Question about cross tolerence

[Too many doses]

This isn't a very advanced question but I feel it belongs here.

How biologically does cross tolerence work? I was trying to research the biology on why one can rotate meds with out necessarily upping ones dose ( equianalgesic doses). I understand that there are many different types of receptors, but Im talking drugs that hit the exact same receptors even partially. I only found articles that were advanced beyond my limited understanding of science.
Any answers would be greatly appreciated .

 

[spindevil14]

my orthapaedic surgeon told me that there are different opioid receptors for different opiates. say there are 6 receptors if you are taking oxy it only uses say 4 of the receptors. when you build an oxy tolerance it is only to those 4 receptors. if you where to switch to codeine or some other opiate it would use the other receptors including one that already has the opiate tolerance from the oxy. therefore you would have a little tolerance but not a full one. is that understandable? im kinda shitty at typing what i mean to say. i tried to pm you back but im a greenlighter and i cant pm for like 100 more minutes? so please check back in the future

 

[sekio]

Cross tolerance develops because...
1. drugs share receptor targets & activity
2. activation of receptors causes future downregulation/internalisation/desensitization of the receptors. ("tolerance")
3. After long term treatment the receptors are less sensitive to chemicals that interact with them (due to there being less active receptors to bind to). So if you e.g. take tons of morphine, your mu opioid receptor will be downregulated, and other drugs that bind to MOR will be less effective.

Generally, drugs that "avoid" cross tilerance either work by a different mechanism (for instance, not activating receptors fully, or by having secondary effects that synergize). This might explain why you can switch opioid drugs with "less" cross tolerance than expected.