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Anes. Pharm I Test 2


Where do opioid agonists bind to opioid receptors? presynaptic and postsynaptic sites in the CNS (brain and spinal cord) and peripheral sites (primary afferent neurons).
Opioids act like ________ _________ that normally activate opioid receptors. endogenous peptides
What are 3 examples of endogenous peptides that normally activate opioid receptors? enkephalins, endorphins, and dynorphins
What are the 4 phases of nocioception (the pain pathway)? transduction, transmission, perception, modulation
Unlike inhalation agents, opioids do not cause changes in _____________ autregulation
What are 4 favorable opioid properties? analgesia, preservation of blood flow auto regulation (CNS, heart, kidneys), minimal cardiac depression with maintenance of hemodynamics, blunting of autonomic responses to sympathetic stimulation (surgical stress, laryngoscopy)
By getting opioids on board before surgery starts, you can decrease what 2 things? catecholamine release and endocrine response to surgical stress
What is the principle effect of opioid receptor agonism? a decrease in neurotransmission
What 2 things does activation of the opioid receptor cause? 1).closure of the voltage-gated Ca++ channels on presynaptic nerve terminals; 2).Opening of K+ channels to hyper polarize cell, causing inhibition of postynaptic neurons
What does the closure of the voltage-gated Ca++ channels in presynpatic nerve terminals once the opioid receptor is activated cause? a reduction of the release of neurotransmitters
What are the 6 neurotransmitters whose release is affected by opioid receptor activation? glutamate, acetylcholine, dopamine, norepinephrine, serotonin, and substance P
This type of receptor which opioids bind to constitutes 80% of all known receptors and includes muscarinic, adrenergic, gamma-aminobutyric acid, and somatostatin receptors. Guanine (G) protein-coupled receptors
When the opioid receptor is activated and K+ channels are opened the cell is hyper polarized, meaning what? hyper polarization of the cell means inhibiting the post-synaptic neurons & preventing excitation or propagation of action potentials
Is Ca++ channel closure presynaptic or postsynaptic? presynaptic
Is K+ channel opening and resultant hyper polarization of the cell presynaptic or postsynaptic? postsynaptic
What occurs during the transduction phase of the of the pain pathway? noxious stimuli (chemical, thermal, mechanical) is converted to an electrical impulse in sensory nerve endings
What occurs during the transmission phase of the pain pathway? conduction of electrical impulses to the CNS
What occurs during the modulation of pain phase of the pain pathway? altering pain transmission - both inhibitory and excitatory mechanism modulates pain impulse transmission in peripheral and CNS
What occurs during the pain perception phase of the pain pathway? occurs at the thalamus with the cortex input for discrimination of specific sensory experiences
What are the Mu1 and Mu2 receptor agonists? endorphins, morphine and synthetic opioids
What are the 6 effects of Mu1 receptors? analgesia (spinal & supraspinal), euphoria, miosis, bardycardia, hypothermia, urinary retention
What are the 4 effects of Mu2 receptors? Which on of these is the principle effect of this type of receptor? analgesia (spinal), respiratory depression, physical dependence, constipation; respiratory depression is primary effect of of this receptor
True or False: cloning supports the existence of Mu1 and Mu2 receptors separately False! Cloning does NOT support the existence of Mu1 and Mu2 receptors separately. Mu receptors are the universal site of action for all endogenous opioid receptors.
What are the Kappa receptor agonists? dynorphins and agonist-antagonists
What are the 6 effects of kappa receptors? analgesia (spinal & supraspinal), sedation, dysphoria, miosis, diuresis, respiratory depression
True or False: the analgesia effect from kappa receptors is stronger than that of Mu receptors False! analgesia from kappa receptors is NOT as strong as that of mu receptors
Why do opioid agonist-antagonist drugs not cause respiratory depression? they antagonize mu 2 receptors (primary effect of Mu2 is respiratory depression)
What are 2 valid indications for opioid agonist-antagonist drugs? laboring patients and chronic opioid abusers
What is the agonist for delta receptors? enkephalins
What are the 5 effects of the delta receptors? analgesia (spinal, supraspinal), respiratory depression, physical dependence, urinary retention, mild constipation
Which receptor has worse potential for constipation: Mu 2 or Delta? Mu 2
Which receptor has worse potential for respiratory depression: Mu2, kappa, or delta? Mu 2
Opioids directly inhibit the ascending transmission of nociception information from where? the spinal cord dorsal horn
Opioids activate pain control pathways that descend from the midbrain, via the rostral ventromedial medulla to the ________________ spinal cord dorsal horn
Which types of receptors are present in high concentrations in the dorsal horn of the spinal cord? mu, kappa, and delta
What are 3 supraspinal locations where opioid receptors are found? rostral ventral medulla, locus ceruleus, midbrain periaqueductal gray area
Exogenous opioids act on the brain circuits by stimulation the release of what? endogenous opioid peptides
True or false: studies have shown that opioids have effects outside the CNS true
Do opioids have direct cardiovascular effects on healthy, supine, normovolemic patients? No. Little direct effect even if very large doses (10x) are given
Opioids have ______ effect on myocardial contractility little
Opioids are a ______ option for patients with CHF/decreased LV function great
Opioids ________ sympathetic nervous system tone and response to stimulation decrease
What are 4 examples of decreased sympathetic nervous system tone caused by opioids? venous dilation (pooling), decreased venous return, decreased CO & BP, orthostatic hypotension
Sufentanil and Alfentanil caused direct relaxation of _____________ aortic smooth muscle
What is the reason for a decreases in heart rate seen with opioids? stimulation of vagal nucleus in the medulla, SA node depression, slowed conduction through the AV node
Opioid-induced bradycardia is response to what? atropine or glycopyrrolate
A synergistic drop in BP occurs when opioids are combined with what? benzodiazepines or nitrous oxide
A reduced size of MI was found to occur when one of these two drugs was administered proper to occlusion of coronary artery morphine and remifentanil
Which opioid has antimuscarinic effects and may cause tachycardia? meperidine (demerol)
Opioids cause a decreased responsiveness to PaCO2 causing the CO2 response curve to shift which way? to the right
Through direct effect at mu2 receptors, opioids cause direct depression of what? brainstem ventilation centers
Opioids cause a decreased release of Ach from neurons in the medullary respiratory centers which may effect respiratory depression. This can be reversed by which anticholinesterase drug? Why? physostigmine; because it crosses the blood brain barrier; it may reverse respiratory depression without reversing analgesia
High doses of opioids may result in _______ without loss of consciousness apnea
How do opioids cause a decrease in minute ventilation? by slowing down the respiratory rate but increasing tidal volumes
What factors accentuate the ventilatory depression caused by opioids? older age, occurrence of natural sleep
What factors attenuate the ventilatory depression caused by opioids? pain of surgery
Ventilatory depression causes an increase in what? PaCO2
What patient populations would poorly tolerate an increase in PaCO2 secondary to ventilatory depression caused by opioids? patients with increased ICP, asthma, COPD, or for pulmonale
Which effect of opioids causes death with overdose? respiratory depression
Is cough suppression secondary to opioids attributed to the same effect of opioids that causes respiratory depression? No; it is a separate effect from ventilatory depression. it is due to the effect on medullary cough centers
With opioid usage, respiration are tied to amount of __________ stimulation; important for the CRNA to assess respirations during minimal stimulation
Opioids cause a dose-dependent depression of ____________ in the airways ciliary activity
Increased airway resistance might be result of effect on bronchial smooth muscle and an indirect effect of ________________ histamine release
The principal effects of opioids are on what body system? the CNS
Opioids are most effective on which type of pain? visceral continuous dull pain
Opioids are least effective on which type of pain? chronic, neuropathic pain
Opioids provide analgesia to tackle what two components of pain? they reduce both the sensory and affective (emotional) components of pain
Are opioids anesthetic? NO!
True or false: opioids provide reliable amnesia False! Opioids DO NOT provide reliable amnesia, though they may cause sedation
What dosage of opioid can cause amnesia or lack of movement? There is NO dose of opioid that can cause anesthesia! Unconsciousness & sedation are not the same as anesthesia!
How do opioids affect MAC of inhalational anesthetics? opioids reduce MAC of inhalational anesthetics
Sedation occurs in up to ____ of patients receiving morphine 60%
_______ precedes the onset of analgesia sedation
True or false: opioids promote deep sleep False! Opioids disrupt normal REM and non-REM sleep
As long as hypercarbia is avoided, opioids cause cerebral vaso___________, a _________ in cerebral blood flow, and a(n) _________ in ICP constriction; decrease; decrease
Opioids _________ cerebral oxygen consumption decrease; however, effect is less than that of barbiturates
List some reasons why opioids should be used with caution in patients with head injuries sedative effect and miosis makes neuro checks difficult, hypoventilation causes increase in PaCO2 causing cerebral vasodilation and an increase in ICP, increased sensitivity to opioids if blood brain barrier not intact
Opioids cause miosis related to an excitatory action on the ____________ autonomic nervous system
True or false: pupillary constriction is an accurate indication of opioid levels False! other drugs can cause miosis as well, not reliable indicator
What is stiff chest syndrome? an intensification of tone of large muscles of the thorax and abdomen related to opioid administration
Which specific opioid drugs are associated with the incidence of stiff chest syndrome? fentanyl, sufentanil, alfentanil
What can help prevent stiff chest syndrome? slow administration of opioid, avoidance of nitrous oxide during induction
What are 2 methods of treating stiff chest syndrome? Reversal with narcan or muscle relaxation with NMBs
What patient population and circumstances would you most likely see stiff chest syndrome in? pediatrics; most common with large doses of opioids
Other than stiff chest syndrome, what can sufentanil cause that would make ventilating a patient difficult? closure of vocal cords
Incidence of difficult ventilation with administration of sufentanil is _______ considering both possible causes 84 - 100%
Nausea and vomiting related to opioid use is thought to be caused by direct stimulation of the ________________ on the floor of the fourth ventricle chemoreceptor trigger zone (CRZ)
What are 4 reasons (other than the chemoreceptor trigger zone stimulation) as to why opioids can cause nausea and vomiting? increased gastric secretions, delayed gastric emptying, vestibular component (ambulatory patients affected more), pain
What is a method to combat nausea and vomiting r/t opioids in ambulatory surgery patients? load them up with IV fluids to combat orthostatic hypotension which contributes to nausea & vomiting
What can opioids cause that mimics angina pectoris? biliary spasm - sphincter of Oddi specifically; increases intrabiliary pressure causing epigastric distress & chest pain
What medications can relieve the biliary spasm caused by opioids? nitroglycerin, naloxone (narcan), glucagon
True or false: the EKG tracing will show changes that mimic cardiac changes when patient experiencing intrabiliary spasm r/t opioid administration True! However, the EKG changes will go away if pt treated with nitro, narcan, or glucagon
Due to sphincter of Oddi spasms, opioid administration can interfere with intraoperative cholangiograms. What medication might the surgeon ask the CRNA to administer to ensure blockage not due to biliary spasm? glucagon
Why do opioids cause urinary retention? increase in bladder sphincter tone & increase in detrusor muscle tone causing urgency
What are some of the implications related to opioids easily crossing the placenta? though NOT teratogenic, opioids may cause depressed neonate & neonate of addicted mother can go through withdrawal
True allergies to opioids are rare. Histamine release, urticaria, or local reaction are more common with which 2 opioids and why? morphine and meperidine; morphine > meperidine in terms of histamine displacement, fentanyl class of drugs does not
What are 2 ways in which opioids may actually help nausea and vomiting rather than cause it? decrease pain, which often contributes to N/V; higher or repeat IV dosing can depress vomiting center in the medulla
What is the rational for pretreating with H1 and H2 blockers before administering morphine? these drugs do not prevent displacement of histamine caused by morphine but prevent significant changes in BP and SVR r/t histamine
What is tolerance as it relates to opioid use? development of increased dose needed to achieve same analgesia as previously experienced with smaller dose; usually requires 2 - 3 weeks to develop
What opioid effects can a person develop tolerance to? analgesic, euphoric, sedative, respiratory depression, emetic
What 2 opioid effects can patients not develop tolerance to? miosis, constipation
What are 3 theories that account for the development of opioid tolerance? opioid receptor desensitization, down-regulation of receptors, up-regulation of cAMP system
What is physical dependence as it related to opioid use? development of both psychological, compulsive desire and physical need for opioid; addiction more likely with agonists than agonist-antagonists
Dependence on morphine requires ______ to develop, but some degree of physical need developed within _______ of continuous use 25 days; 48 hours
Discontinuation of opioids in those who are physically dependent produces what 4 symptoms? yawning, diaphoresis, lacrimation, coryza
Opioids affect the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis. What are the results of opioid affecting these two systems? decreased plasma cortisol levels with prolonged therapy; increased prolactin, decreased LH, FSH, testosterone, and estrogen
Why is demerol (or morphine) a good drug for post op shivering? What are the implications of administering it for this purpose? decreases shivering secondary to resetting the temperature equilibrium point in the hypothalamus; if you give them opioid for this reason, you must provide warmth to prevent low body temperature
How does prolonged opioid exposure depress the immune system? alters the development, differentiation and function of bone marrow progenitor cells, macrophages, and T cells
True or false: opioid receptors are present on immune cells True!
What is the triad of symptoms seen with opioid overdose? miosis, hypoventilation and coma
Opioids rapidly leave the blood compartment and move to highly perfused tissues such as.....? brain, lungs, liver, kidneys, spleen
Significant amount of opioids can be taken up by the ______ on "first pass uptake" and can be returned to circulation later. lungs
The amount of uptake of opioids by the lungs is influenced by what 3 things? prior accumulation of another drug or inhalation anesthetic administration decreases uptake of opioid by lungs; smokers have increased uptake of opioid by the lungs (this means they are resistant to opioids)
The effect of small opioid doses is terminated by __________; larger doses depend on __________ redistribution; metabolism
Most opioids are chiefly metabolized by the _______ with varying clearance rates and elimination half lives liver
Clearance is dependent on what? hepatic blood flow; so in decreased cardiac output there will be longer effect
Which opioid is different from the others in terms of metabolism? How? Remifentanil; metabolized by ester hydrolysis by plasma esterases (NOT affected by plasmacholinesterase deficiency)
Which 2 opioids have active metabolites? morphine and meperidine
What do the active metabolites of morphine cause? M6G is more potent than morphine and has same effects
What does the active metabolite of meperidine cause? normeperidine is a CNS stimulant which could cause seizures (more likely with repeated doses in renal failure patients)
Which opioid has the lowest lipid solubility and therefore the slowest onset? morphine; takes 15 - 30 minutes to reach equilibration between brain and blood (peak CNS effect)
What is the duration of action of morphine? 4 hours; this is why it is a great drug for post op pain
Doses of up to __________ are used as IM premedication or IV as portion of general anesthetic 0.1 - 0.2 mg/kg (ideal dose 0.05 - 0.1 mg/kg)
Morphine decreases the MAC of volatile anesthetics in a dose-dependent manner with the ceiling effect at _________ 65% MAC
Only <0.01% of morphine administered enters the CNS at peak plasma concentrations. What 4 things account for this? low lipid solubility, high degree of ionization at physiologic pH, protein binding, rapid conjugation with glucoronic acid (metabolism)
Unlike the fentanyl class of drugs, morphine is not taken up by the _____ in first pass lungs
Which patient would you be more concerned about the potential for overdose of morphine with: liver failure or renal failure? Renal failure - r/t elimination rate of active metabolites
When liver metabolism is impaired, increased rates of _____________ of morphine may be possible renal metabolism
What are 4 differences in how women respond to morphine when compared to men? greater analgesic potency, slower offset and onset, no effect on apneic threshold, hypoxic sensitivity decreased
Meperidine was discovered during the search for a synthetic ________ like drug atropine; meperidine and atropine have a similar chemical structure
Meperidine causes an increase in __________ and some large airway _________ heart rate; bronchodilation
Meperidine can cause myocardial depression at doses above _______ 2 mg/kg (which is just 2x normal dose)
What is the reason for the link between meperidine and PONV, especially in pediatrics? sensitizes the labyrinthine apparatus resulting in dizziness and N/V
Meperidine is a synthetic opioid agonist at ___ and ____ receptors mu and kappa
What is the potency of Meperidine (demerol) when compared to morphine? it is one tenth as potent as morphine
What is the lipid solubility of Meperidine (demerol) when compared to morphine? 11x more lipid soluble than morphine
What percentage of meperidine is protein bound? 60%
What is the dose of meperidine used to supplement anesthesia in pediatrics? 0.5 - 1 mg/kg
What is the typical duration of meperidine? 2 - 4 hours
Serotonin syndrome may be caused by interaction of meperidine with what drugs? antidepressant MAO inhibitors
What are the symptoms of serotonin syndrome? HTN, tachycardia, diaphoresis, hyperthermia, confusion, agitation, hyperreflexia; severe = coma, seizures, coagulopathy, metabolic acidosis
What is the distribution 1/2 time of fentanyl? less than 28 minutes
Fentanyl is _______ lipid soluble highly
What is fentanyl's potency in comparison to morphine? 100x more potent than morphine
What is the typical dosage of fentanyl? 1 - 2 mcg/kg
Small doses of fentanyl have a _______ duration related to ___________ short (20 - 40 minutes); redistribution
Larger doses of fentanyl have a ________ duration related to ___________ longer; acculumation
What percentage of the initial IV dose of fentanyl is taken up by the lungs? 75%
Repeat doses of fentanyl accumulate in what 3 places? muscle, fat, and lungs
What is the elimination 1/2 life of fentanyl? 3.1 - 6.6 hours; but it has a clinically shorter duration than morphine r/t inactive metabolites
What percentage of IV dose of fentanyl leaves the plasma in less than 5 minutes? 80%
How are plasma concentrations of fentanyl maintained? through redistribution of drug back into plasma
Is elimination of fentanyl prolonged or lessened in the elderly? prolonged; decrease the dose for the elderly
Is the elimination of fentanyl prolonged with hepatic cirrhosis? No
What is the dosage of fentanyl when used as a balanced technique to blunt circulatory responses? 2 - 20 mcg/kg IV
What dosage of fentanyl significantly reduces the dose of proposal needed for placement of an LMA? 0.5 mcg/kg
Compare the MAC reduction of fentanyl to the MAC reduction of morphine more effective in reducing MAC than morphine; ceiling effect 40% MAC reduction for small doses
What are 3 advantages of fentanyl? no direct myocardial depression, no histamine release or displacement, suppresses stress response to surgery
What are 3 disadvantages of fentanyl? sympathetic stimulation in response to pain, unreliable amnesia, post-op respiratory depression
Compare the CV effects of fentanyl to morphine. fentanyl causes more of a decrease in heart rate than morphine
Doses of 30 mcg/kg of fentanyl change _______________ but do not interfere with the use and interpretation SSEP or somatosensory evoked potential
Fentanyl use in head injury patients can cause a(n) _________ in ICP even with unchanged PaCO2 increase
Fentanyl has a _________ drug interaction with benzodiazepines synergistic
True or false: fentanyl has been known to cause reflex coughing in pre-op True
Which is the most potent opioid currently available? Sufentanil; 10x more potent than fentanyl and 1000x more potent than morphine
What percentage of sufentanil is taken up by the lungs? 60%
What is the elimination 1/2 life of sufentanil? 2.5 hours
A pre-induction dose of sufentanil may cause ________ but not ________________ apnea; loss of consciousness
Stiff chest syndrome is common with sufentanil doses of _______ prior to induction 10 - 15 mcg
Sufentanil has a _____ intense, _______ lasting analgesia than fentanyl with _____ respiratory depression more; longer; less
What is the MAC reduction possible with Sufentanil? up to 70%
Describe the dosing for an infusion of Sufentanil? loading dose of 1 mcg/kg and then infusion rate of 1 mcg/kg/hr
When would the CRNA need to turn off an infusion of Sufentanil to ensure proper awakening? 30 - 45 minutes prior to emergence
After infusion for 3 hours, sufentanil will decrease ____ more rapidly than fentanyl and alfentanil 80%
After infusion for 8 hours, sufentanil will decrease ____ more rapidly than fentanyl or alfentanil 50%
What is the potency of alfentanil when compared to fentanyl? 1/5th as potent as fentanyl
What is the elimination 1/2 life of fentanyl 1.1 - 1.6 hours
Alfentanil is not as lipid soluble as fentanyl, however only ___ ionized form at physiologic pH 10%; this causes faster onset or effect site equilibration
Which opioid is the best choice for a single, brief stimulus? alfentanil (examples = laryngoscopy, restrobulbar block)
96% of alfentanil is cleared within ________________ 60 minutes of administration
When should an infusion of alfentanil be discontinued in order to prevent delayed awakening? 15 - 25 minutes prior to emergence
What is the dose of Alfentanil used for direct laryngoscopy? 15 mcg/kg 90 seconds before blunts SBP and HR response; 30 mcg/kg blunts catecholamine response
What is the induction dose of alfentanil? 150 - 300 mcg/kg given rapidly (risk of stiff chest syndrome)
What is the elimination half time of remifentanil? 6 - 10 minutes
How is remifentanil metabolized? by non specific plasma and tissue esterases into inactive metabolites which are excreted by the kidneys
Hypothermia slows clearance of remifentanil by ____ 20%
Compare alfentanil and remifentanil in terms of inter patient variability alfentanil = BIG interpatient variability; remifentanil = little variability
What is the context sensitive half time of remifentanil? 4 minutes; it is independent of infusion time
Remifentanil causes a ___ decrease in SNP two minutes after infusion 30%
The rapid equilibration time of remifentanil means what in terms of titrability? easily titrated
What are 4 clinical uses for remifentanil? laryngosopy, retrobulbar block, L&D, rapid recovery desired (craniotomy, carotid endarterectomy)
Which opioid comes in powder form and must be reconstituted? remifentanil
What is the induction dosing of remifentanil? 1 mcg/kg over 60 - 90 seconds or 0.5 - 1 mcg/kg prior to IV anesthetic agent
What is the remifentanil dose used for monitored anesthesia care (MAC)? 0.05 - 0.1 mcg/kg/min with midazolam (versed)
1.5 mg of hydromorphone is equivalent to ___ of morphine or ___ of fentanyl 10 mg of morphine; 100 mcg of fentanyl
What is the dose of hydromorphone? 0.02 - 0.06 mg/kg
What is the onset of hydromorphone? What is the duration? onset: 5 minutes; duration: 4 - 5 hours
Which drug is better for renal failure patients and why: morphine or hydromorphone? hydromorhpone because it has inactive metabolites
Created by: Mary Beth