Clinical Pharmacology I - Pharmokinetics

Question 1

What is the standard definition of pharmacokinetics?

Answer 1

What the BODY does to the DRUG

Question 2

What is the standard definition of pharmacodynamics?

Answer 2

What the DRUG does to the BODY

Question 3

Which two processes do you need to take into account to determine the amount of drugs that a person uses?

Answer 3

Pharmacokinetics and pharmacodynamics

Question 4

What does ADME mean?

Answer 4

A: Absorption
D: Distribution
M: Metabolism
E: Elimination

Question 5

What is meant with absorption?

Answer 5

Intake into the body

Question 6

What is meant with distribution?

Answer 6

Division/partition throughout the body

Question 7

What is meant with metabolism?

Answer 7

Conversion in the body

Question 8

What is meant with elimination?

Answer 8

Excretion from the body via urine, bile and feces

Question 9

How much of the medication that is administered via IV is taken up by the body?

Answer 9

100%

Question 10

Which two factors do you have to take into account when you determine the amount of oral medication that is taken up by the body?

Answer 10

• How much of the medicine is absorbed?
• Form of the medicine (delayed-release, enteric-coating, etc.)

Question 11

How do you accomplish delayed-release?

Answer 11

Equip the pill with coating to ensure that the gastric acid can’t get through –> drug intact when it reaches the intestine

Question 12

When are oral dosage forms not useful?

Answer 12

During intensive care and/or after surgery

Question 13

Why is oral dosage not useful during intensive care and/or after surgery?

Answer 13

The stomach and intestine are often delayed or functionally immobile

Question 14

What is the definition of bioavailability?

Answer 14

The fraction of an administered dose of unchanged drug that reaches the systemic circulation

Question 15

What is the term for bioavailability?

Answer 15

F or BB

Question 16

What is the F of metoprolol and what does that mean?

Answer 16

30-70%. This means that this percentage of the administered dose reaches the systemic circulation.

Question 17

Why does the F value not correspond to the dose of oral?

Question 18

Tobramycin has a low F value. Why would you take this orally?

Question 19

Which kind of administration is the most easy to give and why?

Answer 19

IV. Absorbed instantly

Question 20

What is the order of administration routes? (fast to slow)

Answer 20

• Intravenous (IV)
• Intramuscular
• Subcutaneous
• Oral
• Rectal

Question 21

How does medication spread through the body? (4)

Answer 21

• Hydrophilic tissues: blood and muscles
• Lipophilic tissues: dermis, nerves and fat tissues
• Brain: blood-brain barrier
• Placenta/breastmilk

Question 22

Which formula’s can you use for the volume of distribution?

Answer 22

• Vd = Ab/C
• Vd = F x Dose / plasma concentration

Question 23

What do Ab and C mean?

Answer 23

Ab = quantity of drug in the body system
C = concentration in the blood

Question 24

Which substances have a high Vd and why?

Answer 24

Lipophilic substances, because they distribute to the fat

Question 25

Which substances have a small Vd and why?

Answer 25

Hydrophilic substances, because they distribute to the water

Question 26

What are the fluid compartments in the body?

Answer 26

- Intracellular fluid (within cells) - Extracellular fluid (outside cells) - Interstitial fluid (surrounding cells) - Plasma (blood)

Question 27

How can you give an unborn baby medication?

Answer 27

Low-dose for the mother

Question 28

What happens to the Vd when using drugs that diffuse to the intracellular fluid?

Answer 28

The Vd is equal to the total body water

Question 29

What happens to the Vd when using drugs that bind strongly to the tissue?

Answer 29

The Vd is higher than the total body water

Question 30

Name examples of drugs that diffuse to the intracellular fluid (2)

Answer 30

- Ethanol - Benzylpenicilin

Question 31

Name examples of drugs that bind strongly to the tissue (3)

Answer 31

- Fentanyl - Propofol - Digoxin

Question 32

Iets met body composition differences

Question 33

What is biotransformation?

Answer 33

Metabolism: chemical conversion in the body

Question 34

Which substances are created during biotransformation?

Answer 34

Metabolites (active OR inactive)

Question 35

Where does most of the conversion happen in the body and which enzymes are needed?

Answer 35

In the liver via the cytochrome P450 system

Question 36

Why do certain drugs need to be metabolized in the liver?

Answer 36

Most drugs are lipophilic. The drug must be converted to a water soluble form to be excreted by the kidneys

Question 37

What can change the "normal" breakdown of a drug? (2)

Answer 37

- Genetic polymorphisms - Drug-drug interactions

Question 38

True or false: "Slow metabolizers generally don't really have side-effects"

Answer 38

False. Slow metabolizers generally suffer from more severe side-effects

Question 39

To what is codeine metabolized in the liver and which enzyme is responsible for this conversion?

Answer 39

Morphine. CYP2D6

Question 40

What can be said about the effect of codeine for the different metabolizer types?

Answer 40

- UR: high [morphine], increased effect - NM: average [morphine], normal effect - SM: low [morphine], decreased effect

Question 41

What happened to the baby that died when the mother took codeine?

Answer 41

- Mother was an ultra-rapid metabolizer - Biotransformation by CYP2D6 to morphine - Over-dose of morphine reached the baby

Question 42

How can a high blood concentration of codeine that has been adminstered to the mother cause morphine intoxication of a baby?

Answer 42

- Directly into fetus via placenta - Breastmilk

Question 43

What will be drawn up when you don't respond to a drug as expected?

Answer 43

Pharmacokinetic profile

Question 44

When are dose adjustments necessary when drugs are primarily eliminated via the urine?

Answer 44

If a patient suffers from renal dysfunction

Question 45

Why are pharmacokinetics important?

Answer 45

To investigate and predict reactions to medicines

Question 46

What is meant with 'intra-patient'?

Answer 46

One person reacts differently to the same medication in multiple or repeated dosings

Question 47

What is meant with 'inter-patient'?

Answer 47

Differences between a group in how individuals react to a medication

Question 48

Which parameters play a role in onset?

Answer 48

- C max: maximum concentration - T max: time when the maximum blood concentration is reached

Question 49

Which parameter plays a role in duration?

Answer 49

Cl: clearance. Elimination out of the body

Question 50

What is clearance?

Answer 50

The volume of plasma cleared of the drug per unit time (liter/hour)

Question 51

Which parameter plays a role in half-life?

Answer 51

T1/2: time necessary to decrease the blood concentration of a medication by 50%

Question 52

How can the half-life be prolonged?

Answer 52

- Renal impairment - Intoxication

Question 53

What is the general rule for when the medication should be out of the blood?

Answer 53

4-5x T1/2

Question 54

When is a level steady?

Answer 54

3-5x T1/2

Question 55

Which parameter covers the exposure to the drug?

Answer 55

AUC = area under the curve when plasma drug concentration is plotted vs time

Question 56

Which parameters go up when clearance is decreased?

Answer 56

- Half-life - AUC

Question 57

What is a pitfall if you give antibiotics to someone on the sub-therapeutic level?

Answer 57

Antibiotic resistance