Pharmacokinetics 1

Question 1

What does pharmacology mean?

Answer 1

Origin, nature, chemistry, effects and uses of drugs

Question 2

What does toxicology mean?

Answer 2

Study of the adverse effects of chemical, physical or biological agents

Question 3

What does pharmacodynamics mean?

Answer 3

What the drug does to the body

Question 4

What does pharmacokinetics mean?

Answer 4

What the body does to the drug

Question 5

What are the 5 stages that a drug will undergo pharmacokinetically as it passes through the body?

Answer 5

(Liberation) Absorption Distribution Metabolism Excretion

Question 6

(Write some on routes of drug administration)

Answer 6

ye

Question 7

What is the bioavailability of a drug?

Answer 7

Fraction of unchanged drug that reaches the systemic circulation
IV injection gives 100% bioavailability

Question 8

What are the four ways that small molecules cross cell membranes?

Answer 8

1) Diffusing directly through the lipid
- Lipid solubility highly importan
2) Diffusing through aqueous pores
- More likely important for diffusion of gases
3) Transmembrane carrier protein
- e.g. solute carriers
4)
Pinocytosis
- Mostly macromolecules, not drugs

Question 9

Describe the solubility of hydrophilic and lipophilic drugs

Answer 9

Hydrophilic drugs are soluble in aqueous, polar media.

Lipophilic drugs are soluble in fats and non-polar solutions

Question 10

What parts of the cell will hydrophilic and lipophilic drugs pass through respectively?

Answer 10

Blood plasma, cytosol and interstitial fluid are aqueous, polar media.
The interior of the lipid bilayer and fat are non-polar.

Question 11

Why is drug absorption linked to ionisation?

Answer 11

Many drugs are weak acids or bases
• Ionised:unionised ratio depends on pH
• Ionised drugs have low lipid solubility

Question 12

What are the pH ranges of areas of the body?

Answer 12

Gastric acid (pH 1.0–3.0) Large intestine (pH 8.0) Small intestine (pH 5.0–6.0) Plasma (pH 7.4)

Question 13

In what situations will there be barriers to drug absorption?

Answer 13

The route of administration is affected by both drug and by patient factors so unless the drug is injected directly to the systemic circulation, there are always going to be barriers to absorption

Question 14

What are the main drug properties that affect absorption?

Answer 14

lipophilicity and ionisation

Question 15

What factors affect drug distribution?

Answer 15

Degree of drug ionisation Lipid solubility
pH of compartments
Cardiac output and blood flow 
Capillary permeability
Plasma protein binding

Question 16

According to compartment model what step does an intravenous dose Q skip to reach peripheral compartment (k12->

Answer 16

Absorption (kabs) ->Volume Vd a single well-stirred compartment

Question 17

What do biphosphonates travel to?

Answer 17

Phosphonate groups have a high affinity for calcium

Quickly distributed to the skeleton

Question 18

Give an example of a couple of biphosphonates up to no good in my neighbourhood

Answer 18

Oral alendronate
– Daily/weekly
IV zoledronate
– Yearly

Used to treat bone diseases like osteoporosis

Question 19

What is required for a drug to take effect on the body

Answer 19

A drug must be free to distribute widely or bind to its receptor

Question 20

Discuss protein binding in pharmacokinetics

Answer 20

A drug must be free to distribute widely or bind to its receptor
Many drugs bind to plasma proteins

Fraction of unbound drug can be as low as 1%
• Competition for binding sites can cause big increases in free drug concentrations

Question 21

What are some drugs that bind to plasma proteins?

Answer 21

– Albumin
– α-1 acid glycoprotein
– Lipoproteins
– Globulins

Question 22

What relationship do warfarin and aspirin have in common?

Answer 22

98% of warfarin bound to albumin Aspirin has high affinity for albumin

Question 23

What effect does the relationship between aspirin present in the body have on administered warfarin

Answer 23

Less warfarin is able to bind to albumin so there is a greater percentage of unbound warfarin

Question 24

Where is body water distributed?

Answer 24

To four main compartments - specialist compartments exist and factors such as perfusion influence distribution

Question 25

What impacts the distribution between the compartments that contain body water?

Answer 25

The degree of distribution between these compartments depends on tissue- and drug- dependent factors

Question 26

Why is an understanding of drug distribution important?

Answer 26

Side-effects of some drugs can be minimised by limiting their distribution via the route of administration

Question 27

Give an example of some muscarinic ACh receptor agonists?

Answer 27

Pilocarpine
Non-selective muscarinic agonist
Constriction of pupils (miosis)
Glaucoma (to decrease IOP)
Xerostomia (following head/neck radiotherapy)

Bethanechol
Non-selective muscarinic agonist
Bladder and gastrointestinal hypotonia

Question 28

What are the learning outcomes of this section?

Answer 28

To define the four main criteria of ADME.
To list the major routes of drug administration plus their benefits and drawbacks.
To relate the general chemical properties of a drug to its subsequent absorption and distribution throughout the body.
To explain the general concept of pharmacokinetic compartments.
To discuss the effects of protein binding upon the distribution and availability of drugs within the body.
To identify the major physiological factors affecting drug absorption and distribution.