Pharmacokinetics - Drug Elimination

Question 1

Routes of drug elimination

Answer 1

1. Kidneys
2. Liver - bile
3. Intestines
4. lungs
5. Milk in pregnant women

Question 2

What flows through capillaries into bowman’s capsule

Answer 2

Free drug (not any bound drug)

Question 3

What does not influence the passage of drugs into the glomerular filtrate

Answer 3

1. Lipid solubility

2. pH

Question 4

What happens at the proximal tubule

Answer 4

1. Secretion of weak acids and weak bases into the renal tubule
2. Bases and acids carry bound drug into tubule via active transport (secretion)

Question 5

What happens at the distal tubule

Answer 5

If drugs are not polar enough, they will be reabsorbed into circulation

Question 6

Which part of the tubule is most sensitive to changes in pH and drug absorption

Answer 6

Distal tubule

Question 7

How can you eliminate weak acids by manipulating the pH of the urine

Answer 7

Make the urine alkaline (which will keep drug in urine for elimination)

Question 8

How can you eliminate weak bases by manipulating the pH of the urine

Answer 8

Make the urine acidic (which will keep drug in urine for elimination)

Question 9

what is the purpose of changing the pH of the urine

Answer 9

You want to “trap” the ions in order to keep the drugs ionized (polar) in order for them to be excreted and not reabsorbed

Question 10

The more ionized

Answer 10

The more easily excreted

Question 11

The more lipid soluble the more

Answer 11

difficult to eliminate (will want to be reabsorbed)

Question 12

The more polar

Answer 12

the easier to excrete

Question 13

Half - life

Answer 13

The time it takes to reduce the plasma drug concentration by half

Question 14

What causes 1/2 life to be increased

Answer 14

1. Diminished renal plasma flow
2. Diminished hepatic blood flow
3. Renal disease
4. Decreased metabolism (drug inhibition or hepatic insufficiency)

Question 15

What causes 1/2 to be decreased

Answer 15

1. Increased hepatic blood flow
2. Decreased protein binding
3. Increased metabolism

Question 16

Duration of drug action

Answer 16

The total amount of time the drug is present in the plasma or tissues and produces clinical effects

Question 17

Clearance

Answer 17

Estimates the amount of drug cleared from the body per unit of time

Question 18

Time required for elimination of drug

Answer 18

Time it takes for body to eliminate the drug. Depends on the drugs half-life and other metabolic factors.

Question 19

Steady state

Answer 19

A state in which the rate of administration equals that of elimination of the drug (drug concentration plateaus)

Question 20

How are steady state and infusion rate related

Answer 20

Have a direct relationship. If the Infusion rate is doubled, the plasma concentration achieved at steady state is doubled

Question 21

How are steady state and clearance related

Answer 21

Inverse relationship. If clearance is inhibited (decreases) steady state will increase.

Question 22

What does Css stand for

Answer 22

Steady state concentration

Question 23

What affect does a faster rate of infusion have on time needed to achieve steady state

Answer 23

None, a faster rate will only increase the concentration, not the time.

Question 24

What if you need to reach steady state sooner

Answer 24

Use a loading dose

Question 25

What is the equation for determining the time to steady state

Answer 25

Tss = 5 x half-life

Question 26

What happens to steady state if you double the dose

Answer 26

It will double the steady state level

Question 27

Creatinine clearance

Answer 27

Tests to see how much creatinine is in the blood vs the urine. If there is a high level of creatinine in the blood than the kidneys are not functioning properly

Question 28

Creatinine clearance equation (cockroft and gault)

Answer 28

(140-age) X weight/

72 X serum creatinine all multiplied by 0.85 (for women)

Question 29

What happens if the kidneys are working properly

Answer 29

Increase in drug circulating in body. Will not be properly eliminate/excreted

Question 30

Therapeutic range

Answer 30

Dosage range or blood plasma concentration that is usually expected to achieve the desired therapeutic effects. Some pts will have no relief, some will have toxic side effects

Question 31

Therapeutic index

Answer 31

AKA therapeutic window. Comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.