L4: receptor theory 3 antagonists

name the 5 classes of antagonism

1. chemical 

2. pharmacokinetic

3. physiological

4. non-competitive

5. competitive

describe how a chemical antagonist works

substances combine in solution so the effects of the active drug is lost

name an example of chemical antagonism

inactivation of heavy metals (e.g. mercury, lead, cadmium) who’s toxicity is reduced with the addition of a chelating agent (e.g. dimercaprol)

describe how a pharmacokinetic antagonist works

drug interference to reduce the amount of drug absorbed, metabolised, or excreted

name an example of a pharmacokinetic antagonist

some antibiotics stimulate metabolism of warfarin (anticoagulant) - reducing its effective concentration in bloodstream

describe how a physiological antagonist works

two different drugs have opposing actions in the body to cancel out effects of endogenous molecules

name an example of a physiological antagonist

noradrenaline raises arterial blood pressure by acting on β1 adrenergic receptors in the heart + α1 receptors in peripheral blood vessels, while histamine acts on H1 receptors to lower arterial blood pressure by causing vasodilation

describe how a non-competitive antagonist works

blocks a step in the process between receptor activation + response by either binding to a site distinct from agonist binding site or acting downstream of a receptor on key aspects of a signalling mechanism 

name an example of a non-competitive antagonist

verapamil + nifedipine inhibit L-type Ca²⁺ channels to cause relaxation of smooth muscle + lower blood pressure

describe how a competitive antagonist works

competes with agonist for occupancy of a receptor

what are the 2 types of competitive antagonism

reversible + irreversible

name an example of a competitive antagonist

atropine + ACh on guinea pig ileum

what does a schild plot show

relationship between dose ratio + antagonist concentration

how can the affinity of an antagonist be determined using a concentration-response curve

measuring the dose ratio (shift) for an agonist caused by addition of increasing concentrations of a competitive antagonist

on a schild plot how do you determine pA2

x-intercept and K_D (affinity of antagonist)

if a drug is a competitive inhibitor, what should the schild plot look like

linear relationship

what is the calculation for K_D using a schild plot

10^-1*pA₂

what is the result on of adding partial agonists to a full agonist on a concentration-response curve

shift to the right - behaves like a competitive antagonist

describe an example of irreversible competitive antagonism

effects of the alkylating drug dienamine on histamine responses in the guinea pig ileum