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Flashcards in Pharmacokinetics Deck (54):
1

What is pharmokinetics?

Looks at what the body does to drugs

2

What are the 4 main processes involved in the processing of drugs by the body?

Absorption
Distribution
Metabolism
Elimination

3

Administration of drugs can be grouped into which 2 categories?

Enteral = entry into the body via GI tract

Parenteral = entry into the body by all other routes (not GI tract)

4

What are the 3 methods of administering drugs enterally?

Oral
Sublingual
Rectal

5

What are some parenteral methods of administering drugs?

Subcutaneous
Intravenous
Intramuscular
Inhalation
Intranasal
Transdermal

6

How are most drugs usually administered? Where is most of the drug absorbed?

Orally

In the small intestine

7

What happens to drugs administered orally in the stomach?

There is little absorption here - mixes with chyme ---> small intestine

8

By which methods are drugs absorbed at the molecular level? (3)

Passive diffusion
Facilitated diffusion
Secondary active transport

9

Which drugs are likely to be absorbed by passive diffusion?

Lipophilic steroids
Weak acids/bases can diffuse passively - effectively lipophilic

10

Which drugs are likely to be absorbed by facilitated diffusion?

Molecules with an ionic charge, using its electrochemical gradient

11

What are SLCs

Solute carriers used to absorb drugs by facilitated diffusion

12

What two types of SLC are there? What does each SLC transport?

OATs (weak acids)
OCTs (weak bases)

13

Where are SLCs highly expressed?

In the GI, hepatic and renal epithelia

14

Does secondary active transport use ATP?

No

15

How is secondary active transport driven?

By pre-existing electrochemical gradients

16

Give an example of a drug that is transported via secondary active transport?

Fluoxetine - cotransported with Na ions

17

What factors can affect drug absorption?

Blood flow
Surface Area/GI length
Lipophilicity of the drug
Density of SLC expression
GI motility
Food/pH

18

How are drugs metabolised in the liver?

By cytochrome P450 (phase 1 enzyme) and conjugating (phase 2 enzyme)

19

What is first pass metabolism? What effect does this have on the [drug] reaching the systemic circulation?

Metabolism of drugs in the liver by phase 1 and phase 2 enzymes ---> decreases [drug] reaching systemic circulation

20

What is bioavailability?

The fraction of a defined does that reaches its way into a specific body compartment

21

What is used as a reference when calculating the bioavailability of a drug?

IV used as a reference to compare to other routes

22

Bioavailability values are always...

Between 0 and 1 (decimal preferred)

23

What is the importance of the bioavailability value, how is it used?

Used to inform choice of administration route

24

How are drugs distributed in the body?

By bulk flow from arteries to capillaries

Then by diffusion from capillaries to interstitial fluid to cell membranes to targets

25

What factors affect drug distribution in the body?

Drug lipophilicity/hydrophilicity
Capillary permeability
Drug pKa and local pH
Presence of OATs and OCTs

26

What can drugs bind to which prevent them reaching their target sites?

Blood plasma proteins, such as albumin/globulins

27

What is the nature of the bonding of drugs to plasma proteins?

Not strong, bound and unbound in equilibrium

28

How many litres of water are there in the body of a typical adult?

42 litres

29

How is the 42 litres of water found in a typical adult split into intracellular and extracellular?

Intracellular = 28 litres (2/3)
Extracellular = 14 litres (1/3)

30

How is the 14 litres of extracellular water found in a typical adult split?

3 litres in the plasma
11 litres interstitial

31

What is Vd (volume of distribution) a measure of?

Summarises the movement of the drug through body compartments

32

What does a small Vd value mean?
What does a large Vd value mean?

Low penetrance of the drug into interstitial and intracellular compartments

Greater penetrance of the drug into interstitial and intracellular compartments

33

How does drug metabolism largely take place?

In the liver via phase 1 and phase 2 enzymes

34

What do enzymes in the liver do to drugs to enhance renal elimination?

Increase their ionic charge

35

What happens to lipophilic drugs during elimination?

They diffuse back into the plasma

36

What typically happens to drugs after metabolism?

They are inactivated

37

What is phase 1 metabolism carried out by? Where are the enzymes found?

Cytochrome P450 enzymes

On the ER

38

What happens to drugs in metabolism?

They are given an increased ionic charge - through oxidation/reduction reactions (phase 1 metabolism) or through conjugating (phase 2)

39

Give an example of a drug that is metabolised into its active form by phase 1 metabolism?

Codeine to morphine

40

What is phase 2 metabolism carried out by?

Hepatic enzymes

41

What is the function of phase 2 metabolism?

Enhances hydrophilicity by further increasing ionic charge

Enhances renal elimination

42

What is CYP450 induction? How can this affect the effectiveness of the drug?

Where certain drugs induce specific CYP450 isoenzymes

Can result in decreased plasma levels of the drug and activity of certain drugs as they are being metabolised at a greater rate

43

What is CYP450 inhibition? What affect can this have on the effectiveness of the drug?

Certain drugs can inhibit specific CYP450 isoenzymes

Results in increased plasma levels of the drug and increased activity as metabolism of drug is slowed

44

Most drug elimination is carried out by the...

Kidney

45

How are drugs eliminated in the kidneys?

Via active tubular secretion

There is a high expression of OATs and OCTs which carry ionised molecules into the proximal tubule for secretion

46

What is clearance of a drug?

The RATE of elimination of a drug from the body

47

Generally Total Body Clearance is equal to...

Hepatic clearance + Renal clearance

48

What is clearance measured in?

Ml/min

49

What 2 factors is drug half life dependent on?

Drug clearance
Volume of distribution of a drug

50

What is drug half life?

The amount of time over which the [drug] in plasma reduces to half of its initial concentration when it was first measured

51

Assuming there are plenty of OATs/OCTs and phase 1/2 enzymes, metabolism and excretion of a drug is said to be _________ to the [drug] and is described as showing __________ kinetics

Proportional

First order

52

When does zero order kinetics for a drug occur?

When the elimination processes are saturated
At higher doses for most drugs - zero order kinetics will occur

53

Drugs at or near the dose that gives zero order kinetics are more likely to result in....

Adverse drug reactions
Toxicity

54

Eliminations are more likely to become saturated in what circumstances?

Reduced hepatic/renal capacity