Pharmacology lecture 3- effects of agonists Flashcards
`What is an agonist
An agonist is a drug which interacts with receptors
The resulting drug-complex generates a response.
Has the ability to alter the activity of a receptor, also known as the agonist’s efficacy.
The efficacy of an agonist may be positive, causing an increase in the receptor activity, or negative causing a decrease in the receptor’s activity.
What os occupancy
proportion of the receptors occupied is known
What is the occupancy equation
Occupancy = Number of receptors occupied / Total no of receptors
What are full agonists
bind (have affinity for) and activate a receptor, displaying full efficacy at that receptor. For example isoproterenol which mimics the action of adrenaline at β adrenoreceptors; morphine, which mimics the actions of endorphins at μ-opioid receptors in the CNS.
what is a partial agonist
(such as buspirone, aripiprazole) have only partial efficacy at the receptor relative to a full agonist.
what is potency
measure of the concentration of a drug at which it is effective.
important value when determining the dose of a drug
what is efficacy
the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level after binding to a receptor.
Efficacy can take a value between 0 to 1, the higher the value, the stronger the response
Factors of efficacy
the total number of receptors for that drug present in the tissue
the type of coupling exist between the receptor and response
and the intrinsic efficacy of the drug at the receptor.
What is intrinsic efficacy
is determined by the ability of drug-receptor complex to activate the secondary mechanism (cellular transduction system) eg, G protein.
Intrinsic efficacy can take a value of between 0 to infinity
What does it mean when a drug has higher efficacy
means that maximum obtained effect is higher
For example: Morphine used for sever pain, however, paracetamol used for minor pain
What is affinity
It is a measure of how strong a drug binds to its receptor
Characterised by KD or KA (equilibrium dissociation constant).
Drugs with higher affinity have lower KD
Why some agonists induce a max response and others can’t?
Factors affecting the size of response:
Characteristics of tissue involved: total number of receptors, nature of receptors and response coupling
The agonist-receptor complex itself, agonists with higher intrinsic efficacy induce a bigger response although they have similar affinity and act on the same receptor.
Spare Receptors:
To generate a full response, it is not necessary for an agonist to occupy ALL receptors: only a fraction of the total number of receptors needed to be occupied. This leads to the idea of spare receptors.
Factors affecting the response to a drug in a patient:
Genetic factor, Weight, State of health and disease
Age, gender
Function of organs such as liver and kidney
Pre-medication, Placebo effect
Tolerance/dependence/desensitisation (tachyphylaxis)
Hypersensitivity and Idiosyncratic Reactions
when does drug tolerance occur
occurs when a subject’s reaction to a drug (such as a painkiller) decreases so that larger doses are required to achieve the same effect. Tachyphylaxis is a medical term referring to the rapid development of drug tolerance.
