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Mechanism: • Often receptor desensitization • Can be due to depletion of mediators (e.g., norepinephrine stores) Features: • Develops within minutes to hours • Often reversible if drug stopped for a short time Examples: • Nitroglycerin: rapid tolerance if used continuously • Nasal decongestants (oxymetazoline): loss of effect within hours • Tolerance = Takes Time → gradual • Tachyphylaxis = Fast → rapid • Think: tachy = fast, philaxis = protection loss → rapid loss of effect Understanding the nuances between tolerance and tachyphylaxis is crucial for effective treatment strategies

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For each dose level and dosing day separately, geometric least square mean (GLSM), geometric mean ratio (GMR), and 90%CI are calculated