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E: Quantitative Pharmacology > Drug absorption and distribution > Flashcards

Flashcards in Drug absorption and distribution Deck (53):
1

Name the 4 states of drug disposition

  1. Absorption
  2. Distribution
  3. Metabolism
  4. Excretion

2

Absorption?

The process by which a drug enters the blood stream from its site of administration.

Occurs in several sites in the body

3

Distribution?

The process by which a drug leaves the circulation and enters the tisseus perfused by the blood.

Once in tissues, further blood-independent distrubtion may occur by diffusion.

4

Metabolism?

The process by which tissue enzymes catalyse the chemical conversion of a drug to a more polar for that it can readily excreted from the body.

5

Excretion?

The proces that remove the drug from the body.

6

Elimination?

Metabolism + excretion

7

Overview of drug disposition?

AS8

8

Name the 4 physiochemical factors controlling drug absorption?

  1. Solubility
  2. Chemical stability
  3. Lipid to water coefficient
  4. Degree of ionisation

9

Solubility

The drug must dissolve in order to be absorbed.

Must have a degree of water solubility 

10

Chemical stability?

Some drugs are destroyed by acid in the stomach or enzymes in the GI tract.

eg. insulin- not given orally as it is polypeptide (therefore destroyed by acid)

11

Lipid to water coefficient

 Absorption of a drug must commonly relies upon diffusion across the biological membranes.

Drugs must have a degree of hydrophobic and hydrophilic characteristics. 

12

What happens to the rate of diffusion when the lipid solubility of a drug is increased?

Rate of diffusion is increased.

13

Partition coefficient ?

The measure of the difference in solubility of the compound between two compartments

14

Difference in parition coefficient for hydrophobic and hydrophilic drugs?

Hydrophobic drugs will have a high partition coefficient- ie prefer to be distributed to hydrophobic compartments such as the lipid bilayers.

Hydrophilic drugs will have a low parition coefficient- ie. prefer to be distributed in aqueous compartments such as blood serum.

15

Degree of ionisation?

Many drugs exist as weak acids or basses existing in both ionised (A-, BH+) and unionised (AH, B) forms

16

Acidic degree of ionisation?

See AS9

17

Basic degree of ionisation?

See AS9

18

The meaning of pH?

See AS10

 

19

What form of ionisation will readily diffuse across the lipid bilayer?

Unionised form

20

pKa?

Degree of ionisation

21

pKa=pH?

50% of drugs is ionised

50% unionised

22

Henderson-Hassebalch equation?

See AS11

23

ionised forms of acid and basic?

A- 

BH

24

Unionised forms of acid and basic?

AH

B

 

25

Absorption of weak acids are faciliated by?

The pH of the stomach lumen.

 

26

Where are bases readily absorbed?

Until they reach the small intestine

27

Are weak or strong acid/bases readily absorbed?

Weaker acids/basics are more readily absorbed

28

Where is the majority of absorption takes place?

In the small intestine

Because of the large surface area

29

Acidic drugs are less ionised in what kind of environment?

Acidic environment

30

Basic drugs are less ionised in what kind of environment?

Basic environment

31

Gastrointestinal motility?

Modified by?

The rate of the stomach emptying and movement throughout the intestines.

Modified by some drugs and the presence of food (ie. absorption will increase with food present)

32

Name the 5 factors that affect GI absoption

  1. Gastrointestinal motility
  2. pH at the absorption site
  3. Blood flow in the stomach and intestine
  4. For way the drug is maufactured
  5. Physiological interactions

33

How does the pH affect the GI absorption

pH varies along the length of the GI tract

34

How does the blood flow affect the GI absorption

Increased by the presence of food.

More blood: the faster the rate of absorption

35

How does the way the drug is manufactured effect the GI absorption?

The drug can be customised to be take effect in the intestine and not the stomach or any other site

36

How does the physiological interactions affects the GI absorption?

The rate of absorption is sometimes comprimised when other compounds are present such as other drugs or calcium-rich foods

37

Oral avaliability?

The fraction of drug that reaches the systemic circulation after oral ingestion.

 

Amount in systemic circulation/ Amount administered

 

38

Systemic avaliability?

The fraction that reaches the systemic circulation after absorption

Amount in systemic circulation/ Amount reached.

39

First-pass metabolism

Drugs (orally) are absorbed can be inactivated by enzymes in the gut wall and liver before reaching the systemic circulation and body tissues

40

Enteral route of drug administration

Via the GI tract

41

Name the 4 enteral route of drug administration?

  1. Oral
  2. Sublingual (below tongue)
  3. Rectal
  4. Buccal (drug on cheek)

42

What is the partenal route of drug administration?

Avoids the GI tract

 

43

Name the 6 parental route of drug administration?

  1. Intravenuous 
  2. Intramuscular
  3. Subcutaneous (needle to fatty tissue)
  4. Inhalation
  5. Transdermal (patches)
  6. Topical (directly onto the skin)

44

What must the drug be located before it can be distributed to body fluid compartments?

Must be in the systemic circulation

45

Graphical representation of the different body fluid compartments and the volumes each hold?

See AS12 

46

What is the interstitial water?

The fluid in the space between cells 

eg. fluid that lines the spinal cord, brain and joints

47

What is the intracellular water

The fluid contained inside the cell membranes

48

What 2 kinds of drugs are able to move between compartments?

  1. Free drug molecules that are not bound to proteins.
    1. Unionised drugs
    2.  

49

Volume of distribution

Vd= dose/ plasma concentration

 

 

50

Why is volume of distribution equation needed?

As drugs are not evenly distributed in the body.

 

51

Vd< 5L?

Drug retained in the vascular compartment

52

Vd< 15L?

Restricted to extracelular water

53

Vd> 15L?

Distribution throughout the body