What are agonists?
Designed to evoke a response
When would an agonist be used?
disease of insufficiency
When would an antagonist be used?
disease of excess
What are the 2 types of antagonists?
competitive and non-competitive
What is a reversible antagonists?
- does not produce a biological effect directly, but competes with an agonist for binding to the receptor
- affinity but no efficacy
- no change on maximum response
What determines the relative antagonism?
relative amounts of agonist and antagonist
What are non-competitive antagonists?
- irreversible
- as reactive groups on drugs form covalent bonds with receptors
- some bind allosterically
What is the impact of non-competitive antagonists on the log-dose response curve?
- reduces max response of agonist
- reduces potency and efficacy
How long do irreversible antagonists last?
when receptor is replaced or recycled
What is pharmacological antagonism?
- antagonist acts at the same target receptor as the agonist
- competitive or non-competitive
What is pharmacokinetic antagonism?
- drug interaction
- antagonist reduces [agonist] in the body
- reducing absorption or distribution
- increasing metabolism or excretion
What is physiological antagonism?
2 drugs or substances which have opposing physiological actions acting by different receptors
How could an antagonist be used to increase heart rate?
- antagonist for the M2 receptor
- reduces potency of ACh
- prevents heart rate being slowed
How could an agonist be used to increase HR?
- adrenaline acts on B1 receptors
- agonist would increase HR
What are spare receptors and why are they needed?
- receptors that are not activated when a full agonist produces a maximal response
- spare receptors increase speed of response
What are partial agonists?
even if 100% of receptors are occupied by the agonist, there is never a maximum response. Low efficacy.
Describe how a partial agonist may act as an agonist and antagonist…
- on its own, acts as a weak agonist
- in the presence of a full agonist, it becomes a weak antagonist as it competes with full agonist for receptors
What are 3 non-receptor drug targets?
- ion channels; agonist or antagonist
- enzymes; inducer, inhibitor, pro-drug and false substrate
- transporters; allosteric, false substrate, bind to carrier site
What is tolerance?
upon repeated administration of some drugs, increasing doses need to be given to achieve the same effect
fast: tachyphylaxis slow: tolerance
