BP 6 – Pharmacokinetics: Absorption and distribution

Question 1

Where do drugs accumulate?

Answer 1

In the fat/bone

Question 2

How does the drug absorbed and cross through the cell membrane?

Answer 2

Passive diffusion down concentration gradient - moves to the area with less drug concentration 
Active transport (especially GI tract) - selectively absorbed

Question 3

What type of compounds are absorbed faster and more easily across cell membranes?

Answer 3

Lipid-soluble compounds (must be in solution)

Question 4

How are drugs taken?

Answer 4

Enteral - oral route (stomach/SI), sublingual and rectal/vaginal

Parenteral - injection, IV, intramuscular, subcutaneous, transdermal, inhaled, intrathecal

Question 5

Why is the stomach not an important site of absorption?

Answer 5

Many drugs are not absorbed here as has a low pH

Question 6

What type of drugs are absorbed in the stomach?

Answer 6

Mainly weak acids

Small amounts of aspirin, NSAIDs and alcohol

Question 7

What is the top and bottom of the stomach called?

Answer 7

Top - fundus

Bottom - pylorus

Question 8

What are the layers of the stomach outer to inner?

Answer 8

Serosa, muscle layers, submucosa, mucosa

Question 9

What is the pH from duodenum to terminal ileum?

Answer 9

pH 6 to 7.4

Question 10

What type of drugs are absorbed in the SI?

Answer 10

Most weak bases

Question 11

Why is the SI a good site of absorption?

Answer 11

Large, highly permeable, vascularised SA

Question 12

What are the advantages of oral administration?

Answer 12

Safe, conventional and economical

Question 13

What are the disadvantages of oral administration?

Answer 13

• Irritant drugs cause sickness
• Cannot give to vomiting patients
• Some drugs destroyed by gut acid/flora
• Intestinal absorption can be erratic

Question 14

What are the factors affecting GI absorption?

Answer 14

Gut motility
Gut pH
Physio-chemial interactions
Partile size and formation

Question 15

What antibiotic binds to Ca rich foods?

Answer 15

Tetracycline

Question 16

Define bioavailability.

Answer 16

Fraction of administered drug dose that enters systemic circulation

Question 17

Define first-pass metabolism.

Answer 17

In intestine and liver before drug reaches systemic circulation

Question 18

What is the bioavailability for an iv dose?

Answer 18

1

Question 19

What is the bioavailability fir an extra-vascular dose, e.g. oral?

Answer 19

<1

Question 20

What are the limitations of bioavailability?

Answer 20

Each individuals enzyme activity, gastric pH, gut motility and does not consider the rate of absorption

Question 21

When is sublingual administration used?

Answer 21

In cardiac patients, getting to ICA very fast

Question 22

What are the benefits of sublingual administration?

Answer 22

Fast response
Utilises venous drainage from the mouth to the superior vena cava
Avoids 1st pass metabolism

Question 23

Why is vaginal/rectal absorption used?

Answer 23

Bypasses the GI first pass effects
Rich blood supply
Absorption may be fast and extensive

Question 24

What is the pH for vaginal/rectal absorption?

Answer 24

pH 7-8

Question 25

What are the advantages clinically of vaginal/rectal absorption?

Answer 25

Useful when drug causes nausea and vomiting, or if the patient is already vomiting

Question 26

What are the rectum drainage?

Answer 26

Middle and inferior rectal veins go the systemic circulation | Superior rectal vein - is portal vein to the liver

Question 27

What are the advantages of intravenous injection?

Answer 27

Predictable, very rapid action Alternative route for drugs which are irritant by (im) Iv infusion for ill, hospitalised patients

Question 28

What are the disadvantages of intravenous injection?

Answer 28

Difficult /painful Risk of infection Cost and safety Immediate adverse effects

Question 29

What is the advantage of subcutaneous or intramuscular injection?

Answer 29

Faster systemic effect than oral administration/ local effect

Question 30

What is an example of subcutaneous or intramuscular injection?

Answer 30

Local anaesthetic

Question 31

What are the important ways in which drugs cross cell membranes?

Answer 31

Passive diffusion through lipid Diffusion through aqueous channel Carrier mediated transport

Question 32

Do ionised or unionised substances have high lipid solubility?

Answer 32

Unionised

Question 33

Do ionised or unionised substances have low lipid solubility?

Answer 33

Ionised

Question 34

What does pKa measure?

Answer 34

Strength of acid/base

Question 35

If pH of solution = pKa of drug, what is said about the drugs ionisation?

Answer 35

The drug is 50% ionised

Question 36

Why can aspirin move across the cell membrane in the stomach?

Answer 36

Aspirin is mostly unionised (neutral) | Aspirin also has a pKa of 3.5

Question 37

What is drug distribution throughout the body dependent on?

Answer 37

Ability to cross the cell membranes - membrane permeability - lipid solubility Blood flow into individuals - blood perfusion Extent of its plasma protein binding Tissue binding

Question 38

Why can the lungs and the liver get drugs rapidly distributed to them?

Answer 38

Tissues are well perfused

Question 39

What tissues are poorly perfused?

Answer 39

Fat, muscle and skin therefore the distribution rate is slower

Question 40

What tissues does drug distribution go through?

Answer 40

Blood vessel --> Interstitium --> Tissue cell

Question 41

When are drugs active, when they are free or plasma protein bound?

Answer 41

Free (unbound) drugs are active

Question 42

What does drug binding to plasma proteins depend on?

Answer 42

Concentration of free drug Affinity for the binding sites Concentration of plasma proteins

Question 43

What happens to the therapeutic effects if a drug is highly plasma protein bound?

Answer 43

Prolonged therapeutic effects and also slower acting

Question 44

Why does tetracycline accumulate slowly in bones and teeth?

Answer 44

Has a high affinity to calcium - therefore should not be used in children

Question 45

What is the calculation of the volume of distribution?

Answer 45

Total dose or drug in the body divided by the drug conc in plasma

Question 46

What shows a large volume of distribution?

Answer 46

Drugs accumulate outside the plasma in peripheral tissues e.g. stored in fat

Question 47

What shows a small volume of distribution?

Answer 47

Drugs confined to the plasma - are too large to cross the capillary wall easily

Question 48

What 2 key binding proteins are in the plasma? and where are they produced

Answer 48

Albumin Alpha 1 acid glycoprotein Produced in the liver

Question 49

What drugs bind to albumin?

Answer 49

Mostly basic and some neutral

Question 50

What drugs bind to alpha 1 acid glycoprotein?

Answer 50

Mostly acidic and some neutral

Question 51

When does albumin become depleted?

Answer 51

Malnutrition | Cirrhosis

Question 52

When does alpha 1 acid glycoprotein become elevated?

Answer 52

Acute phase protein, elevated in some diseases (cancer), inflammation