Opioid Analgesics Flashcards

Question

Test: Which receptor least likely to cause urinary retention

Answer 1

- lipophilic, but not as lipophilic as barbiturates, but still get effect. most are absorbed PO, some undergo significant 1st-pass effect, small dose effects are terminated by redistribution, multiple doses and gtt's are terminated by metabolism - most metabolized in the liver (except remifentanil) - excreted primarily by kidneys - "pharmacogenetics"

Answer 2

- in healthy pts, bradycardia with sustained BP (worse in combo with induction drugs). - impairment of SNS response, orthostatic hypotension d/t venous pooling, histamine release - doesn't sensitize the heart to catecholamines though - synergism with BZ's, NO, causes myocardial effects - cardiac protectant effect

Answer 3

enhances myocardial resistance to oxidative and ischemic stress -sigma and kappa receptors

Answer 4

"slow deep breaths" - dose-dependent depression of ventilation (but they try to keep their minute ventilation so just increase VT) via mu and delta rec's - Interfere with pontine and medullary ventilatory centers (regulate rate and rhythm of breathing) - Decreased responsiveness to CO2 (by decreasing ACh release in the medullary center of the brain) - RIGHT Shift in O2-CO2 response curve (the body wants to release more O2, bc CO2>O2) - Could have ETCO2 60 and they’re not breathing heavily - OD sx: pinpoint pupils, slow deep breaths - Bronchial effects (decrease ciliary action, increase airway resistance via bronchial smooth muscle and histamine release) - cough suppression

Answer 5

Extremes in age, Natural sleep, Pain Also think about tolerance to narcotics! Extremely old and young pts are more affected by this

Answer 6

Depression of medullary cough centers Codeine (bulky substitution on number 3 carbon position) Dextromethorphan – dextrorotary – cough suppression without analgesia or respiratory depression Falyar – have given opioids and during induction pt was coughing

Answer 7

"opioids are not anesthetics... sedate but awareness possible!" "sedate patients are not pain free!" -decrease cerebral blood flow, and possibly ICP (in the absence of hypoventilation) -use cautiously in head trauma pts -an increase in CO2 will still cause cerebral vasodilation!) *alter wakefulness, miosis (so can't assess that), depression of ventilation, increased sensitivity when BBB is compromised -DO NOT alter the effects of NMBs

Answer 8

inhibit ascending transmission of nociceptive info activate descending pathways could have a set of nerves sending excitatory pain signals and it be the same set of nerves that could modulate them to slow down

Answer 9

ANS component of Edinger-Westphal nucleus of oculomotor nerve - can be antagonized by atropine (bc chemically similar) but this is the least of the worrisome SEs - severe arterial hypoxemia can result in the presence of morphine

Answer 10

-Opioids have no effect on nerve conduction -Skeletal muscle hypertonus “truncal rigidity” Following large doses of opioid (phenylpiperidine), related to mu receptors acting on DA and GABA receptors -Evidence supports resistance d/t laryngeal musculature contracture (tx: NMB or naloxone) example of woman with true laryngospasm who got 20 of succ

Answer 11

opioids will induce some sort of sedative effect, but doesn't mean they're not uncomfortable morphine induces sedation that precedes analgesia in up to 60% of pts

Answer 12

Inappropriate for cholecystectomy: morphine is the most guilty!! -RUQ pain -Opioids cause spasm of biliary smooth muscle and the sphincter of Oddi Tx: Glucagon 2mg, IV will reverse smooth muscle spasm (doesn't antagonize analgesic effects) -Morphine can contract pancreatic ducts -Increase in amylase and lipase levels -Mimics acute pancreatitis

Answer 13

- Decreased gastric motility, propulsive activity and emptying time - Can increase risk of aspiration or delay drug absorption - Opioid-induced constipation - Can be debilitating in chronic users - Methylnaltrexone can antagonize effects – only works in the gut - Narcan works everywhere

Answer 14

No - the chronic pain pathway is not the same as the acute pain pathway. Pain can initiate itself anywhere along that pathway

Answer 15

- (mostly bc of this) Stimulation of receptors in the chemoreceptor trigger zone in the medulla (Serotonin type 3 receptors (5HTZ) and Dopamine type 2 receptors) - Increased GI secretions and delayed gastric emptying (more gastric acid in there, not feeling comfortable) --> more N/V - N/V not common in recumbent patients - Vestibular effect? - Opioids, anesthetic gases, reversal agents make you sick

Answer 16

- Opioid-induced augmentation of detrusor muscle tone results in urgency, but… - Tone of urinary sphincter enhanced, making voiding difficult

Answer 17

* Morphine* causes BVs to dilate (--> warm, flushed skin) - Histamine release, not an allergy --> conjunctival erythema, pruritis, might even cause a rash - Example of Dr. Funk getting morphine intrathecal  crazy itching

Answer 18

Readily cross the placenta, results in neonatal depression - Morphine greater than meperidine - Chronic use can cause neonatal physical dependence - Naloxone may precipitate neonatal abstinence syndrome -(neuromusc blocking and general anesth’s don’t cross) – but any drug with any lipophilicity (opioids) will cross the placenta and take effect

Answer 19

- Cholinergic system is a positive modulator of opioid analgesia * Physostigmine – enhances * Atropine – antagonizes (meperidine is structurally similar to atropine) - Ventilatory effects can be exaggerated by other drugs: * Amphetamines * Phenothiazines * MOA’s (or MAOIs) * Tricyclics * **benzodiazepines

Answer 20

- Depression of ventilation (slow deep breathing) - Triad: Miosis, Hypoventilation, Coma/unresponsive - Hypotension and sz’s develop if arterial hypoxemia persists - Treatment: Mechanical ventilation**, Supplemental O2**, Antagonist Always 1st worry about oxygenation, ventilation, HD stability

Answer 21

- “provocation” of coughing – cause unclear? - Imbalance of sympathetic and vagal nerve innervation - Stimulation of juxtacapillary irritant receptors? ** more with fentanyl induction - Fentanyl, sufentanil and alfentanil Not seen with morphine and hydromorphone

Answer 22

- Pharmacodynamic tolerance and physical dependence: downregulation - Cross-tolerance can occur between all opioids - Tolerance without physical dependence possible, but not vice versa - Pharmacodynamic tolerance - (it’s an agonist -->) Receptor desensitization and downregulation; upregulation of cAMP - 2-3 wks (MSO4,morphine sulfate) – much quicker with more potent drugs - Everything except… miosis and bowel motility (doesn’t matter what dose of the drug you get, you’ll be constipated. Once you get it you get it)

Answer 23

NMDA! - downregulates spinal glutamate receptors - pt on LT opioids might not be as responsive to ketamine as someone who is not

Answer 24

(takes 2-3 weeks to become dependent) - Initial sx’s: yawninig, diaphoresis, lacrimation - Insomnia and restlessness are common - Cramps, N/V/D -peak at 72 hrs, then decline in the next 7-10 days - “Worst at 3 days, but can last up to 2 weeks” - During w/d, tolerance is quickly lost

Answer 25

Produces: -Analgesia, euphoria, sedation, and decreased [ ] -N, body warmth, pruritis (nose), dry mouth, extremity heaviness -Increases pain threshold, modifies perception of noxious stimulation -Effective against visceral, muscles, joints, etc. against slow dull pain, *when given preemptively.* (Must be most vigilant in period right before/after incision)

Answer 26

- Onset 15-30 mins; slow compared to other opioids (eg fentanyl) (fentanyl could be 1-3 minutes). If you’re giving it with induction drugs, give it in the holding area preop - Only a small portion of morphine reaches the CNS - Poor lipid solubility - BUT HIGH DEGREE OF IONIZATION at phys pH - Protein binding - decrease in plasma [ ] mainly d/t metabolism - Rapid conj w/ glucuronic acid by the liver

Answer 27

^CO2 --> vasodilation --> ^blood flow *Falyar was going to check on this* This has more effect on drug effect than the ionized:unionized ratio. Stoelting says that alkalosis yields more nonionized (active) form, but acidosis has higher plasma and brain [ ] of drug, so cerebral blood flow is more important for delivery of morphine

Answer 28

Accumulates rapidly in kidneys, liver and muscle, does not undergo first-pass uptake in the lungs - Both the liver and the kidneys: * Primary metab is by conj with glucuronic acid * Renal metab significant, okay in liver pts - Metabolites include * 75% morphine-3-glucuronide (inactive) * **morphine-6-glucuronide 5-10% (active, and maybe more potent than the morphine itself) - nomorphine and codeine [Falyar to check this – morphine is a metabolite of codeine, but the most important one is morphine-6]

Answer 29

- “Metabolized mostly in kidneys,” has to be conjugated so that it’s made polar to get out of the body - Decrease in plasma [ ] primarily through metab - Plasma [ ] higher in * Elderly and neonates (clearance decreased 1st 4 days of life), and children

Answer 30

- Metabolite of morphine - Longer duration of action than morphine - Higher analgesic potency (65-fold higher than morphine!)

Answer 31

- Synth in 1939 – phenylpiperdine ring - Usually used for postop shivering (brain has been reset when they wake up from anesthetics) - Analogues (comparable drugs): Fentanyl, sufentanil, alfentanil and remifentanil - Structurally similar to atropine – mild antispasmodic effects - Mu-receptor agonist - Clinical uses - decrease significantly over the yrs - Anti-shivering postop - Stimulation of kappa receptors - Shivering Dose 4.5 mg (Pitman said 12.5mg then repeat??) - In high doses negative cardiac inotropic effects, histamine release

Answer 32

- 1/10 as potent as morphine - Duration of action 2-4 hrs - In equal *analgesic* doses, in produces similar effects to morphine (1 mg drug A and 10 mg of drug B) - Sedation, euphoria, N/V, depression of ventilation

Answer 33

- Extensive first-pass metab by liver (limits PO use) - Extensive metab: * 90% demethylization to normeperidine (active metabolite) * 10% hydrolysis to meperidinic acid * If you have any renal issues where you can’t excrete the drug, and you have an active metabolite, breaking it down is not really helping the situation bc the metabolite is also exerting an effect - Excretion is principle elimination route * pH dependent (more acidic, greater fx of drug excreted unchanged) * decreased renal fn can result in accum of metab’s

Answer 34

(similar to atropine in structure, think about what that does!) - May cause increase in HR, mydriasis * Modest atropine-like effects * HIGH doses --> decrease myocardial contractility - Delirium and sz’s * Reflects an accumulation of normeperidine (high CNS effects) * Elderly pt with renal failure** [who shouldn’t get meperidine!] - May elicit serotonin syndrome in pts taking MAOI’s or fluoxetine - Promptly crosses the placenta, may exceed maternal [ ]s - Less biliary tract spasm - Withdrawal develops more rapidly and is shorter in duration

Answer 35

-½ as active as meperidine -T1/2 is 15 hrs, >30 hours in renal failure -Could see sedation IN THE RIGHT PATIENT (so renal pts haha) -↑ sensitivity in elderly (↓ plasma protein = ↑ circulating volume) -May be involved in meperidine delirium – seen in pts receiving drug for 3+ days (related to accumulation) -PCA cannot be recommended Eventually undergoes hydrolysis to meperidinic acid

Answer 36

N-dealkylation and hydroxylation

Answer 37

morphine >> phenylpiperidines

Answer 38

similar to morphine - secondary peaks (release from pulmonary 1st pass uptake) - bradycardia, sz (like etomidate), slow deep breathing - modest increase in ICP less likely to cause hypotension (no histamine release)

Answer 39

thienyl analogue of fentanyl - analgesia (0.1-0.4 ug/kg) - induction dose that would be required for laryngoscopy may cause chest wall rigidity (vs laryngeal tightness? check bagging and put oral airway in)

Answer 40

- MORE protein binding than fentanyl (to alpha 1 glycoprotein) * Enhanced effects in neonates - Rapid redistribution terminates effects (Highly lipid soluble), ↑ Vd - Significant 1st pass pulmonary uptake - Rapidly metab by N-dealkylation*** primary (makes inactive metabolites) and O-demethylation (active - desmethyl sufentanil, which must be conjugated) - longer effects if renal impairment - -> takeaway must be able to conjugate, and must be able to renally clear it - Clearance sensitive to hepatic blood flow (think 0.7) - Normal renal fn important to clearance

Answer 41

sufentanil

Answer 42

- “Not as good as fentanyl”, only redeeming quality is rapid onset - Less potent than fentanyl; shorter duration of action - Rapid onset of action after IV admin - High fraction of unionized drug - Small Vd – pKa 6.5 such that nonionized dominates [B/BH+]

Answer 43

- Rapid onset/offset d/t prompt on-sight equilibrium - 90% of the drug exists in nonionized form at physiologic pH - Principally bound by alpha1 glycoproteins - Metabolized by 2 independent pathways * Piperdine N-dealkylation to noralfentanil * Amide N-dealkylation to N-phenylpropionamide - Vd less than fentanyl

Answer 44

fentanyl | more than morphine, alfentanil, sufentanil

Answer 45

alfentanil, [9 B / 1 BH+] --> 90% nonionized

Answer 46

longer duration of action

Answer 47

low-dose narcan gtt

Answer 48

propofol, fentanil, sufentanil, lidocaine

Answer 49

- 15 μg/kg IV – blunts stim of laryngoscopy - 30 μg/kg IV – catech response to noxious stim - 150-300 μg/kg IV – produces unconsciousness (induction) - Combo with inhaled anesthetic 15-150 ug/kg/hr

Answer 50

Associated with - More significant decrease BP - Diminished incidence of nausea and vomiting - Acute dystonia - Avoid in untreated Parkinson’s patients

Answer 51

Selective mu agonist - Potent like fentanyl (similar dosing on dose-effect curve) - Blood-brain equilibration like alfentanil Although it is a phenylpiperidine derivative: -Structurally different bc of ester-linkage (water soluble linkage) *Impacts Vd (fentanyl 3-4 L/kg) this is 0.5 L/kg *Non-specific Plasma esterases in blood metabolize it. So you could turn it off and 3-4 minutes it’s gone. *Very synergistic with propofol (esp if you can’t have paralysis) [Buuuuut we’ve been combating surgical insult --- and all of a sudden they have nothing. So you can cause hyperalgesia & a hyperdynamic state (which can be worse than just not treating the pain in the first place). Need to consider a LT option for pain. Can titrate longer acting opioid like dilaudid (doesn’t impact breathing as much) to bridge the pt. And dilaudid’s onset is like 10minutes, so you need to start giving it before you turn the remifentanil off]

Answer 52

Brief action, titratable, doesn’t accumulate, rapid recovery Clinical uses -Cases requiring transient profound analgesic effect (retrobulbar block, direct laryngoscopy, tracheal intubation)

Answer 53

Anesthesia induction: 1 ug/kg bolus, followed by gtt of 0.05-0.2 Ug/kg/min 0.5-1 ug/kg/min for 10 min prior to induction agent (ENT cases, any type of neck surgery where they want to know nerve fn, spine cases, can’t have paralytic. Synergistic effect of remi and prop, but not going to accumulate like sufentanil or fentanyl) (Most likely wouldn’t use this agent for induction - Dr. Funk’s example – use for pins for neurosurgery, but won’t need analgesia again for a long time) - Analgesia - 0.25-1.0 ug/kg IV or 0.05-0.2 Ug/kg/min *also for anesthesia induction* - Sedation: 0.05-0.1 ug/kg/min in combo with midaz 2 mg

Answer 54

- Small Vd - “Whatever is nonionized is REALLY nonionized.” - Rapid clearance (will accumulate less than other opioids) - PK similar in obese and IBW pts - CS ½ is 4 minutes - Metab by non-specific plasma esterases - No active metabolites - Not affected by pseudocholinesterase defic - PK unchanged by renal or hepatic failure

Answer 55

- It’s important to admin a longer acting opioid for postop analgesia - Can induce “seizure like” activity (add to the list: etomidate, fentanyl, remifentanil) - …. If I were worried about a drug that will cause hyperalgesia, it would be this one, bc it just turns off. - Other effects: N/V, Depress ventilation, ↓ systemic BP, Hyperalgesia – secondary to acute opioid tolerance, Ketamine and magnesium can block this

Answer 56

(main long-acting opioid) - A derivative of morphine (1926) - 5x more potent (8-10 mg morphine for pain --> 2 mg dilaudid) - Slightly shorter duration of action - Less hydrophilic than morphine - Faster onset (more lipophilic --> works faster!) - More sedation – BUT sedate patients are not necessarily pain-free‼! - Less euphoria (doesn’t mean it’s not as addictive!) - Effective alternative to treat moderate-severe pain - Can cause agitation and myoclonus (etomidate, fentanyl, remifentanil, hydromorphone)

Answer 57

Synthetic opioid - Oral opioid in chronic pain settings - Attractive for withdrawal and drug suppression Long terminal half-life – 12 hrs - Requires infrequent dosing - Also long effect time – have to consider how long the drug is attached to the receptor. Also consider the size of the drug when it attaches to the receptor, and if it’s like succinylcholine and needs to be broken down by an esterase it could take longer. - Think of this more in terms of chronic addiction drug, not for chronic pain drug. A lot of chronic pain clinics are not giving non-narcotics. Or are given as taper so you don’t get withdrawal – plus you don’t get as much of a high with methadone. - Large variation among individuals Dr. Funk’s Example of pt who got methadone (respiratory depression outweighs its effects on pain) who then gets dilaudid – resp depression from both → unresponsive‼

Answer 58

Opioid withdrawal - Can substitute for morphine at ¼ the dosage - 20 mg IV, produces postop analgesia >24 hours - But not as much euphoria Tx of chronic pain - Low abuse potential - NMDA antagonist activity may be beneficial for neuropathic pain - Principle disadvantage is prolonged and unpredictable T1/2 - Drug can accumulate and cause depression of ventilation

Answer 59

``` (Similar to morphine) Depression of ventilation Miosis Constipation Biliary tract spasm ``` Sedative and euphoric effects less (get into trouble when you double dose)

Answer 60

Synthetic codeine analog - Can be given orally, IM or IV for moderate to severe pain - Weak/moderate Mu agonist - Less potent than morphine - Useful for chronic tx – less addictive - Enhances fn of descending inhibitory pathways - Metabolized by CYP 450 (Metabolite O-desmethyltramadol has modest analgesic effects) Disadvantages - Interacts with coumadin anticoagulants - Drug-related sz’s (may lower sz threshold) - High incidence of N/V - Zofran may interfere with analgesic component - Reuptake of 5-hydroxytryptamine (another name for serotonin)

Answer 61

Synthetic opioid. Started as a natural drug (opiate), but we made it synthetic. Versus fentanyl has always been manmade (opioid). - Originally claimed to have no addictive qualities - Differs from morphine in that it rapidly penetrates the CNS, where it is hydrolyzed to active metabolites (Monacetylmorphine and Morphine) Compared to morphine - More rapid onset - Less N - Greater liability for physical dependence

Answer 62

- These drugs bind to mu receptors but produce limited responses or no effect - Antagonists – have UPREGULATION of receptors * So they need to keep taking their meds prior to surgery * But we need to give other meds to get them to 100% efficacy Advantage - Produce analgesia - Limited depression of ventilation - Have a “ceiling effect” - Reserved for pts who can’t tolerate a pure agonist

Answer 63

agonst-antagonist Resembles pentazocine -Agonist effects are 20x greater -Antagonist effects are 10-30x greater -Low affinity for mu receptors: Produces antagonism for mu receptors (so in order to avoid constipation, urinary retention, etc.) -Moderate affinity for kappa receptors (Analgesia and anti-shivering) PK - Rapidly absorbed after IM injection - Metab in liver and excreted primarily in the bile - Inactive metab – hydroxybutorphanol - T1/2 is 2.5-3 hrs

Answer 64

o Most common: Sedation, nausea, diaphoresis - Dysphoria – don’t feel well, feel weird. (Think of Kappa receptors) - Depression of ventilation - Causes ↑in catecholamine response: ↑d HR, BP, PAP, CO - Mild biliary and GI tract symptoms - Limits effects of concomitant opioid agonists (could use ketamine, NSAIDS, peripheral nerve blocks) - Withdrawal following acute discontinuation in chronic therapy

Answer 65

agonist-antagonist - Chemically related to oxymorphone and naloxone (mu receptors) - Equal analgesic potency of morphine; ¼ antagonist potency as nalorphine PK - Metabolized in liver - T1/2 is 3-6 hrs - Antagonist effects occur at mu receptors - If given before an opioid, may diminish effects of morphine-like drugs perioperatively - If given after admin of opioid, it can reverse (for 2-3 hrs) depression of ventilation effects but maintain analgesia. After the 2-3 hours depression of ventilation comes back SEs - Sedation most common - Less dysphoria than pentazocine and butorphanol - Depression of ventilation has ceiling effect (30 mg) - Depression of ventilation is similar to that of morphine until 30 mg IM of nalbuphine is exceeded, after which no further depression of ventilation occurs (ceiling effect) - Catecholamine stimulation effects * May be beneficial in cardiac pts needing sedation and analgesia * Might not be giving these drugs as often but you could give them and then get less of the hypotension and bradycardia

Answer 66

- Nagelhout – agonist-antagonist, paper that says that it’s just a weak agonist - Usually given for chronic pain - Derived from thebaine * Potent analgesic (0.3 mg IM = 10 mg morphine) - Clinical uses * Postop pain related to CA, renal colic and MI SEs - Drowsiness, N/V, depression of ventilation - Similar to morphine but may be prolonged - Resistant to antagonism by naloxone - Pulmonary edema? (1 paper) - Dysphoria unlikely - Can precipitate w/d in pt taking morphine - Low abuse risk

Answer 67

Opioid antagonists with mild structural changes. Substitution of an alky group for a methyl group Pure mu antagonists include - Naloxone*** - Naltrexone - Nalmefene

Answer 68

***Used to tx opioid induced hypoventilation, depression of ventilation in the neonate d/t maternal admin, treat deliberate drug OD, detect suspected physical dependence (Effects don’t last as long as the opioid) - Dose 1-4 ug/kg IV -(we're going to stick to the lower end of that range bc our patients are going through surgery but might've given too much narcotic, as opposed to 1st responders who are giving it to pts who OD’d) - Short T1/2 – 30-45 minutes - "effects of the reversal agent don't last as long as the narcotic" - 5 ug/kg/hr can fix depression of ventilation without affecting analgesia - Oral route 1/5 as potent d/t 1st pass hepatic metabolism - Metabolized by liver by conjugation with glucuronic acid **** - Naloxone-3-glucuronide - [Remember remifentanil has ester-linkage – ester plasmaesterase] - [should you ever give naloxone for remifentanil? NO. just turn off the gtt]

Answer 69

SEs: - Reversal of analgesia - May be possible to titrate to maintain analgesia and reverse hypoventilation - *** Don’t want to bolus large doses bc you don’t want to reverse all of the agonist - If no pain to 100% pain they can become hyperdynamic  cardiac arrest, stroke - N/V - May occur simultaneously with awakening or just after - ↑ SNS activity - Sudden onset of pain - Tachycardia, HTN, pulmonary edema - Cardiac dysrhythmia – VF - Administration of opioid dependent parturient may result in fetal w/d Role of Tx of shock - In animals, large doses of naloxone improve myocardial contractility and outcomes - Dose >1 mg/kg required, suggesting effects are not opioid receptor mediated, or mediated by delta and kappa receptors

Answer 70

- prob not the right answer for acute OD of drugs - Oral antagonist with sustained effects >24 hours - Used in tx of alcoholism

Answer 71

***longer duration of action (low-dose Narcan gtt) -Pure opioid antagonist -6-methylene analogue of naltrexone -15-25 ug IV until effect achieved (MAX dose 1 mcg/kg) -Equipotent to naloxone -Prophylactic administration decreases N&V and pruritis in patient with IV PCA PRIMARY ADVANTAGE – longer duration of action PK: Metabolized in the liver by hepatic conjugation SEs -Pulmonary edema seen (more related to huge SNS response, will get backup into the lungs)

Answer 72

- Given PO - Quaternary ammonium opioid receptor agonist (can’t cross BBB, effects limited to gut) - Highly ionized; difficult to penetrate CNS - Attenuates morphine induced delayed gastric emptying, ↓ constipation - Decreases incidence of nausea

Answer 73

- Histamine release - Orthostatic hypotension - N/V - Fentanyl does not cross-react with morphine derivatives - “if you have an allergy to morphine, you will not have an allergy to fentanyl” - Only 3+ cases of true fentanyl allergy recorded to date - If you have allergy to morphine, you don’t necessarily have an allergy to fentanyl. Itching is known SE of morphine.

Answer 74

- Opioid receptors are present on immune cells - T&B lymphocytes, dendritic cells, neutrophils, macrophages and microglia - Immunosuppression – depression of natural killer (NK) cell - Following prolonged exposure - Abrupt withdrawal - Pain itself can impair immune function - Poorly controlled pain can affect immune fn → ↑ r/f infection → longer hospital stays

Answer 75

- Opioids shown to ↓ amount of anesthetic gas required | - Given prior to surgical incision

Answer 76

-Alternative to intermittent bolus, allows pt to address own analgesic requirements Advantages: - ↓d healthcare provider workload, ↑d pt satisfaction, ↓d opioid consumption, inherent safety - Studies show PCA provides marginally better analgesia, but better pain satisfaction - Remifentanil PCA in the first stage of labor has been shown to provide good analgesia while minimizing neonate

Answer 77

- You can inject some straight through dura into the CSF. - Opioids placed intrathecally target mu receptors in the substantia gelatinosa in the spinal cord - Unlike local anesthetics, neuraxial placement of opioids does not result in sympathectomy, sensory block or weakness - Epidural placement of opioids results in - Mu receptors and systemic absorption - Offers minimal to no over IV administration [WHAT] - Uptake into fat, systemic absorption and diffusion across dura - C-sxn can give some fentanyl, it’s right there on the SC. It’s lipophilic, so it works immediately. And it doesn’t have to go thru the bloodstream, so you give a TINY dose. - 10-15 ug TOTAL fentanyl - Think of acute respiratory depression & acute pain mgmt Conversely, morphine is not lipophilic, so it’s not quick, even a few hrs. It will circulate in the CSF. Then it gets to the midbrain, and cause delayed resp depression. - LT pain mgmt, followed by delayed respiratory depression - ITCHING (more than IV dose)

Answer 78

- Uptake into fat, systemic absorption or diffusion across dura - Passage through dura dependent on lipophilicity - Only 3% of epidural morphine crosses the dura to enter the CSF - Less lipid soluble drugs more likely to stay in CSF - Morphine movement cephalad can result in delayed depression of ventilation - Coughing and straining can facilitate process - Lumbar to cisterna magna (1-2 hours) 4 and lateral ventricles 3-6 hours) - Epidural injection results in similar blood concentrations produced by IM injection - Epinephrine can enhance intrathecal effects of morphine

Answer 79

- Dose dependent - Four classic side effects of neuraxial opioids are 1. Pruritis – most common; seen in OB, ?dose related? most likely related to cephalad migration and interaction with trigeminal nucleus. 2. Nausea and vomiting 3. Urinary retention – most common in young males, likely due to interaction of opioid with spinal cord receptors in the sacrum and 4. Depression of ventilation – most serious side effect, occurs faster with lipophilic. CSF migration and interaction with ventral medulla (morphine). - Pulse oximetry, Oxygen - Naloxone effective in attenuating side effects - More concerned with this if the pt has been given a longer-acting opioid

Answer 80

- Clinically important depression of ventilation has been observed in newborns of mother receiving epidural opioids - [ ] of fentanyl, sufentanil negligible in breast milk