Drug distribution Flashcards
What is drug distribution?
Movement of a drug to/from blood and tissues of the body
Factors that affect drug distribution
- Cardiac output and blood flow
- Plasma protein binding
- Lipid solubility
- Degree of drug ionisation
- pH of compartments
- Capillary permeability
List in order the level of blood flow to the tissues in the body
- Kidneys
- Liver
- Heart
- Brain
- Skeletal muscle
- Fat
What does initial rate of distribution depend on?
blood flow
What is the predominate plasma binding protein?
Albumin
What binds to albumin?
- Lipid-soluble drugs bind non-specifically
- Weak acids bind to a specific saturable site
What does hyperalbuminemia cause and how does it affect free drug levels?
Dehydration
Decreases free drugs levels
What does hypoalbuminemia cause and how does it affect free drug levels?
Causes:
- Burns
- Renal disease
- hepatic disease
- malnutrition
Increases free drug levels
What affects the albumin conc in the blood?
- pH
- Temperature
- Drug interaction
Describe lipophilic drugs
soluble in fats and non-polar substance
Rate of distribtuoon is dependent on the rate of delivery to tissues (blood flow)
Describe hydrophilic druhs
highly soluble in aqueous, polar media
Rate of distribution is dependent on diffusion characteristics of the drug
List some drugs that are bases
- Amphetamine
- Atropine
- Noradrenaline
- Coedine
- Diazepam
List some drugs that are acids
- Paracetamol (weak)
- Phenytoin
- Warfarin
- Aspirin
- Penicillins (strong)
What does the ratio of ionised-unionised drug depend on?
pH
Describe the lipid solubility of ionised drugs
low lipid solubility meaning they will not diffuse across the cell membrane
What type of drug as a fast rate of diffusion?
lipophobic
What are the 3 types of capillaries
Continuous, discontinuous, fenestrated
What is an example of a functional and physical barrier in the body that will only let certain drugs through?
Blood Brain Barrier
What type of drugs can move through the BBB without a specific transport mechanism?
lipophilic e.g. beta-blocker
Explain how the plcaenta is a specialised physical barrier
- Tight endothelial cell junctions in maternal and fetal capillaries
- Partially protective, except with:
- lipid soluble drugs
- unionised forms of weak acids and bases
**Drug is less likely to leave the fetal circulation and be eliminated from the mother in these cases
What does understanding the amount of fluid in each compartment of the body allow?
helps understand where blood is likely to go and with it drugs depending on their chemical properties
Breakdown of fluid in an adult body
- Extracellular flui = 15L
- Plasma = 3
- Interstitial fluid = 12
- Intracellular fluids = 27L
- Total = 42L
What is contained the the EXC fluid?
Large, water soluble molecules
What is contained within the plasma?
Highly plasma-bound molecules
Highly charged molecules
Very large molecules (e.g. heparin)
