《药理学》课程PPT教学课件（Central Nervous Sys）19 opioid analgesics and antagonists

opioid analgesics and antagonistOpioids are usually understand to include all ofthe natural and semisynthetic alkaloidderivatives from opiumMorphine is the prototypical opioid agonistAll drugs in this category act by binding to opioidreceptors in the CNS to produce effects that mimic theaction of endogenous opioid peptides

opioid analgesics and antagonist Opioids are usually understand to include all of the natural and semisynthetic alkaloid derivatives from opium. Morphine is the prototypical opioid agonist All drugs in this category act by binding to opioid receptors in the CNS to produce effects that mimic the action of endogenous opioid peptides

The classification of the painAcute pain:which does not outlast the initiatingpainful stimulus, include Burns,myocardialinfarctionChronic pain: outlasts the initiating stimulussuch as cancer ,arthritis and neuropathic painSuch drugs eliminate pain by either decreasingthe underlying cause of the pain or decreasingthe transmission of nociceptive impulses andpain perception

The classification of the pain Acute pain:which does not outlast the initiating painful stimulus, include Burns, myocardial infarction Chronic pain: outlasts the initiating stimulus such as cancer ,arthritis and neuropathic pain Such drugs eliminate pain by either decreasing the underlying cause of the pain or decreasing the transmission of nociceptive impulses and pain perception

I. Basic pharmacology of the opioid analgesicsClassification :full agonistsmorphineOpioid drugdezocinepartialagonistsnaloxoneantagonists

I. Basic pharmacology of the opioid analgesics Classification : full agonists morphine Opioid drug partial agonists dezocine antagonists naloxone

EndogenousOpioidsThe endogenous opioids are naturally occurringpeptides include:enkephalins, β -endorphin and dynorphinsenkephalins were first discovered in the brainwhich means from the head.The endogenous opioids modulate most of thecritical functions of the body, includinghormonal fluctuations, thermoregulation

Endogenous Opioids The endogenous opioids are naturally occurring peptides include: enkephalins, β -endorphin and dynorphins enkephalins were first discovered in the brain which means from the head. The endogenous opioids modulate most of the critical functions of the body, including hormonal fluctuations, thermoregulation

mediation of stress and anxiety, production ofanalgesia, and development ofopioid toleranceand dependence. The endogenousopioidsmaintain homeostasis, amplify signals fromthe periphery to the brain, and serveasneuromodulatorsof the body's responsetoexternal stimuli. As such, the endogenousofopioids are critical to themaintenancehealth and a sense of well-being

mediation of stress and anxiety, production of analgesia, and development of opioid tolerance and dependence. The endogenous opioids maintain homeostasis, amplify signals from the periphery to the brain, and serve as neuromodulatorsof the body’s response to external stimuli. As such, the endogenous opioids are critical to the maintenance of health and a sense of well-being

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