Drug distribution Flashcards
What happens once a drug has been absorbed
must be available for biological action and distribution to the tissues
Define drug distribution
Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body activating the drug
What kind of drug is biologically active
an unbound drug
What is Tmax and Cmax
The time to maximum plasma concentration (Tmax)
maxiumum plasma concentration (Cmax)
The area under the drug concentration-time curve represents
the amount of drug which reaches the systemic circulation and is available for action
The bioavailability of a drug is dependant on
extent of absorption and first pass metabolism
Drugs binding to proteins in the plasma can be affected by
Renal failure Hypoalbuminaemia (Low plasma proteins) Pregnancy Other drugs Saturability of binding
The less bound a drug is to plasma protein increases its ability to
cross the cell membrane and be activated
When is plasma protein binding matter
when binding is above 90%
because if unbound level changes above 90% there is a massive proportional increase in the amount of free drug
also important when tissue distribution is small
Volume Of Distribution
overall distribution of drug within the body observed in blood concentrations
The greater volume distribution increases the time of what
clearance
Define clearance
the theoretical volume of fluid from which a drug is completely removed over a period of time - basic measure of elimination
What is clearance dependant on
concentration
Urine flow rate
metabolism
biliary excretion for hepatic clearance.
What organs help clearance
Liver
Kidney
maybe gut
If liver and kidneys not working what is the result
accumulated drug resulting in toxicity
Define the half life
the time taken for the drug concentration in the blood to decline to half of the current value
What is half life dependant on
volume of distribution and rate of clearance
If half life of drug prolonged and medicine is continued this increases the volume distribution leading to
toxicity
What do we need to know to work out how often a drug can be administrated
half life
Define Drug elimination
the removal of active drug and matabolites from the body
What are the two parts of drug elimination
Drug metabolism
drug elimination
What are the primary organs for drug excretion
the kidneys
Where are drugs usually metabolised
Liver
where will all unbound drugs be filtered at
glomerulus in kidneys as long as they aren’t to big
Factors that affect the glomerular filtration rate will reduce
the clearance of the drug
what is entero-hepatic circulation
Many drugs are then reabsorbed from the bile into the circulation
when does entero-hepatic circulation stop
when drug is metabolised in the liver or excreted by the kidneys
where are drugs usually conjugated - i.e. the chemical substances is terminated
the liver
Damage to the liver may reduce the rates of conjugation resulting in
reabsorption or an accumulation resulting in toxicity
What are the factors that effect drug distribution
Plasma protein binding
Blood flow - tissue mass ratio
Membrane characteristics - blood brain barrier
Transport mechanisms
Diseases and other drugs (esp renal failure, liver disease, obesity)
Elimination
where are some drugs selectively accumulated and what can this lead to
kidneys
eye
bone
selective toxicity
What is the transfer of drugs to the brain modified by and why
blood brain barrier - as is much less permeable to water-soluble drugs than is the membrane between plasma and other tissues
what does the duration and intensity of the pharmacological effect depend mostly on
renal function
