Pharmacokinetics 1

Question 1

What are the four main processes in drug therapy?

Answer 1

Pharmaceutical process
Pharmacokinetic process
Pharmacodynamic process
Therapeutic process

Question 2

Which ways can drugs be administered?

Answer 2

Focal or systemic.

Question 3

What is focal administration?

Answer 3

When a drug is targeted to the desired organ or tissue.

Question 4

What types of systemic administrations are there?

Answer 4

Enteral and parenteral administration.

Question 5

What is enteral administration?

Answer 5

Oral, sublingual and rectal. SOR

Question 6

What is parenteral administration?

Answer 6

Any other means of administration. Subcutaneous, Intramuscular, Intravenous, Inhalation and Transdermal
SIIIT

Question 7

What are advantages of focal administration?

Answer 7

Concentrates the drug at site of action

Less systemic absorption and fewer side effects

Question 8

Which route do enteral drugs take?

Answer 8

The GI-tract.

Question 9

Which route do parenteral drugs take?

Answer 9

Any other route than GI-tract.

Question 10

What is transit time?

Answer 10

The time the drug is in the GI-tract. During this time the drug will continuously be absorbed into the blood system or tissue along the GI-tract.

Question 11

Where is most enteral drug absorption taking place?

Answer 11

In the small intestines.

Question 12

How are drugs absorbed?

Answer 12

By passive diffusion
Facilitated diffusion
Primary and secondary active transport
Pinocytosis

Question 13

Give examples of types of drugs that are absorbed by passive diffusion.

Answer 13

Lipophilic drugs and weak acids and bases.

Question 14

When pH is equal to pKa what is this an indication of?

Answer 14

That the half of the acid has dissociated.

Question 15

What is the predominant form of lysine with a pK of 10.5 in a physiological pH of 7.4?

Answer 15

Lysine will be protonated.

Question 16

What is the predominant form of aspartate with a pK of 2.8 in a physiological pH of 7.4?

Answer 16

Aspartate will be deprotonated.

Question 17

Which drugs can be absorbed via passive diffusion?

Answer 17

Lipophilic drugs and weak uncharged acid and bases that are either protonated or deprotonated.

Question 18

Valproate is a weak acid with a pKa of 5. The gut’s pH is around 6. This means that the most of valproate will be deprotonated and charged, however around 10% of the valproate is protonated and lipophilic. Why is this important?

Answer 18

This means that there will be a rather slow uptake of the drug. As 10% of the valproate is taken up the equilibrium will continuously shift so that there is always 10% valproate that is protonated.

Question 19

What are drugs absorbed by via facilitated diffusion?

Answer 19

SLCs also called solute carrier transport.

Question 20

There are two types of SLCs. Which?

Answer 20

Organic Anion Transporters and Organic Cation Transporters. OATs and OCTs.

Question 21

Where can OATs and OLCs most commonly be found?

Answer 21

In GI, hepatic and renal epithelia.

Question 22

What are drugs absorbed by via secondary active transport?

Answer 22

Via SLCs as well.

Question 23

How are the drugs absorbed via secondary active transport?

Answer 23

Usually via a pre-existing electrochemical gradient. An example of that is as Na+K+ATPase sets up a gradient for Na+, Na+ will enter the cell with the drug by co-transport. This is the case of Prozac.
H+ can also help in co-transport of drugs.

Question 24

Give some factors that affect drug absorption.

Answer 24

GI-surface area and length.
Drug lipophilicity and pKa
SLC expression density
Blood flow - increased after a meal
GI motility - slow after a meal
Food/pH - food can either reduce or increase uptake. Low pH can destroy some drugs.

Question 25

What is the first pass of metabolism of drugs?

Answer 25

Absorption to the liver. Most drugs are deactivated by the liver, however a few are actually activated. Metabolism also occur in the GI-tract.

Question 26

In the gut wall and liver some drugs are metabolised by two major enzyme groups. Which?

Answer 26

Cytochrome P450s which are phase 1 enzymes

Conjugating enzymes which are phase 2 enzymes

Question 27

Where can you usually find phase 1 and phase 2 drugs?

Answer 27

In the liver but also gut wall.

Question 28

What is the purpose of first pass metabolism?

Answer 28

To reduce drug availability reaching the systemic circulation. This affects therapeutic potential.

Question 29

How can you avoid first pass metabolism?

Answer 29

By avoiding the oral route or the enteral route all together. However usually it is avoid by instead using parenteral, rectal or sublingual drugs.

Question 30

What does the amount and rate of the an oral drug depend on?

Answer 30

Depends on 1st pass metabolism and gut absorption
Rate depends on pharmaceutical factors, gut absorption like pH, pKa, lipophilicity, GI surface area and length, SLC expression density etc.

Question 31

There are other factors affecting drug distribution. Which?

Answer 31

Degree of drug binding to plasma and/or tissue proteins.

Question 32

What plasma or tissue proteins can drugs bind to?

Answer 32

Albumin, globulins

Lipoproteins like acid glycoproteins

Question 33

What happens to the drugs when albumin binds to it?

Answer 33

It’s not considered a free drug anymore and cannot be taken up by the target tissue. Only free drug molecules can bind to target sites.

Question 34

What are the functions of plasma proteins?

Answer 34

They can bind to drugs in order to make them not available for uptake. This means they act as a reservoir and can be used later on. The binding forces are not strong which means there is a bound to unbound equilibrium like the valproate protonated pKa principle.
It can bind up to close to 100%. Warfarin is bound by 90%, aspirin 50%.

Question 35

Briefly explain the therapeutic window.

Answer 35

The therapeutic window is a window of where you want the drug to be. This is the desired therapeutic effect. To the left is the minimum effective dose and to the right is the maximum tolerated dose.

Question 36

What happens if you don’t achieve minimum effective dose?

Answer 36

The drug will not have it desired therapeutic effect.

Question 37

What happens if a drug exceeds it therapeutic window and ends up beyond the maximum tolerated dose?

Answer 37

A drug will have unwanted adverse effects as it is in a toxic concentration.

Question 38

What does it mean when a drug is said to have a small therapeutic window?

Answer 38

You don’t have a lot of wiggle room. The difference in dosage can be detrimental to its effect. A small change in the concentration of the drug can cause unwanted adverse effect or it might not have an effect at all.

Question 39

What can influence the therapeutic window?

Answer 39

How fast a drug is released in the system. A fast release can easily cause a toxic concentration and a slow release might not achieve the desired effects.

Question 40

What is volume of distribution?

Answer 40

The amount of a drug that is distributed if the drug was introduced instantaneously, intravenous for example.
It is a theoretical volume.

Question 41

Why do we used volume of distribution?

Answer 41

It provides a summary measure of drug molecular behaviour in distribution.

Question 42

How is it obtained?

Answer 42

By extrapolation of plasma levels at zero time.

Question 43

What does a small volume of distribution mean?

Answer 43

There’s a low penetration of the drug into interstitial and intracellular fluid compartments. Meaning most of the drug is still in the plasma.

Question 44

What does a high volume of distribution mean?

Answer 44

There’s a greater penetration of the drug into interstitial and intracellular fluid compartments. This means a low plasma drug concentration.

Question 45

What would affect the volume of distribution?

Answer 45

The charge of the drug, whether it is lipophilic or not. Whether it is prone to protein binding.
Changes in body weight
Renal failure
Changes in regional blood flow
Hypoalbuminimea

Question 46

A charged drug, a highly lipophilic drug and a drug with degree of plasma protein bindings are introduced into the body. Rank their volume of distribution assuming nothing else is at play.

Answer 46

From highest to lowest:
Highly lipophilic drug
Plasma protein bound drug = charged drug

Question 47

Give some features of warfarin regarding to protein binding, volume of distribution and therapeutic window.

Answer 47

High protein binding (90%)
Small volume of distribution
Narrow therapeutic window

Question 48

What are class 1 drugs?

Answer 48

Object drugs.

They are used at a dose lower than the number of albumin binding sites.

Question 49

What are class 2 drugs?

Answer 49

Precipitant drugs.
They are used at a dose greater than the number of binding sites. This means they will displace the class 1 drug.

Question 50

Why could introducing a class 2 drugs when a class 1 has already been administered be detrimental?

Answer 50

Because the class 2 drug will displace the class 1 drug meaning that the class 1 drug won’t be bound anymore to their proteins in the same concentration. This gives a higher concentration of free drug of the class 1 drug in the blood plasma and it might have unwanted adverse effects as it is not planned to be released in such a way.

Question 51

Give an example of the above.

Answer 51

Warfarin is protein bound and a class 1 drug. 90% is bound and has a narrow therapeutic window. Aspirin is a class 2 drugs. If aspirin is taken at the same time it will displace and free warfarin. Warfarin can then be taken up in greater amounts and might give unwanted adverse effects due to its small therapeutic window.