Drug Distribution

Question 1

what is the aim of good therapeutics?

Answer 1

to deliver medicines to the site of action at effective concentrations

Question 2

what is the aim of multiple dose therapy?

Answer 2

to keep drug levels as stable as possible

Question 3

how does the drug travel?

Answer 3

I.V bolus does → inside blood vessel (drug moves fast in well perfused area) → outside blood vessel (drug moves to less perfused area at slower rate)

Question 4

what order of kinetics do drugs follow?

Answer 4

• usually 1st order with few exceptions
• means that a constant fraction of the drug is removed at a time
• the time to remove a dose is independent = half life!

-very few drugs follow zero order where constant amount of drug is removed at a time

Question 5

what is the saturation point?

Answer 5

rate of elimination is constant

Question 6

what is the volume of distribution?

Answer 6

Vd = total amount of drug / [plasma]

• indicates the extent of distribution of drug
• clinically important for adjusting dosage
• influenced by lipid/H20 solubility, binding to plasma proteins

Question 7

what is elimination?

Answer 7

describes the activity of metabolism enzymes and excretion mechanisms

Question 8

what is plasma clearance?

Answer 8

• volume of plasma cleared of drug per time (ml/min)
• CL = rate of elimination / [drug plasma]
• is a constant for 1st order reactions
• as CL increases, t1/2 decreases

Question 9

what are the CL equations?

Answer 9

CL = rate of elimination / [drug plasma]

CL = dose x F / AUC

• AUC: area under curve
• F: fraction of drug in circulation compared to dose

Question 10

what is the cause of low bioavailability?

Answer 10

• poor absorption
• chemical reactions
• first pass metabolism

Question 11

what is the choice of route guided by?

Answer 11

• bioavailabity
• chemcial properties of the drug
• convenience
• need to control specificity of action
• desired onset/duration/offset action

Question 12

what is a multiple dosing regimen?

Answer 12

• doses are taken multiple times a day before [drug] falls to 0
• [drug] varies depending on drug t1/2 and dose interval
• leads to a steady state

Question 13

what is a steady state?

Answer 13

• where dosing rate = rate of elimination

- usually requires 4/5 t1/2s (4-5 doses)

Question 14

how do you measure dosing rate?

Answer 14

dosing rate = CL x Css

Css: [drug] at steady state

Question 15

are steady state levels flat?

Answer 15

• no, contains fluctuations
• fluctuation size is inversely proportional to no. of daily doses
• fluctuations create potential for sub-therapeutic treatments and toxicity
• drug w long t1/2 achieves steady state faster by loading dosage