PharmacodynamicssA:mechanism of actionOpioid agonists produce analgesia by binding tospecific receptors in brain and spinal cord regions1.Receptor types (μ, 8 ,and k )μreceptor: μ,μl2Oreceptor: 0,2k receptor: KKK
Pharmacodynamics: A:mechanism of action Opioid agonists produce analgesia by binding to specific receptors in brain and spinal cord regions 1.Receptor types (μ,δ,and κ ) μreceptor: μ1 μ2 δreceptor: δ1 δ2 κ receptor: κ1 κ2 κ3
2.Relation of physiologic effects to receptor typeμ, R: mediate the analgesic and euphoric effectsof the opioids and physical dependence on themμ,R: mediate the bradycardiac and respiratorydepressanteffectsR: mediate spinal analgesic effects and have beenimplicated in the modulation of tolerance toμ-opioidsk R: mediate spinal analgesia, miosis, sedation, anddiuresis
2.Relation of physiologic effects to receptor type μ1 R: mediate the analgesic and euphoric effects of the opioids and physical dependence on them μ2R: mediate the bradycardiac and respiratory depressant effects δR: mediate spinal analgesic effects and have been implicated in the modulation of tolerance to μ-opioids κ R: mediate spinal analgesia, miosis, sedation, and diuresis
3.Cellular Mechanisms of Actionadenyl cyclaseMorphine+Opioid receptorscyclic adenosine monophosphate (cAMP)reduce calcium influxincrease potassium effluxmorphine decrease the release of dopamine, serotonin,and nociceptive peptides, such as substance P, resultingin blockage of nociceptive transmission
3.Cellular Mechanisms of Action Morphine+Opioid receptors adenyl cyclase cyclic adenosine monophosphate (cAMP) reduce calcium influx increase potassium efflux morphine decrease the release of dopamine, serotonin, and nociceptive peptides, such as substance P, resulting in blockage of nociceptive transmission
4.Tolerance and Physical DependenceThe biochemicalmechanisms are unclearwithTolerancefrequentlyrepeatedofdosesadministrationoftherapeuticmorphine or its surrogates,there is a gradualloss in effectiveness.to reproduce the originalresponse,a larger dose must be administrated
4.Tolerance and Physical Dependence The biochemical mechanisms are unclear. Tolerance : with frequently repeated administrationof therapeutic doses of morphine or its surrogates,there is a gradual loss in effectiveness.to reproduce the original response,a larger dose must be administrated
Physical Dependence :the cessation of opioiddrug administrationleads to an observableabstinence syndrome.signs of withdrawalinclude chills, fever,diarrhea,sweating,vomiting,yawning,Thedizziness, andhypertension.nausea,onset of symptoms occurs 6 to 12 hours aftercontinues for severalthe last drug dose anddays
Physical Dependence : the cessation of opioid drug administration leads to an observable abstinence syndrome. signs of withdrawal include chills, fever, sweating, yawning, vomiting, diarrhea, nausea, dizziness, and hypertension. The onset of symptoms occurs 6 to 12 hours after the last drug dose and continues for several days