7 drug distribution Ngu

Question 1

Identify the four major factors influencing drug distribution in the body

Answer 1

Drug’s lipophilicity

blood flow to particular tissue

tissue mass –> more mass = more distribution

Plasma binding proteins –> albumin(acidic drugs), glycoproteins(basic drugs), lipoproteins(basic/neutral drugs)

Question 2

Predict the impact of drug binding to plasma proteins on drug interactions and half lives.

Answer 2

drug interaction -> displacement from plasma protein will increase plasma conc of displaced drug –> possible toxicity even at lower dose

half life: displaced drugs will be eliminated sooner so reduces the half life

Question 3

Account for the special status of drug distribution associated with adipose/bone, brain, eyes, placenta, kidney, liver, testes

Answer 3

adipose/bone: very poorly perfused but accumulations are long term

brain: highly perfused but restricted to eye drops effects localized
placenta: placental barrier pain meds during birth may be safe
kidney: very highly perfused, damage can lead to accumulation of drugs/toxins
liver: very highly perfused, all GI blood flow passes through it, major site of metabolism –> excretion by conjugation to bile can prolong effects due to enterohepatic cycling through GI
testes: circulatory drugs blocked by BT barrier

Question 4

Analyze the relationship between volume of distribution and loading dose, plasma half life.

Answer 4

loading dose: Vd x Target Concentration

Half life: linear relationship to Vd

Question 5

Predict the appropriate dose of a drug for a patient given the plasma concentration and volume of distribution

Answer 5

Vd = dose / Plasma conc
or
dose = Vd x Plasma conc