Other classes of proteins that have been identified as drug receptors
enzymes
transport proteins
structural proteins
Functions of receptors (3)
determination of relation between concentration and pharmacologic response
regulatory and signaling proteins are significant targets
receptors are key determinants of toxicity and efficacy levels of drugs
Increasing a dose will
eventually plateu
Relationship between drug concentration and its effect (equation)
E=(Emax X C)/(C+EC50)
EC50
concentration of drug that produces 50% of the maximal effect
Binding of a drug to a receptor (equation)
B=(Bmax X C)/(C+Kd)
Kd
concentration of drug at which half maximal binding occurs
If Kd is low
binding affinity is high
transduction process that links drug occupancy of receptors and pharmacologic response
coupling
Spare receptors
more receptors available than needed for a pharmacological response
myocardial cells contain a large portion of spare B adrenoreceptors
Sensitivity of a cell or tissue to a particular concentration of agonist depends on
Affinity of the receptor for the agonist
degree of spareness
Use of the spare receptor concept
allows one to see the effect of the drug dosage without considering biochemical details of the signaling response
using spare receptor concept to calculate drug concentrations needed (equation)
(B/Bmax) = (C/[C+Kd])
reduce receptor activity below that observed when there is no ligand present
inverse agonists
Competitive antagonist
occupies some receptors
may need more agonist to see effects
Schild equation (concentration of agonist needed in the presence of a competitive antagonist)
(Equation)
C'/C = 1 + ([I]/Ki)
I = fixed concentration of a competitive antagonist
Ki = dissociation constant of the antagonist
Schild equation use
to determine Ki for a competitive antagonist
degree of inhibition produced by a competitive antagonist depends on the concentration of
the competitive antagonist
clinical response to a competitive antagonist depends on
the concentration of agonist that is competing for binding receptors
irreversible alpha adrenoceptor antagonist
phenoxyenzamine
allosteric modulators
bind a separate site on the receptor protein and alter receptor function without inactivating the receptor
benzodiazepines
Protamine that is positively charged at physiologic pH can counteract the effects of heparin (negative charge) by binding the drug and making it unavailable. This is an example of:
Chemical antagonist
Physiologic antagonism
between endogenous regulatory pathways mediated by different receptors