Talk:Drug tolerance

message: Tachyphylaxis is not simply another word for drug tolerance; rather, it is a special kind of sudden onset drug tolerance that is far quicker than would be expected from simple receptor related conformational changes or from transductional related second messenger or ionotropic changes. 
For example, cocaine is said to be subject to tachyphylaxis insofar as once dopamine is released from the terminal vessicles, and its reuptake at the DAT is inhibited by the cocaine molecule, MAO B and COMT metabolize the dopamine into DOPAC (Dihydroxyphenylacetic acid) and HOVAC (Homovanillic acid). Until new dopamine is made again through the slow process starting  from either the amino acids tyrosine in which the phenol is hydroxylated into a catechol group, or from phenyalanine, which is hydroxylated into tyrosine and then its phenol group is hydroxylated into a catechol group. Both these products with their catechol groups, are now dihydroxyphenylalanine or DOPA, which is then decarboxylated into dopamine. 
The production of new dopamine is a very slow process relative to metabolism by MAO-B or COMT; both of which, in turn are slow in relations to standard deactivation of transmitter in the synaptic cleft through reuptake at the Dopamine Transporter (DAT), and is the reason for the tachyphylaxis in this case.
Let us compare the much less common concept and the antonym bradyphylaxis, which is said to occur in drugs like the barbiturates, where the tolerance to the drug may subjectively increase insofar as the effect desired; however, on a molecular level, there is very little happening at the allosteric binding site in the chloride channel of the GABA-A/omega (BDZ) receptor that hyperpolarizes these inhibitory neurons in which the chloride channels remain open. About the only type of tolerance associated with an increase in the LD50 that occurs at all is related to an increased metabolism by induction of CYP450 on the ER, particularly in smokers; however, barbiturates themselves are slight enzyme inducers which increase their own metabolism. But molecularly, very little else changes with repeated use of barbiturates, and the LD50 remains about the same even through dependence. This is exemplified by the deaths of the 4 men in whose lab the first marketed barbiturate, Veronal, was produced, insofar as they all eventually overdosed on the drug they brought to market.
MobiusDick
:This is a big wall of text but I agree with the beginning entry that tachyphylaxis is an emergency.  As with long term beta agonist therapies there is a suspected problem with tachyphylaxis and asthma rescue medications. Matzerath1 (talk) 02:20, 4 December 2011 (UTC)
thread_title: Tachyphylaxis

message: This article appears to have been written with some good technical information from individuals well-educated on the subject (as opposed to individual's just repeating what they heard about drug tolerance on TV or non-scientific internet sources). However, its a shame that the writers didn't decide to write more on the subject, or even make the article comprehensive for that matter. Listing two types of tolerance (pharmacodynamic and pharmacokinetic) was good, but the article should list more sub-types of each (instead of just giving one example). There are certainly more types of pharmacodynamic drug tolerance than just receptor down-regulation; how do we explain tolerance to drugs such as dextro-amphetamine? - which is not a receptor agonist but instead achieves its effects through the release of endogenous neurotransmitters. Or what about drugs that have reverse tolerance, or a more complicated evolving tolerance (serotonin re-uptake inhibitors come to mind). It would at least be advised to mention the process of drug tolerance as being more intricate instead of just mentioning receptor down-regulation or CYP450 enzymes. I don't have an educated college-level structural foundation on the subject to make the article comprehensive, nor do I know all of the correct terminology expected of the pharmacological science community, but it would seem that the writer(s) of this article do possess expertise on the subject.  — Preceding unsigned comment added by SpunkySkunk347 (talk • contribs) 09:21, 7 December 2011 (UTC)
replies: text: If you can write what you know, it can be edited to be even more accurate... it might also be completely accurate in-itself! Matzerath1 (talk) 07:43, 10 December 2011 (UTC)
thread_title: Article Incomplete

message: https://link.springer.com/referenceworkentry/10.1007/978-3-642-27772-6_272-2  this will be a wealth of information for you. Cgraham10 (talk) 12:58, 20 March 2017 (UTC)
thread_title:  source for more information.  

message: I think that the drug desensitization, and injecting larger & larger doses of an allergen is not a tolerance, simply because tolerance is reversible, and the desensitization should be somehow long-lasting.
I think the desensitization depends on making the immune system behave as if these allergen are normal body antigens, may be by killing the immune cells that are directed towards these "friendly" antigens.
Yasir muhammed ali (talk) 03:55, 27 March 2018 (UTC)
thread_title:  Shouldn't be a type of tolerance 

message: Is Tolerated illness a duplicate article of this one? If not, a disambiguatory hatnote might still be useful.  talk 07:40, 16 May 2021 (UTC)
thread_title:  [[Tolerated illness]] merge? 

message: Seems to be entirely lacking. There's this sentence: "A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the receptor, desensitizing it through constant interaction."
So what causes tolerance is desensitization. Very helpful. 86.63.168.150 (talk) 23:56, 22 February 2024 (UTC)
thread_title:  Explanation of cause