Tolerance Flashcards
What is tolerance?
a physiological adaptation to a drug after repeated use
Why is drug tolerance such a dangerous thing?
Because tolerance leads to addiction
What is pharmacokinetic tolerance?
When drug tolerance is a result of an increase (induction) of metabolic enzyme
- repeated use causes more rapid metabolism
What is pharmacodynamic tolerance?
When drug tolerance is the result of receptors lessening their responses, in favour of using drug’s signals instead
What are the two characteristics of pharmacodynamic tolerance?
- desensitization
2. downregulation
What is desensitization?
Decline in post-synaptic receptor responsiveness (change takes effect within hours)
What is downregulation?
It is comprised of two systems:
a) sequestration
b) reduced transcription
What is sequestration?
Removal of some post-synaptic receptors (through phagocytosis) with repeated introduction of a drug into the synapse
What is reduced transcription?
When less receptors are being made due to the presence of more drug in the synapse
What happens when phosphorylation occurs at a different site than usual?
The active binding site can change, thus decreasing the drug’s affinity (for GPCR’s and ligand-gated ion channels)
- could also reduce the interaction between GPCR and its receptor
What is another effect of phosphorylation?
It can reduce the conformational change of a ligand-gated ion channel (dependent on the post-synaptic receptor)
What is a competitive antagonist?
Enough agonist can overcome the the effect of the antagonist
What is a noncompetitive antagonist?
No amount of agonist can fully overcome the antagonist activity
What is an indirect agonist?
Mimics the effect of NT but does not bind to the receptor
What is a full agonist?
When the agonist has the same full effect as the NT (and will activate receptors to their maximum effect)
What is a partial agonist?
When the agonist does not have as much of an effect, regardless of dose
What is an inverse agonist?
It looks like an antagonist (on a Dose-Response curve) but acts as an opposite NT
What is the MAIN difference between an antagonist and an inverse agonist?
An inverse agonist has an effect on the receptor, while an antagonist does not have any effect on the receptor for which it binds to
When is it useful to have a partial agonist instead of a full agonist?
When the therapeutic index of a drug is very narrow
