Drug Distribution

Question 1

Many drugs bind to proteins in the plasma. Give two examples of plasma proteins which may bind to a drug

Answer 1

Albumin and alpha1-glycoprotein (phenytoin)

Question 2

What kind of drug is the only active form?

Answer 2

Unbound

Question 3

The amount of bound drug can be altered by what factors?

Answer 3

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

Question 4

Explain why protein binding is important

Answer 4

Maths and shit

Question 5

What is the Apparent Volume of Distribution (Vd)?

Answer 5

It is defined as the volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration

Question 6

The greater the Vd…

Answer 6

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

Question 7

What is clearance?

Answer 7

It is defined as the theoretical volume of fluid from which a drug is completely removed over a period of time - a measure of elimination

Question 8

What are the units of clearance?

Answer 8

Units of time (ml/min)

Question 9

What is the half life of a drug?

Answer 9

It is defined as the time taken for the drug concentration to decrease by half

Question 10

What will prolongation of a drugs half life do?

Answer 10

Increase the toxicity of the drug

Question 11

Knowledge of half lives will help us to determine what about a given drugs administration?

Answer 11

How often it needs to be administered

Question 12

Plasma levels of a drug take many doses before they stabilise, usually 4-5 half-lives. What might this necessitate?

Answer 12

A loading dose (initially higher dose)

Question 13

What is drug elimination?

Answer 13

The removal of active drug and metabolites from the body - determining the length action of a drug and comprised of drug metabolism and drug excretion

Question 14

What is the primary excretory organ for drugs?

Answer 14

The kidneys

Question 15

What three principle mechanisms are used in the kidneys for drug excretion?

Answer 15

Glomerular filtrate, passive tubular reabsorption and active tubular secretion

Question 16

Renal damage therefore is important in causing what?

Answer 16

Drug toxicity

Question 17

Where and how are all unbound drugs filtered out of the blood?

Answer 17

The glomerulus in the kidneys as long as they aren’t too big

Question 18

How are some acidic and basic compound drugs filtered out of the blood?

Answer 18

Actively secreted into the proximal convoluted tubule

Question 19

Active tubular secretion is the most important process in elimination of what drugs?

Answer 19

Protein bound cationic and anionic drugs

Question 20

What kind of drugs are reabsorbed and where?

Answer 20

Un-ionised weakly acidic drugs at the distal tubule and collecting duct

Question 21

How are drugs secreted into bile?

Answer 21

Both actively and passively

Question 22

Many drugs are absorbed from the bile back into circulation; what is this called?

Answer 22

Entero-heaptic circulation

Question 23

For how long does enter-hepatic circulation continue for?

Answer 23

Until the drug is metabolised in the liver or excreted in the kidneys

Question 24

Metabolism of a drug often leads to what?

Answer 24

Conjugation of the drug

Question 25

What happens to the conjugated drug in the liver?

Answer 25

It is not reabsorbed from the intestine