Excretion Lecture

Question 1

Define elimination

Answer 1

Irreversible loss of drug from the body via either of the processes of metabolism or excretion

Question 2

Define metabolism

Answer 2

Loss of drug from the body by chemical conversion

- Primarily occurs in the liver

Question 3

Define excretion

Answer 3

Loss of drug from the body by diffusion, filtration, evaporation or transport process
- Primarily occurs in the kidney or liver

Question 4

Define pharmacokinetics

Answer 4

Expresses the rate of elimination of a drug as the change in drug concentration with the passage of time: dc/dt-C^n= -kC^n
n= 0 is zero order
n= 1 is first order

Question 5

Define rate constant

Answer 5

Function of the slope of the elimination line seen when fall in drug conc is plotted vs time

Question 6

Define volume of distribution

Answer 6

Apparent volume into which a drug “appears” to be dissolved, if the conc is mearsured in the blood

Question 7

Define half life

Answer 7

Amount of time require for the concentration of the drug to fall by one-half in the blood stream

Question 8

Define clearance

Answer 8

Amount of blood “cleared” of the drug by a define process in a unit of time
- Refers to the body’s ability to rid itself of a drug, waste or other substance
= rate of elimination/drug concentration

Question 9

Zero order kinetics?

Answer 9

C^0 = 1; rate of elimination is unrelated to concentration

Question 10

First order kinetics?

Answer 10

C^1 = C; rate of elimination is dependent on concentration

Question 11

Define total clearance

Answer 11

sum of all possible routes of metabolism and excretion of the substance being considered

Question 12

Define metabolic clearance

Answer 12

liver metabolism + other organ metabolism

Question 13

Define excretory clearance

Answer 13

Renal and biliary + other excretion

Question 14

Define renal clearance

Answer 14

Action of the kidneys only

Question 15

Define hepatic clearance

Answer 15

Action of the liver only

Question 16

What are metabolic and transport processes mediated by?

Answer 16

Enzymes or transporters which can be saturated at a given drug concetration

Question 17

What are three processes involved in renal excretion?

Answer 17

Glomerular filtration
Tubular reabsorption
Tubular secretion

Question 18

Define glomerular filtration

Answer 18

Filtration based on size

• Plasma like filtration
• 5,000-20,000 MW
• – which is why we do not lose drugs that are bound to albumin because they are too large to be filtered

Question 19

Define tubular reabsorption

Answer 19

Removes useful solutes and returns them to the blood stream

Question 20

Define tubular secretion

Answer 20

Removes wastes from the blood and secretes them into the filtrate –> Increases the loss

Question 21

Why for many drugs (Ceftazidime and Cefepime) is there clearance greatly dependent upon renal function?

Answer 21

Bc it varies with GFR

- Reduced GFR occurs with aging and a number of diseases leading to dramatic delay of drug clearance for the body

Question 22

Renal clearance can also be effected by?

Answer 22

Amount of free drug in plasma because that is the drug available for glomerular filtration and secretion

Question 23

What is renal tubular reabsorption?

Answer 23

99% of filtered fluid is reabsorbed in the renal tubules

- Passive diffusion and active transport

Question 24

What are factors that influence reabsorption?

Answer 24

Urine flow: too rapid may not have time to catch the stuff it needs
Urine pH: can make a molecule into something that cannot be reabsorped
Lipophilicity of a drug:
Transport modulation: drugs can modify transports so things are not lost or lost

Question 25

What is hepatic excretion?

Answer 25

Drugs can be actively transported form the plasma to the bile and then into the intestines for elimination in feces
- Needs to be at least 400 MW to get into the bile, if it can’t be conjugated to glucuronic acid and gotten up to that weight then it will be turned back into the blood stream

Question 26

What is enterohepatic circulation (recycling effect)?

Answer 26

Drugs excreted into the bile may be freed by enzymes in the intestinal flora
- Then they can be reabsorbed and pass through circulation again –> increased half life and decreased clearance

Question 27

What is pulmonary elimination?

Answer 27

Drugs that are volatile will equilibrate between capillary blood and alveolar gas and be eliminated as an evaporated substance in expired air
- Ketoacidosis in diabetic: smell of acetone on their breath

Question 28

Drug elimination in breast milk?

Answer 28

No active secretion, only passive diffusion
Concentration in milk reflects free concentration in blood
Milk is slightly acidic compared to blood

Question 29

What can chloramphenicol cause in infants?

Answer 29

Possible bone marrow suppression

Question 30

What can diazepam cause in infants?

Answer 30

Accumulation and sedation

Question 31

What can heroin cause in infants?

Answer 31

Prolong neonatal dependence

Question 32

What can methadone cause in infants?

Answer 32

Possible withdrawal syndrome if breast feeding is suddenly stopped

Question 33

What can Propylthiouracil cause in infants?

Answer 33

Suppression of thyroid function

Question 34

What can tetracycline cause in infants?

Answer 34

Permanent staining of teeth

Deposits in long bone

Question 35

How is drug excretion in saliva and sweat important?

Answer 35

Way to test for illegal drugs
Non-invasive and suitable for a variety of drug test
Some drugs are interferred with in saliva bc of pH though

Question 36

Define total body clearance

Answer 36

Sum of the clearances by all the possible routes of elimination