Advanced | Opioids and Clinical application Flashcards by Hashim Abdullah

A 52-year-old female with a history of hypertension and rheumatoid arthritis (ASA II) presents for an elective cataract procedure under monitored anesthesia care (MAC). She has been on antidepressants for the past few weeks. During the procedure, after receiving an IV bolus for shivering, she suddenly develops hypertension, tachycardia, diaphoresis, hyperthermia, confusion, and agitation. Which medication could have MOST likely caused her symptoms?

A. Meperidine

B. Nalbuphine

C. Butorphanol

D. Tramadol

A. Meperidine

This is a classic presentation of Serotonin Syndrome.

Administration of meperidine to patients receiving antidepressant drugs (monoamine oxidase
inhibitors, fluoxetine) may elicit this syndrome.

Stoelting Pharmacology | 6th edit

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Intermediate group of OPIOIDS are the following EXCEPT:

A. Morphine
B. Methadone
C. Oxycodone
D. Sufentanil

D. Sufentanil

Opioids can be classified according to strength or potency based on the plasma concentrations at which they exert their
effects (C50 or the plasma concentration causing a 50% effect).

Strong opioids include fentanyl, sufentanil, and remifentanil.

An intermediate group includes morphine, methadone, oxycodone, and buprenorphine.

Weak opioids include codeine and tramadol

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All opioids show a decrease in plasma concentration with initiation of cardiopulmonary bypass. Which of the following opioid will MOST likely have the highest decrease in plasma concentration during the initiation of cardiopulmonary bypass?

A. Fentanyl

B. Morphine

C. Sufentanil

D. Alfentanil

A. Fentanyl

Stoelting Pharma | 6th edit

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A 10 year old male was admitted to the PACU after an uneventful surgery. 2 hours post-op, He complained of pain at the surgical site. The anesthesia resident upscaled the opioid and gave IV bolus. After several minutes, the patient complained with the same pain score but this time with pruritus and nausea vomiting. Which of the following opioid was most likely used?

A. Codeine
B. Morphine
C. Alfentanil
D. Buprenorphine

A. Codeine

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At the PACU, the anesthesia resident planned to give pain regimen to specifically target nociceptive pain. This type of pain BEST responds to:

A. NMDA receptor antagonists
B. α2-agonists
C. α2–δ subunit calcium channel ligands
D. NSAIDS

D. NSAIDS

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Which of the following are correctly paired with respect to opioid and its receptors:

A. Morphine - Mu1 and Kappa partial-antagonist

B. Meperidine - ORL1 antagonist

C. Fentanyl - Kappa partial antagonist

D. Methadone - Mu1 antagonist

E. Buprenorphine - Mu agonist & Kappa antagonist

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TRUE or FALSE

Tolerance to opioid-induced respiratory depression develops more slowly than tolerance to pain relief

TRUE

Tolerance is a dynamic process and after a long period of abstinence from opioids, the risk of opioid toxicity increases.

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TRUE of Context-Sensitive halftime:

A. This is the time needed for the
opioid’s plasma concentration to decrease by 50% from a steady-state concentration.

B. The value of context-sensitive halftime is ALWAYS constant but is dependent on the duration of the infusion of the opioid.

C. The CSt½ of remifentanil is DEPENDENT of the infusion duration due to its rapid elimination from plasma by nonspecific plasma esterases in plasma

A. This is the time needed for the
opioid’s plasma concentration to decrease by 50% from a steady-state concentration

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Which of the following opioid has the FASTEST ONSET?

A. Alfentanil
B. Fentanyl
C. Remifentanil
D. Hydromorphone

A. Alfentanil

ALFENTANIL has the FASTEST onset time of all opioids (~90 seconds);

pKa = 6.5

It crosses the blood-brain barrier rapidly despite high protein binding.

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The analgesia produced by mu (μ) opioid receptor agonism in the brain is specifically located in:

READ

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In PCA (patient-controlled analgesia), the minimum time interval that must elapse between dose administrations is known as:

A. Lockout Interval
B. Half-life
C. Lockout Rescue
D. Intermittent Bolus Per Interval Time

A. Lockout Interval

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The capacity to experience withdrawal when opioids are tapered or when an opioid reversal agent is given:

A. Addiction
B. Tolerance
C. Dependence
D. Withdrawal

C. Dependence

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While doing a preoperative evaluation, you elicited in the history that the patient is currently taking oral morphine amounting to >60mg/day. This patient is also known as:

A. Opioid-naive
B. Opioid-exposed
C. Opioid-tolerant
D. Opioid-addict

C. Opioid-tolerant

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Perioperatively, holding the oral formulation of Naltrexone for 3 days prior to surgery is imperative and scheduling surgery for at least 4 weeks after the last dose is done. The clinical significance to this is due to which of the following?

A. These patients can experience opioid receptor upregulation due to chronic opioid antagonism with naltrexone

B. These patients can experience opioid receptor downregulation due to chronic opioid antagonism with naltrexone

C. These patient will have an opioid plateau which will require higher dose of opioid agonists

D. These patient will have an opioid plateau which will require lower dose of opioid agonists

A. These patients can experience opioid receptor upregulation due to chronic opioid antagonism with naltrexone

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A 66 year old man with COPD who underwent colectomy 12 hours ago has been receiving an epidural infusion of fentanyl at a rate of 100mcg/hour. Which of the following is least likely to develop?

A. Hypotension
B. Nausea
C. Pruritis
D. Respiratory depression
E. Urinary retention

A. Hypotension

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A 35 year old ASA 1 patient came in for his follow up post-op at the pain clinic. He was given Methadone on top of other analgesics for the management of pain. Which of the following is the equipotent dose of 1 mg IV methadone if to be given through oral route?

A. 1 mg

B. 0.01 mg

C. 10 mg

D. 0.1mg

A. 1 mg

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Equianalgesic conversion ratio for intravenous to epidural/intrathecal varies, depending on the meningeal permeability of the opioid. Which is ACCURATELY paired in terms of the equianalgesic dosing of ppioids in neuraxial routes?

A. 10mg of IV morphine: 0.1mg of epidural morphine

B. A. 1mg of IV hydromorphone: 0.1mg of epidural hydromorphone

C. 100mcg of IV fentanyl: 33 mcg of epidural fentanyl

D. 2mg epidural morphine: 0.1mg of intrathecal morphine

C. 100mcg of IV fentanyl: 33 mcg of epidural fentanyl

When converting from one oral opioid formulation to another, incomplete cross-tolerance between the opioids must be accounted for and the dose reduced accordingly.
Equianalgesic conversion ratio for intravenous to epidural/intrathecal varies, depending on the meningeal permeability of the opioid.

Pubmed | Opioid rotation: the science and the limitations of the equianalgesic dose table

What is the correct order of the following opioids considering its lipophilic properties, from most to least lipophilic?

A. Morphine—Remifentanil—Alfentanil—Sufentanil

B. Sufentanil—Fentanyl—Alfentanil—Morphine

C. Remifentanil—Alfentanil—Fentanyl—Sufentanil

D. Sufentanil—Remifentanil—Alfentanil—Fentanyl

E. Sufentanil—Morphine—Fentanyl—Remifentanil

B. Sufentanil—Fentanyl—Alfentanil—Morphine

phenylpiperidine-derivative synthetic opioid are highly lipophilic in contrast to morphine which is highly hydrophilic.
Alfentanil is an analogue of fentanyl that is less potent (one-fifth to one tenth) and has one-third the duration of action of fentanyl.
The analgesic potency of sufentanil is 5 to 10 times that of
fentanyl, which parallels the greater affinity of sufentanil for opioid
receptors compared with that of fentanyl.

Which of the following statement pertaining to meperidine is MOST ACCURATE?

A. Meperidine is not likely to cause respiratory depression in neonates

B. Meperidine is the opioid of choice when spasm of the spincter of Oddi or increased biliary pressure is to be avoided

C. Naloxone effectively reverses symptoms of neurotoxicity caused by normeperidine accumulation

D. Active metabolite accumulation aft er repeated doses of meperidine is unlikely in patients with normal kidney function

E. Meperidine does not cause miosis

Meperidine does not cause miosis but rather tends to cause mydriasis, reflecting its modest atropine-like actions.
TRIVIA: Meperidine is the only opioid considered adequate for surgery when administered intrathecally (Stoelting’s Pharmacology)

A 70 kg 20 year old athlete receives nitrous oxide and oxygen, thiopental and 1.25mg (25mL) of fentanyl during a knee reconstruction procedure lasting 3 hours. Post-operatively he does not awaken or resume spontaneous breathing for 3 hours. The most likely explanation for the prolonged effect of fentanyl is:

A. Dose dependent elimination half-life

B. Genetically slow biotransformation

C. Large volume of distribution

D. Presence of active metabolic at high concentration

E. Time required for hepatic elimination

Tolerance is NOT effectively developed for which opioid side effect?

A. Euphoria
B. Miosis
C. Nausea and vomiting
D. Sedation

B. Miosis

DICTUM:

Miosis at Constipation do not respect TOLERANCE!

A 50 year old cancer patient is on chronic morphine therapy. He came in for evaluation of what seem to be an age-related cataract. As an anesthesiology resident, you know that one of the potential problem for this patient is TOLERANCE. Which of the following side effect of chronic morphine is NOT subject to tolerance?

A. Analgesia
B. Respiratory depression
C. Constipation
D. Miosis
E. Both C and D

E. Both C and D

DICTUM:

Miosis at Constipation do not respect TOLERANCE!

Compared with morphine, a single epidural administration of fentanyl is associated with:

A. delayed onset of analgesia

B. increased incidence of pruritis

C. increased incidence of respiratory depression

D. longer duration of action

E. more restrictive segmental spread

Which of the following is NOT AN INDICATION of REMIFENTANIL administration?

A. Intraoperative infusion as adjuvant for anesthesia and surgery

B. PCA analgesia

C. Sedation in the ICU

D. Treatment of obstetric labor pain

E. Adjuvant to labor analgesia

A patient with deactivating mutation in the cytochrome P450 2D6 gene may have ineffective analgesia from which of the following opioids? A. Morphine B. Codeine C. Fentanyl D. Methadone

B. Codeine

A 30 year old patient on methadone prescription complained of constipation just barely 1 week from the start of the regimen. In order reverse this side-effect without compromising the analgesic effect, you will MOST likely give: A. Naloxone B. Nalmefene C. Naltrexone D. Methylnaltrexone

D. Methylnaltrexone

When given as a single bolus, FENTANYL produce a more rapid onset and shorter duration of action compared with MORPHINE. This is primarily due to: A. Lipid solubility B. Protein binding C. Volume of distribution D. Context-sensitive half-time

A. Lipid solubility

Dr. Yusoph was on her last day of NORA rotation. While assisting her senior resident in an elective ERCP, the gastroenterologist asked her what drug can be used to produce a relaxation of the sphincter muscles. Dr. Yusoph can ACCURATELY answer the inquiry with which of the following drug? A. Glucagon B. Meperidine C. Atropine D. Nifedipine

A. Glucagon

Opioid-induced muscle rigidity can also be clinically reversed by the following drugs/agents EXCEPT: A. Naloxone B. 0.5 MAC Sevoflurane C. Subanesthetic dose of Midazolam D. Subanesthetic dose of Sodium Thiopental

B. 0.5 MAC Sevoflurane

After a clinical dose of oxycodone for post-operative analgesia, a 19 year old male reports feeling of "euphoria". Which of the following opioid receptors is most likely responsible for the observed effect? A. Mu-1 B. Mu-2 C. Delta D. Kappa

A. Mu-1

Which of the following partial u-opioid agonist has a local anesthetic property and blocks voltage-dependent Na+ channels through the the local anesthetic binding site: A. Buprenorphine B. Alfentanil C. Nalbuphine D. Methylnaltrexone

A. Buprenorphine

The anti-shivering effects of meperidine may reflect stimulation of which particular opioid receptors? A. κ receptor B. mu-1 receptor C. mu-2 receptor D. delta receptor

A. κ receptor Meperidine may be effective in suppressing postoperative shivering that may result in detrimental increases in metabolic oxygen consumption. The anti-shivering effects of meperidine may reflect stimulation of κ receptors (estimated to represent 10% of its activity) and a drug-induced decrease in the shivering threshold (not present with alfentanil, clonidine, propofol, or volatile anesthetics). Stoelting Pharmacology | 6th edit

A 7 year old male is scheduled for elective surgery. You decided to pre-operatively give an oral transmucosal fentanyl in lozenge preparation. This is designed to deliver a target amount of which of the following dosage? A. 1 to 2 μg/kg B. 5 to 20 μg/kg C. 15 to 30 μg/kg D. 2.5 to 5 μg/kg

B. 5 to 20 μg/kg * Fentanyl may be administered as a transmucosal preparation (oral transmucosal fentanyl) in a delivery device (lozenge mounted on a handle) designed to deliver 5 to 20 μg/kg of fentanyl. The goal is to decrease preoperative anxiety and facilitate the induction of anesthesia, especially in children. * In children 2 to 8 years of age, the preoperative administration of oral transmucosal fentanyl, 15 to 20 μg/kg 45 minutes before the induction of anesthesia, reliably induces preoperative sedation and facilitates induction of inhalation anesthesia. Stoelting Pharma | 6th edit

What is primary reason why FENTANYL will less likely result to HYPOTENSION in contrast to MORPHINE?

Unlike morphine, fentanyl, even in large doses (50 μg/kg IV), does not evoke the release of histamine. As a result, dilatation of venous capacitance vessels leading to hypotension is unlikely.

A 40-year-old male is admitted to the Post-Anesthesia Care Unit (PACU) immediately following surgery. General anesthesia with Total Intravenous Anesthesia (TIVA) and a strong opioid were used during the procedure. If the patient exhibits signs of opioid-induced respiratory depression, Naloxone would be the primary treatment to reverse the overdose. Which of the following statements is NOT accurate regarding the reversal of opioid-induced respiratory depression? A. Respiratory depression from opioids occurs at higher receptor occupancy rates than analgesia B. Naloxone causes a parallel leftward shift of the opioid dose–response relationship C. Naloxone antagonizes all the pharmacologic effects of opioids D. The rate of decay of naloxone in plasma is relatively fast resulting in “renarcotization” when used to reverse opioid with a longer plasma half-life than naloxone

B. Naloxone causes a parallel leftward shift of the opioid dose–response relationship * It should be a parallel RIGHTWARD shift of the opioid dose–response relationship * All the other statements are accurate. Barash | 9th edit

A 20-year-old male is admitted to the Post-Anesthesia Care Unit (PACU) immediately following surgery. General anesthesia with Total Intravenous Anesthesia (TIVA) and Remifentanil was used during the procedure. The patient was extubated with stable vitals noted. At the PACU, the patient exhibits signs of opioid-induced respiratory depression but with a relatively hemodynamic stability. If Naloxone is to be used, which of the following will MOST likely restore a spontaneous breathing? A. 80 ug IV as a starting IV bolus B. 10 ug IV as a starting bolus C. cumulative IV bolus dose of more than 400 ug D. All of the above

A. 80 ug IV as a starting IV bolus * opioid concentrations are often just above the threshold for respiratory depression, and intravenous titration of naloxone 40 to 80 μg bolus doses to cumulative doses of less than 400 μg is often sufficient to restore spontaneous breathing. Respiratory depression from opioids occurs at higher receptor occupancy rates than analgesia. Therefore, analgesia is not compromised with careful titration of naloxone to respiratory effect. Barash | 9th edit

Which of the following will LEAST likely respond to an IV bolus of Naloxone in an attempt to reverse the opioid-induced respiratory depression? A. Remifentanil B. Buprenorphine C. Fentanyl D. Morphine C. Methadone

B. Buprenorphine The naloxone titration opioid reversal approach is adequate for most opioids, with the exception of opioids with a high affinity for the MOR, such as buprenorphine or carfentanil. In that case, a continuous naloxone infusion (2 to 4 mg/h) will cause a slow but steady resumption of breathing activity. Barash | 9th edit * Buprenorphine is a partial agonist of μ receptors and shows resistance to reversal from naloxone. (Open anesthesia)

Which of the following is associated with the application of a transdermal fentanyl patch? (A) Achievement of a peak plasma level within one hour (B) Continued uptake after patch removal (C) Dose-independent plasma clearance (D) Tachyphylaxis when used for cancer pain (E) Naloxone-resistant toxicity

(B) Continued uptake after patch removal

Compared with epidural administration of hydrophilic opioids, epidural administration of lipophilic opioids is associated with: (A) earlier onset of pruritus (B) greater motor block when combined with local anesthetics (C) higher incidence of delayed respiratory depression (D) lesser sensitivity to reversal of analgesia by naloxone (E) slower onset of analgesia

(A) earlier onset of pruritus DICTUM: Lipid solubility > faster onset > earlier appearance of side-effects

What is the main reason that a lower dose is needed for intrathecal opioids compared to the epidural route?

Opioids administered in the intrathecal space acts directly on the mu receptors in the spinal cord, thereby requiring a lower dose (5-10 times less than the epidural dose). Neuraxial opioids provide analgesia by acting on mu receptors in the substantia gelatinosa of the spinal cord. Opioids administered in the epidural space must diffuse across the dura to bind to mu receptors in the spinal cord.