blood vessel itself --> driving force that pushes filtrate out of capillaries

Question 28

What is the inward pressure?

Answer 28

Hydrostatic pressure of fluid within the urinary space Pulling force exerted by albumins left in capillaries that tend to pull water back into circulatory system

Question 29

What is tubular reabsorption?

Answer 29

Solutes and water are removed from the tubular fluid and transported into the blood

Question 30

What happens to reabsorbed solutes and water?

Answer 30

Returned to the bloodstream and not excreted as urine

Question 31

Describe passive diffusion during tubular reabsorption

Answer 31

Passing through plasma membranes of the kidney epithelial cells by concentration gradients

Question 32

Describe active transport during tubular reabsorption

Answer 32

Membrane-bound ATPase pumps (such as NA+/K+ ATPase pumps) with carrier proteins that carry substances across the plasma membranes of the kidney epithelial cells by consuming ATP.

Question 33

Describe cotransport during tubular reabsorption

Answer 33

This process is particularly important for the reabsorption of water. Water can follow other molecules that are actively transported, particularly glucose and sodium ions in the nephron

Question 34

How is water mainly reabsorbed?

Answer 34

By the cotransport of glucose and sodium.

Question 35

What is the Na+/K+ ATPase?

Answer 35

An ATPase pump that consumes ATP to facilitate the active transport of ions in the filtrate of the nephron

Question 36

What is tubular secretion?

Answer 36

Opposite process of reabsorption --> transfer of materials from peritubular capillaries to the renal tubular lumen Urine is the substance leftover in the collecting duct following reabsorption and secretion

Question 37

What substances are secreted into the tubular fluid for removal from the body?

Answer 37

``` Potassium ions (K+) Hydrogen ions (H+) Ammonium ions (NH4+) Creatinine Urea Some hormones Some drugs (e.g., penicillin) ```

Question 38

What is the tubular secretion of H+ and NH4+ involved in?

Answer 38

Blood pH regulation

Question 39

What type of process is pH regulation primarily?

Answer 39

A respiratory process, but tubular secretion assists