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N926 Pharmacology > Opioids > Flashcards

Opioids Flashcards

1
Q

What does opioid produce

A

analgesia

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2
Q

what does opioid not produce?

A
  • Loss of touch
  • Loss of proprioception
  • Loss of consciousness
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3
Q

opium chemical structure

A
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4
Q

What is the relationship b/w cholinergic system and opioid analgeisa?

A

positive modulator

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5
Q

drug enhances cholinergis system

A

physostigmine

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6
Q

drug antagonzies cholinergic

A

atropine

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7
Q

Ventilatory effects can be exaggerated by other drugs

A
  • Amphetamines
  • Phenothiazines
  • MOA’s
  • Tricyclics
  • benzos
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8
Q

opioid breathing pattern

A

slow deep breathing

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9
Q

opioid OD triad

A
  • Miosis
  • Hypoventilation
  • Coma
  • Hypotension and seizures develop if arterial hypoxemia persists
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10
Q

opioid OD treatment

A
  • Mechanical ventilation
  • Supplemental oxygen
  • Antagonist
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11
Q

reflex coughing

A

Provocation” of coughing – cause unclear?
•Imbalance of sympathetic and vagal nerve innervation
•Stimulation of juxtacapillary irritant receptors?

Fentanyl, sufentanil and alfentanil
• Not seen with morphine or hydromorphone

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12
Q

opioids causing reflex coughing

A

Fentanyl, sufentanil and alfentanil
•Not seen with morphine or hydromorphone

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13
Q

Opioid WITHDRAWAL ABSTINANCE SYNDROME

A

•Initial symptoms - yawning, diaphoresis, lacrimation
•Insomnia and restlessness are common
•Cramps, nausea, vomiting and diarrhea peak at 72 hours,
then decline in the next 7-10 days

During withdrawal, tolerance is quickly lost

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14
Q

what receptors activated during long term opioid use?

A

NMDA

Down regulates spinal glutamate receptors

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15
Q

Opioid, what kind of tolerance and what kind of dependence?

A

Pharmacodynamic tolerance and physical dependence

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16
Q

What kind of tolerance happens b/w opioids?

A

Cross-tolerance can occur between all opioids

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17
Q

opioid.

relationship b/w dependence and tolerance

A

Tolerance without physical dependence possible, but not vice
versa

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18
Q

During tolerance, what is upregulated and what is downregulated?

A

Receptor desensitization and down regulation; up regulation of cAMP
•2-3 weeks (MSO4)…much quicker with more potent drugs

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19
Q

Opioid. what is exception for tolerance

A

Everything except…miosis and bowel motility

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20
Q

effects produced by morphine

A

Produces
•Analgesia, euphoria, sedation and decreased concentration
•Nausea, body warmth, pruritis (nose), dry mouth, extremity heaviness
Increases pain threshold, modifies perception of noxious
stimulation

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21
Q

What kind of pain does morphine relieves?

A

Effective against visceral, muscles, joints, etc.
•Against slow dull pain

  • when given preemptively.
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22
Q

Morphine onset

A

Onset 15-30 mins; slow compared to other opioids (e.g. fentanyl)

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23
Q

Morphine lipid, only small portion reaches CNS d/t

A
  • Poor lipid solubility
  • High degree of ionization at physiologic pH
  • Protein binding
  • Rapid conjugation by the liver
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24
Q

Morphine metabolites

A

75% morphine-3-glucuronide (inactive), morphine-6-glucuronide 5-10% (active), normorphine and codeine

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25
Q

Morphine, mpaired renal function can result in

A

accumulation and
unexpected respiratory depression

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26
Q

Morphine Decrease in plasma concentration primarily through

A

metabolism

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27
Q

Morphine

Plasma concentration higher in:

A
  • Elderly
  • Neonates (clearance decreased first 4 days of life)
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28
Q

Metabolite of Morphine
duration of action

A

morphine-6-glucuronide

•Longer duration of action than morphine

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29
Q

Metabolites of morphine

analgesic potency

A

Higher analgesic potency (65—fold higher than morphine)

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30
Q

meperidine analogues

A

Fentanyl, sufentanil, alfentanil and remifentanil

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31
Q

What is meperidine mainly used for? What is it structually similar to?

A

Structurally similar to atropine, mild antispasmodic effects

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32
Q

What receptor does meperidien work on? How?

A

Mu-receptor agonist

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33
Q

Mu1 receptors fxn

A
  • analgesia (supraspinal and spinal)
  • euphoria
  • myosis
  • bradycardia
  • urinary retention
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34
Q

mu2 receptor fxn:

A
  • analgesia (spinal)
  • depression of ventilation
  • physical dependence
  • constipation
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35
Q

Kappa receptors:

A

results in inhibition of neurotransmitter release:

  • Analgesia (supraspinal and spinal)
  • dysphoria, sedation
  • myosis
  • diuresis
  • lesser extent-hypoventilation and high intensity pain
  • Agonist-antagonist often act principally on K receptors
    • low abuse potential
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36
Q

delta receptors

What kind of ligand does it respond to?

A

responds to endogenous ligands known as enkaphlins: May serve to modulate Mu receptor activity

  • analgesisa (supraspinal and spinal)
  • respiratory depression
  • physical dependense
  • urinary retention
  • constipation
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37
Q

Allodynia –

A

perception of non-noxious stimuli as pain

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38
Q

Analgesia

A

absence of pain perception

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39
Q

Anesthesia

A

absence of all sensation

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40
Q

Anesthesia dolorosa –

A

pain in an area that lacks sensation

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41
Q

Dysesthesia –

A

unpleasant sensation with or without a stimulus

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42
Q

Epicritic

A

non-noxious sensation

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43
Q

Hypoalgesia –

A

diminished response to noxious stimulation

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44
Q

Hyperalgesia

A

exaggerated response to noxious stimulation

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45
Q

Hyperesthesia

A

increased response to mild stimulation

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46
Q

Hyperpathia

A

persistence of a sensation after the stimulus

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47
Q

Hypoesthesia

A

reduced cutaneous sensation

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48
Q

Neuralgia

A

pain in the distribution of a nerve or group of nerves

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49
Q

Nociception

A

neural response to traumatic or noxious stimuli

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50
Q

Paresthesia

A

abnormal sensation perceived without a stimulus

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51
Q

Protopathic

A

noxious sensation

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52
Q

Radiculopathy

A

functional abnormality of one or more nerve roots

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53
Q

Two distinct classes of opium

A
  • phenanthrenes
  • benzylisoquinoline
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54
Q

What is included in phenanthrenes

A

morphine, codeine, thebaine

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55
Q

what is included in benzulisoquinolines

A

papaverine (control spasm to decrease cerebral ischemia), noscapine

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56
Q

Modifications to morphine molecule result in

A

codeine and heroin…

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57
Q

SYNTHETIC OPIOIDS contains what structure

A

Contain a phenanthrene nucleus

• Synthesized rather than modified

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58
Q

Opioid PO absorption

A

Modestly absorbed orally
• Some undergo significant first-pass effect

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59
Q

synthesized opioid derivatives

A

• Morphine – levorphanol
• Methadone
• Benzomorphan – pentazocine
• Phenylpiperidine – meperidine, fentanyl

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60
Q

what are the fentanyls and they are different in what?

A

Fentanyl, sufentanil, alfentanil and remifentanil

• Different with regards to potency, rate of equilibrium in the plasma, and site of action

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61
Q

Opioid receptors are

A

G protein-coupled receptors

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62
Q

Opioid receptor Principle effect

A

Principle effect is to decrease neurotransmission

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63
Q

Opioids mimic the actions of

A

of endogenous ligands

• Enkephalins, endorphins and dynorphins

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64
Q

name the endogenous ligands

A

Enkephalins, endorphins and dynorphins

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65
Q

Where are opioid receptors located?

A

spine, brain and periphery

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66
Q

Pre synaptic

A

– inhibit release of acetylcholine,

dopamine, norepinephrine and Substance P

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67
Q

Post synaptic –

A

increased K+ conductance = decreased function

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68
Q

May regulate functions of what other ion channels

A

NMDA

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69
Q

Opioids do not work by:

A
  • Block nerve impulses
  • Alter responsiveness of afferent nerve endings to noxious stimulation
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70
Q

Where are opioid receptors in the brain?

A
  • Periaqueductal gray
  • Locus ceruleus
  • Rostral ventral medulla
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71
Q

Where are opioid receptors in spinal cord?

A

Primary afferent and interneurons of the dorsal horn

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72
Q

Four types of opioid receptors

A

Mu
Kappa

Delta

Sigma

73
Q

Opioid Small dose effects terminated through?

• Effects of multiple doses and infusions terminated by?

A
  • Small dose effects terminated through redistribution

• Effects of multiple doses and infusions terminated by metabolism

74
Q

Most opioids are metabolized in? Exceptions?

How are metabolites of opioids?

A

the liver • Exception is remifentanil
• Some opioids have active metabolites

75
Q

Opioids Excreted primarily by

A

the kidneys

76
Q

Opioids COMMON CV SIDE EFFECTS

A

In healthy patients, bradycardia with sustained

B/P

Impairment of SNS response (orthostatic hypotension)

  • Venous pooling
  • Histamine release

Does not sensitize the heart to catecholamines

Synergism with other drugs often causes myocardial effects

  • Benzodiazepines
  • Nitrous oxide

Cardiac protectant effect

• Enhances myocardial resistance to oxidative and ischemic stresses through Sigma and kappa receptors

77
Q

Opioids COMMON RESPIRATORY EFFECTS

  • Opioids produce a _____ depression of ventilation

• Via ____and _____ receptors in the brainstem

  • Interfere with _____ and _____ ventilatory centers

• Regulate ____ and ______ of breathing

  • Decreased responsiveness to _____
    • By decreasing _____ release in the_____center of the brain
    • Shift to the _____ in the CO2 response curve
  • Decreased ____ accompanied by compensation in ____
  • Bronchial effects
    • Decrease ______
    • Increase _______
  • _____ smooth muscle
  • _____ release
  • Factors that affect depression of ventilation:
  • ___
  • ____
  • ____
A
  • Opioids produce a dose-dependent depression of ventilation

• Via mu and delta receptors in the brainstem

  • Interfere with pontine and medullary ventilatory centers

• Regulate rate and rhythm of breathing

  • Decreased responsiveness to CO2
    • By decreasing acetylcholine release in the medullary center of the brain
    • Shift to the right in the CO2 response curve
  • Decreased RR accompanied by compensation in TV
  • Bronchial effects
    • Decrease ciliary action
    • Increase airway resistance

• Bronchial smooth muscle • Histamine release

  • Factors that affect depression of ventilation:
  • Advanced age
  • Natural sleep
  • Pain
78
Q

Opioid cough suppression

A

Depression of medullary cough centers

Codeine (bulky substitution on number 3 carbon position)

Dextromethorphan – dextrorotary – cough suppression without analgesia or respiratory depression

79
Q

Opioid Common CNS effects\

  • Opioids are not ____; ____ possible
  • Most effective for ___ and ____ pain*
  • Sedative and ____ effects; a sedated patient is not pain free
  • Analgesic effects are two-fold:
    • Inhibit ____ transmission of ____ information
    • Activate ____ pathways
  • ____ cerebral blood flow, and possibly ____*
  • Used cautiously in head trauma patients
  • Alter ___
  • ____
  • Depression of ____

• Increased sensitivity when ____ is compromised
-Do not alter effects of ____drugs

Miosis due to action on autonomic nervous system component of _____ of oculomotor nerve

  • Can be antagonized by atropine
  • Severe _____can result in presence of morphine
A
  • Opioids are not anesthetics; awareness possible
  • Most effective for visceral and dull pain*
  • Sedative and euphoric effects; a sedated patient is not pain free
  • Analgesic effects are two-fold:
    • Inhibit ascending transmission of nociceptive information
    • Activate descending pathways
  • Decrease cerebral blood flow, and possibly ICP*
  • Used cautiously in head trauma patients
  • Alter wakefulness
  • Miosis
  • Depression of ventilation

• Increased sensitivity when BBB is compromised
-Do not alter effects of neuromuscular blocking drugs

Miosis due to action on autonomic nervous system component of Edinger-Westphal nucleus of oculomotor nerve

  • Can be antagonized by atropine
  • Severe arterial hypoxemia can result in presence of morphine
80
Q

muscle rigidity

A

Opioids have no effect on nerve conduction

Skeletal muscle hypertonus ”truncal rigidity”
• Following large doses of opioid (phenylpiperidine)
• Related to mu receptors acting on dopamine and GABA channels

  • Evidence supports resistance due to laryngeal musculature contracture
  • Treat with NMB or naxolone
81
Q

Morphine induces _____ that precedes analgesia

• In up to ______of patients

Assumption that ____occurs when ______ is relieved…

A

Morphine induces sedation that precedes analgesia

• In up to 60% of patients

Assumption that sleep occurs when pain is relieved…

82
Q

Opioids on biliary tract and treatment of complication

A

Opioids cause spasm of biliary smooth muscle and the sphincter of Oddi

• Glucagon 2mg, IV will reverse smooth muscle spasm •

Does not antagonize analgesic effects

Morphine can contract of pancreatic ducts

  • Increase in amylase and lipase levels
  • Mimics acute pancreatitis
  • 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

83
Q

Opioids nausea and vomiting

Stimulation of ________ trigger zone in the _____

  • _____receptors
  • ______receptors

Increased ______ and delayed _______

NV not common in _____ patients

• ______ effect?

A

Stimulation of chemoreceptor trigger zone in the medulla

  • Serotonin type 3 receptors
  • Dopamine type 2 receptors

Increased GI secretions and delayed gastric emptying

NV not common in recumbent patients

• Vestibular effect?

84
Q

genitourinary side effects

A

Opioid-induced augmentation of detrusor

muscle tone results in urgency, but tone of urinary sphincter enhanced, making voiding difficult

85
Q

opioid induced cutaneous changes

A
  • Morphine causes blood vessels to dilate

• Warm, flushed skin

  • Histamine release – not an allergy
  • Conjunctival erythema
  • Pruritis
86
Q

opioid PLACENTAL TRANSFER

A

Readily cross the placenta
• Result in neonatal depression
• Morphine greater than meperidine

Chronic use can cause neonatal physical dependence

• Naxolone may precipitate neonatal abstinence syndrome

87
Q

Opioid drug interactions

A

Cholinergic system is a positive modulator of opioid analgesia

  • Physostigmine – enhances
  • Atropine – antagonizes

Ventilatory effects can be exaggerated by other drugs:

  • Amphetamines
  • Phenothiazines
  • MOA’s
  • Tricyclics
88
Q

Long term effect of opioids use?

A

Long-term opioid use activates NMDA receptors • Down regulates spinal glutamate receptors

89
Q

Codeine, what kind of opioid?

A

Naturally occurring opioid

90
Q

chemical structure difference b/w codeine and morphine and significance?

A

(methyl for hydroxyl at 3 carbon)

• limits first-pass hepatic metabolism – can be given orally

91
Q

Codeine

How much % is demythylated into what?

A

approximately 10% O-demethylated into morphine

• Accounts for most of its analgesic ability

92
Q

codeine t1/2

A

3-3.5 hours

93
Q

what other codeine metabolite might have some analgesic effect?

A

codeine-6-glucuronide may have some analgesic effects

94
Q

How is codeine used to treat pain?

A

Weak opioid not used for treatment of severe pain • Usually combined with acetaminophen

95
Q

codeine dosing

A
  • 15 mg – oral cough suppressant
  • 60 mg = 650 mg of aspirin
  • 120 mg IM = 10 mg morphine
96
Q

Codeine side effect

A
  • Mild physical dependence
  • Minimal sedation, nausea, vomiting and constipation
  • Dizziness possible
  • Unlikely to produce apnea
  • Not recommended IV secondary to histamine and hypotension
97
Q

When was meperidine first synthesized? what does meperidine have on its structure?

A

Synthesized in 1939 – phenylpiperdine ring

98
Q

What type of receptor does meperidine work on?

A

Mu-receptor agonist

99
Q

Meperidine CLINICAL USES

What receptor does meperidine work on?

In high dosese, what side effects?

A

Decreased significantly over the years Anti-shivering postoperatively

• Stimulation of kappa receptors

In high doses
• Negative cardiac inotropic effects

• Histamine release

100
Q

meperidine potency compared to morphine

A

1/10 as potent as morphine

101
Q

meperidine DOA

A

2-4 hours

102
Q

meperidine In equal analgesic doses, it produces similar _____ to morphine

A

Sedation, euphoria, nausea, vomiting, depression of ventilation

103
Q

What Limits meperidine oral usefulness

A

Extensive first pass metabolism by liver

104
Q

How’s meperidine metabolized?

A
  • 90% demethylization to normeperidine
  • 10% hydrolysis to meperidinic acid
105
Q

Meperidine excretion

A

Excretion is principle elimination route

  • pH dependent (more acidic, greater fraction of drug excreted unchanged)
  • Decreased renal function can result in accumulation of metabolites
106
Q

meperidine side effects

A

May cause increase in heart rate, mydriasis • Modest atropine-like effects
• HIGH doses decrease myocardial contractility

Delirium and seizures
• Reflects an accumulation of normeperidine (high CNS effects)

May elicit serotonin syndrome in patients taking MAO inhibitor or fluoxetine

Promptly crosses the placenta, may exceed maternal concentrations Less biliary tract spasm
Withdraw develops more rapidly and is shorter in duration

107
Q

Normeperidine:

  • _____as active as meperidine
  • Elimination half-time ____

• ____hours in renal failure

  • Increased sensitivity in ____

• _____ plasma protein = _____ circulating volume
- May be involved in meperidine ____ – seen in patients

receiving drug for ____days (related to accumulation)

  • _______ cannot be recommended
  • Eventually undergoes _______ to meperidinic acid
A
  • 1⁄2 half as active as meperidine
  • Elimination half-time 15 hours

• >30 hours in renal failure

  • Increased sensitivity in elderly

• Decreased plasma protein = increased circulating volume
- May be involved in meperidine delirium – seen in patients

receiving drug for 3+ days (related to accumulation)

  • PCA cannot be recommended
  • Eventually undergoes hydrolysis to meperidinic acid
108
Q

Fentanyl is ________opioid analgesic in anesthesia

A

most widely used

109
Q

Fentanyl has ____ structure

A

Phenylpiperidine ring

110
Q

Fentanyl ____ x more potent than morphine

A

75-125

111
Q

Fentanyl ________ onset and _______ duration of action

  • Lipid ________
  • _______terminates effect of single dose*
A

Rapid onset and shorter duration of action

  • Lipid soluble
  • Redistribution terminates effect of single dose*
112
Q

fentanyl ______responsible for large first pass uptake

A

Lungs responsible for large first pass uptake

113
Q

Fentanyl Extensively metabolized by ____ and _______

• Pharmacologic activity of metabolites is _______

A

Extensively metabolized by N-dealkylation and hydroxylation

• Pharmacologic activity of metabolites is minimal

114
Q
A
115
Q

fentanyl Elimination half-time is _____ than morphine
• ______ Vd – more than ______% leaves the plasma in less than __ minutes

A

Elimination half-time is longer than morphine
• Large Vd – more than 80% leaves the plasma in less than 5 minutes

116
Q

Fentanyl

Elderly

  • _____ elimination time due to________
  • Age-related decreases in

___

___

___

___

A

Elderly

  • Prolonged elimination time due to decreased clearance
  • Age-related decreases in hepatic blood flow, microsomal enzyme activity, and albumin production (highly protein-bound)
117
Q

Fentanyl ____ does not significantly prolong elimination half-time

A

Cirrhosis does not significantly prolong elimination half-time

118
Q

Fentanyl context sensitive half-time increases with infusion >____hours • Reflects _____ and _____ into _____

A

Context sensitive half-time increases with infusion > 2 hours • Reflects redistribution and saturation into inactive tissue sites

119
Q

Fentanyl clinical use:

Block ______ to surgical response

• ____IV dose prior to induction of anesthesia

Analgesia

  • _____IV dose provide analgesia
  • Sudden changes in level of surgical stimulation
A

Block sympathetic stimulation to surgical response • 1-3 ug/kg prior to induction of anesthesia

Analgesia

  • 1-3 ug/kg IV provide analgesia
  • Sudden changes in level of surgical stimulation
120
Q

Fentanyl

Surgical anesthesia as sole anesthetic _______ (dose) to produce surgical anesthesia

_____ hemodynamics, ______cardiac depressant effect, ____histamine

Recall?, respiratory ______post op, lack of ____ to surgical stim at any dose

A

Surgical anesthesia as sole anesthetic

50-150 ug/kg to produce surgical anesthesia

Stable hemodynamics, lack of cardiac depressant effect, no histamine

Recall?, respiratory depression post op, lack of response to surgical stim at any dose

121
Q

Fentanyl

Oral ______
• Peds – ____ min prior to induction ______(dose); preop sedation

A

Oral Transmucosal
• Peds – 45 min prior to induction 15-20 ug/kg; preop sedation

122
Q

fentanyl transdermal
• _____related pain; produce ___, ____ concentration x __ days
• When applied preop and left in place x ___ hr, reduces ______

A

Transdermal
• Cancer related pain; produce long, stable concentration x 3 days
• When applied preop and left in place x 24 hr, reduces IV requirements

123
Q

Fentanyl

SIDE EFFECTS

Similar profile to_____

“Secondary____”

• May reflect release from _____uptake

_____ evoke histamine release; hypotension ____

Bradycardia is ____ prominent

• Carotid sinus ____ control

Associated with modest ____ in ICP d/t ______?

Seizure activity; myoclonus

• Inhibition of _____

Marked synergism with ____and ____

A

SIDE EFFECTS

Similar profile to morphine

“Secondary Peaks”

• May reflect release from pulmonary uptake

Does NOT evoke histamine release;

hypotension unlikely

Bradycardia is more prominent

• Carotid sinus baroreceptor control

Associated with modest increases in ICP

• Vasodilatory?

Seizure activity; myoclonus

• Inhibition of inhibitory neurons

Marked synergism with propofol and versed

124
Q

Sufentanyl

_____analogue of fentanyl

Potency is _____times that of fentanyl

A

Thienyl analogue of fentanyl

Potency is 5-10 times that of fentanyl

125
Q

Sufentanyl clinical uses

Analgesia

• _____dose produces longer analgesia and less respiratory depression than fentanyl

Induction
• Doses required for laryngoscopy may cause chest wall rigidity*

A

Analgesia

• .1-.4 ug/kg produces longer analgesia and less respiratory depression than fentanyl

Induction
• Doses required for laryngoscopy may cause chest wall rigidity*

126
Q

Sufentanyl PK

_____ protein binding compared to fentanyl

  • Alpha 1 _____
  • Enhanced effects in ____

______ terminates effects

  • _____ lipid soluble
  • ____ Vd

Significant first pass ______

A

Extensive protein binding compared to fentanyl

  • Alpha 1 glycoprotein
  • Enhanced effects in neonates

Rapid redistribution terminates effects

  • Highly lipid soluble
  • Increased Vd

Significant first pass pulmonary uptake

127
Q

Sufentanyl PK

Rapidly metabolized by _____ and _____

  • ____ metabolites are inactive
  • ______ – _____ sufentanil

Clearance sensitive to _____

Normal ____ function important to clearance

A

Rapidly metabolized by N-dealkylation and O-demethylation

  • N-dealylation metabolites are inactive
  • O-demethylation – desmethyl sufentanil

Clearance sensitive to hepatic blood flow

Normal renal function important to clearance

128
Q

Alfentanyl

_____ potent than fentanyl; ____ duration of action

____ onset of action after IV administration

  • ___ fraction of unionized drug
  • ____ volume of distribution
A

Less potent than fentanyl; shorter duration of action

Rapid onset of action after IV administration • High fraction of unionized drug
• Small volume of distribution

129
Q

Alfentanyl

PHARMACOKINETICS

_____ onset and _____ due to prompt on-sight equilibration

  • ___% of the drug exists in nonionized form at physiologic pH
  • Principally bound by _____

Metabolized by ___ independent pathways

  • _____ to _____
  • _____ to _____

Vd ____ than fentanyl

A

PHARMACOKINETICS

Rapid onset and offset due to prompt on-sight equilibration

  • 90% of the drug exists in nonionized form at physiologic pH
  • Principally bound by alpha 1 glycoproteins

Metabolized by two independent pathways

  • Piperdine N-dealkylation to noralfentanil
  • Amide N-dealkylation to N-phenylpropionamide

Vd less than fentanyl

130
Q

alfentanyl clinical uses

Dosing
• _____ IV – blunts stimulation of laryngoscopy
• _____ IV – catecholamine response to noxious stimulation

  • __-___ ug/kg IV – produces unconsciousness (induction)
  • combo with inhaled anesthetic ___-____ug/kg/hr
A

Dosing
• 15 ug/kg IV – blunts stimulation of laryngoscopy
• 30 ug/kg IV – catecholamine response to noxious stimulation

  • 150-300 ug/kg IV – produces unconsciousness (induction)
  • combo with inhaled anesthetic 15-150 ug/kg/hr
131
Q

Alfentanyl

SIDE EFFECTS / COMPLICATIONS

Associated with:
• ____ significant decrease BP
• Diminished incidence of ____

  • Acute ____
  • Avoid in untreated _____patients
A

SIDE EFFECTS / COMPLICATIONS

Associated with:
• More significant decrease BP
• Diminished incidence of nausea and vomiting

  • Acute dystonia
  • Avoid in untreated Parkinson’s patients
132
Q

Remifentanyl

Selective ___receptor agonist
• Potent ____ fentanyl
• Blood-brain equilibration like _____

Although it is a phenylpiperdine derivative:

• Structurally different because of ____

Very synergistic with ____

Benefits include:
• _____
• _____
• _____

• _____

A

Selective mu agonist
• Potent like fentanyl
• Blood-brain equilibration like alfentanil

Although it is a phenylpiperdine derivative:

• Structurally different because of ester linkage

Very synergistic with Propofol

Benefits include:
• Brief action
• Titratable
• Does not accumulate

• Rapid recovery

133
Q

remifentanyl CLINICAL USES

Cases requiring___&_____analgesic effect

  • ____ block
  • Direct _____
  • _______

Anesthesia Induction
• ______bolus, followed by and infusion of _____ for _____ minutes prior to induction agent

Analgesia

• ______ IV or _____ug/kg/min

Sedation
• ______ in combination with midazolam ___mg

A

CLINICAL USES

Cases requiring transient profound analgesic effect

  • retrobulbar block
  • Direct laryngoscopy
  • Tracheal intubation

Anesthesia Induction
• 1 ug/kg bolus, followed by and infusion of .5-1 ug/kg/min for 10 minutes prior to induction agent

Analgesia

• .25-1.0 ug/kg IV or .05 – 2. ug/kg/min

Sedation
• .05-.1 ug/kg/min in combination with midazolam 2 mg

134
Q

remifentanyl PK

____ Vd
_____ clearance (will accumulate ____ than other opioids)

• PK ____ in obese and IBW patients

Context sensitive half-time is ____minutes

Metabolized by ______

  • ____ active metabolites
  • Not affected by________ deficiency
  • PK ____ by renal or hepatic failure
A 
Small Vd
Rapid clearance (will accumulate less than other opioids)

• PK similar in obese and IBW patients

Context sensitive half-time is 4 minutes

Metabolized by non-specific plasma esterases

  • No active metabolites
  • Not affected by pseudocholinesterase deficiency
  • PK unchanged by renal or hepatic failure
135
Q

Remifentanyl

SIDE EFFECTS

It is important to administer a ________for postoperative analgesia

Can induce “______” activity

Other effects:
• _____
• _____
• _____

_____ – secondary to acute opioid tolerance

• ____ and ____ can block this

A

SIDE EFFECTS

It is important to administer a longer acting opioid for postoperative analgesia

Can induce “seizure like” activity

Other effects:
• Nausea and vomiting
• Depress ventilation
• Decrease systemic BP

Hyperalgesia – secondary to acute opioid tolerance

• Ketamine and magnesium can block this

136
Q

HYDROMORPHONE

A derivative of ______ (____) • ___ times more potent
• Slightly ____ duration of action

Less ____ than morphine

  • ___ onset
  • ___ sedation
  • ___ euphoria

Effective alternative to treat ______ pain

Can cause ___ and ____

A

HYDROMORPHONE

A derivative of morphine (1926)

  • 5 times more potent
  • Slightly shorter duration of action

Less hydrophilic than morphine

  • Faster onset
  • More sedation
  • Less euphoria

Effective alternative to treat moderate - severe pain Can cause agitation and myoclonus

137
Q

METHADONE

_____ opioid
• ____ opioid in ____ pain settings
• Attractive for ____ and _____

_____ terminal half-life
• Requires ____ dosing

_____ variation among individuals

A

METHADONE

Synthetic opioid
• Oral opioid in chronic pain settings
• Attractive for withdrawal and drug suppression

Long terminal half-life
• Requires infrequent dosing

Large variation among individuals

138
Q

methadone opioid withdrawal

Can substitute for _____ at ____ the dosage
• ____mg IV, produces postoperative analgesia >___ hours

A

Can substitute for morphine at 1⁄4 the dosage
• 20 mg IV, produces postoperative analgesia > 24 hours

139
Q

methadone

SIDE EFFECTS

Similar to ____
• Depression of ___

  • ____
  • _____
  • _____spasm

___ and ____ effects less

A

SIDE EFFECTS

Similar to morphine
• Depression of ventilation

  • Miosis
  • Constipation
  • Biliary tract spasm

Sedative and euphoric effects less

140
Q

methadone

TREATMENT OF CHRONIC PAIN

____ abuse potential

____ antagonist activity may be beneficial for _____ pain

Principle disadvantage is ____ and ____ half-life

• Drug can accumulate and cause ______

A

TREATMENT OF CHRONIC PAIN

Low abuse potential

NMDA antagonist activity may be beneficial for neuropathic pain

Principle disadvantage is prolonged and unpredictable half-life

• Drug can accumulate and cause depression of ventilation

141
Q

Tramadol

Synthetic _____ analog

Can be given ___, ___ or ____ for ____ pain

  • Weak/moderate ___ agonist
  • ___ potent than morphine
  • Useful for ___ treatment – less ___

• Enhances function of ____ inhibitory pathways

Metabolized by _____
• Metabolite _____has _____ analgesic effects

A

TRAMADOL

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 treatment – less addictive

• Enhances function of descending inhibitory pathways

Metabolized by CYP 450
• Metabolite O-desmethyltramadol has modest analgesic effects

142
Q

Tramadol

DISADVANTAGES

Interacts with _____ Drug-related ____ (may lower ____)

High incidence of ______

______may interfere with analgesic component

• Reuptake of _____

A

DISADVANTAGES

Interacts with Coumadin anticoagulants Drug-related seizures (may lower seizure threshold) High incidence of nausea and vomiting

Ondansetron (Zofran) may interfere with analgesic component

• Reuptake of 5-hydroxytryptamine

143
Q

Heroin

____ opioid
Originally claimed to have ____ qualities

Differs from ____ in that it rapidly penetrates the ___where it is hydrolyzed to active metabolites

  • ____
  • _____

Compared to morphine
• More ___ onset
• Less ____
• Greater liability for _____

A

Synthetic 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
  • Morphine

Compared to morphine
• More rapid onset
• Less nausea
• Greater liability for physical dependence

144
Q

OXYMORPHONE

Addition to ____ group to ____

____times as potent as ____
Increased_____
Potential for ____

Can be given ___

A

OXYMORPHONE

Addition to hydroxyl group to hydromorphone 10 times as potent as morphine
Increased nausea and vomiting
Potential for physical dependence

Can be given orally

145
Q

OXYCODONE

Oral agent commonly used for treating ____
____ as potent as morphine, ____ duration of action
Great _____potential…newer preparations prevent ____

A

OXYCODONE

Oral agent commonly used for treating acute pain
Twice as potent as morphine, similar duration of action
Great abuse potential…newer preparations prevent IV injection

146
Q

HYDROCODONE

Oral agent for treating____
____ potency and duration of action to morphine

Potential for ___

A

HYDROCODONE

Oral agent for treating acute pain
Similar potency and duration of action to morphine Potential for abuse

147
Q

PROPOXYPHENE

Oral agent used to treat pain not relieved by ____

_____ absorbed after ____

____ first-pass hepatic metabolism

• ____ to _____

Common side effects
• _____causes severe damage to veins

Mild _____ symptoms

Off the market in ____

A

PROPOXYPHENE

Oral agent used to treat pain not relieved by aspirin

Completely absorbed after oral intake

Extensive first-pass hepatic metabolism

• Demethylation to norpropoxyphene

Common side effects
• IV use causes severe damage to veins

Mild withdrawal symptoms

Off the market in 2010

148
Q

OPIOID AGONIST-ANTAGONIST

These drugs bind to ____ receptors but produce ___ responses or ___ effect

Advantages
• __
• ___

Have a ”___”
• Reserved for patients who _____

A

OPIOID AGONIST-ANTAGONIST

These drugs bind to mu receptors but produce limited responses or no effect

Advantages
• Produce analgesia
• Limited depression of ventilation

Have a ”ceiling effect”
• Reserved for patients who can’t tolerate a pure agonist

149
Q

PENTAZOCINE

_____ derivative
• ___ and ____ receptor agonists

Clinical Uses
• Relief of ____
• Treatment of ____

Pharmacokinetics
• ____ first pass hepatic metabolism
• Metabolism by ____ of ____

Effects are enough to precipitate ___

A

PENTAZOCINE

Benzomorphan derivative
• Delta and kappa receptor agonists

Clinical Uses
• Relief of moderate pain
• Treatment of chronic pain

Pharmacokinetics
• Extensive first pass hepatic metabolism
• Metabolism by oxidation of terminal methyl groups

Effects are enough to precipitate withdraw

150
Q

PENTAZOCINE

Side effects
• ___, ____ and ____

• ____ miosis

Increasing the dose over _____ cause no more effects

Produces increase in _____

___ the placenta; ___ cause______
____ associated with dysphoria, fear of ____

A

PENTAZOCINE

Side effects
• Sedation, diaphoresis and dizziness

• NO miosis

Increasing the dose over 30mg cause no more effects Produces increase in circulating catecholamines

Crosses the placenta; may cause fetal depression
High doses associated with dysphoria, fear of impending death

151
Q

BUTORPHANOL

Limited _____ use

Resembles _____

  • Agonist effects are ____times greater
  • Antagonist effects are ____ times greater

___ affinity for ___ receptors

• Produces antagonism

__ affinity for ___ receptors

• used for ___ and ____

A

BUTORPHANOL

Limited intraoperative use

Resembles pentazocine

  • Agonist effects are 20 times greater
  • Antagonist effects are 10-30 times greater

Low affinity for mu receptors

• Produces antagonism

Moderate affinity for kappa receptors

• Analgesia and anti-shivering

152
Q

butrophanol PK

____ absorbed after ____ injection
Metabolized in ____ and excreted primarily in the___

• ___ (active or inactive) metabolite - ____

Elimination half-time is___

A

Rapidly absorbed after IM injection
Metabolized in liver and excreted primarily in the bile

• Inactive metabolite - hydroxybutorphanol

Elimination half-time is 2.5-3 hours

153
Q

NALBUPHINE

Chemically related to ___ and ____

___ properties of morphine;

___antagonist of nalorphine

Pharmacokinetics
• Metabolized in the ___
• Elimination half-time ____

Antagonist effects occur at ___ receptors

  • If given before an opioid, may ___ effects of ____drugs perioperatively
  • If given after administration of opioid, it can reverse (___hours) ____effects but maintain ___
A

NALBUPHINE

Chemically related to oxymorphone and naloxone

Analgesic properties of morphine; 1⁄4 antagonist of nalorphine

Pharmacokinetics
• Metabolized in the liver
• Elimination half-time 3-6 hours

Antagonist effects occur at mu receptors

  • If given before an opioid, may diminish effects of morphine-like drugs perioperatively
  • If given after administration of opioid, it can reverse (2-3 hours) depression of ventilation effects but maintain analgesia
154
Q

Nalbuphine

SIDE EFFECTS

____ most common
Less ____ than pentazocine and butorphanol

Depression of ventilation has ___ effect (dose)

______ stimulation effects
• May be____in cardiac patients needing sedation and analgesia

A

SIDE EFFECTS

Sedation most common
Less dysphoria than pentazocine and butorphanol

Depression of ventilation has ceiling effect (30 mg)

Catecholamine stimulation effects
• May be beneficial in cardiac patients needing sedation and analgesia

155
Q

BUPRENORPHINE

Derived from _____
• Potent ____ (___ IM = ___ mg Morphine)

Clinical uses
• Postoperative pain related to ___, ___ and ____

A

BUPRENORPHINE

Derived from thebaine
• Potent analgesic (.3 mg IM = 10 mg Morphine)

Clinical uses
• Postoperative pain related to cancer, renal colic and MI

156
Q

Buprenorphine

SIDE EFFECTS

___, ___, ____ and ___ of ventilation

  • Similar to ___ but may be ___
  • Resistant to ___ by ___

Pulmonary ___?

___ Unlikely

Can precipitate ___ in patient taking ___

___ abuse risk

A

SIDE EFFECTS

Drowsiness, nausea, vomiting and depression of ventilation

  • Similar to morphine but may be prolonged
  • Resistant to antagonism by naloxone

Pulmonary edema? Dysphoria Unlikely

Can precipitate withdrawal in patient taking morphine

Low abuse risk

157
Q

DEZOCINE

Opioid ___ similar to morphine
• _____dose
• High ___, moderate ____ receptor affinity

Clinical uses
• _____

Metabolized ____ and eliminated ___ conjugate

Minimal ____ effects
Exhibits a ____ effect for depression of ____

_____ is minimal

A

DEZOCINE

Opioid A-A similar to morphine
• .15mg/kg
• High mu, moderate delta receptor affinity

Clinical uses
• Postoperative pain

Metabolized liver and eliminated glucuronide conjugate

Minimal catecholamine effects
Exhibits a ceiling effect for depression of ventilation

Dysphoria is minimal

158
Q

OTHER OPIOID A-A

Nalorphine
• ____ potency to morphine
• Not used clinically due to ____ effects

Bremazocine
• ____ a potent as morphine

  • Interacts selectively with ___ receptors
  • In animals…no ____, ____
A

OTHER OPIOID A-A

Nalorphine
• Similar potency to morphine
• Not used clinically due to dysphoric effects

Bremazocine
• Twice a potent as morphine

  • Interacts selectively with kappa receptors
  • In animals…no depression in ventilation, physical dependence
159
Q

MEPTAZINOL

____ opioid agonist; selective for ____receptors

  • ___ depression of ventilation
  • ___ onset; duration ____
  • ____oral bioavailability (%)

Pharmacokinetics
• ____ metabolism to inactive glucuronide conjugates

• Excreted by ___

Side Effects
• __ physical dependence,

___miosis, ___constipation
• _____
• ____ be substituted for opioid agonist in physical dependence

A

MEPTAZINOL

Partial opioid agonist; selective for mu1 receptors

  • NO depression of ventilation
  • Rapid onset; duration <2 hours
  • Low oral bioavailability (<10%)

Pharmacokinetics
• Liver metabolism to inactive glucuronide conjugates

• Excreted by kidneys

Side Effects
• No physical dependence, miosis, constipation
• Nausea and vomiting
• Cannot be substituted for opioid agonist in physical dependence

160
Q

OPIOID ANTAGONISTS

Opioid agonists with mild _____ changes

• Substitution of an ____ group for a ___ group

Pure ___ antagonists include

  • __
  • __
  • ___
A

OPIOID ANTAGONISTS

Opioid agonists with mild structural changes

• Substitution of an alky group for a methyl group

Pure mu antagonists include

  • Naloxone
  • Naltrexone
  • Nalmefene
161
Q

NALOXONE

Used to treat opioid induced ____, depression of ___ in the ___ due to maternal administration, treat ___overdose, detect suspected ____

Dose ____IV
Short half-life ____minutes

_____(dose) can fix depression of ventilation without affecting analgesia

Oral route ____as potent due to first pass hepatic metabolism

Metabolized by __ by ___ with ____acid

• metabolite _____

A

NALOXONE

Used to treat opioid induced hypoventilation, depression of ventilation in the neonate due to maternal administration, treat deliberate drug overdose, detect suspected physical dependencde

Dose 1-4 ug/kg IV
Short half-life 30-45 minutes

5 ug/kg/hr can fix depression of ventilation without affecting analgesia

Oral route 1/5 as potent due to first pass hepatic metabolism

Metabolized by liver by conjugation with glucuronic acid

• Naloxone-3-glucuronide

162
Q

Naloxone

SIDE EFFECTS

- Reversal of analgesia

• May be possible to titrate to maintain ___ and reverse ____

  • ____
    • May occur simultaneously with awakening or just after

Increased ______activity

  • Sudden onset of ____
  • CV response______
  • Cardiac dysrthythmia – ____

Administration to the opioid dependent parturient may result in _____

A

SIDE EFFECTS

Reversal of analgesia

• May be possible to titrate to maintain analgesia and reverse hypoventilation

Nausea and vomiting
• May occur simultaneously with awakening or just after

Increased sympathetic nervous system activity

  • Sudden onset of pain
  • Tachycardia, hypertension, pulmonary edema
  • Cardiac dysrthythmia – vfib

Administration to the opioid dependent parturient may result in fetal withdrawal

163
Q

Naloxone ROLE IN TX OF SHOCK

In animals, large doses of naloxone improve ____ and _____.

Dose _____required, suggesting effects are not _____, or mediated by __ and __ receptors

A

ROLE IN 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

164
Q

NALTREXONE

Oral _____ with sustained effects > ____hours

Used in treatment of ____

A

NALTREXONE

Oral antagonist with sustained effects > 24 hours

Used in treatment of alcoholism

165
Q

NALMEFENE

____ opioid antagonist
• 6-methylene analogue of _____
• _____ IV until effect achieved (MAX dose ____)

_____ potent to naloxone

Prophylactic administration decreases _____and ____ in patient with IV PCA

PRIMARY ADVANTAGE – ____ duration of action

A

NALMEFENE

Pure opioid antagonist
• 6-methylene analogue of naltrexone
• 15-25 ug IV until effect achieved (MAX dose 1ug/kg)

Equipotent to naloxone

Prophylactic administration decreases N&V and pruritis in patient with IV PCA

PRIMARY ADVANTAGE – longer duration of action

166
Q

Nalmefen PHARMACOKINETICS

Metabolized in the ___ by ____

Side effects
• _____seen

A

PHARMACOKINETICS

Metabolized in the liver by hepatic conjugation

Side effects
• Pulmonary edema seen

167
Q

METHYLNALTREXONE

______ opioid receptor agonist
____ ionized; ____ to penetrate CNS
Attenuates morphine induced_____

Decreases incidence of _____

A

METHYLNALTREXONE

Quaternary opioid receptor agonist
Highly ionized; difficult to penetrate CNS
Attenuates morphine induced delayed gastric emptying

Decreases incidence of nausea

168
Q

ALVIMOPAN

Newer ________opioid antagonist

  • Oral bioavailability ____%
  • Relies on ______ for metabolism

Treat ____ and opioid-induced ____

Increase in ______with long-term use

A

ALVIMOPAN

Newer mu selective oral peripheral opioid antagonist

  • Oral bioavailability 6%
  • Relies on gut flora for metabolism

Treat ileus and opioid-induced constipation Increase in cardiac events with long-term use

169
Q

OPIOID ALLERGY

TRUE opioid allergies are ___

caused by

  • ____
  • ____
  • ______

Fentanyl _____cross-react with morphine _____

• Only____cases of true fentanyl allergy recorded to date

A

OPIOID ALLERGY

TRUE opioid allergies are rare

  • Histamine release
  • Orthostatic hypotension
  • N&V

Fentanyl does not cross-react with morphine derivatives

• Only 3+ cases of true fentanyl allergy recorded to date

170
Q

OPIOID IMMUNE MODULATION

Opioid receptors are present on _____ cells

• ____, ____, ____, _____ and _____

Immunosuppression – depression of ____cell

  • Following ____ exposure
  • ____ withdrawal

_____can impair immune function

A

OPIOID IMMUNE MODULATION

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

171
Q

Opioid

ANESTHETIC EFFECTS

Opioids shown to _____ amount of anesthetic gas required

• Given ____ to surgical incision

A

ANESTHETIC EFFECTS

Opioids shown to decrease amount of anesthetic gas required

• Given prior to surgical incision

172
Q

PATIENT CONTROLLED ANALGESIA

Alternative to ______, allows patient to address own analgesic requirements

Advantages include

• Decreased healthcare provider ____, ____ patient satisfaction, ____ opioid consumption, ___ safety

Studies show PCA provides ____ better analgesia, but better pain ____

Remifentanil PCA in the first stage of labor has been shown to provide ____ analgesia while minimizing____ effects.

A

PATIENT CONTROLLED ANALGESIA

Alternative to intermittent bolus, allows patient to address own analgesic requirements

Advantages include

• Decreased healthcare provider workload, increased patient satisfaction, lower 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 effects.

173
Q

NEURAXIAL OPIOIDS

Opioids placed _____ target _____ receptors in the ____ in the spinal cord

Unlike local anesthetics, neuraxial placement of opioids does not result in ______, _____ or ______

Epidural placement of opioids results in
• ____ receptors and _____ absorption
• Offers minimal to no over IV administration
• Uptake into ___, _____ absorption and diffusion across ___

A

NEURAXIAL OPIOIDS

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
• Uptake into fat, systemic absorption and diffusion across dura

174
Q

NEURAXIAL OPIOIDS

Pharmacokinetics

• Uptake into ___, ____ absorption or diffusion across ___

  • Passage through dura dependent on ____
  • Only ____% of epidural morphine crosses the dura to enter the ____
  • Less lipid soluble drugs more likely to stay in ____
  • Morphine movement cephalad can result in ____ depression of ventilation
  • ___ and ____ can facilitate process
  • Lumbar to cisterna magna (__hours) 4 and lateral ventricles ___hours)

Epidural injection results in ____ blood concentrations produced by IM injection

______ can enhance intrathecal effects of morphine

A

NEURAXIAL OPIOIDS

Pharmacokinetics

  • 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

175
Q

neuraxial opioids

SIDE EFFECTS

Dose dependent

Four classic side effects of neuraxial opioids are
• ____ – most common; seen in OB, ?dose related? most likely

related to _____migration and interaction with _____ nucleus.

  • ______
  • _______–most common in young males,likely due to

interaction of opioid with____receptors in the ___ and
• ____ – most serious side effect, occurs faster

with ___. CSF migration and interaction with ventral medulla (morphine).

  • What monitor device to use?_____
  • ____ effective in attenuating side effects
A

SIDE EFFECTS

Dose dependent

Four classic side effects of neuraxial opioids are
• Pruritis – most common; seen in OB, ?dose related? most likely

related to cephalad migration and interaction with trigeminal nucleus.

  • Nausea and vomiting
  • Urinaryretention–mostcommoninyoungmales,likelydueto

interaction of opioid with spinal cord receptors in the sacrum and
• 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
176
Q

Neuraxial opioids

SIDE EFFECTS

_____
_____rare with neuraxial opioids

Reactivation of ____virus (most likely involves ____migration and interaction with _____ nucleus

____, ____ and ____ (reversible with ____), delay in ____, ____

______ damage (possibly related ______)

A

SIDE EFFECTS

Sedation
Myoclonus rare with neuraxial opioids

Reactivation of herpes virus (most likely involves CSF migration and interaction with trigeminal nucleus

Miosis, nystagmus and vertigo (reversible with naloxone), delay in gastric emptying, priapism

Spinal cord damage (possibly related toxic preservatives)

177
Q

Neuraxial opioids

NEONATAL MORTALITY

Clinically important _____ has been observed in newborns of mother receiving epidural opioids

Concentration of ___, ____ negligible in breast milk

A

NEONATAL MORTALITY

Clinically important depression of ventilation has been observed in newborns of mother receiving epidural opioids

Concentration of fentanyl, sufentanil negligible in breast milk

178
Q

which opioids crosses placenta more easily? meperidine or morphine?

A

morphine

N926 Pharmacology (16 decks)

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