ADME

Question 1

What are the 2 main types of drug administration?

Answer 1

• Enteral
• Parental

Question 2

Define enteral

Answer 2

via GI tract

Question 3

Define parenteral

Answer 3

Not via GI tract

Question 4

What is the main disadvantage of sublingual administration?

Answer 4

Drug must be lipid soluble (only suitable for small molecules)

Question 5

Give 3 examples of enteral administration

Answer 5

• oral
• Sublingual
• Rectal

Question 6

What is the main advantage of rectal and sublingual administration?

Answer 6

Little 1st Pass effect

Question 7

What are the advantages of intramuscular administration?

Answer 7

The drug sits in the muscle for a long time and is released slowly (ensures more vulnerable patients take the drug)

Question 8

Give 3 examples of parenteral administration

Answer 8

• Intravenous
• Intramusclar
• Subcutaneous

Question 9

What is the oral bioavaliability of a drug?

Answer 9

Fraction of an oral dose that ends up in the systemic circulation

Question 10

How is oral bioavaliability measured?

Answer 10

• The same dose of a drug is administered 2 different ways and a Cp time graph is generated
• Alternatively F can be found for 2 or more drugs given orally at different times provided the dose is the same

Question 11

Why is isolated tissue used in oral bioavaliability studies?

Answer 11

It allows the drug to be easily washed off and addition of another drug made

Question 12

Does bioavaliability affect the EC₅₀ of a drug?

Answer 12

Yes

Question 13

What factors affect the oral bioavaliability of a drug?

Answer 13

• Poor absorption from the gut
• Breakdown of drug in gut
• First Pass effect

Question 14

What is the 1st pass effect?

Answer 14

• When drugs enter the bloodstream they first pass through the liver before entering the systemic circulation
• The Liver contains many enzymes and so some drugs are heavily metabolised in the liver

Question 15

What factors affect drug absorption at a membrane?

Answer 15

• Lipid solubility
• Ability to cross via passive diffusion

Question 16

What factors affect absorbance of a drug?

Answer 16

• pKa of drug and pH of absorbing surface
• drug preparation
• area of absorbing surface
• rate of blood flow to absorbing surface ([gradient])
• Food in stomach

Question 17

Why can only the unionized form of a drug cross mucosal membranes?

Answer 17

Otherwise they are not lipid soluble enough

Question 18

What is drug distribution?

Answer 18

Penetration of the drug into tissues and organs from the blood

Question 19

What does the extent of distribution depend on?

Answer 19

• Lipid solubility
• Tightness/extent of plasma protein binding
• Rate of blood flow to tissues

Question 20

What is the usual affect of high lipid solubility on distribution?

Answer 20

Tends to increase extent of distribution

Question 21

What is apparent volume of distribution?

Answer 21

Volume of water in which drug would have to be distributed to give its plasma concentration

Question 22

What are the units of apparent volume of distribution?

Answer 22

Volume or volume/mass

Question 23

Can apparent volume of distribution be larger than total body water?

Answer 23

Yes

Question 24

What is useful about calculating volume distribution?

Answer 24

• Partly determines plasma half life in blood
• Used in pharmacokinetics calculations to design dosing schedules

Question 25

Does apparent volume of distribution change?

Answer 25

Not usually

Question 26

Why might apparent volume distribution change?

Answer 26

* Age (due to decreased intracellular water and increased fat) * Obesity (lipid soluble drugs)

Question 27

What is elimination?

Answer 27

Overall removal of drug from the body

Question 28

Where does metabolism occur in the body?

Answer 28

* Liver (most important) * Lungs * Kidneys * Plasma

Question 29

What is half life of a drug?

Answer 29

The time taken for the plasma concentration of a drug to fall to half its initial value

Question 30

What is clearance?

Answer 30

The amount of plasma which is cleared of its drug content in unit time

Question 31

What are the features of 1st order drug elimination?

Answer 31

* half life is constant * most common kinetics * rate of elimination depends on how much drug is present

Question 32

What are the features of 0 order drug elimination?

Answer 32

* half life increases * saturation of elimination process * rate of process is independent of [drug]

Question 33

What is a pseudo 0 order elimination?

Answer 33

At [high] elimination process is saturated and so appears 0 order but as time increases the elimination becomes 1st order

Question 34

What is the C_ss?

Answer 34

The steady state concentration where rate of elimination=rate of infusion

Question 35

Approximately how many half lives are required for the C_ss to be reached (for 1st order kinetics)?

Answer 35

5

Question 36

How does infusion rate affect the C_ss?

Answer 36

The actual value of Css depends on the infusion rate but the time to reach it will not vary

Question 37

Generally how are drugs and metabolites which are not lipid soluble excreted?

Answer 37

Via the kidneys

Question 38

How can urinary excretion of a weak acid be increased?

Answer 38

Make the urine more alkaline

Question 39

How can urinary excretion of a weak base be increased?

Answer 39

Make urine more acidic

Question 40

Why is a prodrug sometimes used?

Answer 40

If the drug has low bioavaliability so otherwise would not get to the site

Question 41

What are the 3 types of metabolites drugs can form?

Answer 41

* inactive * active * toxic

Question 42

Give an example of a drug which is metabolised to produce an active metabolite

Answer 42

Codeine (metabolised to morphine)

Question 43

What occurs in phase 1 of hepatic drug metabolism?

Answer 43

A drug derivative formed by introducing a reactive site into or exposing a reactive site on the drug molecule

Question 44

Why do phase 1 metabolism reactions make the drug derivative more reactive?

Answer 44

So it is more likely to undergo phase 2 reactions

Question 45

What occurs in phase 2 metabolic reactions?

Answer 45

The joining together of species formed in phase 1 with polar molecules making metabolites less lipid soluble and so easier to excrete in urine

Question 46

Is phase 2 catabolic or anabolic?

Answer 46

Anabolic

Question 47

Is phase 1 anabolic or catabolic?

Answer 47

Catabolic

Question 48

Do drugs have to undergo phase 1 metabolism?

Answer 48

No

Question 49

Where do phase 1 reactions usually occur?

Answer 49

On the endoplasmic reticulum of liver cells

Question 50

Where do phase 2 reactions usually occur?

Answer 50

In the cytosol of liver cells

Question 51

What is enzyme induction?

Answer 51

The process by which over some time some drugs can induce increased expression of cytochrome p450 enzymes

Question 52

What is the problem with enzyme induction?

Answer 52

Can cause the failure of some drugs to produce a clinical effect

Question 53

What factors affect drug metabolism?

Answer 53

* Enzyme induction * Enzyme inhibition * Genetic polymorphism * Disease * Age

Question 54

What is the effect of enzyme induction on clearance?

Answer 54

It is increases clearance

Question 55

What is the effect of enzyme induction on C_ss?

Answer 55

Decreases it

Question 56

What is enzyme inhibition?

Answer 56

The process by which some drugs directly inhibit P450 enzymes, this occurs immediately after the drug is taken (no delay like induction)

Question 57

What is problem with enzyme inhibition?

Answer 57

It takes much longer for a drug to be broken down so can cause toxicity

Question 58

Disease of which organs affects drug metabolism most?

Answer 58

* Liver * Kidneys * Thyroid (affects metabolising enzymes) * Heart (affects rate of delivery of drug to liver/kidney)

Question 59

How does age affect drug metabolism?

Answer 59

Generally the rate of drug metabolism is lower in the very young and old

Question 60

What affects the rate of elimination of a drug which is eliminated by a process of 1st order kinetics?

Answer 60

The concentration of drug