Drug Absorption Flashcards
What is the pharmaceutical process?
Producing the drug - so basically getting the drug into the patient
What is the pharmacokinetic process?
getting the drug to the site of action - basically what the body does the drug
What is the pharmacodynamic process?
producing the correct pharmacological effect - what the drug does to the body
What is the therapeutic process?
producing the right therapeutic effect
What are the four basic factors what determine the pharmacokinetics of a drug?
absorption, distribution, metabolism, elimination
ADME
What does the pharmacokinetics allow understanding of?
dosage, drug administration, drug handling, patient variability, potential for harm
Why is it important to have a good understanding of a drug’s pharmacokinetics?
to individualise patient drug therapy, monitor mediations with a narrow therapeutic index and decrease the risk of adverse effects whilst maximising pharmacological response of medications
To have biological action where must must drugs enter and be distributed to?
enter bloodstream
distributed to site of action
What are the different ways drugs can be taken?
orally intravenously subcutaneously intramuscularly sunlingually rectally inhaled transdermally nasally
Are intravenous drugs absorbed? and why are they more dangerous?
no - injected straight into blood
more dangerous if allergic or wrong dose as immediately in blood
What is subcutaneous administration? Give an example of a drug administered in this way.
Injection under skin
insulin
What is intramuscular administration? Give an example of a drug administered in this way.
Deep into muscle
Hep B vaccine
What is sublingual administration? Give an example of a drug administered in this way.
Under the tongue - absorption from buccal mucosa angia medication (e.g. GTN) - useful as it bypasses the liver so doesn't get metabolised
What does transdermal administration of a drug normal involve?
medicated adhesive patch that is placed on skin and delivers set amount of mediation
avoids first pass metabolism
What is absorption?
Absorption is defined as the process of movement of unchanged drug from site of administration to the systemic circulation
There always a correlation between plasma concentration of a drug and what?
Therapeutic response
What are the important factors when it comes to oral absorption?
amount of drug which enters the systemic circulation
speed at which it happens
Define Tmax and explain how it is important.
Tmax = the time to peak concentration of a drug
important when you need to treat something quickly, you want it to get to a therapeutic range quickly
Define Cmax and explain how it is important.
Cmax = peak concentration
Want to make sure it is in a therapeutic range but not toxic
What does a higher Tmax mean?
An earlier drug concentration peak, so more rapid absorption taking place
Cmax would only be increased under what circumstances?
if dose increased
What is the AUC and what does it relate to?
Area under the drug concentration-time curve
represents total amount of drug which reaches the systemic circulation
What is the therapeutic range?
range of concentrations over which a drug is active
What is the therapeutic index?
the range over which a drug is active and safe (above this drug toxicity occurs, below this drug is inactive)
What does the AUC allow estimation of?
the amount of drug that reaches the circulation and is available for action
What is the bioavailability of a drug?
The proportion of the drug that enters the circulation and so can have an active effect
What is the bioavailability of an IV drug?
100%
What are the factors affecting bioavailability in oral absorption?
Formulation (e.g. slow release preparations) ability of drug to pass physiological barriers (dependent on particle size, lipid solubility, pH and ionisation) gastrointestinal effects (gut motility, food, illness) first pass metabolism
What ways can a drug pass across membranes?
passive diffusion (if lipid soluble and small enough) filtration bulk flow active transport facilitated diffusion ion-pair transport endocytosis
Do drugs ionise in water?
most drugs do not completely ionise in water
as most drugs are weak acids or bases, the degree of ionisation depends on the pH of the environment
Will ionised or unionised forms of a drug be present in the body, which would pass the cell membranes?
Both forms present
Ionised drug will not pass membrane
the unionised form should distribute across the membrane until equilibrium is reached - equal conc at both sides
An acidic drug will be more concentrated in the compartment with high pH due to what?
ion trapping
Small changes in pH do what to the ionisation of a drug and its absorption/diffusion?
small influences in pH greatly influence the ionisation of a drug and so the rate of absorption or diffusion
To pass a lipid bilayer what must a drug be?
in a solution and be lipid soluble
What is a lipid-water partition coefficient?
the ability of a drug to diffuse across a lipid barrier - it is the ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact
Give an example of a drug that is non lipid soluble and as a result is not absorbed at all.
Gentamicin
What does the passive diffusion of a drug across a membrane depend on?
lipid solubility and degree of ionisation
Active Absorption
relatively unusual
e.g.s iron, K, Na, Ca
uptake of levodopa by brain
energy dependent
to undergo most drugs resemble naturally occurring compounds
drug is reversibly bound to a carrier system
Where does filtration normally occur? And with what kind of substances?
in channels in cell membrane
low molecular size (smaller than diameter of pore) molecules
What is the driving force for filtration?
Hydrostatic or osmotic pressure difference across the membrane
How can gut motility affect drug absorption?
speed of gastric absorption affects speed at which drug reaches site of action
can be affected by other drugs, food/drink, illness
How can illness affect drug absorption?
malabsorption (eg Coeliac disease) can increase or decrease rate of absorption
migrane reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs
e.g. c. diff treated w/ vancomycin - altered lining of bowel so drug can be absorbed in bowel
What is first pass metabolism?
Metabolism of the drug prior to reaching systemic circulation
can be a limit on oral route for some drugs, e.g. insulin can’t be taken orally
Where are the sites that first pass metabolism can take place?
Gut lumen (acid, enzymes) gut wall (metabolic enzymes) liver (hepatic enzymes) factors can be changed by other drugs and disease
What does first pass metabolism vary between?
varies between different people
Subcuntaneous/intramuscular depend on what and avoid what?
depend on blood flow to site (only need small volume)
avoids first pass metabolism
not all drugs can be given in this way
Rectal absorption tends to be slow, but when is it used?
for drugs that cause irritation of the stomach
What are important considerations for the mode of administration?
purpose and site of drug action (local absorption, avoid first pass metabolism) disease effects patients ability to take medicine speed of action reliability of absorption
