Opioid 4-28

Question 1

What is the Morphine IM injection onset, peak and DOA?

Answer 1

*Onset 15-30 minutes
*Peak 45-90 minutes
*Duration of effect 4 hours

Question 2

Why does morphine have limited CSF penetration?

Answer 2

• Poor lipid solubility,
• highly ionized at physiologic pH,
• protein binding

Question 3

How is morphine metabolized?

Answer 3

Conjugation with glucuronic acid to form morphine-3-glucuronide and morphine-6-glucuronide (active metabolite)

Question 4

How is morphine eliminated?

Answer 4

Via kidneys

Question 5

What are the cardiovascular effects of morphine, in: supine and normovolemic pt? how about supine to standing?
Bradycardia is due to what?
how about catecholamine?

Answer 5

• Supine and normovolemic patients unlikely to experience myocardial depression or hypotension;
• but supine to standing may cause orthostatic hypotension secondary to blunted sympathetic tone (decreased venous return, cardiac output, and blood pressure).
• Bradycarida is secondary to increase vagal tone in medulla and decreased sinoatrial and atrioventricular node conduction
• Does not sesitize myocardium to catecholamine; tachycardia and hypertension is related to pain response.

Question 6

What cardiovascular change can occur when moving from supine to standing after morphine administration?

Answer 6

Orthostatic hypotension secondary to blunted sympathetic tone (decreased venous return, cardiac output, and blood pressure)

Question 7

What causes bradycardia with morphine use?

Answer 7

Increased vagal tone in medulla and decreased SA/AV node conduction

Question 8

Does morphine sensitize the myocardium to catecholamines?

Answer 8

No

Question 9

What causes tachycardia and hypertension in patients receiving morphine?

Answer 9

Related to pain response, not morphine itself

Question 10

What is a common side effect of morphine?

Answer 10

Histamine release

Question 11

How to prevent histamine release from morphine IV administration?

Answer 11

• Administer no more than 5 mg/minute,
• keep patient supine or slightly head down,
• maintain normovolemia

Question 12

What is the effect of morphine combined with nitrous oxide?

Answer 12

Depressed cardiac output and systemic vascular response

Question 13

What is the effect of morphine combined with benzodiazepines?

Answer 13

Decreased systemic vascular resistance (SVR)

Question 14

How potent is meperidine compared to morphine?

Answer 14

1/10 the potency of morphine (1 mg morphine = 10 mg meperidine)

Question 15

What structural similarity does meperidine have?

Answer 15

Structurally similar to atropine (phenylpiperidine)

Question 16

Meperidine duration of action

Answer 16

2–4 hours

Question 17

How is meperidine metabolized?

Answer 17

Liver demethylation to normeperidine and further hydrolysis to meperidinic acid

Question 18

How is meperidine eliminated?

Answer 18

Excreted via kidneys

Question 19

Normeperidine potency compared to meperidine

Answer 19

Normeperidine is ½ as potent as meperidine

Question 20

Normeperidine elimination half-life in normal vs renal patients

Answer 20

15 hours in normal patients, 35 hours in renal patients

Question 21

What CNS effects can normeperidine cause?

Answer 21

Myoclonus, seizures, hallucinations

Question 22

What postoperative symptom does meperidine suppress?

Answer 22

Postoperative shivering (kappa receptor effect)

Question 23

Is meperidine effective for diarrhea or as an antitussive?

Answer 23

No

Question 24

How potent is fentanyl compared to morphine?

Answer 24

75–125 times more potent (1 mg morphine ≈ 0.01 mg fentanyl or 10 mcg)

Question 25

Fentanyl onset and duration compared to morphine

Answer 25

More rapid onset and shorter duration

Question 26

What percentage of fentanyl undergoes first-pass pulmonary uptake?

Answer 26

75% of the dose

Question 27

How is fentanyl metabolized?

Answer 27

N-demethylation to norfentanyl (less analgesic potency of fentanyl)

Question 28

How is fentanyl eliminated?

Answer 28

Excreted via kidneys

Question 29

What happens to fentanyl's elimination half-life in elderly patients?

Answer 29

Prolonged due to decreased clearance and decreased available albumin for protein binding

Question 30

How do opioids behave during cardiopulmonary bypass?

Answer 30

Plasma concentrations decrease, most significantly with fentanyl

Question 31

Which opioids show more stable plasma concentrations during cardiopulmonary bypass?

Answer 31

Sufentanil and alfentanil

Question 32

Fentanyl dosing for analgesia

Answer 32

1–2 mcg/kg IV

Question 33

Fentanyl dosing for adjuvant anesthesia

Answer 33

2–20 mcg/kg IV

Question 34

Fentanyl dosing for sole anesthesia

Answer 34

50–150 mcg/kg IV

Question 35

What are the advantages of fentanyl?

Answer 35

No direct myocardial depression, no histamine release, suppression of surgical stress response

Question 36

What are the disadvantages of fentanyl?

Answer 36

May not prevent sympathetic responses to pain, possible patient awareness, postoperative ventilatory depression

Question 37

What are the routes of administration for fentanyl?

Answer 37

IM, IV, transmucosal/buccal, transdermal

Question 38

What is the use of transmucosal/buccal fentanyl?

Answer 38

Preoperative anxiety relief, facilitates induction, but increases risk of nausea/vomiting

Question 39

What are the details of the fentanyl transdermal patch?

Answer 39

25–100 mcg/hr patches; peak concentrations reached in ~18 hours

Question 40

What is a side effect of fentanyl related to ventilation?

Answer 40

Persistent or recurrent ventilatory depression

Question 41

How does fentanyl affect baroreceptors?

Answer 41

Blunts carotid sinus baroreceptor reflex to hypotension

Question 42

What is the effect of rapid IV administration of fentanyl?

Answer 42

May cause seizure activity

Question 43

What is the effect of fentanyl on intracranial dynamics?

Answer 43

Modest increase in ICP with decreased MAP and CPP

Question 44

How does fentanyl interact with midazolam?

Answer 44

Potentiates hypnosis and ventilatory depression

Question 45

How does fentanyl interact with propofol?

Answer 45

Decreases required dose of propofol

Question 46

How potent is sufentanil compared to fentanyl and morphine?

Answer 46

5–10x fentanyl potency (1 mcg sufentanil = 10 mcg fentanyl = 1 mg morphine)

Question 47

What is the half-life of sufentanil relative to other opioids?

Answer 47

Intermediate between fentanyl and alfentanil

Question 49

How fast is sufentanil's onset compared to fentanyl?

Answer 49

Sufentanil: 6.2 minutes vs. fentanyl: 6.8 minutes

Question 50

Why is sufentanil's onset rapid?

Answer 50

High lipophilicity

Question 51

How is sufentanil eliminated in elderly patients?

Answer 51

Elimination is prolonged due to decreased clearance

Question 52

What percentage of sufentanil undergoes first-pass pulmonary uptake?

Answer 52

60%

Question 53

Protein binding comparison of sufentanil and fentanyl?

Answer 53

Sufentanil 93% vs. Fentanyl 85%

Question 54

Why are neonates more sensitive to sufentanil?

Answer 54

Low alpha1-acid glycoprotein leads to ventilatory depression at lower doses

Question 55

How is sufentanil metabolized?

Answer 55

Liver N-dealkylation and O-demethylation (desmethyl sufentanil = 10% activity)

Question 56

How is sufentanil excreted?

Answer 56

Via kidneys as metabolites (<1% unchanged)

Question 57

Alfentanil potency compared to fentanyl?

Answer 57

1/5 to 1/10 of fentanyl (1 mcg alfentanil = 0.1 mcg fentanyl)

Question 58

Alfentanil duration of action compared to fentanyl?

Answer 58

1/3 the duration of fentanyl

Question 59

Why is alfentanil onset so rapid?

Answer 59

90% non-ionized at physiologic pH; onset ~1.4 minutes

Question 60

Alfentanil lipid solubility and protein binding vs. fentanyl?

Answer 60

Lower lipid solubility, higher protein binding

Question 61

How is alfentanil metabolized?

Answer 61

Liver piperidine N-dealkylation to noralfentanil, and amide N-dealkylation to N-phenylpropionamide

Question 62

Alfentanil plasma clearance timeline?

Answer 62

96% cleared within 60 minutes

Question 63

Alfentanil urinary excretion?

Answer 63

<0.5% unchanged

Question 64

Why is alfentanil's usefulness limited?

Answer 64

High interpatient variability due to CYP3A4 activity