Drug distribution

Question 1

Plasma protein binding

Answer 1

Carriers for poorly soluble metabolites

• drugs drugs bind to these + are transported around circulation
• reversible binding
• influence drug pharmacokinetics

Question 2

How do drugs bind to serum albumin (plasma protein)

Answer 2

Thermodynamic motion leads to chance collision

• Electrostatic binding forces can be overcome by thermal energy
• 90% drug bound is = 90% of molecule being bounded of the time

Question 3

Competition for plasma protein binding sites lead to…

Answer 3

drug interactions

Question 4

What drugs can access blood brain barrier

Answer 4

Lipophilic/transported drugs can access

Question 5

Blood brain barrier

Answer 5

Effective diffusional barrier

- tight junctions between endothelial cells, pericytes + glial limitans are barriers to drug escape

Question 6

How can drug enter placenta

Answer 6

Drug must pass into maternal blood pool + enter foetal circulation (passive diffusion/active transport)
- risk of teratogenic/embryotoxic effects

Question 7

Which drugs can/ cannot enter placenta

Answer 7

Lipophilic drugs can

Drugs with high plasma protein binding affinity do not

Question 8

How do drugs enter breastmilk

Answer 8

Alveolar apical cells form a tight junction limited lipid barrier between capillaries + alveolar lumen
- diffusion into milk limited by lipophilicity + size

Question 9

Adipose tissue is a major reservoir for…

Answer 9

Lipophilic drugs

Question 10

Where is adipose tissue

Answer 10

Skin (subcutaneous), around intestinal organs (visceral), breasts + bone marrow

Question 11

What s adipose tissue composed of

Answer 11

Adipocytes - cells with large intracellular vacuoles filled with lipids

• lipid soluble drugs can accumulate in reservoir
• increase in adipocyte, size in obesity

Question 12

Which compartments are drugs distributed

Answer 12

Extracellular fluid (plasma, interstitial fluid, lymph)
Intracellular fluid (cell contents)
Transcellular fluid (CSF, peritoneal, intraocular, synovial etc.)
Fat
Bound to protein

Question 13

Volume of distribution

Answer 13

Apparent volume of plasma that would accommodate total drug amount at the measured plasma concentration

Question 14

Calculate Vd

Answer 14

total amount of drug/plasma concentration

Question 15

If Vd is more than 40 litres

Answer 15

Indicates some storage of drug in tissue

Question 16

If Vd is less than 15 litres

Answer 16

drug is largely restricted to plasma + interstitial fluid

Question 17

How can critically-ill patients alter distribution parameter

Answer 17

Changes in capillary permeability due to inflammation
Decrease in blood pressure and organ perfusion in septic shock
Fluid resuscitation increases Vd

Question 18

How can pre-existing disease alter distribution parameter

Answer 18

Hepatic disease causes decrease in serum albumin levels

Renal dysfunction changes fluid volumes

Question 19

How can obesity alter distribution parameter

Answer 19

Ideal versus actual body weight

Accumulation of lipophilic drugs and other xenobiotics (e.g. organophosphate poisoning)

Question 20

How can active transport alter distribution parameter

Answer 20

Import of drugs across lipid barrier by transporters
Export of drugs from cells by P-glycoproteins
Non-linear relationship between plasma extracellular + intracellular concentrations

Question 21

Distribution of drug after administration is determined by

Answer 21

Reversible binding to plasma proteins
Perfusion of tissue by blood
Structure of vascular endothelium
Lipophilicity of drug

Question 22

When choosing antibiotic, must consider…

Answer 22

site of infection + drug distribution

Question 23

Aminoglycosides are hydrophilic, can they accumulate in adipose tissue

Answer 23

No - danger of toxicity