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Flashcards in Drug distribution and excretion Deck (25):
1

Distribution

Reversible transfer of a drug between the blood and the extra vascular fluids and tissues of the body eg muscle, fat, brain

2

What 6 things effect tissue distribution?

Disease and other drugs
tissue perfusion
Membrane characteristics
Plasma protein binding
Elimination
Transport mechanism

3

Membrane characteristics

Blood-brain barrier
Blood testes-ovary barrier, lipid soluble drug, active transport

4

Plasma protein binding

Drug bound to albumin eg phenytoin
Binding is reversible and can be changed in response to renal failure, pregnancy etc.

5

Is an unbound drug active or inactive

Active

6

What 3 things effect the therapeutic range

- Clearance
- Volume of distribution
- Half life

7

Clearance (ml/min)

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

8

What is clearance dependent on?

- Metabolism and biliary secretion
- Concentration and urine flow

9

Volume of distribution (Vd)

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

10

What does a greater Vd mean?

Greater ability to diffuse into/through membrane

11

What should the Vd be?

42L

12

Half life (t1/2)

Time taken for the drug concentration in the blood to decline to half of current value
Depends on Vd and clearance

13

What does an increased half life mean?

Increased toxicity

14

To have an effect what should a drugs concentration and half life be?

- Steady concentration between therapeutic range
- 4-5 half lives before stabilisation

15

Drug elimination

Removal of active drug and metabolites from body
Determines length of action

16

What does drug elimination depend on?

Drug metabolism (liver) and excretion (kidneys)

17

What are the primary organs for drug excretion?

Kidneys - renal failure cause toxicity

18

How much does glomerular filtration filter a day?

190L of unbound drug

19

Passive tubular reabsorption

Through tubule into circulation - distal tube and collecting duct - unionised eg weak acid

20

Active tubular secretion

Secrete into proximal tube ( acid and alkali)
Protein bound cationic and anionic drug

21

How much drug elimination does bilary secretion make up?

5-95%

22

How much bile does the liver secret a day?

1L

23

Describe biliary secretion

Drugs secreted into bile and reabsorbed in circulation -enterohepatic circulation
Occurs until drug metabolised in liver or excreted

24

What does metabolism in liver lead to?

Conjugation of drug - not reabsorbed from intestine

25

What does liver damage lead to?

Decreased conjugation and biliary secretion
Build up and reabsorption of drug = TOXICITY