Distribution- pharmacokinetics Flashcards
Factors that affect the distribution of a drug [10]
- Its molecular size
- Ionisation
- Lipid and water solubility
Blood flow
Blood and placental barriers
Plasma binding proteins
pH
Disease state of the individual
Volume of distribution
Volume of distrubution
Factor that affects the distribution of drugs.
Volume of distribution = Dose of drug (mg) / Plasma concentration of drug (mg/L)
This describes the movement of the drug across different barriers:
- Plasma (smallest volume)
- Interstitial fluid
- Intracellular fluid (largest volume)
The greater the volume of distribution, the more the drug can penetrate into cells.
Dosage
Derived from the volume of distribution of a drug.
Dose = Volume of distribution x plasma concentration of drug
Greater dosage increases volume of distribution
Examples of drugs that have a high plasma protein binding
Warfarin
Phenytoin
Ibuprofen
Furosemide
Sulphonamide
Drug distribution
The process of a drug reversibly moving away from site of administration to tissues throughout the body.
Examples of drugs with a very high volume of distribution
Ethanol
Amiodarone
Digoxin
Morphine
All of these are very lipid soluble and have a long half life.
Drugs with moderate volume of distribution
These drugs have are very water soluble but not lipid soluble
- Allows them to penetrate up to extracellular fluid (15L)
Examples:
- Insulin
- Amoxicillin
These drugs are dosed according to the ideal body weight.
Plasma binding protein
Drugs with low water solubilities tend to bind with plasma proteins
- The protein is usually albumin.
- This decreases volume of distribution.
This binding forms a drug-protein complex that is a reversible process.
The unbound portion of the drug initiate a clinical effect whereas the bound portions are inactive.
Drug interaction- plasma binding protein
Some drugs have the ability to displace a drug bound to plasma protein.
This can increase the effect of the displaced drug- can lead to toxicity.
