Pharmacokinetics Flashcards
What are some routes of administration?
oral nasal sublingual rectal transdermal pulmonary injection
What is sublingual administration?
drug is absorbed through the buccal (mucus) membrane under the tongue
What is transdermal administration?
through the skin
What is pulmonary administration?
inhalation
Which route of administration does not avoid 1st pass metabolism?
oral
Which is the safest route of administration and why?
oral/peroral
- the drug is highly metabolised in the liver and a lot is absorbed by the intestines making overdose very unlikely
- non-invasive administration
What is 1st pass metabolism?
the concentration of a drug is greatly reduced before it reaches the blood due to breakdown by the stomach and liver enzymes
How can 1st pass metabolism be used to alter medical use?
extended-release formulation
e.g. d-amphetamine coupled to L-lyside; when metabolised the amino acid is cleaved off leaving the active amphetamine
How does the route of administration affect the action of a drug?
drug peak concentration and half-life vary by route of administration
e.g. cocaine
inhalation; rapid onset and peak conc, short duration of action
intranasal; slower onset and peak conc, long duration of action
What is half-life?
time for a plasma drug concentration to fall to half of its peak level
Give an example of the differing action of drug administration
fentanyl; highly potent opiate
- transdermal; prolonged, steady analgesic effect
- sublingual; rapid adjustment of pain levels
- pulmonary; inhalation of gas can cause extremely rapid incapacitation or death
What route of administration will medical professionals tend to use?
one with the minimum effective concentration over an extended period of time
What factors affect absorption and distribution?
drug lipid solubility
ionisation
blood circulation as site of administration
surface area of absorbing surface
amount of drug destroyed by 1st pass metabolism
number of membrane layers to blood
How does drug solubility affect absorption?
some drugs are lipid soluble and will easily diffuse passively
bigger molecules are less likely to diffuse
How does drug ionisation affect absorption?
less ionisation = more lipid solubility = more absorption = more effect
How does drug and solvent composition affect absorption?
drugs that are weak acids ionise more in basic environments
drugs that are weak bases ionise more in acidic environments
How do blood and stomach acid affect ionisation?
blood is slightly alkaline
stomach acid is very acidic
What is pKa?
the pH of the solution in which 50% of the drug is ionised and 50% is not
How do ions become trapped?
ionised drugs are less effective at crossing membranes
when drugs become too highly ionised they can no longer move forwards or backwards through the membrane becoming stuck in a particular compartment
What is the blood brain barrier?
a mechanism of keeping the brain environment as stable as possible
How do we know there is a blood brain barrier?
when dyes were administered IV they spread everywhere except the brain and CSF
Which brain areas lie outside the blood brain barrier?
area postrema; detects toxins and initiates vomiting median eminence (in hypothalamus); allows the release of hormones
What is the difference in structure between a typical and a brain capillary?
typical; intracellular clefts allow flow of ionised molecules
brain; glial cells and astrocytes pack the capillary preventing intracellular clefts, only lipid-soluble (passive) diffusion
What are the different membrane layers available for injection?
subcutaneous; epithelium intramuscular; muscle intravenous; blood vessel intra-peritoneal; intestine cavity intracranial; brain intra-cerebro-ventricular; brain
How are drugs inactivated?
usually through metabolism (biotransformation) which produces ionised molecules that do not have brain access
How are drugs expelled?
ionised metabolites become trapped in kidney tubules and are then excreted
What individual variation can be explained by metabolism differences?
e.g. alcohol - acetaldehyde - acetic acid via alcohol dehydrogenase
How can variation in alcohol dehydrogenase explain individual variation in the effects of alcohol?
alcohol is metabolised by alcohol dehydrogenase
- women have lower levels
- alcoholics have higher levels
- older people have reduced liver function, lower levels
- genetic variation
