Drug distribution Flashcards
What is drug distribution?
Dispersion of a drug among fluids and tissues of the body
What is the aim of good therapeutics?
• Aim of good therapeutics is to deliver medicine to their site of action at effective concentrations
What is the aim in multiple dose therapy?
In multiple dose therapy, aim is to keep levels as stable as possible of drug
Where are drugs going?
• From I.V to inside the blood cell
○ Drug moves fast into well-perfused areas
○ Drug moving into poor perfused areas
• Can go from blood vessels to outside blood vessels
What is the time course of the concentration of drug in circulation?
- Drug moves fast into well-perfused areas
- Then Drug moving into poor perfused areas
- Then Drug metabolised and eliminated from the body
What is first order kinetics?
- Constant half-life
- Constant clearance
- Constant fraction of drug is removed
- Time to remove drug independent of dose
- No saturation of process
What is zero order kinetics?
- Half life and clearance fluctuate with concentration of drug
- Constant amount of drug removed
- Bigger the dose the longer the time to remove it
- As dose decreases, no saturation therefore returns to 1st order kinetics
What are pharmacokinetic parameters?
• Half-life
• Volume of distribution
• Clearance
Bioavailability
Equation for apparent volume of distribution
• Total amount of drug/[plasma]=Apparent volume of distribution
What does apparent volume of distribution indicate?
• Indicates the extent of distribution for a drug
Why is the volume of distribution important?
• Clinically important for adjusting dosage
What is the volume of distribution influenced by?
• Influenced by lipid/water solubility, binding to plasma proteins
What is plasma clearance?
• Volume of plasma cleared of drug per time
Equation for clearance
CL=Rate of elimination/[drug plasma]
What is plasma clearance a constant for?
• Constant for 1st order reactions
What happens when plasma clearance increases?
• As plasma clearance increases, half life decreases
What considerations need to be taken?
- Most medicine not taken by i.v
- Most given as multiple doses
- Kinetics may be altered by age and disease
What is bioavailability a measure of?
Measures extent of absorption
• Fraction(F) of drug in circulation compared to dose
What is low bioavailability caused by?
- Poor absorption
- Chemical reactions at site of delivery
- First-pass metabolism
What is choice of route guided by?
• Bioavailability • Chemical properties of drug • Convenience • Need to control specificity of action Desired onset/duration/offset of action
What does multiple dosing lead to?
• Multiple dosing:
○ Leads to steady state
○ Amount of drug absorbed equates amount of drug eliminated
What does concentration of drug variation depend on?
• Concentration of drug variation depends on half life and dose interval
What does multiple dose therapy compromise?
○ Minimisation of drug level variability
Simplicity
What is the time to plateau?
Time to plateau is 4-5x drug half life
How can the achievement of steady state be accelerated?
• Drugs with long half lives achievement of steady state can be accelerated using a loading dose
When is maintenance dose used?
Maintenance dose used when concentration of drug starts to drop to ensure concentration remains in therapeutic range
What does fluctuations create?
Fluctuations create potential for sub-therapeutic treatment or toxicity
