Distribution Flashcards
Bioavailable
The proportion of drug which has reached the systemic circulation and carried on to exert a pharmacodynamic effect at its target site
Distribution
Where the drug goes to in the body and how it gets there
What 4 drug factors can affect absorption?
- lipid/water solubility 2.plasma protein binding 3.molecule size 4.affinity for certain areas (fat/muscle/bone)
What 3 patient factors affect drug distribution?
1.Body composition 2. number of plasma proteins 3. other drugs- interactions
Blood flow- (drug reaches vascular areas first- brain, heart and lungs)
Biological barrier such as BBB
What 3 ways can drugs cross the cell membrane?
1.Passive diffusion
2. Facilitated Diffusion
3. Active transport
What molecules can enter different areas of the body more easily?
Small molecules with a low molecular weight which are lipid soluble
What happens when there is more drug within the plasma than without?
The drug will try and leave the plasma to equalize the concentration in tissues and in blood
What affects the drugs ability to leave the bloodstream?
The extent to which a drug is bound to plasma proteins
What makes a drug inactive?
Temporary storage of some drug molecules bound to plasma proteins
When do bound molecules dissociate from plasma proteins?
When free drug molecules pass into the tissues, to maintain the ratio of bound drug versus free drug in the plasma
What are more acidic drugs likely to bind to?
Albumin
What are lipid soluble drugs?
More highly protein bound
When are molecules released from plasma proteins?
As free drug is used to keep the plasma concentration and the amount reaching the target site steady
What happens if more drug is bound?
The less drug will pass into the tissues
Plasma proteins hold the bound drug until…
The free drug has exerted its pharmacodynamic action and then release a proportional amount of what has been used
What can malnutrition, pregnancy, age, severe burns and liver disease lead to?
A reduced concentration of proteins, reduced binding capacity and an increase in the plasma concentration of a drug
How are drugs carried to the their target site?
By plasma proteins
What happens to plasma proteins?
They are synthesized in the liver
What happens to a proportion of drugs which are protein bound?
They are anticipated to be temporarily inactive and dose recommendations take this is into account
What happens if there are too few proteins?
There will be more free drug in the plasma than anticipated
What happens to high plasma concentrations of active drug?
Can lead to side effects at unintended drug targets
What can a high concentration of free drug be?
Supra therapeutic
What can affect the distribution of some drugs?
Competition for plasma proteins
What happens if one drug is expected to be highly protein bound and there is competition for plasma binding?
There is more free drug in the plasma
What does free drug do? What can this lead to?
Free drug can leave the plasma and exert an effect, there may be greater clinical effect at the target site or even the toxic effects at other sites
What happens if a dose is based on being highly plasma protein bound and the plasma protein binding is reduced?
If the drug is one that is widely distributed to the tissues this can create adverse systemic effects
High volume of distribution
Very lipid soluble- can cross cell membranes to leave the vascular compartment
Drugs which work in the CNS such as opioids are designed to
Cross the BBB
What will happen to amount of drugs that are lipid soluble and taken regularly for a long time?
They will cross the BBB
What do some drugs have?
An affinity for certain tissues
What do benzodiazepines bind to?
Fat
What does gentamicin bind to?
Albumen
What do tetracyclines bind to?
Bones and teeth
What are drugs with a high affinity for plasma proteins designed to do and why?
They are designed to stay in the blood as this is where their pharmacodynamic action takes place
If drugs have an high affinity for a certain area what is there a risk of?
Accumulation
What do drugs such as benzodiazpines have? What does this have?
A high affinity for fatty tissue which has a low blood supply
What does this mean?
It takes some time for the benzodiazepines to accumulate in the fatty tissue and reach a steady state
What may happen if the drug has accumulated in the fatty tissue?
The drug may continue to be slowly released from reservoirs in fat stores once drug administration has ceased
What changes with age?
The relative size of body compartments changes with age
Fluid component- higher water content in muscle cells in younger children
Circulating fluid volume greater in pregnancy
What decreases in older adults?
Muscle mass
What change can alter drug distribution?
In a pt’s extra vascular fluid compartment volume
Where will drugs that are widely distributed distribute to first?
The most highly vascularized tissues first (heart, lungs and brain)
What happens to distribution in areas with a poor perfusion?
Distribution is much slower and less gets there
If a drug has a low volume of distribution what will the drug do?
Remain tightly bound to plasma proteins
What happens to water soluble drugs?
They are usually confined to the bloodstream and have a low volume of distribution throughout the tissues
Gentamicin has a low volume of distribution what does this mean?
There is a likelihood of toxicity due to consistent high plasma levels pf drug
What happens to drugs with a high volume of distribution?
Drug distributed out of the circulatory system
What sort of molecules have a high volume of distribution?
Lipid soluble drugs and small molecules
What are lipid soluble drugs? What does this mean?
Not ionized, they can pass easily into the fatty tissue and so have a high volume of distribution
Why is diazepam an effective drug for seizures?
it is highly lipid soluble - it can travel through the rectal mucosa, into the circulation, reach the CNS, cross the BBB and control seizures in seconds
What are the 8 factors that affect drug distribution?
- blood flow- circulation to the target site
- extent of plasma protein binding
- disease- can affect the number of plasma proteins
- lipid solubility
- affinity for certain areas
- natural prevention
- volume of distribution
- altered kinetics
What can cytokine release by the immune system can affect?
Distribution of drugs and the dose needed
Free drug
Molecules not attached to plasma proteins
Wash out period
A “washout period” in the context of medication refers to a break or a period of time during which a patient stops taking a specific medication, usually before starting a new treatment or when transitioning between different medications. The purpose of the washout period is to allow the body to clear the previous drug from the system, reducing the risk of drug interactions or side effects that may arise when switching medications.
What will happen to the concentration in the plasma after drug molecules entered the tissue and found their target site?
Concentration in the plasma will be less
What will molecules start to do?
Move with the concentration gradient
What will molecules do?
Move from the highest concentration, which is in the tissues, back into the area if low concentration, which is plasma, to maintain an equilibrium
