Drug Elimination and Renal Clearance - Pre Lecture

Question 1

What is drug elimination?

Answer 1

The irreversible removal of drug from the body by any route

Question 2

What are the major pathways of elimination?

Answer 2

1. Excretion of intact drug
2. Biotransformation of drug metabolism

Question 3

What are the routes of excretion?

Answer 3

1. Urine
2. Bile
3. Sweat
4. Saliva
5. Milk
6. Bodily fluids
7. Lungs

Question 4

What occurs during the Biotransformation of drug metabolism?

Answer 4

Conversion of molecule to a metabolite by enzymatic or non-enzymatic process

Question 5

What is the summation of many complex rate processes?

Answer 5

Drug elimination

Question 6

How do we quantify elimination?

Answer 6

Cl

Question 7

What is the assumption of Cl?

Answer 7

Assuming compartments are homogenous with uniform distribution

Question 8

What is clearance?

Answer 8

Volume of fluid cleared of drug per unit of time (L/h)

Question 9

How do you express Cl mathematically?

Answer 9

Cl = Vdk
Cl = elimination rate/plasma concentration
Cl = Dose/AUC

Question 10

What is the mathematically expression of elimination rate?

Answer 10

CpCl = CpkVd

Question 11

Describe the decline of plasma concentration during 1st order in regards to clearance?

Answer 11

Elimination rate will change, ration of elimination rate to plasma concentration will stay the same

Question 12

What is importance of clearance in regards to systemic exposure?

Answer 12

Encompasses efficacy and toxicity

Question 13

What is the difference between half-life and clearance?

Answer 13

Half-life: terminal phase of drug disposition
Cl: Entire system

Question 14

Why is volume concept used and not amount?

Answer 14

All drugs are dissolved and distributed within fluids of the body

Question 15

What are the 3 models of clearance?

Answer 15

1. Compartmental
2. Physiologic
3. Noncompartmental

Question 16

What is the compartmental model of clearance?

Answer 16

Static volume and 1st order processes are simpler, Cl=Vk

May not always be correct

Question 17

What is the physiologic model of clearance?

Answer 17

Looks at specific organs and bases clearance on organ blood flow (Q) and extraction of drug from this organ

Question 18

What is the noncompartmental model of clearance?

Answer 18

Examines AUC and allows us to not make assumptions inherent of modeling, assumes log-linear elimination

Question 19

What are the kidney functions?

Answer 19

1. Remove metabolic waste
2. Maintain fluid and electrolyte balance
3. Endocrine functions to regulate BP and RBC production

Question 20

How much of the kidney is our body weight?

Answer 20

0.5%

Question 21

What is the cardiac output of the kidneys?

Answer 21

20-25%

Question 22

What is glomerular filtration?

Answer 22

Blood passing through the kidney into glomerular portion while it is filtered

Question 23

How much blood does the blood filter a day

Answer 23

180L

Question 24

How much of blood filtered is excreted?

Answer 24

1-1.5L

Question 25

How much of filtered fluid is reabsorbed?

Answer 25

99%

Question 26

What molecules are filtered?

Answer 26

Small

Question 27

What molecules are reabsorbed?

Answer 27

Essential nutrients and water

Question 28

What is waste?

Answer 28

Concentrated urine that is removed from the body

Question 29

What are the properties of drugs that are excreted unchanged by the kidneys?

Answer 29

1. Non volatile 2. Water soluble 3. Low MW 4. Not metabolized or slowly metabolized

Question 30

What are the mechanisms associated with kidney excretion?

Answer 30

1. Filtration 2. Secretion 3. Reabsorption

Question 31

What transport is filtration?

Answer 31

Passive

Question 32

Where does filtration occur?

Answer 32

Glomerulus

Question 33

What is ions are filtered?

Answer 33

Either

Question 34

How does protein binding effect filtration?

Answer 34

Only free drug

Question 35

What influences filtration?

Answer 35

Protein binding

Question 36

What transport is secretion?

Answer 36

Active

Question 37

Where does secretion occur?

Answer 37

Proximal tubule

Question 38

What ions are secreted?

Answer 38

Weak acids and bases

Question 39

How does drug protein effect secretion?

Answer 39

No effect

Question 40

What influences secretion?

Answer 40

Competitive inhibitors

Question 41

What transports are reabsorption?

Answer 41

Passive and active

Question 42

What does reabsorption take place?

Answer 42

Distal tubule

Question 43

What ions are reabsorbed?

Answer 43

Nonionized

Question 44

How does drug protein effect reabsorption?

Answer 44

N/a

Question 45

What influences reabsorption?

Answer 45

Urinary pH and flow

Question 46

What are the equations of renal clearance?

Answer 46

Clr= urine excretion rate/plasma con = fe(Cl) =fe(F)(Dose)/AUC = Ae/AUC fe: fraction excreted in urine Ae: amount excreted in urine

Question 47

What compounds do we examine for clearance?

Answer 47

1. Inulin 2. Creatinine

Question 48

What is the inulin?

Answer 48

1. Excreted by glomerular filtration 2. Compare drug Cl to inulin Cl and determine whether a drug is subject to reabsorption, filtration, or secretion

Question 49

What is creatinine?

Answer 49

1. Filtered but also secreted to a lesser extent 2. CrCl is measured to determine filtration capacity of the kidney (GFR)