Pharma absorption and distribution of drugs Flashcards
What is pharmacokinetics?
describes how drugs move through the body
Describe the general trend of a plasma drug concentration time graph
at the start there is an increase in the plasma concentration as the drug is absorbed
absorption then begins to slow
the concentration of the drug then decreases over a longer period of time due to metabolism and excretion
what is the therapeutic index?
is the difference between the effective and toxic concentration of a drug
drugs with larger therapeutic indexes tend to be safer
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is absorption?
the movement of a drug from the site of administration to the plasma
what is distribution?
how the drug gets to its target tissue
What is Metabolism and Excretion
the breakdown and then removal of a drug from its site of action
List the 4 factors that effect drug absorption
Route of administration
Blood flow surrounding and at site of administration
Good blood flow maintains a steep diffusion gradient
Dose
the larger the dose the larger the concentration gradient
drug solubility
lipophobic drugs readability dissolve in blood plasma
lipophilic drugs need transport being proteins in the blood
What are the three types of drug administration?
Enteral
Percutaneous
Parental
How does blood flow affect distribution?
Some organs have very high perfusion therefore will see the drug first e.g. brain liver, heart
some have very low perfusion e.g. adipose tissue
What is the main plasma binding protein for lipophilic drugs?
what does this mean?
Albumin
means an equilibrium exists at the site of action between the bound drug and albumin complex and the drug itself
How can diffusion barriers effect distribution?
Blood brain barrier and placenta highly controlled areas drugs may not be able to enter
What is tissue binding?
the preference of drug for a particular tissues receptors effects its distribution
What is ion trapping?
how does it affect distrobution?
Drugs are usually weak acids therefore have a equilibrium between an ionised and unionised form
only the ionised form can cross the CSM
yet drugs collect where ionisation is favoured
Where do weak acids collect and are absorbed best? Why does this happen?
In low pH’s equilibrium shifts to the right favouring the unionised HA form. As such weak acidic drugs diffuse and are distributed best in acidic environments
In basic environments (high pH’s) dissociation is favoured therefore drugs collect here e.g. urine
Where do weak bases collect and where are they absorbed best? Why?
In high pH’s (basic environments) the equilibrium shifts to favour the unionised form therefore they readily diffuse and are absorbed in these environments.
they accumulate in acidic environments e.g. the stomach as the equilibrium is shifted to favour dissociation
What is fat trapping? Why is this significant?
lipid soluble drugs collect in fat this absorption is slow as there is a low blood supply to adipose tissue
as such the elimination form these environments is also slow and the drug may be release slowly form these areas long after the plasma concentrations have dropped.
Accounts for biphase elimination
this can be an issue if you are dosing overweight patients
Where does first pass metabolism mainly occur?
The liver
metabolism also occurs in the kindly lungs and Gi tract
What is phase 1 metabolism
NB Phase 1 and Phase 2 metabolism occur at the same time
Oxidation of drugs using CYP450 enzymes that introduce hydroxyl groups and make drugs more soluble therefore easier to excrete
What is phase 2 metabolism?
conjugation of charged groups via cytoplasmic sulfotransferases –> this makes the drug even more hydrophilic and therefore makes it easier to excrete
What are the consequences of first pass metabolism?
Why does this vary?
usually deactivated drugs
can also activate some prodrugs
people have different concentrations and variations of enzymes present hence the growing need for personalised medicine
Give an example of a drug that is activated during first pass metabolism.
Tamoxifen is converted to 4 hydroxytamoxifen via CYP2D6 enzyme, used in breast cancer treatment
What is the main organ involved in drug excretion
kidney
How is the liver and other organs involved in Drug excretion?
Liver secretes metabolised drugs into bile –> can be an issue if then reabsored in the Gi tract as drug remains in a enterohepatic circulation loop
Lungs can expel gasses from metabolism of drugs and drug vapours in air
Saliva sweat and milk are other forms of secretion
