Drug Distribution Flashcards
What is the aim of good therapeutics?
To deliver medicines to their site of action at effective concentrations
What is the aim in multiple dose therapy?
To keep the levels as stable as possible
What speed do drugs move at in well-perfused areas?
Fast
What order kinetics do most drugs obey?
First order
What is first order kinetics?
Rate of uptake is proportional to [drug]
What does a first order kinetics linear graph look like?
Exponential decay curve
What does a first order kinetics log graph look like?
Linear line
What is constant clearance?
A constant fraction of the drug is removed
What is constant half-life?
The time to remove the drug is independant of dose
What is zero order kinetics?
A constant amount of drug is always removed (eg always 2mg)
Name some saturable processes
Elimination, enzyme, transporters in the liver and kidney
When do drugs show zero order kinetics (generally)
When it is saturated or something isnt working
What are the pharmacokinetic parameters (4)?
Volume of distribution (vd)
Half life (t(1/2))
Clearance (Cl)
Bioavailability (F)
What is the apparent volume of distribution?
Gives an idea of where the drug is in terms of vascular space
How do you work out the apparent volume of distribution?
Total amount of drug/ [plasma]
What does the apparent volume of distribution help with?
Dose calculation
What is the vascular space?
4L
What is extra vascular space?
6L
What is the apparent volume of distribution influenced by?
Lipid/water solubility, binding to plasma proteins
What does a small volume of distribution mean?
Drug is mostly retained in circulation, generally because they’re binding very strongly and very lightly to the plasma proteins so they’re not getting out
What does a large volume of distribution mean?
Takes longer for the drug to be eliminated from the body
What is the plasma clearance?
Volume of plasma cleared of drug per unit time (ml min-1)
Give the formula for plasma clearance
Plasma clearance = rate of elimination / [drug plasma]
Which type of reaction is plasma clearance a constant for?
First order reactions
What does an increase in plasma clearance mean for the half life of a drug?
Smaller half life
What is bioavailability?
Fraction of drug in circulation compared to dose
What does bioavailability measure?
Extent of absorption
What can low bioavailability be caused by(3)?
Poor absorption
Chemical reactions at site of delivery
First - pass metabolism
What is the choice of delivery route guided by (5)?
Bioavailability Chemical properties of drug Convenience Need to control specificity of action Desired onset/ duration/ offset of action
What does the [drug] variation depend on?
Half life and close intervals
What does multiple dosing lead to?
A steady state
When are additional doses of drug administered?
Before [drug] falls to zero
What does multiple dosing compromise?
Minimisation of drug level variability
Simplicity
What info do you need to accumulate drugs properly (6)?
Desired therapeutic concentration Steady state level Volume distribution Bioavailability Half life Clearance
Give the formula for dosing rate
Dosing rate x F = CL x target conc
How long does it take for a drug to reach its steady state?
4-5 x drug half-life
What is the quickest way to reach a steady state?
Administration of a loading dose
What is a loading dose?
Big dose to get the level up to a certain point, then a smaller maintenance dose to maintain it in the therapeutic range
How long does it take to reach a new plateau when the dose is changed?
4 half lives
