drug movement Flashcards
what is pharmacodynamics?
what the drug does to the body
- involves drug acting at particular drug target resulting in activation or inhibiting of cellular signalling pathway
what is pharmacokinetics?
what the body does to the drug
- involves how easily the drug is absorbed in the body & how distributed in certain tissues & how metabolised
how can we characterise pharmacokinetic processes?
by calculating the measures such as the apparent volume of distribution (Vd) , elimination half-life, clearance or the bioavailability of a drug.
how can we characterise pharmacodynamics?
by looking at the affinity, potency or efficacy of a drug and calculating such things as Ki, EC50, or Emax
what is goal of pharmacokinetics?
finding dose that will be safe & have high efficacy
what is ROAand what is used to help determine?
routes of administration - used to help work out dose
- some ROA straight forward like IV, some are more complicated like oral
what is IV ROA?
drug goes straight into blood circulation, avoiding first pass metabolism
what is oral ROA?
goes through GI tract which means drug highly metabolised and less efficacious
e.g. salbutamol given orally would be less efficacious
what is the effect of increasing plasma concentration of drug?
- you want the drug to have plasma concentrations that makes therapeutic effects
- if plasma concentration increased then makes toxic effects
- if plasma concentration decreased then sub-therapeutic effects
what is EC50 and on graph of plasma concentration & response what does it mean if:
a) below EC50?
b)between EC50 & Emax?
EC50 = the half life
a) sub-therepeutic
b) therepeutic
what does NOAEL & LOAEL stand for on graph of plasma concentration & response/adverse effects and what are they used for?
NOAEL = no observed adverse effect level
= it’s the concentration in plasma when no adverse effects
LOAEL = lowest observed adverse effect level
- they’re measured to try help map out range where drug efficacious = the therapeutic window
what does a narrow therapeutic window mean?
only small window of benefits before starts having severe damaging affects
why do we do pharmacokinetic analysis?
to help us determine the dose (e.g., mg of a drug) that will result in the appropriate blood plasma concentration (mg/L or mol/L) to be safe and effective
what are the ways drugs can move around in our body?
bulk flow = via circulatory system
diffusion = of drug molecules over short distances
solubility is also important as lipid soluble drugs more likely to diffuse across lipid bilayer membranes
large drug molecules = move slower than small one
what are cell and plasma membranes barriers between?
cell membrane = barrier between aqeous compartments of body
plasma membrane = seperates extracellular & intra-cellular compartments
what are the 4 ways small molecules can pass across membrane? (all past knowledge)
- passive diffusion
- faciliated diffusion
- active transport
- endocytosis
what are types of transport that cause saturation kinetics and what does that mean?
facilitated diffusion & active transport
- they both involve carrier proteins that work at fixed rate so when high drug concentration it makes a pile up which means protein can’t keep up and gets saturated
what are the principal sites of carrier mediated drug transport?
- blood brain barrier
- GI tract
- placenta
- renal tubule
- biliary tract
other than diffusion or active transport - what is another way drugs can get across membrane?
they can become un-ionised -> drugs can be ionised or unioinised, they can switch depending on environments pH levels
what does the proportion of ionisation of a drug depend?
both the pKa of the drug and the local pH
what is the pKa?
pH at which 50% of drug is ionised and 50% un-ionised
(acid-dissociation constant)
what can the henderson-hasselbach equation be used to determine?
the proportions of ionised & un-ionised drugs in a given pH environment
(pKa = pH + log (AH/A-))
whats an example and explain the process of a drug ionising to move across membrane?
aspirin, pKa = 3.5
- it becomes un-ionised so it can pass through gut mucosal barrier with simple passive diffusion
->it then enters different pH environment so then becomes ionised again and therefore trapped in plasma
what is relationship between acidic/basic drugs and ionisation levels in acidic/basic environment?
acidic drugs = less ionised in acidic environment (HA)
basic drugs = less ionised in basic environment