Pharmacokinetics Flashcards
What do drug effects depend on?
The mechanism of action and effects on cellular proteins, receptors, ion channels, enzymes and transporters
The drugs physiochemical properties; affinity, efficacy and potency
The concentration
What is meant by absorption?
How the drug enters the body
What is meant by the distribution of the drug?
Compartments and how it reaches the targets
What is meant by the metabolism of a drug?
How it is processed in the body
What is meant by the excretion of a drug?
How the drug leaves the body
How might a drug be distributed in the body?
Bulk flow in the bloodstream via the cardiovascular system
Diffusion eg has to cross blood vessels
The diffusion co-efficient of a drug is related to what?
Its size; it increases if the molecule is small
Larger molecules take longer to diffuse
How is lipid solubility measured?
With the partition co-efficient- this is how easily a drug dissolves into a lipid space vs an aqueous space
What property of a drug makes it dissolve freely?
if it is uncharged
Increasing how easily a drug dissolves causes what to increase in the body?
The rate of absorption from the gut increases
The rate of penetration into the brain and other tissues increases
Renal elimination also increases
What are the ways that drugs can be adinistered?
Intravenous, Intramuscular, Intrathecal, Inhalation, Oral/Ractal, and the percutaneous route
Describe what happens to drugs that are administered intravenously?
Drugs enter the plasma
Can be exctreted via sweat and milk (from breast)
Avoids gut metabolism
Needs a qualified practioner for administration
Describe what happens to drugs that are administered intramuscularly?
From muscle drugs travel to plasma
Avoids metabolism in the gut
The rate of absorption depends on which muscle is is injected
An example is insulin
Describe what happens to drugs that are administered Intrathecally?
Drug is injected into the CSF which goes to the brain and plasma
Drug is injected into the spinal cord
Used when drugs for CNS are required and when only a regionable effect is required
Used to administor local anaestetic for child birth - ideal as the drug does not want to be passed on to the baby
Describe what happens to drugs that are administered through inhalation?
Drug goes directly to the lungs
This is viable for gases only eg general anaestetics
Target for action can also be in the lungs eg in asthma
Describe what happens to drugs that are administered orally or rectally?
Most desirable due to easy administration
The drug has to pass through the gut
Diffusion across the intestines depends on gut motility and capsule size
Capsules can cause both fast and slow absorption depending on the rate required
What is meant by the term bioavailability?
The fraction of the ingested drug as part of the fraction in the plasma eg how much of the drug ends up in the plasma?
Describe what happens to drugs that are administered via the percutaneous route?
Drugs go through the skin eg it is applied on patches
Absorption across the skin is slow and poor but is useful for slow and continuous conditions
Example opiate patches for the brain
What factors affect absorption?
Site/ method of administration
Molecular weight
Lipid solubility
pH and ionisation
What is the pKa?
The pH at which 50% of the molecule is in its dissociated form
At a low pH what will happen to weak acids?
They will be ionised
What is the henderson husslebuck equation?
Pka = pH + log10 (HA/A-)
What is the Pka of asparin?
3.5
What enviroments favour the dissocation of acids?
Basic enviroments where the pH is greater than 7
Where do weak acids get trapped and give an example?
They get trapped in basic compartments for example the renal tubules. Urinary acidification slows excretion of weak acids
What is the effect of increasing pH in the CNS?
It causes weakly acidic drugs to be extracted from the CNS into the plasma where the get ‘trapped’
This decreases neurotoxicity eg when someone has been poisoned b asparin
What is the pH of gastric juice?
3
What is the pH of plasma?
7.4
What is the pH of urine?
8
At what pH will ionisation of a weak acid be greatest?
An alkaline pH
If a large proportion of the drug is dissociated (acidic) i the kidneys what does this mean?
The excretion of the drug is accelerated
If a drug is a base in the gut what happens to it?
It is not excreted and is trapped in the gut
What are large polar molecules like antiobiotics dependent on?
Transporters
What are sugars, amino acids and metal ions dependent on?
Saturation and competitive inhibtion
What can cross the blood brain barrier and what can’t?
Lipid soluble molecules can cross eg ethanol and caffeine
Water soluble molecules can not as the endothelial cells form tight junctions which are impermeable to water molecules
Why can antibiotics reach targets in their brain in cases of meningitis when they normally would not?
During inflammation tight junctions become leaky. Once these are disrupted the antiobiotics can move through so they have better access
How can body fat affect drugs?
The drug may be distirubuted to and enter body fat and therefore not the target. The concentration of the drug must then be altered.
What are the two phases of biochemical reactions?
Catabolic reactions
Anabolic reactions
List examples of enzymes in the liver
Cytochrome p450, alcolohol dehydrogenase, MAO
What are pro-drugs?
Drugs that only become active after being metabolised
Describe what happens for apsparin to be eliminated
Asparin encounters an enzyme in the liver where its acetyl group is replaced with an OH group to form salicylic acid
It is then conjugated with glucose to form glucoronide so it has decreased access to tissue
How many p450 genes are there?
57
What can be the effect of brussel sprouts on p450
It increases the rate at which they metabolise drugs
How can drugs be eliminated?
Urine (renal excretion), Faeces (Gi excretion), Milk or sweat, Expired air (lung excretion)
What can affect excretion?
The health of the liver or kidney - can be compromused due to age or alcohol misuse or disease
What is the time constant of a drug?
The time for concentration to decrease by half
What is meant by a drug that shows saturation kinetics?
A drug which shows no plateau on a graph ie has a linear shape
Example is alcohol - shows saturation kinetics due to alcohol dehydrogenase limit
These can have clinical side effects and toxicity
