Drug Distribution

Question 1

What does drug distribution refer to?

Answer 1

The Reversible Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body (for example, fat, muscle, and brain tissue).

Question 2

What does tissue distribution depend on?

Answer 2

Plasma protein binding

Tissue perfusion

Membrane characteristics

Blood-brain barrier

Blood-testes/ovary barrier

Lipid soluble drugs

Actively transported

Transport mechanisms

Diseases and other drugs (esp renal failure, liver disease, obesity)Elimination

Question 3

What can be said about an unbound drug (not bound to plasma protein)?

Answer 3

Only unbound drug is biologically active.

Question 4

What can change the amount of bound drug?

Answer 4

Renal failure

Hypoalbuminaemia

Pregnancy

Other drugs

Saturability of binding

Question 5

When does protein binding matter?

Answer 5

When there is a very large percentage of the drug that is bound to plasma proteins

• a small increase in unbound level has a massive percentage change of the free drug level (4% to 6% means a 50% increase in free drug levels)

Question 6

What are the parameters of the therapeutic range?

Answer 6

volume of distribution, clearance and half-life

Question 7

What is the volume of distribution?

Answer 7

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

Question 8

What does a greater Vd indicate?

Answer 8

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

Question 9

What is the Vd in theory

Answer 9

42L (in equal distribution in the body)

Question 10

What is the definition of clearance?

Answer 10

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

Question 11

What is the measurement of clearance?

Answer 11

Measured in units of time (ml/min)

Question 12

What does clearance depend on?

Answer 12

Dependent on concentration and urine flow rate for renal clearance.

Dependent on metabolism and biliary excretion for hepatic clearance.

Question 13

What is the definition of half life?

Answer 13

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

Question 14

What is half life dependant on?

Answer 14

Volume of distribution and rate of clearance.

Question 15

What is the result of prolongation of the half life of a drug?

Answer 15

Will increase the toxicity of a drug.

Due to reduction in clearance

Due to a large volume of distribution (amiodarone)

Question 16

How many doses are usually required before plasma levels of a drug stabilise?

Answer 16

4-5 half-lives

Question 17

What is drug elimination?

Answer 17

Removal of active drugs and metabolites from the body

Question 18

What are the two components of drug elimination?

Answer 18

Metabolism (usually in the liver)

Excretion (kidney, biliary system/gut, lung, milk)

Question 19

What are the three main mechanisms for drug excretion by the kidney?

Answer 19

1. Glomerular filtration
2. Passive tubular reabsorption
3. Active tubular secretion

Question 20

What is renal damage often a cause of?

Answer 20

Drug toxicity

Question 21

What system is important for the elimination of protein bound cationic and anionic drugs?

Answer 21

Active tubular secretion

Question 22

What kind of drugs are passively reabsorbed from the renal tubule into the circulation?

Answer 22

Un-ionised drugs

At this point they are concentrated and the diffusion occurs at the distal tubule and the collecting duct

Question 23

What accounts for 5%-95% of drug elimination?

Answer 23

Biliary secretion

Question 24

What is the entero-hepatic circulation?

Answer 24

The reabsorption of drugs from the bile to the circulation

Question 25

When does the reabsorption of drugs from the bile to the circulation stop?

Answer 25

When the drug has been completely excreted by the kidney or metabolised by the liver

Question 26

What is conjugation of a drug? Often caused by the metabolism of the liver

Answer 26

The combination of toxic substances formed by drugs with glucaronic or suphuric acid in the liver

• It is a means by which the biological activity of a certain chemical is terminated and the substance is made ready for excretion

Question 27

Is the conjugated drug reabsorbed by the small intestine?

Answer 27

NO

Question 28

What may happen after damage to the liver?

Answer 28

Reduce rates of conjugation and biliary secretion and so allow the build up or reabsorption of the drug with resultant toxicity