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Opioids

Pharm (Test 2)

QuestionAnswer
Define opioid. drugs which are naturally derived for opium (extract from the poppy plant); also refers to synthetically produced drugs which have opium- or morphine-like properties
What is the origin of the word "opioid"? opos- the greek word for "sap"
What is the origin of the word "narcotic"? derived from the greek word meaning "stupor"
True or False: Opioid and narcotic can be used interchangeably. True; narcotic has a negative legal connotation
What is the origin of the name "morphine"? named after Morpheus, the greek god of dreams
What is the newest opioid? remifentanil
What are 4 favorable properties of opioids? 1)ANALGESIA 2)preservation of blood flow autoregulation 3minimal cardiac depression and maintenance of hemodynamics 4)blunting of autonomic responses to sympathetic stimulation (laryngoscopy, surgical stress)
What is the mechanism of action of opioids? opioid agonists bind to opioid receptors at presynaptic and postsynaptic sites in the CNS (brainstem and spinal cord) and peripheral sites (primary afferent neurons)
Are opioids agonists or antagonists? AGONISTS; opioids act like the endogenous peptides that normally activate these opioid receptors (enkephalins, endorphins, and dynorphins)
The principal effect of opioid receptor agonism is a(n) (increase or decrease?) in neurotransmission. decrease
Activation of the presynaptic opioid receptors cause... closure of the voltage-gated Ca2+ channels on presynaptic nerve terminals to cause a REDUCTION of the release of NT (glutamate, ACh, dopamine, Norepi, serotonin, and substance P)
Activation of the postsynaptic opioid receptors cause... opening K+ channels to HYPERPOLARIZE the cell, thus causing INHIBITION of the postsynaptic neurons
What are the 4 parts of the pain pathway? 1)transduction, 2)transmission, 3)modulation, 4)perception
Describe the transduction phase of the pain pathway. 1)noxious stimuli (chemical, thermal, mechanical energy) is converted to an electrical impulse in sensory nerve endings
Describe the transmission phase of the pain pathway. 2)conduction of the electrical impulses (action potential propagation) to the CNS -- major connections for these nerves in dorsal horn of the spinal cord and thalamus w/ projections to the cingulate, insular, and somatosensory cortexes
Describe the modulation phase of the pain pathway. 3)altering pain transmission -- both inhibitory and excitatory mechanism modulates pain impulse transmission in peripheral and CNS
Describe the perception phase of the pain pathway. 4) occurs at the thalamus with the cortex impt for discrimination of specific sensory experiences
How do opioids affect the pain pathway? 1) directly inhibit the ascending transmission of nociception information from the SC dorsal horn (transmission) 2)activate pain control pathways that descend from the midbrain, via the rostral ventromedial medulla to the SC dorsal horn (modulation)
What 4 receptors do opioids bind to? mu1, mu2, kappa, delta
What affect do opioids have on the mu1 receptors? agonist
What affect does opioid activation of the mu1 receptors cause? analgesia (spinal and supraspinal), euphoria, miosis (pupil constriction), bradycardia, hypothermia, urinary retention
What receptors are the universal site of action for all endogenous opioid receptors? Mu
What affect do opioids have on the mu2 receptors? agonist
What affect does opioid activation of the mu2 receptors cause? analgesia (spinal), RESPIRATORY DEPRESSION, physical dependence, marked constipation
What affect do opioids have on the kappa receptors? agonist
What affect does opioid activation of the kappa receptors cause? analgesia (spinal, supraspinal) (not as strong as mu), sedation, dysphoria, miosis, diuresis, respiratory depression (not as much as mu)
What are some agonists for mu receptors? endorphins, morphine, synthetic opioids
What are some agonists for kappa receptors? dynorphins, agonist-antagonists
What affect do opioids have on delta receptors? agonist
What affect does opioid activation of delta receptors cause? analgesia (spinal, supraspinal), respiratoy depression, physical dependence, urinary retention, mild constipation
What are some agonists for delta receptors? enkaphalins
Which receptors are present in high concentrations in the dorsal horn of the spinal cord? mu, kappa, and delta (all cause spinal analgesia)
Where are opioid receptors distributed in the supraspinal region? in the pain-modulating descending pathways (rostral ventral medulla, locus ceruleus, midbrain periaqueductal area)
Which receptors are present in the supraspinal areas? mu1, kappa, and delta
Which receptors are located outside of the CNS and where are they located? How do we know this? mu; on the peripheral terminals (distal end) of sensory neurons; sites of inflammation are sensitive to peripheral opioid actions (injecting morphine into the knee after surgery)
Which patients show little cardiovascular compromise from opioids? healthy, supine, normovolemic (even at large doses 10X)
Why are opioids often used in cardiac anesthesia? have little effect on myocardial contractility
How do opioid affect the patient hemodynamically? decreases sympathetic nervous system tone and response to stimulation (venous dilation, dec. venous return, dec. CO and HR, orthostatic hTN) especially in hypovolemic pts
How do sufentanil and alfentanil specifically affect a pt's hemodynamics? cause direct dilation of aortic smooth muscle
Why are opioids helpful in pts with acute pulmonary edema? decreases venous return and afterload; also, reduced perception of SOB and anxiety
Describe the reason for bradycardia w/ opioid use. 1)stimulation of the vagal nucleus in the medulla 2)SA node depression, slowed conduction through AV node
Opioid-induce bradycardia (is or isn't?) responsive to atropine. is
Opioids can have a synergistic decrease in BP when combined with what other medications? benzo's or nitrous oxide
Describe the "cardiac protective effect" of some opioids. cardiac protective effect found with morphine and remifentanil (reduced size of MI when administered prior to occlusion of coronary artery); (delta, kappa, and non-cardiac mu receptors)
Which opioid can cause tachycardia and why? meperidine (has antimuscarinic effects)
How do opioid cause respiratory depression? through effect at mu2 receptors, direct depression of the brainstem ventilation centers; decreased release of ACh from neurons in the medullary respiratory centers may affect this depression
How does opioid-induced respiratory depression affect the pt's response to PaCO2? decreased responsiveness to PaCO2 (curve shifts to the right)
How does unconsciousness affect opioid-induced respiratory depression? intensifies it; (including natural sleep)
What is a way to reverse opioid-induced respiratory depression w/o reversing analgesia? physositgmine
True or False: High doses of opioids may result in apnea without loss of consciousness. True: must remind pt to breathe
In what ways do opioids affect respiratory rate, tidal volume, and minute ventilation? slows respiratory rate with increased tidal volume (yet still decreased minute ventilation); increased Vt not enough to compensate for decreased RR
What are some things that accentuate or attenuate the effects of opioids on ventilatory depression? accentuated by older age and occurrence of natural sleep; attenuated by pain of surgery (apnea ceases w/ incision)
What types of patients may not be able to tolerate the increased PaCO2 levels associated with opioid-induced respiratory depression? pts w/ increased ICP, asthma, COPD, or cor pulmonale
How do opioids affect the cough centers? cough suppression; separate effect from ventilatory depression; effect on medullary cough centers
Which opioids most have an effect on cough? codeine, dextromethorphan (dextrotatory isomer of opioid=no analgesia)
What is dextromethorphan? dextrotatory isomer of opioid for cough suppression; no analgesia
What are 2 possible theories for renarcatization post-op? 1)mobilization of opioid from skeletal muscle following rewarming, increased blood flow, and mvmt; 2)reduction in stimulation post-extubation
How do opioids affect mvmt of airway secretions? opioids cause a dose-dependent depression of ciliary activity in the airways
What are 2 ways that opioids can affect airway resistance? increased: 1)effect on bronchial smooth muscle; 2)indirect effect of histamine release
What components of pain do opioids affect? sensory and affective (emotional)
Opioids are most effective for what type of pain? visceral, continuous, dull pain (high doses can relieve any pain)
Opioids are least effective for what type of pain? neuropathic
True or False: At high doses, opioids can provide analgesic/anesthetic effects? False: There is no anesthetic dose of opioid
True or False: Even at high doses, opioids will not render a pt immobile. True: must use muscle relaxants or inhalation agents
True or False: Clinically used doses of opioids impair both auditory and visual learning True
True or False: Opioids reduce MAC of inhalational anesthetics. True; but it is impossible to achieve 100% MAC reduction.
Sedation occurs in up to ______% of pts receiving morphine. 60
Which comes soonest after the administration of morphine: analgesia or sedation? sedation
True or False: Although opioids can cause sedation, opioids disrupt normal REM and non-REM sleep. True
Describe the cerebral hemodynamic changes caused by opioids. If hypercarbia is avoided, opioids cause cerebral vasoconstriction, a dec. in cerebral blood flow, a dec. in cerebral O2 consumption, and a dec. in ICP
For what 4 reasons, should you use opioids w/ caution in pts with head injuries? 1)sedative effects make neuro checks difficult; 2)pupillary effects (miosis); 3)hypoventilation effects (inc. PaCO2 causes vasodilation and inc. ICP) 4)increased sensitivity to opioids in BBB is not intact
Describe the effect of opioids on a pt's pupils. miosis=pupillary constriction is considered a sign of the pt being narcotized; r/t an excitatory action on the autonomic nervous system; because other drugs (atropine) can alter reflex, this shouldn't be diagnostic
Describe the effect of opioid on large muscles in the thorax and abdomen. Trunchal rigidity=intensification of tone of large muscles of thorax and abdomen "Stiff chest syndrome"
Which opioids are most associated with trunchal rigidity? rapid administration of large doses of highly lipid-soluble opioids (fentanyl, sufentanil, alfentanil)
By what mechanism does trunchal rigidity occur? inhibited release of GABA in the muscles and increased dopamine production
In what ways does trunchal rigidity affect ventilation? reduces compliance, increased pressures w/ manual ventilation, decreases venous return d/t inc. pressures
How can you prevent trunchal rigidity? slow administration, avoidance of N2O during induction
How can you relieve trunchal rigidity? antagonist (Narcan) (mostly in PACU or ICU) or relaxed w/ NMB (if occurs during induction)
In what way can opioid administration affect vocal cords? closure of vocal cords
Which opioid is most associated with closure of vocal cords? sufentanil; causes difficulty ventilating
What is the incidence of difficult ventilating with sufentanil and why? 84-100%; when considering both causes (trunchal rigidity and closure of vocal cords)
Describe the way in which opioids can cause nausea/vomiting. caused by direct stimulation of the chemoreceptor trigger zone= floor of the 4th ventricle; may also reflect the effect of increased gastric secretions and delayed emptying; N/V also caused by pain
True or False: N/V caused by opioids may have a vestibular component b/c ambulatory pts are effected more than those confined to bed. True
Which opioid depresses the vomiting center in the medulla? morphine; IV dose reaches vomiting center quickly to counter the stimulation of the chemoreceptor trigger zone)
Which routes of opioid admin. are most associated w/ N/V? PCA and epidural opioids
Describe the way opioids may cause epigastric pain. biliary spasm (Sphincter of Oddi); inc. intrabiliary pressure causing epigastric distress/biliary colic that closely resembles angina pectoris (even EKG changes)
Which drugs can relieve biliary spam caused by opioids? nitroglycerine; narcan; glucagon (given to rule out angina)
How can administration of opioids interfere with intraoperative cholangiograms? biliary spam blocks dye (can look like an obstruction)
How can opioids affect bladder tone? urinary retention; increase in bladder sphincter tone; increased detrusor muscle tone causing urgency
Opioids (can or can't?) cross the placental barrier. opioids cross placenta easily
Describe the effect of opioids on neonates. 1)may result in depressed neonate; 2)neonates of addicted mothers can go through withdrawl; 3)NOT teratogenic (commonly used in anesthesia for non-delivery procedure)
True or False: True allergy to opioids is rare. True; most are associated w/ itching
How do opioids cause itching? histamine release
Explain the effects of histamine release caused by opioids. urticarial (itching), cutaneous vasodilation (flushing and warmth), conjunctival erythema
Which opioids are most associated with histamine effects? morphine and meperidine
Pts can develop tolerance to opioids in what amount of time? 2-3 wks
Opioid tolerance makes pt tolerant to which effects of opioids? analgesic, euphoric, sedative, respiratory depression, emetic
Opioid tolerance does NOT include tolerance to which effects of opioids? miosis, constipation
What are 3 theories for opioid tolerance? 1)opioid receptor desensitization 2)down-regulation of receptors 3)up-regulation of the cAMP system
What does NOT cause opioid tolerance? enzyme induction (shown by increase in the rate of metabolism of opioids occurs) (we would see inc. in rate of metabolism if we had enzyme induction, but we don't)
True or False: Physical dependence/addiction is more likely with opioid agonists than agonist-antagonists. True
Dependence on morphine requires _____days to develop; some degree of physical need develops within ______days of continuous medication. 25; 2
Describe some opioid withdrawal symptoms. yawning, diaphoresis, lacrimation, coryza (several nasal congestion)
Describe the effects of the activation of the hypothalamic-pituitary-adrenal axis. decreased plasma cortisol levels occur w/ prolonged opioid therapy
Describe the effects of the activation of the hypothalamic-pituitary-gonadal axis. alters hormone release: increased prolactin, decreased luteinizing hormone, follicle stimulating hormone, testosterone, and estrogen cntn.
Describe how opioid admin. affects temperature regulation. decreases temperature regulation d/t resetting equilibrium point in thalamus
How does prolonged opioid exposure affect the immune system? depresses the immune system; alters the development, differentiation, and function of bone marrow progenitor cells, macrophages, T cells
Opioid receptors (are or aren't?) present on immune cells. are
Pain (can or can't?) alter the immune system. can
Describe the s/s of opioid overdose. 1)respiratory depression 2)pupils symmetric and constricted 3)muscles flaccid 4)likely airway obstruction 5)pulmonary edema
What is the TRIAD of opioid overdose? miosis, hypoventilation, coma
What is the treatment for opioid overdose? mechanical ventilation w/ O2, opioid antagonist (narcan), which may cause acute withdrawal
Describe the distribution of opioids. rapidly leaves the blood compartment and move to highly perfused tissues like brain, lungs, liver, kidneys, and spleen
What are the average distribution half lives of opioids? rapid: 5-20 min
Significant amounts of opioids are taken up by the ____________ on "fist-pass uptake"; this can be returned to circulation later. lungs
The amount of uptake of opioids into the lungs is influenced by what 3 things? 1)prior accumulation of another drug (decreases); 2)smokers (increases); 3)inhalation anesthetic administration (decreases)
The effect of small opioid doses is terminated by _____________; larger doses depend on _______________. small doses=redistribution; large doses=metabolism
Most opioids are chiefly metabolized by the _____________ with varying clearance rates and elimination half lives. liver
Clearance of opioids is dependent on ________________. hepatic blood flow
How is remifentanil metabolized? ester hydrolysis by plasma esterases
Which opioids' metabolism is affected by the simultaneous infusion of propofol and how? alfentanil and sufentanil; useful doses of propofol inhibit the degredation of alfentanil and sufentanil by 50-60% and up to 90% with higher propofol doses