L5: Introduction to Pharmacokinetics Flashcards
What is a therapeutic window?
Range of concentration of a drug between maximum safe and minimum effective concentrations.
What are the pillars of pharmacokinetics?
- Absorption - transfer of drug to circulation (how quickly the drug is absorbed to the system)
- Distribution - where drug reaches (how is it distributed)
- Metabolism - (how drug is acted upon)
- Elimination - removal of a drug
What are the main routes of drug administration?
- enteral (involves the gastrointestinal tract)
- parenteral (independent of the GI tract)
What are the routes of parenteral drug administration?
-
injection:
i) intramuscular (to muscles);
ii) subcutaneous (to subcutaneous);
iii) intravascular (to veins);
iv) epidural (to epidural space) -
topical administration:
i) cream,
ii) drops,
iii) inhaled
What are the routes of enteral drug administration?
Most common, but least predictible
- oral: swallowing, tablet/liquid
- sublingual (under tongue)
- buccal (absorbed through membranes of the mouth)
What are the advantages of oral administration?
- convenient - can be self-administered, pain free, easy to take
- absorption - takes place along the whole length of the GI tract
- cheap - compared to most other parenteral routes
What are the disadvantages of oral administration?
- sometimes inefficient - only part of the drug may be absorbed
- irritation to gastric mucosa - nausea and vomiting
- destruction of drugs by gastric acid and digestive juices (e.g. erythromycin)
- interaction with food (e.g. digoxin - fibre binding)
- unpleasant taste of some drugs
- onset of effect is slow
- cannot be used in unconscious patients
- first-pass effect - drugs absorbed from the gut are initially transported to the liver via the portal vein
What is first pass effect?
Hepatic metabolism of a pharmacological agent when it is absorbed form the gut and delivered to the liver via the portal circulation.
What is the correlation between the first-pass effect size and a drug reaching systemic circulation?
the greater the first-pass effect, the less a drug will reach the systemic circulation when it is administered orally
How is the route of administration for the drug chosen?
- physical characteristics
- speed which the drug is absorbed
- need to bypass hepatic metabolism
- need to achieve high concentrations at particular sites
What are the factors influencing the rate of absorption?
- routes of administration
- dosage forms
- concentration of the drug
- physiochemical properties of the drug
- protein binding
- types of transport
- circulation at the site of absorption
What are the mechanisms of solute transport across membranes?
- passive diffusion
- filtration and bulk flow
- endocytosis
- ion-pairing
- active transport
What are the barriers to absorption?
- mucous layers (orally administered)
- protein binding (drugs bind bulky proteins)
- fat isolation (sequestered in fat, when dissolves in fat)
- placenta
- blood-brain barrier
- cell membrane most ubiquitous
What does pKa for drug absorption determine?
pH at which 50% of a drug is ionised;
ionization usually increases with opposing pH, ie basic drugs ionized in acidic solutions
When do weak acid drugs become highly ionised?
as pH increases
When do weak bases become highly ionised?
as pH decreases
Where are non-ionised forms soluble? Do they cross the membrane?
Non-ionised forms are lipid soluble and cross the cell membrane
Where are ionised forms soluble? Do they cross the membrane?
Ionised forms are water soluble and do not cross the cell membrane
When do drugs become most concentrated?
When they are most ionised
How are ionisation ratios calculated for acidic and basic drugs?
According to Henderson-Hasselbach equation:
for acid drugs: pKa = pH + log10([HA]unionised/[A-]ionised)
for basic drugs: pKa = pH + log10([HB+]ionised/[B]unionised)
