Drug absorption Flashcards
What does ADME stand for
Absorption
Distribution
Metabolism
Excretion
What is absorption
The process by which unchanged drug enter the circulation
What is distribution
Diversion of a drug among fluids and tissues of the body
What is metabolism
Transformation of a drug into daughter compound(s)
What is excretion
Removal of drugs/metabolites from the body
What happens when the route of administration for a drug changes
Different barriers to absorption
Different bioavailability and onset
Oral administration
- many barriers
- Digestive enzymes
- All drugs funnelled through the hepatic portal vein and therefore into the liver
Intravenous injection
- No barrier
- No drug is lost
Tropical cream
-Direct administration
Inhalers
- Direct delivery to the lungs
- Helps with the safety profile as it doesn’t need to reach the level of concentration in the systemic circulation which might have toxic effects
Why is the choice of delivery a compromise
- Speed of onset
- Convenience
- Bioavailability; proportion of administered drug reaching the systemic circulation
- Side effects
- Specificity of action
What is transcellular absorption
Drug travels through cells
What is paracellular absorption
Drug travels in-between cells
How can absorption occur from the most common to the least common
- Passive diffusion
- Facilitated diffusion
- Active transport
What is Fick’s law
Rate of diffusion = Surface area * concentration difference * permeability
How does permeability vary
Molecular size, lipid solubility, presence of charged or ionisable groups
Why are most drugs ionisable
Since they are normally either weak acids or weak bases
What is a weak acidic drug
A proton donor
What is a weak basic drug
A proton acceptor
What does the extent of ionisation depend on
The pH of the environment
What type of medicines are absorbed mot effectively
Uncharged, non-ionisable and lipophilic drugs
What drugs are absorbed least effectively
Charged and ionised drugs
What does the Henderson-Hasselbalch equation show
The position of the equilibrium, showing the extent of ionisation
How is pH calculated for acidic drugs
pH = pKa - log [non-ionised] / [ionised]
How is pH calculated for basic drugs
pH = pKa + log [non-ionised] / [ionised]
When does pH = pKa
When the drug is 50% ionised
How does more of the acidic drug stay unionised
As the pH becomes more acidic
How does more of the basic drug stay unionised
As the pH becomes more alkaline
What are the lipinski rules
An-orally active drug has no more then one violation of the following
- Molecular weight < 500
- No more then 5 H-bond donors
- No more then 10 H-bond acceptors
- Log p < 5 (partion coefficient)
