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Principles of Disease > Drug Distribution > Flashcards

Flashcards in Drug Distribution Deck (38):
1

What does drug distribution refer to?

the reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the bidy.

2

What is tissue distribution dependent on?

-plasma protein binding
-tissue perfusion
-membrane characteristics
-transport mechanisms
-diseases and other drugs
-elimination

3

What proteins do drugs bind to in the plasma?

-albumin
-a1-glycoprotein

4

What must a drug be to be biologically active?

Unbound

5

How can the amount of bound drug be changed?

-renal failure
-hypoalbuminaemia
-pregnancy
-other drugs
-saturability of binding

6

Why does protein binding matter?

- for this to be an important factor the drug must be more than 90% bound and the tissue distribution small

7

What parameters are important to characterise in therapeutic range?

-volume of distribution
-clearance
-half-life

8

What is the apparent volume of distribution?

The volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration

9

What does a greater Vd tell us?

the greater the ability of the drug to diffuse into and through membranes

10

In theory what should the value of Vd be?

42L

11

If the drug stays in the extracellular fluid but cannot penetrate cells what is the theoretical value of Vd?

12L

12

What is the theoretical value of Vd if the drug is highly protein bound?

3L

13

What is the theoretical value of Vd if the drug is sequestered in extravascular lipid compartment?

>40L

14

What is clearance?

the theoretical volume of fluid from which a drug is completely removed over a period of time

15

What is clearance a measure of?

elimination

16

What is clearance dependent on?

-concentration and urine flow rate for renal clearance
-metabolism and biliary excretion for hepatic clearance

17

What is half-life?

the time taken for the drug concentration in the blood to decline to half of the current value

18

What is half life dependent on?

the volume of distribution and rate of clearance

19

Why will prolongation of the half life increase the toxicity of the drug?

-due to reduction in clearance
-due to large volume of distribution

20

How must most drugs be given to have a therapeutic benefit?

chronically

21

When is steady state concentration achieved?

approximately after 4 half times

22

What is the relationship between time to steady state concentration and dosage

they are independent

23

What is drug elimination?

the removal of active drug and metabolites from the body

24

What is drug elimination made up of?

-drug metabolism (usually in the liver)
drug excretion (usually in the kidney but also biliary system/gut, lung, milk)

25

What are the primary organs involved in drug excretion?

kidneys

26

What are the 3 principal mechanisms used in excretion?

-glomerular filtration
-passive tubular reabsorption
-active tubular secretin

27

How much is filtered by the glomerulus each day?

190 litres

28

What will be filtered by the glomerulus?

all unbound drugs as long as their molecular size, charge or shape are not excessively large.

29

What will reduce the clearance of a drug?

factors that affect the glomerular filtration

30

Describe active tubular secretion.

-some drugs are actively secreted into the proximal tubule (acidic and basic compounds)
-this is the most important system for eliminating protein bound cationic and anionic drugs.

31

How does passive tubular reabsorption occur?

-as the filtrate moves down the renal tubule any drug present is concentrated.
-passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation.

32

Where does passive diffusion occur?

In the distal tubule and collecting duct

33

What drugs can be reabsorbed?

un-ionised drugs such as weak acids

34

How much bile does the liver secrete a day?

1 litre

35

How can drugs be secreted in bile?

actively or passively

36

What is entero-hepatic circulation?

many drugs are then reabsorbed from the bile into the circulation

37

What does metabolism in the liver often leads to?

-conjugation of the drug
-the conjugated drug is not reabsorbed from the intestine

38

What may reduce the rates of conjugation and biliary secretion?

damage to the liver which then allows the build up or reabsorption of the drug with resultant toxicity