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Flashcards in Drug distribution Deck (19):
1

What is drug distribution?

Reversible transfer of a drug between the blood and the extravascular fluids and tissues of the body (fat, muscle, brain tissue)

2

Factors that determine distribution

- Plasma protein binding
- Tissue perfusion
- Membrane characteristics

3

Plasma protein binding

- Many drugs bind to proteins in plasma
- Only unbound drugs are active
- Binding is reversible

4

Plasma protein binding can be changed by

- Renal failure
- Hypoalbuminaemia
- Pregnancy
- Other drugs
- Saturability of binding

5

Membrane characteristics

- Blood-brain barrier
- Blood-testes/ovary barrier: lipid soluble drugs, actively transported

6

Therapeutic range is characterised by...

- Volume of distribution
- Clearance
- Half life

7

Volume of distribution

- Volume in which amount of drug would be uniformly distributed to produce observed concentration
- Higher the Vd, the greater the ability of the drug to diffuse to and through membranes
-

8

Volume distribution, if whole body fluid, if just ECF, if highly protein bound or if sequestered extravascular lipid compartment

- Body fluid: 42L
- ECF, cannot penetrate cells: 12L
- Protein bound: 3L
- Extravascular lipid compartment: >40L

9

Clearance

- Measure of elimination: Theoretical volume of fluid from which a drug is completely removed over a period of time.
- Measure in units of time (ml/min)

10

Clearance depends on

- Concentration
- Urine flow rate for renal clearance
- Metabolism
- Biliary excretion for hepatic clearance

11

Half life

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

12

Half life depends on

- Volume of distribution
- Rate of clearance
- Kidneys and/or liver working
- Prolongation of the half-life will increase the toxicity of the drug for these reasons
- Links chemical properties of the drug and ability of the body to metabolise and excrete drugs

13

Chronic administration

- Best way to get therapeutic benefit
- Plasma levels need to be stabilised after 4-5 half lives

14

Drug elimination definition

- Removal of active drug and metabolites from the body
- Determines length of action of the drug
- 2 parts: drug metabolism -> liver. Drug excretion -> kidney but also biliary system, lung, milk

15

3 mechanisms of excretion

- Glomerular filtration
- Passive tubular reabsorption
- Active tubular secretion

16

Glomerular function

- GFR is how you measure renal function
- All unbound drugs will be filtered at the glorulus as long as not too large
- If you lower GFR, you lower excretion

17

Passive tubular resorption

- Concentration gradient created to allow drug to move back through tubule into circulation
- Occurs in distal tubule
- Unionised drugs are resorbed

18

Active tubular secretion

- Actively secreted into proximal tubule
- Important system for cationic and anionic drugs

19

Biliary secretion

- Drugs can be passively or actively secreted into bile
- Many drugs are reabsorbed from bile into the circulation -> entero-hepatic circulation
- Continues until drug is metabolised in the liver or excreted by the kidneys
- Damage to liver may reduce the rates of conjugation and biliary secretion -> build up or reabsorption of drug with resultant toxicity