Distribution Flashcards
What is distribution?
The reversible movement of drugs from the systematic circulation to the cells and interstitial tissues
What do highly porous capillaries allow?
Paracellular diffusion
What does the penetration of drugs into cells depend on?
Molecular size, lipid solubility and degree of ionisation
Why may lipid solubility be important to a drug?
Some drug receptors are situation within cells
What is HMG CoA reductase
The enzyme inhibited by the statin group of drugs used to lower bloop lipids in the treatment of hyperlipidaemia
Why can insulin not cross the plasma membrane?
Too large (large molecular mass)
Why can atracurium not cross the plasma membrane?
Highly ionised
What is perfusion?
Blood flow
Where is onset of action slower?
Skin, fat and bone
What is the distribution of hydrophilic and large molecular weight drugs rate-limited by?
The permeability of the blood-tissue boundary
Why does anaesthetic thiopental have a very short duration of action?
Time-dependent redistribution into fat, depletion in the brain.
What is redistribution
The transfer of a drug from the brain, back into the blood and then into peripheral organs
How do polar drugs exit the blood brain barrier?
Carrier-mediated transport
How do large hydrophilic drugs exit the blood brain barrier?
Fenestrations
How can some drugs be pumped back into the lumen?
P-glycoprotein, situated on the luminal surface of the endothelial cell plasma membrane
Why is the CNS surrounded by a barrier?
Make it difficult for hydrophilic substances to penetrate, tight junctions do not allow paracellular diffusion
Give three examples of drugs which can penetrate the blood-brain barrier by carrier mediated transport
- Salicyclic acid
- Valproic acid
- L-DOPA
How is L-DOPA transported into the brain?
By the L-system, transports large neutral amino acids
What is required in the brain to treat Parkinson’s disease and why is this a problem?
Dopamine, cannot cross the blood brain barrier
What converts L-DOPA to dopamine and why is this a problem?
DOPA decaroboxylase, converts L-DOPA in the periphery, reducing the amount able to cross the BBB
What does carbidopa do?
Blocks DOPA decarboxylase, cannot cross the BBB, serves to increase peripheral L-DOPA levels and does not inhibit dopamine conversion in the brain.
What is the placenta?
A structure that separates foetal and maternal blood
How does the placenta behave?
Like a lipid membrane, acts as a metabolic barrier contains a variety of enzymes cyt p450s, dependent mono-oxygenases and monoamine oxidases to metabolise substrates.
What can bound drugs not do?
Exit the blood system due to the high molecular mass of the protein-drug complex.
What is the effect of aspirin on warfarin?
Increases the unbound concentration and enhances its pharmalogical effects
What is a sequestered drug?
one which has accumulated to a concentration higher than in blood or plasma.
What happens to highly lipid soluble drugs in adipose tissue?
Accumulates such that their concentration in this tissue is many times that in blood.
