Drug-Receptor Interactions Flashcards
State the four types of drug antagonism.
Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmacokinetic antagonism
What is meant by ‘use dependency’ in terms of receptor blockade?
Strength of effect on ion channels dependant on frequency of receptor use, because rapid firing receptors (like nociceptors) have ion channels open more, so antagonists can enter to block more easily, such as in local anaesthetic use.
What is physiological antagonism?
When two drugs act on different receptors in the same tissue and have opposite effects
E.g. noradrenaline will bind to alpha-1 receptors and cause vasoconstriction, histamine will bind to histamine receptors and cause vasodilation
What is chemical antagonism?
Interactions of drugs in solution to reduce concentration of agonist by forming chemical complex
E.g. dimercaprol is a chelating agent that forms heavy metal complexes that are more easily excreted by the kidneys
What is pharmacokinetic antagonism?
When one drug reduces the concentration of another drug at the site of its action
A drug may reduce the absorption, increase the metabolism or increase the excretion of the other drug.
Define drug tolerance.
Gradual decrease in responsiveness to a drug due to repeated administration of the drug.
What are the five main mechanisms of drug tolerance?
Loss of receptors Change in receptors Pharmacokinetic factors Physiological adaptation Exhaustion of mediator stores
Describe the mechanism of receptor loss
Loss of receptors – overstimulation can lead to endocytosis of receptors so there are fewer receptors available on the cell membrane
Describe the mechanism of receptor change
Change in receptors – conformational change in the receptors so that they are desensitized, so a proportion of the receptors are no longer effective
Describe the principle of pharmacokinetic factors
Pharmacokinetic factors – metabolism of the drug is increased after repeated use (e.g. alcohol metabolism switches to faster p450 pathway)
Describe physiological adaptation to drugs
Physiological adaptation – Changes similar to a homeostatic response to maintain a stable internal environment
Describe the exhaustion of mediator stores
Exhaustion of mediator stores – Overstimulation leads to exhaustion of essential intermediate for final effect. E.G. Amphetamine tolerance due to depletion of amines at nerve terminal
What are the four receptor families? Describe how their transmission varies.
Type 1 – ionotropic
Type 2 – metabotropic (G protein coupled)
Type 3 – Enzyme linked (Usually tyrosine kinase)
Type 4 – intracellular steroid type
They decrease in transmission speed going down.
Describe the structure of Type 1 ionotropic receptors.
Consists of 4 or 5 subunits with transmembrane alpha helices
Describe the structure of type 2 receptors.
Consists of 1 subunit but with 7 transmembrane domains (Hence other name 7TM receptor)
