Baby Miller Ch. 6: Opioids

Front 1

opioid definition

Back 1

term used to describe any substance, natural or synthetic, which binds specifically to opioid receptors and produces some agonist (morphine-like) effects

Front 2

what is unique about opioids?

Back 2

they produce analgesia without loss of touch, proprioception, or consciousness

Front 3

clinically used opioids and comparative potencies

Back 3

Morphine 1
Meperidine 0.1
Fentanyl 75-125
Sufentanil 500-100
Remifentanil 250

Front 4

what is the potency of opioids related to?

Back 4

the sterochemical structure of the molecule

Front 5

what structure is most active?

Back 5

levoisomers (the left light-bending form of the enantiomers) (the naturally occuring form of morphine is the levoisomer (l-morphine)

Front 6

semisynthetic opioids

Back 6

result from the minor modification of the morphine molecule

Front 7

synthetic opioids

Back 7

contain the phenanthrene nucleus of morphine, but are made rather than just modifying the naturally occuring morphine

Front 8

mechanism of action of opioids

Back 8

act as agonists at stereospecific opioid receptors in the CNS and peripheral tissues, by mimicing endogenous peptide opioid receptor ligands (endorphins) by binding to the opioid receptors which activates pain-modulating (antinoceptive) systems

Front 9

effect of opioid receptor activation

Back 9

increased potassium conductance leading to hyperpolarization of neuron cellular membranes, causing a decrease in neurotransmission due mostly to inhibition of presynaptic neurotransmitter release (esp ACh and substance P)

Front 10

what does depression of cholinergic transmission due to activation of opioid receptors lead to?

Back 10

opioid-induced inhibition of ACh release at nerve terminals results in significant analgesic properties, and the other side effects of opioids, such as respiratory depression

Front 11

types of opioid receptors

Back 11

classified as mu, delta, or kappa

Front 12

mu receptors

Back 12

morphine-preferring receptors, which are principally responsible for supraspinal and spinal analgesia

Front 13

subpopulations of mu receptors

Back 13

mu-1: activation is speculated to be responsible for analgesia

mu-2: responsible for hypoventilation, bradycardia, and physical dependence

Front 14

all responses evoked by mu-1

Back 14

-supraspinal analgesia
-spinal analgesia
-euphoria
-miosis
-urinary retention

Front 15

specific responses due to mu-2 receptors

Back 15

-spinal analgesia
-depression of ventilation
-bradycardia
-constipation
-physical dependence

Front 16

specific responses to kappa receptors

Back 16

-supraspinal analgesia
-spinal analgesia
-dysphoria
-sedation
-miosis

Front 17

specific responses to delta receptor activation

Back 17

-supraspinal analgesia
-spinal analgesia
-depression of ventilation
-urinary retention
-physical dependence

Front 18

what happens in terms of opioids with advancing age?

Back 18

after about 60yo, there is decreasing sensitivity to pain, and enhanced analgesic response to opioids

Front 19

neuraxial opioids

Back 19

opioids can be placed in the epidural or subarachnoid space in order to activate opioid receptors (principally mu receptors) in the substantia gelatinosa of the spinal cord

Front 20

how does analgesia produced by neuraxial opioids differ from that of IV opioids or reginal infiltration of local anesthetic?

Back 20

neuraxial opioids are not associated with sympathetic nervous system denervation, skeletal muscle weakness, or loss of proprioception

Front 21

analgesia produced by neuraxial opioids

Back 21

is dose-related, and is specific for visceral rather than somatic pain

Front 22

epidural vs. subarachnoid dose

Back 22

the epidural dose is 5-10x the subarachnoid dose

Front 23

what does analgesia following epidural placement of opioids reflect?

Back 23

diffusion of the drug across the dura to gain access to mu opioid receptors on the spinal cord, and systemic absorption to produce effects similar to IV opioids

Front 24

speed of onset of analgesia for epidural opioids

Back 24

is related to lipid solubility, with poorly lipid-soluble opioids such as morphine being much slower but with a longer duration of action than lipid-soluble opioids like fentanyl

Front 25

what happens to opioids placed in the epidural space?

Back 25

undergo significant systemic absorption and passage into the subarachnoid space

Front 26

again, what influences penetration of the dura by opioids?

Back 26

lipid solubility, fentanyl and sufentanil pass much more rapidly than morphine

Front 27

blood concentrations of opioids after epidural injection

Back 27

epidural injection of fentanyl, sufentanil, and morphine produce blood concentrations comparable to IM injection of equivalent doses

Front 28

vascular absorption of intrathecal opioids

Back 28

is insignificant

Front 29

what affects cephalad spread of opioids in the CSF?

Back 29

lipid solubility:
-fentanyl and sufentanil are lipid-soluble and thus will have limited cephalad migration due to uptake into the spinal cord
-morphine is less lipid-soluble and will remain in the CSF for transfer to more cephalad locations

Front 30

how do patient actions and positioning affect opioid spread in the CSF?

Back 30

-coughing and straining will affect movement
-patient positioning will not affect movement

Front 31

what are the side effects of neuraxial opioids due to?

Back 31

the presence of the drugs in the CSF and/or systemic circulation

Front 32

most common side effects of neuraxial opioids

Back 32

-pruritus
-nausea and vomiting
-urinary retention
-depression of ventilation
-sedation

Front 33

depression of ventilation due to neuraxial opioids

Back 33

can get early or late depression of ventilation

Front 34

early depression of ventilation due to neuraxial opioids

Back 34

occurs within 2 hours of neuraxial injection

Front 35

late depression of ventilation due to neuraxial opioids

Back 35

typically occurs 6 to 12 hours after epidural or intrathecal injection of morphine, and is due to cephalad spread of the morphine and interaction with opioid receptors in the ventral medulla

Front 36

factors that increase the risk of delayed depression of ventilation

Back 36

-high dose opioids
-low lipid solubility opioids
-concomitant use of either IV or parenteral opioids, or other sedatives
-lack of opioid tolerance
-advanced age

Front 37

it can be difficult to detect depression of ventilation induced by neuraxial opioids, what is perhaps the most reliable sign, and what are some others?

Back 37

-most reliable is perhaps depressed level of consciousness, likely due to hypercarbia

others include:
-low pulse ox indicating arterial hypoxemia, though supplemental oxygen easily treats this
-low respiratory rate (<8)

Front 38

what is the effective treatment of depression of ventilation produced by neuraxial opioids?

Back 38

naloxone

Front 39

what is the prototype opioid agonist?

Back 39

morphine

Front 40

effects of morphine in humans

Back 40

analgesia, euphoria, sedation, and a decreased ability to concentrate

Front 41

morphine effect on pain

Back 41

the cause of the pain persists, but even small doses of morphine increase the threshold to pain, and modify the perception of noxious stimulation so it is no longer experienced as pain

Front 42

which type of pain is best taken care of by morphine?

Back 42

dull continuous pain is relieved better than intermittent sharp pain

Front 43

morphine in contrast to nonopioid analgesics

Back 43

it is good against pain arising from viscera, as well as from skeletal muscles, joints, and pain from intuguement

Front 44

when is analgesia with morphine most prominent?

Back 44

when it is given before the painful stimulus occurs (preemptive analgesia)

-this is pertinent because should consider giving opioids before acute surgical stimulus begins

Front 45

what may happen if morphine is given in the absence of pain?

Back 45

may get dysphoria rather than euphoria

Front 46

clearance of opioids (in general)

Back 46

is principally by hepatic metabolism, but differences in opioid's lipid solubility accounts for the pharmacokinetic differences seen between the opioids

Front 47

morphine routes of administration

Back 47

can be given IM, orally, or IV. Absorption from the GI tract is unpredictable, so orally administered morphine is as well. IM porphine is well-absorbed, and obviously most morphine in the perioperative period is given IV so it bypasses the unpredictability of enteral.

Front 48

IM morphine onset and peak effects

Back 48

-morphine is well-absorbed from IM injections
-get onset of effect in 15 to 30 min
-peak effect in 45-90 min

Front 49

what is the duration of action of IM morphine?

Back 49

4 hours

Front 50

peak effect of IV morphine

Back 50

-the peak effect, meaning equilibration time between the blood and brain, is delayed for morphine compared to other opioids such as fentanyl or alfentanil

-takes 15-30 min

Front 51

IV morphine in the CNS

Back 51

-only a small amount gains access to the CNS, with estimates being that <0.1% of IV morphine reaches the CNS at the time of its peak effect

Front 52

reasons for poor morphine penetration into the CNS

Back 52

-poor lipid solubility
-rapid conjugation (metabolism) with glucuronic acid

Front 53

morphine metabolites

Back 53

there are 2:

-morphine-3-glucuronide
-morphine-6-glucuronide

Front 54

which is active and which is inactive?

Back 54

morphine-3-glucuronide is inactive, while morphine-6-glucuronide is active and may produce analgesia and depression of ventilation

Front 55

1 other consideration with morphine's metabolites

Back 55

morphine glucuronides are eliminated renally, so elimination may be impaired in renal failure patients causing the metabolites to accumulate, resulting in unexpected depression of ventilation

Front 56

morphine effect on CV system in supine patients

Back 56

-morphine, even when given in large doses such as 1 mg/kg IV to supine normovolemic pts is not likely to produce direct myocardial depression or hypotension

Front 57

conversely, morphine effects on the CV system in other patients

Back 57

-in patients changing from sitting to standing it may produce orthostatic hypotension and syncope

Front 58

what is this presumably due to?

Back 58

drug-induced impairment of compensatory sympathetic nervous system responses

Front 59

how else can morphine cause a decrease in BP?

Back 59

due to drug-induced histamine release, especially after rapid IV administration of large doses (note: the synthetic and shirt-acting opioids do not cause histamine release)

Front 60

do opioids sensitize the myocardium to catecholamines?

Back 60

no

Front 61

what happens when opioid agonists are given in combination with nitrous oxide or benzos?

Back 61

get a decrease in systemic blood pressure which is not seen with the administration of any of those agents alone

Front 62

opioids effect on ventilation

Back 62

all cause a dose-dependent depression of ventilation, primarily through agonism of mu-2 receptors, leading to a direct depressant effect on the ventilation centers of the brainstem

Front 63

how is the depression of ventilation by opioids characterized?

Back 63

-decreased responsiveness of the ventilatory centers to CO2, which is reflected by an inc in PaCO2 and displacement of the CO2 curve to the right

Front 64

length of ventilatory depression follwing opioids

Back 64

lasts for several hours

Front 65

effect of high doses of opioids on ventilation

Back 65

may produce apnea, although the patient will still be awake and able to take a breath if asked to do so

Front 66

how is the effect of opioids on ventilation manifested clinically?

Back 66

by a decreased frequency of breaths, with a compensatory inc in tidal volume

Front 67

effect of all opioids on consciousness

Back 67

even in high doses, do not reliably produce unconsciousness, especially in young patients, which emphasizes that they are not true anesthetics

Front 68

effect of opioids on cerebral circulation

Back 68

-in the absence of hypoventilation they act as cerebral vasoconstrictors, so decrease CBF and possilby ICP
-however, have to be careful in pts with head injury as the depression of ventilation caused by opioids and subsequent accumulation of CO2 will cause an unwanted inc in ICP

Front 69

opiods effect on EEG and neuromuscular blocking drugs

Back 69

-do not produce seizure activity on EEG
-do not interfere with neuromuscular blocking drugs

Front 70

what can be seen with larger doses of opioids, especially if they are given rapidly?

Back 70

-skeletal muscle rigidity, especially of the thoracoabdominal muscles, which can be severe enough to interfere with ventilation and oxygenation

Front 71

how should this "stiff-chest syndrome" be dealt with?

Back 71

by giving a NMB or opioid antagonist

Front 72

what is the miosis caused by opioids caused by?

Back 72

their excitatory action on the oculomotor nerve

Front 73

quantification of the contribution of opioid to total anesthetic requirments

Back 73

-can be quantified by looking at the decrease in MAC of volatiles when opioids are present
-they ahve been shown to dec MAC in a dose-dependent manner up to a ceiling (about a 50% dec in MAC), after which no further dec will be seen with increasing doses of opioids

Front 74

what does this last observation imply?

Back 74

that it is doubtful opioid agonists can provide total amnesia reliably in every patient, even in high doses

Front 75

opioid effect on biliary smooth muscle

Back 75

-will cause spasm of biliary smooth muscle, resulting in an increase in intrabiliary pressure causing epigastric distress and biliary colic, which may be mistaken for angina

Front 76

how can this pain be differentiated from angina?

Back 76

-giving nitroglycerine will relieve the pain from both myocardial ischemia and biliary spasm, but naloxone will only relieve the pain from biliary spasm, not myocardial ischemia

Front 77

opioid effect on the GI tract

Back 77

-opioids, especialy morphine, cause decreased peristaltic activity, and increased tone of the pyloric sphincter causing delayed gastric and intestinal emptying

Front 78

opioid effect on the bladder

Back 78

will increase bladder sphincter tone, making it difficult to spontaneously urinate

Front 79

what is the cause of opiod incuded nausea and vomtiing?

Back 79

durect stimulation of dopamine receptors in the chemoreceptor trigger zone in the floor of the 4th ventricle

Front 80

what is supporting evidence for activation of these dopamine receptors as the mechanism of opiod induced nausea and vomiting?

Back 80

the antiemetic efficacy of dopamine antagonists, such as the butyrophenones

Front 81

what else does morphine do centrally in terms of emesis?

Back 81

it depressed the vomiting center of the medulla

Front 82

what is the consequence of this and of the activation of receptors in the chemoreceptor trigger zone?

Back 82

there is less nausea and vomiting with morphine given IV than IM, since IV morphine reaches both the chemoreceptor trigger zone and the vomiting center in the medulla (which it depresses) with equal speed, whereas not with IM

Front 83

what happens when morphine is given to recumbent patients, and what does this suggest?

Back 83

it is relatively uncommon, suggesting a vestibular component might contribute to opioid-induced nausea and vomiting

Front 84

what are the 2 major limitations to the clinical use of opioids?

Back 84

tolerance and dependence

Front 85

tolerance

Back 85

the development of the need to increase the dose of opioid to achieve the same analgesic effect previously achieved by a lower dose

Front 86

how long does it usually take tolerance to develop?

Back 86

2-3 weeks, although continuous IV infusions of opioids in pain-free animals have shown a profound decrease in analgesia in 2-8 hours

Front 87

which specific effects of opioids persist, and which do not with tolerance?

Back 87

-the miotic and constipating effects persist
-the depression of ventilation does not

Front 88

opioid dependence

Back 88

-addiction
-when the opioid is withdrawn, a typical withdrawl abstinence syndrome of diaphoresis, insomnia, restlessness, and abdominal cramps occurs within 15-20 hours, with a peak in 2-3 days

Front 89

opioids and the immune system

Back 89

-opioids and endogenous opioid peptides modulate the immune system, as shown by alterates in things like neutrophil chemotaxis, phagocytic activity, and the secretion of cytokines
-a link is provided between pain and immunity by the fact that the PNS and CNS are involved in immune function

Front 90

meperidine

Back 90

a synthetic opioid that is 1/10 as potent as morphine

Front 91

what is meperidine structurally similar to?

Back 91

atropine, it even has a mild stropine-like antispasmodic effect

Front 92

what happens well with meperidine that doesnt with morphine?

Back 92

meperidine is well absorbed from the GI tract

Front 93

meperidine metabolites

Back 93

-the principle metabolite is normeperidine, and it produces CNS stimulation at high concentrations

Front 94

what is unique about meperidine among opioids, and how is this thought to happen?

Back 94

it is uniquely effective at suppressing post-op shivering, which is thought to be due to stimulation of kappa receptors

Front 95

differences in CV system effects of meperidine vs. morphine

Back 95

-with meperidine, orthostatin hypotension is more frequent and profound
-meperidine, unlike morphine, rarely causes bradycardia, but may cause an increase in HR similar reflecting its atropine-like effects

Front 96

what do large doses of meperidine result in (also unique among opioids)?

Back 96

decreases in myocardial contractility

Front 97

fentanyl

Back 97

a synthetic ipioid agonist structurally related to meperidine

Front 98

potency of fentanyl

Back 98

75-125 more powerful than morphine

Front 99

onset and duration of action of fentanyl vs. morphine

Back 99

IV fentanyl has a more rapid onset and shorter duration of action than morphine

Front 100

metabolism of fentanyl

Back 100

is a substrate for the CYT P450 enzymes (CYP3A), and is susceptible to drug interactions that reflect interference with enzyme activity (though this is less likely than with alfentanil)

Front 101

onset of fentanyl

Back 101

despite the impression that it has such a rapid onset, there is a distinct time lag between the peak plasma concentration and the peak slowing on the EEG, which reflects the effect-site equilibrium time between the blood and brain, which is 6.4 min

Front 102

why is fentanyl more potent and shorter acting than morphine?

Back 102

-the greater potency and more rapid onset reflect greater lipd solubility which facilitates passage across the blood brain barrier
-the short duration of action reflects rapid redistribution to inactive tissues like fat and skeletal muscles, with associated dec in plasma concentration

Front 103

multiple IV doses/infusion of fentanyl

Back 103

during either of these there is progressive saturation of inactive tissue sites, causing the plasma concentration of the drug to NOT drop rapidly, so the duration of analgesia and the depression of ventilation may be prolonger

Front 104

context sensitive half-time of fentanyl

Back 104

when the duration of continuous infusion increases beyond 2 hours, the CSHT becomes greater than sufentanyl

Front 105

side effects of fentanyl vs. morphine

Back 105

resemble the side effects of morphine, except that histamine release and hypotension dont occur, even with rapid IV boluses

Front 106

other side effects of fentanyl

Back 106

-prior administration of a benzo, and possibly other IV and inhaled anesthetics, alters the CV response to fentanyl, so that bradycardia becomes prominent when fentanyl is given

Front 107

fentanyl with benzos

Back 107

-analgesic doses of fentanyl greatly potentiate the effects of other depressant/sedatives (ie. benzos), causing marked synergism of hypnosis and depression of ventilation

Front 108

other drug interactions with fentanyl

Back 108

any drugs that inhibit the CYP4503A4 enzymes, such as the protease inhibitor ritonavir, can delay clearance of fentanyl, resulting in prolonged effects of the opioid

Front 109

uses of fentanyl

Back 109

can be administered in a wide range of doses for a wide range of effects

Front 110

low doses of fentanyl

Back 110

(1-2 ug/kg IV)

-are used to provide analgesia
-if given before surgical stimulation may decrease the subsequent amount necessary (preemptive analgesia)

Front 111

medium dose fentanyl

Back 111

(2-20 ug/kg IV)

-may be given as an adjuvant to inhaled anesthetics to blunt circulatory responses to direct laryngoscopy for tracheal intubation, or sudden changes to surgical stimulation

Front 112

opioids given after surgical stimulation

Back 112

-are frequently not useful intraoperatively after surgical stimulation has already evoked systemic hypertension
-though intraop tachycardia may respond to small IV doses

Front 113

what should you consider in terms of the timing for treating things such as intraoperative tachycardia?

Back 113

the effect-site equilibrium time, which for fentanyl is 6.4 minutes (and is prolonged when compared to alfentanil and remifentanil)

Front 114

high dose fentanyl

Back 114

(50-150 ug/kg IV)

-can be used alone to produce surgical anesthesia

Front 115

what is the advantage of using opioids for surgical anesthesia?

Back 115

they give stable hemodynamics

Front 116

what is the disadvantage?

Back 116

possible patient awareness, as opioids are not complete anesthetics

Front 117

other routes of administration of fentanyl

Back 117

can be given intranasally or transdermally

Front 118

sufentanil

Back 118

a fentanyl analog, which is 5-10x as potent as fentanyl, and 500-1000x as potent as morphine

Front 119

effect-site equilibrium time of sefentanil

Back 119

similar to fentanyl, about 6.2 min

Front 120

termination of effect of sufentanil

Back 120

-small doses are temrinated by rapid redistribution to inactive tissues
-large or repeated doses can result in a cumulative effect; after an infusion is terminated the plasma concentration decrease is accelerated by metabolism and continued redistribution to peripheral compartments

Front 121

sufentanil context sensitive half-time

Back 121

-is less than alfentanil for infusions up to 8 hours

Front 122

context sensitive half-time of opioids

Back 122

Front 123

how do the effects of sufentanil compare to fentanyl?

Back 123

depression of ventilation and bradycardia may be more profound with sufentanil

Front 124

again, what can large doses of potent opioids, such as sufentanil, cause?

Back 124

skeletal muscle rigidity, especially of the thoracic muscles, possibly making ventilation difficult

Front 125

alfentanil

Back 125

-fentanyl analog
-1/5-1/10 as potent, with 1/3 the diration of action of fentanyl

Front 126

what is the unique advantage of alfentanil over fentanyl or sufentanil?

Back 126

the more rapid onset of action (effect-site equilibrium is about 1.4 min)

Front 127

why is alfentanil quicker?

Back 127

-due to its low pK, so almost 90% of it exists in the lipid-soluble nonionized form at physiologic pH

Front 128

consequences of the rapid peak effect of alfentanil

Back 128

makes it useful to blunt the response of a single, brief stimulus, such as tracheal intubation, or retrobulbar block

Front 129

clearance of alfentanil

Back 129

-there is a 10-fold variation in interindividual systemic clearance of alfentanil as reflected in showing widely varying plasma concentrations after fixed doses
-likely reflects differences in CYP3A4 enzyme activity between individuals

Front 130

remifentanil

Back 130

-opioid with potency similar to fentanyl (250x morphine, vs. 75-125 for fentanyl)

Front 131

remifentanil effect-site equilibrium time

Back 131

similar to alfentanil, is about 1.2 min

Front 132

structure of remifentanil

Back 132

-is unique among opioids because of its ester linkage, which makes it susceptible to hydrolysis by nonspecific plasma and tissue esterases to inactive metabolities

(note these are different from pseudocholinesterase which hydrolyzes sux and mivacurium)

Front 133

consequences of this structure

Back 133

gives remifentanil brevity of action, precise and rapid titratability, noncumulative effects, and a rapid recovery after IV infusion is discontinued

Front 134

context sensitive half-time of remifentanil

Back 134

is independent of the duration of the infusion, and is about 4 minutes

Front 135

uses of remifentanil

Back 135

-can be used for induction, giving 1 ug/kg IV over 60 to 90 seconds
-can be used as the analgesic component of general anesthesia, giving 0.5-2 ug/kg/min IV, or as a sedation technique with this

Front 136

what should you do when stopping remi?

Back 136

give a long-acting opioid to ensure analgesia once remi has quickly worn off

Front 137

remifentanil combined with what is especially synergistic?

Back 137

when combined with propofol, resulting in severe depression of ventilation

Front 138

how can remifentanil be effectively used for labor and delivery?

Back 138

intermittent administration as PCA

Front 139

what unwanted effect can occur after remifentanil infusion?

Back 139

-analgesic requirements postop in patients getting remifentanil intraop are surprisingly high, suggesting it may cause acute opioid tolerance (though not all data supports this)

Front 140

opioid agonist-antagonists

Back 140

-drugs that bind to mu receptors where they produce limited responses (partial agonists) or no effect (antagonist)
-they often exert partial agonist effects at kappa and delta receptors

Front 141

specific opioid agonist-antagonists

Back 141

include:

-pentazocine
-butorphanol
-nalbuphine
-buprenorphine
-nalorphine

Front 142

what are the positives and negatives of the antagonist properties of these?

Back 142

-they lessen the efficacy of subsequently administered drugs
-but, they also have the advantage of providing postop analgesia with the hope of less associated depression of ventilation

Front 143

side effects of opioid agonist-antagonists

Back 143

are similar to opioids, and in addition they may cause dysphoric reactions

Front 144

advantages of opioid agonist-antagonists

Back 144

can produce analgesia with minimal depression of ventilation, and with less physical dependence

Front 145

dosing of opioid agonist-antagonists

Back 145

exhibit a ceiling effect, with increasing doses beyond a certain point not producing any other pharmacologic effects

Front 146

opioid antagonists

Back 146

-minor changes to the structure of opioid agonists can make drugs opioid antagonists
-they have high affinity for opioid receptors, resulting in displacement of opioid agonists from mu receptors, without activation of the mu receptors

Front 147

specific list of opioid antagonists

Back 147

-naloxone
-nalmefene
-naltrexone

Front 148

naloxone dose

Back 148

1-4 ug/kg IV

Front 149

duration of action of naloxone

Back 149

-is short, 30-45 min, and may result in its rapid removal from the brain with return of opioid effects unless more doses of naloxone are given

Front 150

alternative administration form of naloxone

Back 150

can be given as a continuous infusion (3-5 ug/kg/hr IV)

Front 151

side effects of naloxone

Back 151

are basically the result of increased sympathetic activity due to the reversal of analgesia and sudden perception of pain; include:

-tachycardia
-systemic hypertension
-pulmonary edema
-cardiac dysrhythmias, including V-fib

Front 152

bottom line in terms of pK of opioids

Back 152

alfentanil is the lowest, and remifentanil is also relatively low, resulting in their rapid effect-site equilibrium

Front 153

bottom line in terms of percent of nonionization of opioids

Back 153

alfentanil has the highest percentage, resulting in the same thing as above

Front 154

context sensitive half-times of the fentanyl derivatives

Back 154

fentayl: 6.8 min
sufentanil: 6.2
alfentanil: 1.4
remifentanil: 1.1

Front 155

onset, peak intensity, and duration of morphine withdrawal

Back 155

onset: 6-18 hours

peak intensity: 36-72 hours

duration: 7-10 days

Front 156

onset, peak intensity, and duration of heroin withdrawal

Back 156

onset: 6-18 hours
peak intensity: 36-72 hours
duration: 7-10 days

Front 157

onset, peak intensity, and duration of meperidine withdrawal

Back 157

onset: 2-6 hours
peak intensity: 8-12 hours
duration: 4-5 days

Front 158

onset, peak intensity, and duration of fentanyl withdrawal

Back 158

onset: 2-6 hours
peak intensity: 8-12 hours
duration: 4-5 days

Front 159

onset, peak intensity, and duration of methadone withdrawal

Back 159

onset: 24-48 hours
peak intensity: 3-21 days
duration: 6-7 weeks