General Principles — Liz > Opioids > Flashcards

Opioids Flashcards

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1
Q

Use of Opioids in anesthesia: (6)

A
  1. Preoperative pain management
  2. Monitored Anesthesia Care (sedation)
  3. Induction (depends on the case and pt)
  4. Adjunct to anesthesia
  5. Intraoperative pain control
  6. Postoperative pain control
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2
Q

How are opioids classified? (5)

A
  1. Synthesis
  2. Chemical structure
  3. Potency
  4. Receptor binding
  5. Effect at the opioid receptors
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3
Q

Synthesis: Morphine

A

Natural (derived from opium which was isolated from poppy plant)

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4
Q

Synthesis: Hydromorphone

A

Semi-synthetic

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5
Q

Hydromorphone Brand

A

Dilaudid

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6
Q

Synthesis: fentanyl

A

Synthetic

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7
Q

Synthesis: alfentanil

A

Synthetic

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8
Q

Synthesis: sufentanil

A

Synthetic

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9
Q

Synthesis: remifentanil

A

Synthetic

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10
Q

Synthesis: meperidine

A

Synthetic

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11
Q

Strong Potency Opioids

A

Fentanyl, alfentanil, sufentanil, remifentanil

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12
Q

Medium potency opioids

A

Morphine, hydromorphone

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13
Q

What physiochemical properties affect the passage of the drug into the brain across the blood-brain barrier? (4)

A
  1. Molecular size
  2. pKa
  3. Protein binding
  4. Lipid solubility
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14
Q

The pKa of a drug affects…

A

The degree of ionization of the molecule based on the plasma pH

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15
Q

Primary plasma proteins that bind to drugs (acid vs alkaline)

A

Albumin (acidic drugs)

alpha-1-acid glycoprotein

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16
Q

Fentanyl degree of volume distribution and protein binding (not numbers)

A

High Vd, Low protein-binding

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17
Q

Remifentanil volume of distribution? Explain what affects this.

A

Low volume of distribution due to high clearance and/or high protein binding
Low pKa 7.1 also contributes to it’s distribution

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18
Q

The synthetic drugs are called

A

Piperidines

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19
Q

Non-opioid drug that binds to opioid receptors? (Basic concepts right now)

A

Ketamine: NMDA antagonist

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20
Q

What are the opioid receptors?

A

Mu-1

Mu-2

Kappa

Delta

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21
Q

Mu-1 clinical effects

A

Supraspinal analgesia

Bradycardia

Sedation

Pruritus

N/V

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22
Q

Agonists examples that bind to mu-1 receptors (not all are here just 3)

A

Morphine

Meperidine

Fentanyl

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23
Q

Mu-2 Clinical effects

A

Respiratory depression

Euphoria

Physical dependence

Pruritis

Constipation (intestinal lumen)

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24
Q

Examples of agonists that bind to Mu-2 (not all are here just 3)

A

Morphine

Meperidine

Fentanyl

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25
Kappa clinical effects
Spinal analgesia Respiratory depression Sedation Miosis
26
Example of opioid agonists that bind to Kappa receptor (not all are here just 3)
Fentanyl Morphine Nalbuphine
27
Delta receptor clinical effects
Spinal analgesia Respiratory depression
28
Examples of agonists that bind to delta receptors (not all are here just 3)
Oxycodone Beta-Endorphin Leu-enkephalin
29
Piperidines lipophilicity and onset of action (general not exact)
Lipophilic and rapidly cross BBB
30
Fentanyl, alfentanil, and sufentanil location of metabolism and general metabolic pathway.
Metabolized in the liver and catalyzed by the cytochrome P450 enzyme system
31
How much more potent is fentanyl than morphine
100x
32
Use of fentanyl intraoperatively
Blunt sympathetic (cardiovascular) responses to noxious stimulation resulting from laryngoscopy, intubation, skin incision, and surgical stress
33
Requirements for inhalational and propofol after fentanyl administered.
Reduced by about 50%
34
Dosing for fentanyl (general)
1-2 mcg/kg IV
35
Duration of action of fentanyl
About 10-20 minutes (dose dependent also depends on context sensitive half life)
36
What derivative of fentanyl is Sufentanil?
thienyl derivative
37
How much more potent is Sufentanil than fentanyl?
10x more potent
38
How much more potent is sufentanil than morphine?
1000x
39
How much times greater is Sufentanil’s lipophilicity than fentanyl’s?
2x greater
40
How much more potent is Remifentanil than morphine?
100 to 200 x more potent
41
How is Remifentanil metabolized?
metabolized by plasma esterases and nonspecific tissue esterases
42
What does Remifentanil have in its chemical structure that allows it to be metabolized by plasma esterases?
Methyl ester side chain
43
Remifentanil context-sensitive half life
2-3 minutes; most rapidly acting opioid currently available
44
Remifentanil Clearance? What does this mean?
3-5 L/min which exceeds liver blood flow, affirming extrahepatic clearance
45
How is Remifentanil typically administered?
IV infusion due to rapid clearance.
46
Remifentanil: how quickly are plasma levels decreased by 50%?
As little as 40 seconds
47
Why does Remifentanil cause opioid-induced hyperalgesia (OIH)?
1. Rapidly metabolized and does not provide analgesia as soon as the infusion is discontinued (Wash-out effect) 2. NMDA upregulation (activation of the central glutaminergic system) - which is why ketamine can help prevent 3. Central nitric oxide production 4. Facilitation of descending pronociceptive systems
48
what receptor does hydromorphone agonize?
Mu
49
Hydromorphone dilution (2mg/1mL) mixed with 9cc of NS in a 10 cc syringe yields:
.2mg/mL
50
Morphine metabolized by: Morphine metabolites:
Liver (phase II metabolism) Active metabolite: Morphine-6-glucoronide or morphine-3-glucoronide
51
Morphine lipophilicity
Low
52
Morphine excretion?
Renal, some is eliminated in urine without metabolizing due to polarity of chemical structure
53
What types of patients may be at greater risk for respiratory depression resulting from opioids?
Renal dysfunction Hepatic dysfunction Elderly Neonates Drug to drug interactions (inhibitors of CYP3A4 inhibitors)
54
How does opioids induce bradycardia (and hypotension)?
Opioids bind to mu receptors located in the medulla resulting in stimulation of the vagus nerve releasing acetylcholine having direct effect on SA node (bradycardia) Histamine release (hypotension) (Morphine and meperidine)
55
What opioid can causes tachycardia (not compensatory mechanism) and why?
Meperidine because it is structurally similar to atropine
56
Opioids may cause __________ ___________ by inducing contraction of the sphincter of Oddi.
Biliary colic
57
How do opioids induce N/V?
Stimulates the CTZ-(chemoreceptor trigger zone) in the postrema of the brain stem.
58
Risk factors for PONV with opioids?
1. Increased sensitivity of the vestibular apparatus (frequently car sick) 2. Female gender 3. Nonsmoker 4. Direct effects on GI tract 5. PONV history
59
Do opioids transfer from placenta to fetus?
Yes
60
Do opioids transfer through breast milk?
Yes
61
What PMH is especially important in the delivery of opioids. What is the mechanism?
OSA: opioids decrease central hypoxic drive to breathe and CO2 sensitivity
62
Which opioids cannot be given with MAOIs?
Meperidine (Demerol)
63
Risk factors for Chest wall rigidity syndrome (wooden chest syndrome) (6)?
1. High cumulative doses of fentanyl (10-15mcg/kg) 2.Extremes of age 3. Concomitant use of meds that modify dopamine levels (parkinson drugs) 4. Rapid IV admin 5. Critical illness 6. Lipophilic opioids (fentanyl, remifentanil, sufentanil)
64
Treatment options for opioid induced chest wall rigidity?
Treatment with a muscle relaxant or reverse with a full dose of Narcan
65
What med modifies dopamine levels and for what disease process (just one drug)
Pramipexole (Mirapex) for Parkinson’s
66
Does narcan have a higher affinity to opioid receptors?
Yes
67
Duration of effect of Narcan?
15-45 minutes (relatively short requiring redosing or infusion)
68
How do you titrate Narcan infusion?
40mcg titrated q1-2minutes until adequate respirations/ventilation
69
Narcan MOA
Displaces opioid from mu receptors.
70
Adverse effects of reversing the effects of opioids with Naloxone?
Sudden pain Pulm. Edema Cardiac arrythmias HTN Seizures Cardiac arrest
71
What could mimic Narcotic overdose?
Muscular blockade, too much CO2
General Principles — Liz
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