Concentration/response/desensitisation Flashcards
Why do drugs have a plateau effect at a certain point?
As all receptors are occupied, there is no further effect from the drug
Minimal vs maximal dose
Minimal - minimum number of receptor sites must be activated before a response can occur.
Maximal - when all available receptor sites have been activated, at this point response is ‘maximal’ – no matter how much the dose increases you cannot get a bigger response
Potency
The dose required to act on a specific receptor and achieve the same effect. E.g. morphine is more potent than pethidine as it requires a smaller dose to achieve the same effect.
Why is a log dose-response curve for an agonist shifted to the right in the presence of a competitive antagonist acting at the same receptor?
As the competitive agonist takes up some of the receptors sites, blocking the agonist. Due to the competition for the receptor the agonist needs to be increased to create same effect – shifting it to the right
Tachyphylaxis
repeated exposure to the same concentration of a drug – causing decreased responsiveness to the drug.
Up-regulation
in response to weak signals the number of receptors are increased. (Antagonist)
e.g. chronic use of beta-antagonist drugs (beta-blockers) which leads to an increased expression of beta-adrenoceptors
Down-regulation
in response to strong signals the number of receptors are decreased. (Agonist)
when insulin levels are continually high in response to high blood glucose levels (e.g. in Type 2 diabetes)
These high insulin levels lead to the insulin receptors being endo-cytosed and broken down leading to far fewer receptors and reduced sensitivity to insulin (insulin-resistance)
Desenstitisation
refers specifically to a decrease in the response of receptor-second messenger systems, again it is associated with chronic exposure to a particular drug
e.g. GTN patch - needs to be removed at night to reduce development of tolerance
