Drug Absorption Flashcards
Define bioavailability and how it can be calculated
- fraction of unchanged drug that reaches systemic circulation
- compare it to IV drug
- (area under curve for other route)/(area under curve for IV drug) x 100
Define bioequivalence
- generic or therapeutic substitutions for drugs
- generic substitution occurs when different formulation of the same drug is substituted
- eg. using branded vs non-branded paracetamol
- must have bioavailability 80-125% compared to reference product
- therapeutic substitution is replacement of drug with alternative molecules with assumed equivalent therapeutic effect
- can be same or from another class as reference product
- eg. changing a patient from simvastatin to atoravastatin
What are the advantages and disadvantages of the oral route?
Advantages:
- cheap
- safe
- convenient
Disadvantages:
- patient compliance
- variation in bioavailability of drug
Why is there variability in the bioavailability of drugs taken orally?
- there are many barriers the drug needs to cross and there are many ways the drug can be excreted in the body
- eg. destroyed in the gut, gut wall or liver, or not absorbed and excreted in faeces
How does drug particle size and formulation influence absorption?
things like enteric coatings and sustained release formulations can be used to modify where the drug particles are absorbed in the body and how long until the drug is dissolved for absorption
What routes of administration avoid the first pass metabolism?
- buccal/sublingual route absorbs drug in oral cavity and goes directly to large veins instead of through the portal vein to the liver
- not ideal for noxious medicines or foul tasting ones so very limited
- rectal route also bypasses first pass metabolism however poor absorption so also very limited
What are the mechanisms for barrier crossing for GI drugs to be absorbed?
- diffusing directly through lipid (lipid-soluble drug)
- transmembrane carrier proteins (solute carriers)
Describe how ionisation of GI drugs affect its absorption and apply it to weak acids/based drugs
- ionisation of drug depends on environment it is in
- ionised drugs will not be absorbed
weak bases:
- ionised in acidic pH (so no absorption in stomach due to low pH)
- drug will be absorbed in small intestines where pH is higher
weak acids:
- unionised in acidic pH
- however drug will still be absorbed in small intestine due to large surface area for absorption but it will be limited due to ionisation
What is the Henderson Hasselbach equation?
- pKa - pH = log10 [BH+]/[B]
- for weak base
- pKa - pH = log10 [AH]/[A+]
- for weak acid
- answer will show ratio of ionised/un-ionised drug present in that compartment
- if ionised then the drug won’t be able to cross membrane
What are the possible effects of food on drug absorption?
- food tends to slow rate of gastric emptying
- can have no effect
- can decrease absorption (due to change in intestinal motility can have drug stay in stomach for longer time and can interact with acidic environment/other factors eg. enzymes in gut wall)
- can have delayed absorption (for drugs absorbed in small intestines, due to slowed rate of stomach emptying)
- can increase absorption (very lipophilic drugs that require further breakdown, taken with food can increase its solubilisation)
Describe how first pass metabolism can affect drug absorption
- eg. drugs that need to get to CNS to exert its effect
- need to be processed in GI system to be taken up by carriers
- drug particles might not last long in stomach which can decrease the amount of drug taken up to CNS even with a good carrier
Describe how change in GI motility due to disease can affect drug absorption
- GI tract modified in disease states like Crohn’s disease and Coeliac disease
- coeliac disease causes decreased drug absorption due to inflammation of small intestines impairing its absorption ability
- crohn’s disease causes decreased drug absorption by increased GI motility so drug does not spend long enough time in GI tract to be absorbed
- in some cases of crohn’s they can have ulceration or abscesses on GI tract that can cause increased drug absorption due to there already being a breach in the barrier
What are the parenteral routes of administration and their effects on absorption?
Subcutaneous:
- slow absorption due to reduced blood flow to skin
Intramuscular:
- lipophilic drugs absorbed rapidly
- polar drugs through bulk flow/endothelial cell junctions
- lipophobic or high molecular weight drugs get absorbed by lymphatics
What factors affect the rate of onset of drug effects by parenteral route?
- extend of capillary perfusion
- drug vehicle (what it is delivered in)
- factors that alter perfusion
How can you modify inhalation drugs to only have a local effect and not be absorbed into the plasma?
- modify structure
- modify particulate size
- make selective to specific receptors
- make it so it can be rapidly broken down in circulation
