what are the 3 types of antagonists
- competitive antagonist - bind to same binding site as endogenous ligand and compete for the same R
- non-competitive not at receptor - bind to allosteric R –> stops stimulus
- non competitive at receptor - activation of R with opposite effect
the effect of an antagonist depends on:
- the efficacy of the agonist
- the affinity of the antagonist
how does binding to the allosteric site affect the R
- modulation of orthosteric ligand affinity
- modulation of orthosteric ligand efficacy
- modulation of R activation level
what are the advantages of using drugs that bind to the allosteric site
- substantial selectivity between R subtypes
- incomplete antagonism possible
what is surmountable antagonism
antagonism that is able to be overcome
- you can get the response back by increasing the conc of the agonist
what kind of receptor is the beta-adrenoceptor
GPCR
what are the 4 types of receptors
GPCR
ligand gated ion channels
kinase-linked
nuclear
what are the subtypes of nicotinic receptors
NM - muscular
NN - autonomic ganglia
what is the difference between pharmacokinetics and pharmacodynamics
PK - what the body does to the drug
PD - what the drug does to the body
what is the therapeutic windown
the dose between starting to have an effect and toxicity
what is the difference between a full and partial agonist
full - gives maximal effect of activating the R
partial - gives only partial effect of activating the R
what is potency
the smallest amount you can give for an effect
how is potency measured
usually measured by EC50 = half of max
what is efficacy
the strength of the R activation
what are the parts of pharmacokinetics
administration, absorption
distribution
elimination (metabolism, excretion)
(AADME)
most drugs are eliminated at a rate …
proportional to the conc in the plasma
when conc falls, so does the rate of elimination
what factors will affect drug distribution
- molecular size –> small enough to cross vascular endothelium
- ability to bind plasma proteins - unable to get out of vessels
- lipid solubility - go through the cell membrane
which types of drugs can pass through the BBB
lipid soluble
drug reservoirs can lead to…
- prolonging drug action
- can quickly terminate action
- can led to slow distribution
what are 3 drug reservoirs
plasma protein
cells
fat
what is the volume of distribution
the volume of body water in which a drug appears to be dissolved in after it has distributed throughout the body
what is the equation for volume of distribution
amount in body / conc in plasma
what factors influence the volume of distribution
- if drug binds to plasma protein –> greater conc appears in plasma –> VD is small
- if drug binds to tissues/taken up by cells –> drug stripped from the plasma –> VD is large
what is the point of working out the volume of distribution
tells you the dose that you must give to a patient IV to get a desired plasma conc
