distribution Flashcards
What aspects of drugs need to be considered to distribute in bodies?
- particles need to be dissolved
- -> body fluids are hydrophilic so aqueous solubility is needed
- particles need to traverse membranes
- -> membranes are lipophilic so drugs need adequate lipid solubility
How do solutes behave in systems of immiscible solvents?
When solute is present in a system of two immiscible solvents, below saturation and at a set temperature, they follow the distribution law.
This is described by the partition coefficient, which is the ratio of solute conc in oil phase vs the aqueous phase.
What does the partition coefficient represent?
This tells us the lipophilic/hydrophilic nature of a molecule, where this tells us how they will behave in the body.
What is the difference between logP and logD
logP describes how solutes will distribute in two immiscible fluids whereas logD describes how molecules distribute across a boundary
How do lipophilic molecules behave in terms of absorption
Lipophilic molecules are absorbed across membranes better, however there is a limit
If molecules are too lipophilic, they will have decreased water solubility (can’t dissolve) and show increased membrane binding. This increases the possibility of binding to extraneous sites.
How can molecules cross a biological membrane?
passive diffusion
active diffusion
facilitated diffusion
What factors influence passive diffusion of molecules across membranes?
- lipophilicity of the molecule
- water solubility of the molecule. The higher the solubility, the greater the conc gradient created to drive diffusion.
- fraction of unionised drug
- microenvironment of biological compartments and membranes involved
What is the pH partition hypothesis and how does this effect passive diffusion?
The ionisation of a drug is determined by their pKa and the pH of the surrounding medium.
Small unionised molecules will cross a membrane better, so the above factors will influence the ability of molecules to do this.
This hypothesis is described by the Henderson Hasselbalch equation
What is the henderson hasselbalch equation and what does this tell us?
The henderson hasselbalch equation gives the concentration ratio of ionised and unionised species at a given pH.
pH = pKa +/- log ([ionised]/[unionised])
How can ionised drugs be absorbed in the body?
Membranes are negatively charged, and can absorb H+ ions.
This means that when a negatively charged molecule comes close to the membrane, it can interact with a H+ ion that has been absorbed, become unionised, and cross the membrane.
When positively charged (containing H+) molecules comes into proximity with the membrane, the membrane can absorb this positive charge, leaving the molecule unionised and hence able to pass through the membrane.
Why can the pH-partition hypothesis not be applied to the GI tract?
- variability in pH conditions throughout the GI tract
- The anionic nature of a membrane creates a microenvironment around it, where the pH here differs from that of the bulk (slightly lower)
- convective flow of water into and out of the GI tract with affect absorption rates of small molecules
when is pH partitioning relevant? Describe an example
The pH partition hypothesis can be applied to partitioning of molecules between blood and breast milk.
Breast milk has a slightly lower pH (7) compared to blood (7.4), so this can cause partitioning of molecules into breastmilk, being potentially dangerous when breast feeding.
