T2 - Drug Elimination E2

Question 1

What is drug excretion?

Answer 1

The process by which intact drugs and its metabolites are irreversibly removed from the body

Question 2

What is the principle organ for excretion?

Answer 2

Kidneys

Question 3

What are other organs used for excretion besides the kidneys?

Answer 3

1. Lungs
2. Biliary system
3. Salivary
4. Sweat glands

Question 4

What is a nephron?

Answer 4

The functional unit of the kidney involved in excretion

Question 5

What are the components of the nephron?

Answer 5

Vascular and tubular

Question 6

What are glomerulus?

Answer 6

A network of glomerular capillaries

Question 7

What is the filter of the glomerulus?

Answer 7

Bowman’s capsule

Question 8

What happens when blood enters the glomerulus?

Answer 8

Blood is filtered so that free filtrate can pass through the tubule

Question 9

What are the mechanisms of renal excretion?

Answer 9

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

Question 10

What mechanisms remove drugs from circulation?

Answer 10

1. Glomerular filtration
2. Tubular secretion

Question 11

What mechanisms moves drug from inner tube back into circulation?

Answer 11

Tubular reabsorption

Question 12

What drives glomerular filtration?

Answer 12

Passive diffusion

Question 13

What is the size of molecules that undergo glomerular filtration?

Answer 13

MW < 6kDa

Question 14

What is type of drugs undergo glomerular filtration?

Answer 14

Molecules that are unbound to plasma proteins

Question 15

How is glomerular filtration rate determined?

Answer 15

Insulin and creatinine

Question 16

Why is insulin and creatine used to determine GFR?

Answer 16

They undergo filtration without tubular secretion and reabsorption and are not bound to plasma proteins

Question 17

What is the GFR of a healthy individual?

Answer 17

110 - 130 mL/min (180 L/day)

Question 18

What kind of process is tubular secretion?

Answer 18

Active

Question 19

What are secretion transporters of the PCT and what are do they secrete?

Answer 19

1. OATP secrete organic anions (acids)
2. OCT secrete organic cations (bases)

Question 20

What happens is probenecid is taken with penicillin?

Answer 20

Causes a drug-drug interaction where competitive inhibition that inhibits the secretion of penicillin because both drug are secreted from the same transporter

Question 21

What drives tubular reabsorption?

Answer 21

A large concentration gradient across the tubule and plasma is a driving force for passive reabsorption of solutes back into circulation

Question 22

How are small MW drugs reabsorbed?

Answer 22

Reabsorption can take place if drug is sufficiently lipophilic and remains un-ionized

Question 23

How are weak acidic and basic drugs effected by tubular reabsorption?

Answer 23

The pH of the glomerular fitrate influences their ionization

Question 24

How are large MW, polarized, or ionized molecules reabsorbed?

Answer 24

There are not reabsorbed

Question 25

Where do drug molecules go when they escape reabsorption?

Answer 25

They will exit the body through urine

Question 26

What are the factors that influence drug excretion?

Answer 26

1. Phyico-chemical properties 2. Plasma drug concentration 3. Plasma protein binding of the drug 4. Miscellaneous factors such as age, disease, and DDI

Question 27

What are the ways drug elimination can be quantified?

Answer 27

1. Half-life 2. Clearance

Question 28

What is half-life?

Answer 28

The time required for 50% of the drug to be eliminated from the body

Question 29

How is the t1/2 of drugs affected by elimination in the first-order?

Answer 29

T1/2 is independent of dose and concentration

Question 30

What is the most useful parameter to quantify drug elimination?

Answer 30

Clearance

Question 31

Why is clearance referred over t1/2 of quantifying drug elimination?

Answer 31

1. t1/2 is a function of clearance and volume of distribution 2. Half-life fails to provide insight to drug elimination and can’t predict the impact of disease or drug interactions on drug elimination

Question 32

What does ClH quantify?

Answer 32

Drug elimination by hepatic metabolism

Question 33

What does ClR quantify?

Answer 33

Unchanged (not-metabolized) drug elimination by renal excretion

Question 34

What are the components of total clearance in the body?

Answer 34

ClH + ClR