Pharmacokinetics: Absorption and Distribution Flashcards
What is pharmacokinetics?
- what the body does to a drug that is administered
What is pharmacoDynamics?
- what the Drug does to the body once administered
Pharmacokinetics is the branch of pharmacology that is concerned with the movement of drugs within the body. What are the 4 things that can affect the course of the drug once administered?
- use A.D.M.E
- A = absorption
- D = distribution
- M = metabolism
- E = excretion
In order for any drug to be effective, what are the 2 main aspects of the A.D.M.E mnemonic that the drug must overcome?
1 - absorption = overcome physiological barriers
2 - digestion = directed to target tissue in appropriate concentration and overcoming internal physiological barriers)
Even if a drug can be absorbed and distributed around the body, what are 2 limitations that are part of the mnemonic A.D.M.E that the body imposes on any drug?
1 - metabolism = all or very little of the drug may be metabolised
2 - excretion = may be excreted slowly or quickly affecting therapeutic window or toxicity
If the body cannot absorb a drug, what problem can this cause for its clinical use?
- difficult to get its concentration up to a therapeutic level
If the body absorbs a drug, but it cannot be distributed, what problem can this cause?
- drug cannot reach target tissue
- may have off target effects
If the body absorbs a drug, but cannot metabolise the drug, what problem can this cause?
- if drug is not metabolised well, too much of it may circulate in the body
If the body absorbs, distributes and metabolises a drug, but cannot excrete the drug, what problem can this cause?
- drug level may become toxic to the body
What is the most common route of drug administration and why?
- oral
- cheap, convenient, acceptable
- no special skills needed
Injection is one form of drug administration, and there are 3 main types, what are they?
1 - intravenous (quickest)
2 - intramuscular
3 - subcutaneous
Inhalation is one form of drug administration, what is a key example where this is useful?
- asthma
- less adverse effects
- direct effect on tissue
Sublingual is one form of drug administration, what is a key example where this is useful?
- glyceryl trinitrate (GTN) for angina
- absorbed quickly under the tongue
Rectal suppository is one form of drug administration, what is this?
- drugs are place in the anus
When we talk about pharmaceutical properties of a drug, what are we referring to?
- syrups, pills etc…
- what form they take
When we talk about Physicochemical properties of a drug, what are we referring to?
- solubility of drugs
- pH of drug (acidic drugs better absorbed in the stomach; alkaline drugs in the intestine)
- molecular weight (affects diffusion)
When we talk about Physiological properties of a drug, what are we referring to?
- surface area =GIT has a huge surface area
- contact time = digestion is a long process, increaisng absorption
- concentration of the drug on the absorption site
- absorption site (blood flow, increases with food pH)
- interactions with enzyes and bacteria
- transport systems
The oral route of drug administration is by far the most common. What is the main aspect of A.D.M.E that oral drug administration must overcome?
- absorption
The digestive tract is one of the biggest barriers to taking drugs orally. What are a few of the things in the digestive tract that may affect drug digestion?
- pH
- enzymes
- bacteria
- motility
- food
- drugs
What is first pass metabolism?
- a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation
Why are the physicochemical properties inside the GIT important to allow drugs to be administered orally, digested and then absorbed?
- crucial to ensure crossing of the GIT membrane
- drugs must be soluble to be absorbed
- drug must reach GIT where pH is optimally for absorption
- drugs molecular weight must be suitable for absorption
What does biotransformation systems relate to in drugs in the GIT?
- the ability of drugs to resist enzymatic action
- if enzymes break drug down in GIT, it may not be effective or absorbed
What is an example of where the physicochemical properties of a drug are dependent on pH?
- antacids are active once they reach a low pH
- they can raise the pH in the stomach reducing reflux
- patients must have a gap between taking them, otherwise pH will not be low enough for the next dose
What is an example of where the physicochemical properties of a drug are dependent on food being present in the GIT?
- formation of complexes / chelation
- tetracyclines taken with milk is bad
- Ca2+ binds and inactivates tetracyclines
What does bioavailability mean?
- the fraction of a drug that reaches the systemic circulation and the target tissue as an intact drug
What is the formula for calculating bioavailability?
- calculate how much drug reaches target via oral administration
- calculate how much drug reaches target via intravenous (IV) administration
- oral area under the curve (AUC) / IV AUC
- accounts for digestion and metabolism