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Flashcards in Drug Distribution Deck (38)
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1
Q

What does drug distribution refer to?

A

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

2
Q

What is tissue distribution dependent on?

A
  • plasma protein binding
  • tissue perfusion
  • membrane characteristics
  • transport mechanisms
  • diseases and other drugs
  • elimination
3
Q

What proteins do drugs bind to in the plasma?

A
  • albumin

- a1-glycoprotein

4
Q

What must a drug be to be biologically active?

A

Unbound

5
Q

How can the amount of bound drug be changed?

A
  • renal failure
  • hypoalbuminaemia
  • pregnancy
  • other drugs
  • saturability of binding
6
Q

Why does protein binding matter?

A
  • for this to be an important factor the drug must be more than 90% bound and the tissue distribution small
7
Q

What parameters are important to characterise in therapeutic range?

A
  • volume of distribution
  • clearance
  • half-life
8
Q

What is the apparent volume of distribution?

A

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

9
Q

What does a greater Vd tell us?

A

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

10
Q

In theory what should the value of Vd be?

A

42L

11
Q

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

A

12L

12
Q

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

A

3L

13
Q

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

A

> 40L

14
Q

What is clearance?

A

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

15
Q

What is clearance a measure of?

A

elimination

16
Q

What is clearance dependent on?

A
  • concentration and urine flow rate for renal clearance

- metabolism and biliary excretion for hepatic clearance

17
Q

What is half-life?

A

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

18
Q

What is half life dependent on?

A

the volume of distribution and rate of clearance

19
Q

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

A
  • due to reduction in clearance

- due to large volume of distribution

20
Q

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

A

chronically

21
Q

When is steady state concentration achieved?

A

approximately after 4 half times

22
Q

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

A

they are independent

23
Q

What is drug elimination?

A

the removal of active drug and metabolites from the body

24
Q

What is drug elimination made up of?

A
-drug metabolism (usually in the liver)
drug excretion (usually in the kidney but also biliary system/gut, lung, milk)
25
Q

What are the primary organs involved in drug excretion?

A

kidneys

26
Q

What are the 3 principal mechanisms used in excretion?

A
  • glomerular filtration
  • passive tubular reabsorption
  • active tubular secretin
27
Q

How much is filtered by the glomerulus each day?

A

190 litres

28
Q

What will be filtered by the glomerulus?

A

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

29
Q

What will reduce the clearance of a drug?

A

factors that affect the glomerular filtration

30
Q

Describe active tubular secretion.

A
  • 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
Q

How does passive tubular reabsorption occur?

A
  • 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
Q

Where does passive diffusion occur?

A

In the distal tubule and collecting duct

33
Q

What drugs can be reabsorbed?

A

un-ionised drugs such as weak acids

34
Q

How much bile does the liver secrete a day?

A

1 litre

35
Q

How can drugs be secreted in bile?

A

actively or passively

36
Q

What is entero-hepatic circulation?

A

many drugs are then reabsorbed from the bile into the circulation

37
Q

What does metabolism in the liver often leads to?

A
  • conjugation of the drug

- the conjugated drug is not reabsorbed from the intestine

38
Q

What may reduce the rates of conjugation and biliary secretion?

A

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