Pharmacokinetics 1

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug

Question 2

State the 4 main processes of pharmacokinetics

Answer 2

(Liberation)

Absorption
Distribution
Metabolism
Excretion

Question 3

Advantages of plasma used in transporting drugs

Answer 3

Easy convenient sampling pool, in which we can use to measure the amount of drug in the body

OR

A convenient way in which a drug is distributed in the body.

Question 4

State some routes of drug administration

Answer 4

Oral
Sublingual
Inhalational
Topical
Transdermal
Intramuscular
Intravenous

Question 5

Advantages and Disadvantages of the oral route

Answer 5

A: Convenient

D: First pass effect, many variables and barriers

Question 6

Advantages and Disadvantages of the sublingual route

Answer 6

A: No first-pass effect

D: Inconvenient, small dose limit

Question 7

Advantages and Disadvantages of the inhalational route

Answer 7

A: Fast, rapid delivery to blood

D: Requires special properties of drug (vaporised, atomised)

Question 8

Advantages and Disadvantages of the topical route

Answer 8

A: Convenient, Localised

D: Only local

Question 9

Advantages and Disadvantages of the transdermal route

Answer 9

A: Prolonged release

D: Skin very effective barrier

Question 10

Advantages and Disadvantages of the intramuscular route

Answer 10

A: Rapid for aqueous, slow for oil

D: Painful, requires trained personnel

Question 11

Advantages and Disadvantages of the intravenous route

Answer 11

A: Direct, total dose, rapid

D: Requires professional, infection risk, rapid response

Question 12

First-pass effect

Answer 12

Any barrier between the drug being administered to your patient and it getting into the plasma.

Anything that metabolises/transforms/changes the drug due to the interaction of enzymes.

Question 13

Bioavailability

Answer 13

The fraction of unchanged drug that reaches the systemic circulation.

Question 14

Alun - bioavailability definition

Answer 14

How much of the administered dose you would expect to see get into the patients plasma.

Question 15

IV injection bioavailability

Answer 15

100%

Question 16

Bioavailability equation

Answer 16

(AUC oral / AUC IV) x 100%

Question 17

State the 4 ways that small molecules can cross cell membranes

Answer 17

1. Diffusing directly through the lipid
2. Diffusing through aqueous pores
3. Transmembrane carrier protein
4. Pinocytosis

Question 18

Feature of drug to : diffuse directly through the lipid

Answer 18

Drug should be:

• Uncharged
• Lipophilic enough

Question 19

Feature of drug to : use a transmembrane carrier protein

Answer 19

Drug should be:

• Charged
• Hydrophilic

Question 20

When is diffusion through aqueous pores used ?

Answer 20

More likely important for diffusion of gases.

Aqueous pores are VERY small.

Question 21

When is pinocytosis used ?

Answer 21

Mostly macromolecules, not drugs.

(for larger molecules: proteins/peptides)

Question 22

Describe hydrophilic drugs

Answer 22

Hydrophilic drugs are soluble in aqueous, polar media.

Cannot pass through the lipid bilayer

Question 23

Describe lipophilic drugs

Answer 23

Lipophilic drugs are soluble in fats and non-polar solutions.

Question 24

Describe polar media

Answer 24

Blood plasma
Cytosol
Interstitial fluid

Question 25

Describe non-polar solutions

Answer 25

Interior of lipid bilayer and fat

Question 26

Feature of drugs

Answer 26

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

Question 27

Gastric Acid pH

Answer 27

1-3

Question 28

Large Intestine pH

Answer 28

8

Question 29

Small intestine pH

Answer 29

5-6

Question 30

Plasma pH

Answer 30

7.4

Question 31

What drug properties affect absorption ?

Answer 31

Lipophilicity Ionisation

Question 32

When do barriers to absorption arise ?

Answer 32

Unless the drug is directly injected into systemic circulation.

Question 33

Factors that affect distribution

Answer 33

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

Question 34

Compartment model - state some places drugs may go to

Answer 34

(from shortest to longest time) Vessel Rich Group (VRG) - kidneys Muscle Adipose

Question 35

Key feature of compartment model

Answer 35

Not all drugs will distribute evenly around the body Some will go and accumulate in different locations. The further away the drug gets from plasma and the more likely it is to accumulate in distant tissues, the harder it is to get rid of that drug from the body. This is because the route out of the drug from the body is also via the plasma.

Question 36

What are Bisphosphonates ?

Answer 36

Treatment given to reduce the burden of osteoporosis. Work by killing off osteoclasts, (bone resorbing cells which degrade and remove bone from the body)

Question 37

Mechanism of action of bisphosphonates

Answer 37

Phosphate groups have a high affinity for calcium, so the bisphosphonates will bind VERY strongly to bone where there is a high degree of calcium.

Question 38

Key feature of bisphosphonates

Answer 38

Quickly distributed to the skeleton Long time to remove drug as it binds so strongly to bone.

Question 39

State the 2 types of bisphosphonate

Answer 39

Oral alendronate IV zoledronate

Question 40

Oral alendronate

Answer 40

Daily/weekly

Question 41

IV zolendronate

Answer 41

Yearly

Question 42

Why is zolendronate given by IV only ?

Answer 42

Any dietary source of calcium will be bound to by this. It would bind to calcium in the GI tract and not get absorbed.

Question 43

Protein binding

Answer 43

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

Question 44

State some drugs that bind to plasma proteins

Answer 44

Albumin alpha-1 acid glycoprotein Lipoproteins Globulins

Question 45

Albumin

Answer 45

A lot of drugs that will stay in high concentrations in the plasma will bind to albumin and stay there.

Question 46

Importance of drugs binding to albumin

Answer 46

ONLY drugs which are unbound can interact with receptors / get from the plasma into other tissues. So those bound to albumin cannot interact.

Question 47

% unbound drugs

Answer 47

Fraction of unbound drugs can be as low as 1%

Question 48

What does competition for binding sites cause ?

Answer 48

Can cause big increases in free drug concentrations.

Question 49

Feature of warfarin and aspirin

Answer 49

98% of warfarin bound to albumin. Aspirin has a high affinity for albumin... So in the presence of aspirin competition occurs and whichever has the highest affinity for the site is likely to win.

Question 50

Which has a higher affinity for albumin, aspirin or warfarin ?

Answer 50

Aspirin

Question 51

Increased Aspirin levels results in:

Answer 51

Increased warfarin available in the plasma

Question 52

Describe distribution between body fluid compartments

Answer 52

Permeability across tissue barriers Binding within compartments pH partition Fat:Water partition

Question 53

What does degree of distribution between compartments depend on ?

Answer 53

Tissue and Drug dependent factors

Question 54

Where is body water distributed ?

Answer 54

Distributed into 4 main compartments

Question 55

How can side-effects of some drugs be minimised ?

Answer 55

By limiting their distribution via the route of administration.

Question 56

Muscarinic Ach receptor agonists

Answer 56

Pilocarpine Bethanechol

Question 57

Pilocarpine

Answer 57

Non-selective muscarinic agonist Constricts pupils Glaucoma - decrease IOP Xerostomia - following head/neck radiotherapy

Question 58

Bethanecol

Answer 58

Non-selective muscarinic agonist Bladder and GI hypotonia

Question 59

Structure of bethanechol

Answer 59

Quaternary ammonium POLAR substance not readily absorbed

Question 60

Structure of pilocarpine

Answer 60

Tertiary amine