Lecture 34 - Pharmacokinetics 1

Question 1

What are the principles of Pharmacokinetics?

Answer 1

A: absorption
D: distribution
M: metabolism
E: excretion

Question 2

What are the different routes of delivery?

Answer 2

Oral
Sublingual
Intramuscular
Intravenous
Transdermal
Suppository
Inhalational
Topical

Question 3

Which route of delivery gives the fastest delivery into the blood?
What about other routes?

Answer 3

I/ Intravenous
II/ Intravenous
III/ Subcutaneous
IV/ Oral

Question 4

What are the barriers to permeation?

Answer 4

Epithelial linings
Tight junctions
Lipid cell membrane

Question 5

What is the structure of a villous?

Answer 5

Enterocytes with microvilli
Rich blood supply, capillaries
High SA:V ratio

Question 6

Relate the structure to the function of villi

Answer 6

Great SA: for absorption
Capillaries: keeps a constant concentration gradient
Mitochondria: energy for active transport into the cells
Thin intima
Many transporters

Question 7

How can substances cross the epithelium?

Answer 7

Around cells:
- Paracellular

Through cells:

• Transcellular, diffusion
• Transporter

Question 8

How can substances cross the cell membrane?

Answer 8

1 - Diffusion
2 - Through a pore (Aqueous diffusion)
3 - Carrier: active / facilitated
4 - Pinocytosis

Question 9

Which drugs can get into cells the most readily?

Answer 9

Lipid soluble drugs

Question 10

Lipid solubility is dependent on:

Answer 10

• Intrinsic structure

- pH of conditions

Question 11

Describe compartment trapping of Aspirin

Answer 11

1. Aspirin is a weak acid
2. In stomach, it is protonated, neutral
3. Diffuses across cells into blood
4. Blood pH is 7.4
5. Aspirin is ionised in the blood
6. Can no longer diffuse through cells

Question 12

What is ‘distribution’ of drugs?

Answer 12

Which organs and tissues the drug goes to from the blood

Question 13

What is ‘absorption’ of drugs?

Answer 13

How the drug gets into the body

How it gets across cell membranes

Question 14

What is the difference between normal and fenestrated capillaries?

Answer 14

Normal: continuous

Fenestrated: holes, through which material can move

Question 15

Capillaries of which organs are fenestrated?

Answer 15

Liver, hepatic sinusoids
Kidney
Intestines

Question 16

When is pericellular passage possible?

Answer 16

When the capillaries are loose

Question 17

Describe the capillaries in the brain

Answer 17

Very tight junctions

Nothing can move between cells (pericellular)

Question 18

How can a substance get into the brain?

Answer 18

• Be lipid soluble, small, uncharged

- Have a transporter

Question 19

Why are some antihistamines drowsy, and some not?

Answer 19

Old type: lipid soluble, gets into the brain, activates drowsiness centre

New type: (fexofenadine): not lipid soluble, can’t get across blood brain barrier

Question 20

Which types of organs are readily accessible to drugs?

Answer 20

Organs with fenestrated capillaries

Question 21

Describe blood flow to different organs

Answer 21

Different organs get different blood flow

High: brain, kidney, liver, heart

Low: Fat, muscle

Question 22

What is blood-flow dependent distribution?

Answer 22

Delivery depends on different things, depending on whether the organ receives a lot of blood

Low flow: delivery depends on flow and drug concentration

High flow: delivery depends on flow

Question 23

What is thiopental?

Answer 23

An anaesthetic

Question 24

What are the features of thiopental?

Answer 24

Lipid soluble

Question 25

How is thiopental administered?

Answer 25

Intravenous injection

Question 26

When in the peak concentration of thiopental in the brain?

Answer 26

10 minutes after injection

Question 27

When does thiopental peak in muscle?

Answer 27

20 minutes

Question 28

When does thiopental peak in fat?

Answer 28

6 hours

Question 29

Describe the delivery of thiopental to different organs in the body

Answer 29

Initially: goes to brain, then is ejected out after 10 mins Then: goes to muscle Later: slowly builds up in fat

Question 30

Why does thiopental build up in lipid? | Why does it take a long time for thiopental to go here?

Answer 30

Thiopental has an affinity for lipid It takes a while to build up here because there is poor blood flow to fat

Question 31

What determines the drug's stability in the body?

Answer 31

Whether or not it binds to a protein

Question 32

Give an example of a drug binding to a protein in the blood

Answer 32

Thyroxine binds to a globulin (TBG) | Prevents thyroxine from being filtered out by the kidney

Question 33

What does protein binding of drugs affect?

Answer 33

Distribution | Clearance

Question 34

Why does thyroxine only have to be taken once a week?

Answer 34

Because it binds to Thyroxine Binding Protein --> it now has a longer half life

Question 35

What is the function of Albumin?

Answer 35

Generic drug binding protein

Question 36

Where is the vast amount of drug metabolism performed? | What is this called

Answer 36

First Pass Metabolism In the liver

Question 37

"All roads lead to Rome" | What is rome in this metaphor?

Answer 37

The liver is rome Blood from the gut goes directly to the liver

Question 38

Which routes of delivery avoid first pass metabolism?

Answer 38

Sublingual | Inhalational

Question 39

Can drugs be absorbed in the mouth?

Answer 39

Some can Under the tongue, where the epithelium is thin and there is much blood flow

Question 40

Can drugs be absorbed in the eosophagus?

Answer 40

No

Question 41

Can drugs be absorbed in the stomach?

Answer 41

No, it has protective mucous to prevent acid damage

Question 42

Why is the Henderson-Hasselbach equation important?

Answer 42

Drugs may be charged or uncharged in certain pHs

Question 43

When are weak acids charged? When are weak bases charged?

Answer 43

Weak acids: in basic solution Weak bases: in acidic solution