10. Plasma Protein Binding And Tissue Distribution Of Drugs

Front 1

What is the volume of distribution (Vd)?

Back 1

Volume of distribution (Vd) illustrates where in the body the drug is distributed (i.e. only in plasma, in plasma and interstitium, plasma + interstitium + intracellular or inside tissues)

Front 2

What does a higher volume of distribution of a drug indicate?

Back 2

The higher the Vd value for the drug, the more fluid spaces the drug distributes itself into

Front 3

If the Vd of a drug is around 0,10 L/kg, which fluid compartments does it most likely distribute in?

Back 3

The plasma

Front 4

If the Vd of a drug is around 0,50 - 1,00 L/kg, which fluid compartments does it most likely distribute in?

Back 4

All fluid compartments

Front 5

If the Vd of a drug is above 1 L/kg, which fluid compartments does it most likely distribute in?

Back 5

All fluid compartments + tissues

Front 6

What is the body burden?

Back 6

The body burden of the drug is a fancy way to say how much drug is in the body in grams or moles.

Front 7

How can you calculate the body burden?

Back 7

Body burden = Vd x Cplasma = volume of distribution x plasma concentration

Front 8

What are the possible fates of a drug after it reaches the blood?

Back 8

It can bind to plasma proteins, to cells in the blood or it can leave the blood and enter tissues

Front 9

What is the plasma protein binding of a drug?

Back 9

The plasma protein binding of a drug shows the affinity of the drug to bind to plasma proteins.

Front 10

Which plasma proteins are the most important which drugs can bind to?

Back 10

Albumin and α1-acid glycoprotein (AGP).

Front 11

What types of drugs do albumin mostly bind?

Back 11

Acidic drugs.

Front 12

What types of drugs do AGP mostly bind?

Back 12

Basic drugs.

Front 13

Why is the plasma protein binding of drugs important?

Back 13

Drugs which are extensively plasma protein bound:

May have delayed onset of effect

May have prolonged effect and delayed elimination

May displace other drugs that have lower plasma protein binding

May displace endogenous compouns that bind to plasma proteins

May have increased effect when the level of plasma proteins is low

Can't be efficiently removed by haemodialysis

Front 14

In which cases can displacement of endogenous compounds by plasma protein binding be dangerous?

Back 14

Bilirubin can be displaced by certain antibiotics in neonates, as they already have high bilirubin levels and their blood-brain barrier isn't fully mature yet.

Front 15

Which factors influence a drug's volume of distribution?

Back 15

The size of the drug, the degree of plasma protein binding of the drug, and the solubility of the drug.

Front 16

When distributing into tissues, which tissues will a drug distribute into first?

Back 16

Tissues with high blood flow, like lungs, kidneys, heart, brain and liver.

Front 17

Name some drugs which distribute and accumulate in bone.

Back 17

Tetracyclines

Front 18

Which properties should a drug have to penetrate the blood brain barrier?

Back 18

Be lipophilic, small, not extensively plasma protein bound, and/or have a transporter protein on the BBB which transports the drug across.

Front 19

Mention some drugs which penetrate the blood brain barrier.

Back 19

Methyldopa, L-DOPA

Front 20

How can we promote the entry of a drug into the brain?

Back 20

We can give hypertonic mannitol simultaneously with the drug. The hypertonicity causes the endothelial cells of the blood brain barrier to contract, which allow the drug to pass through paracellularly.

Front 21

What drugs can cross the placental barrier?

Back 21

Lipophilic drugs.