Editing Drug tolerance (section)

==Pharmacodynamic tolerance==

Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use. A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the [[Receptor (biochemistry)|receptor]], desensitizing it through constant interaction.<ref>{{Cite journal|last1=Bespalov|first1=Anton|last2=Müller|first2=Reinhold|last3=Relo|first3=Ana-Lucia|last4=Hudzik|first4=Thomas|date=2016-05-01|title=Drug Tolerance: A Known Unknown in Translational Neuroscience|journal=Trends in Pharmacological Sciences|volume=37|issue=5|pages=364–378|doi=10.1016/j.tips.2016.01.008|issn=1873-3735|pmid=26935643}}</ref> Other possibilities include a reduction in receptor density (usually associated with receptor agonists), other mechanisms leading to changes in action potential firing rate, or alterations in protein transcription among others adaptations.<ref>{{cite book |last=Klaassen |first=Curtis D. |title= Casarett & Doull's Toxicology: The Basic Science of Poisons |edition=6th |date=2001-07-27 |publisher=McGraw-Hill Professional |isbn= 978-0-07-134721-1 |pages=17}}</ref><ref>{{Cite journal |last=Pietrzykowski |first=Andrzej Z. |last2=Treistman |first2=Steven N. |date=2008 |title=The molecular basis of tolerance |url=https://pubmed.ncbi.nlm.nih.gov/23584007 |journal=Alcohol Research & Health: The Journal of the National Institute on Alcohol Abuse and Alcoholism |volume=31 |issue=4 |pages=298–309 |issn=1930-0573 |pmc=3860466 |pmid=23584007}}</ref> Pharmacodynamic tolerance to a [[receptor antagonist]] involves the reverse, i.e., increased receptor firing rate, an increase in receptor density, or other mechanisms.

While most occurrences of pharmacodynamic tolerance occur after sustained exposure to a drug, instances of acute or instant tolerance (tachyphylaxis) can occur.<ref>{{Cite journal|last1=Swanson|first1=James|last2=Gupta|first2=Suneel|last3=Guinta|first3=Diane|last4=Flynn|first4=Daniel|last5=Agler|first5=Dave|last6=Lerner|first6=Marc|last7=Williams|first7=Lillie|last8=Shoulson|first8=Ira|last9=Wigal|first9=Sharon|date=1999-10-01|title=Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children*|url=https://www.researchgate.net/publication/12789540|journal=Clinical Pharmacology &#38 Therapeutics|volume=66|issue=3|doi=10.1016/S0009-9236(99)70038-X|issn=0009-9236|pmid=10511066|pages=295–305|s2cid=32069845}}</ref>