Mechanisms of Drug Action 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?
This refers to ion channel blockers The more the tissue on which a drug is acting is being used (i.e. the more active they are), the more effective the blocker will be E.g. normal neurons fire at a relatively low rate so if you put local anaesthetic on them there’ll be fairly limited effects. Nociceptor neurons fire rapidly so their iron channels are open more often meaning that the local anaesthetic can get inside the iron channel and block it more easily.
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 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 each of these mechanisms briefly.
Loss of receptors – overstimulation can lead to endocytosis of receptors so there are fewer receptors available on the cell membrane
Change in receptors – conformational change in the receptors so that they are desensitized, so a proportion of the receptors are no longer effective
Pharmacokinetic factors – metabolism of the drug is increased after repeated use (e.g. alcohol)
Physiological adaptation – sort of like a homeostatic response to maintain a stable internal environment
Exhaustion of mediator stores – this happens with amphetamines –they get into the central noradrenaline synthesis system and replaces noradrenaline in the vesicles so you get a big increase in the production of noradrenaline
What are the four receptor families? Describe how their transmission varies.
Type 1 – ionotropic
Type 2 – metabotropic (G protein coupled)
Type 3 – tyrosine kinase linked
Type 4 – intracellular steroid type They increase in transmission time from 1-4
Describe the structure of type 1 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
Describe the structure of type 3 receptors.
Single protein with 1 transmembrane domain Inside the cell there is an intracellular domain When the agonist stimulates the receptor it activates the catalyst
Describe the structure of type 4 receptors.
These are steroid receptors that are found in the nucleus
What is another name for the DNA binding domain of the steroid-receptor complex?
Zinc fingers
Define Pharmacokinetics and Pharmacodynamics.
Pharmacokinetics – the effect that the body has on the drug Pharmacodynamics – the effect of the drug on the body
What is a partial agonist?
An agonist that generates a less than maximum response
What is the difference between full agonists with a high affinity and full agonists with a lower affinity?
Full agonists with a lower affinity can still generate a maximum response but requires a higher dose than the full agonist with lower affinity
What effect do these two types of antagonist have on dose-response curves?
Competitive – shifts the D-R curve to the RIGHT Irreversible – shifts the D-R curve to the RIGHT and LOWERS the response elicited (it can no longer generate a full response)
