Opioid and Non-Opioids Flashcards
What is the endogenous ligands for the Mu Opioid Receptor?
A. Endorphin
B. Enkephalins
C. Dynorphins
D. Dykephalins
A - Endorphins.
Endorpins are the endogenous ligands for the Mu Opioid Receptor
Enkephalins are the endogenous ligands for the Delta Opioid Receptor
Dynorphins are the endogenous ligands for the Kappa Opioid Receptor
Match the Mu Receptor Subtype to their subsequent effects.
- Mu-1
- Mu-2
- Mu-3
A. Immune Suppression
B. Analgesia (supraspinal and spinal) & Euphoria
C. Respiratory Depression & Physical Dependence
Answer: 1-B, 2-C, 3- A
The Mu-1 Subtype’s effects include analgesia (supraspinal and spinal), bradycardia, euphoria, low abuse potential, Miosis, hypothermia and urinary retention.
The Mu-2 receptor subtype’s effects include bradycardia, respiratory depression, constipation, physical dependence and analgesia (spinal only).
The Mu-3 receptor subtype’s effects include immune suppression.
Where are the opioid receptors found in the brain? (Choose 3)
A. Periaqueductal Grey
B. Interneurons
C. Locus Coeruleus
D. Dorsal Horn
E. Rostral Ventral Medulla
F. Immune Cells
A, C, E
In the brain, opioid receptors are found in the periaqueductal gray, locus coeruleus and rostral ventral medulla.
In the spinal cord, opioid receptors are found int he primary afferent neurons in the dorsal horn and interneurons
In the periphery, opioid receptors are found in sensory neurons and immune cells
Put the following in the correct order:
1. Modulation
2. Transduction
3. Perception
4. Transmission
2, 4, 1, 3
Signal Transduction occurs when the injured tissue releases a variety of chemicals that activate peripheral nerves and/or cause immune cells to release pro inflammatory compounds. The peripheral nerves transduce this into a action potential
Signal transmission occurs when the pain signal is relayed through the three-neuron afferent pain pathway along the spinothalamic tract
Signal modulation occurs when the signal is modified (inhibited or augmented) as it advances towards the cerebral cortex
Signal Perception describes processing of afferent pain signals in th cerebral cortex and limbic system. It tells us how we “feel” about pain.
What drugs target signal transduction?
NSAIDs, Local Anesthetics, Steroids, Antihistamines and Opioids
What is the most important site of signal modulation?
Answer: The Substantia Gelatinosa
The descending inhibitory pain pathway begins in the periaqueductal gray and the rostroventral medulla. It projects to the substantia gelatinous.
How does gender play a role in PK/PD differences in morphine?
In women, Morphine is associated with:
1. Greater analgesic potency
2. Slower onset of action
3. Longer duration of action
4. Lower postoperative opioid consumption
What cardiovascular effects are seen with opioids?
HR: Bradycardia
BP: Minimal effect of BP in healthy patients
Decreased BP with morphine and meperidine
Dose dependent vasodilation
Baroreceptor reflex is not affected by
Myocardial function: Myocardial contractility not affected
** NOTE: Can be affected when combined with N2O
How do opioids cause respiratory depression?
They shift the CO2 response curve to the right and reduce ventilatory response to CO2. Therefore, this decreases RR and increases the tidal volume.
PaCO2 will increase ICP if ventilation is not maintained
What nucleus stimulation causes pupillary constriction during opioid administration?
Edinger Westphal Nucleus Stimulation
this causes increased PNS stimulation of ciliary ganglion and oculomotor nerve (CN3)
this causes pupillary constriction
NOTE: Tolerance does not develop to miosis
What is tolerance and physical dependence due to?
Tolerance and physical dependence on opioids is likely due to a receptor desensitization and increased synthesis of cAMP. These phenomena are not due to enzyme induction.
In comparison to 10mg morphine, What is the equianalgesic doses of the following?
Meperidine:
Hydromorphone:
Alfentanil:
Remifentanil:
Fentanyl:
Sufentanil:
Meperidine: 100mg
Hydromorphone: 1.4mg
Alfentanil: 1000 mcg
Remifentanil: 100 mcg
Fentanyl: 100 mcg
Sufentanil: 10 mcg
In comparison to 10mg IV Morphine, what is the relative potency of the following?
Meperidine:
Hydromorphone:
Alfentanil:
Remifentanil:
Fentanyl:
Sufentanil:
Meperidine: 0.1
Hydromorphone: 7
Alfentanil: 10
Remifentanil: 100
Fentanyl: 100
Sufentanil: 1000
What are the inactive and active metabolites of morphine?
Inactive: Morphine 3-glucuronide (M3G)
Active: morphine-6-glucuronide (M6G)
Why is morphine a poor choice for people on dialysis?
Answer: Patients on dialysis are unable to excrete M6G, so they are prone to accumulation of this metabolite. A larger concentration gradient between blood and the brain helps M6G enter the CNS (Law of mass action).
This is why renal failure patients are more likely to experience respiratory depression and toxicity after morphine.
What patient populations should meperidine be avoided in? worrisome in?
Meperidine should be avoided in patients on dialysis and the elderly population
Meperidine also reduces the seizure threshold and increases CNS excitability so care should be taken when administering to patients with a seizure history
How is Remifentanil dosed and metabolized?
Hydrolyzed in the plasma by erythrocyte and tissue esterases. It behaves like a drug that has a low volume of distribution.
Remifentanil is ALWAYS dosed at lean body weight.
What opioid receptors does Meperidine stimulate?
Answer: Mu and Kappa Opioid Receptors
Meperidine is a synthetic phenylpiperidine opioid and stimulates the mu and kappa opioid receptors
Stimulation of the kappa receptor reduces postoperative shivering.
NOTE: shivering increases oxygen consumption, so meperidine reduces oxygen consumption in the shivering patient.
What happens when meperidine is co-administered with MAOIs?
Answer: Serotonin Syndrome
Meperidine is a weak serotonin reuptake inhibitor
Since MAO dominates serotonin in the synaptic cleft, co-administration of meperidine with a MAO inhibitor can cause SEROTONIN SYNDROME.
S/sx include:
- Hyperthermia
- AMS changes
- Hyperreflexia
- Seizures
- Death
MAOI include: Phenelzine, isocarboxazid, tranylcypromine
What medication is meperidine structurally similar to?
Answer: Atropine
It exhibits anticholinergic effects such as:
- Tachycardia
- Mydriasis
- Dry mouth
What are some instances that methadone would be useful as a racemic mixture?
Answer:
1. Chronic treatment of opioid abuse (prevention of withdrawal)
2. Chronic pain syndromes
3. Cancer pain.
How does methadone decrease pain?
- Mu receptor agonist
- NDMA receptor antagonist (dextrorotary isomer)
- Inhibits reuptake of monoamines in the synaptic cleft
What is the rare consequence of methadone we need to aware of?
Answer: QT Prolongation
It inhibits the delayed rectifier potassium ion channel (IKr)
This can lead to torsades de pointes
It is prudent to evaluate the patient’s preoperative EKG for a prolonged QT interval if you plan to administer methadone
What is Oliceridine, what does it work on and how should you dose it?
Answer: Oliceridine is an IV opioid analgesic that primarily selects the Mu-opioid receptor. It is indicated for adults with acute pain when other opioid analgesics and alternative treatments fail to provide adequate pain relief.
Dosing:
- Bolus Dosing:
o Loading dose IV: 1-2 mg IV
o Supplemental doses 1-3mg Q1-3H PRN
- PCA dosing:
o Loading dose: 1.5mg
o Demand dose: 0.35 – 0.5mg
o Lockout: 6 minutes
NOTE: Cumulative dose should not exceed 27mg
What are the contraindications to Oliceridine?
Answer: Significant respiratory depression, acute or severe asthma in an unmonitored setting and without resuscitative equipment and GI Obstruction (including paralytic ileus)
Can also cause
- Mild QT interval prolongation
- Risk of hypotension
- Lower seizure threshold
- Serotonin syndrome in patients on serotonergic drugs
Describe skeletal muscle rigidity with opioid administration, what medications it is more common with and how to deal with it?
Answer: Historically called “Chest wall Rigidity” or “Stiff Chest syndrome”. Rapid IV administration of opioids can cause skeletal muscle rigidity.
This condition is more common with potent (lipophilic) compounds such as: sufentanil, fentanyl, remifentanil, and alfentanil
Opioid-induced muscle rigidity is believed to be a result of the Mu-receptor stimulation in the CNS
- Ultimately a result from influencing the dopamine and GABA motor receptor pathways
Best treatment is paralysis and intubation
NOTE: Narcan can also reverse rigidity but giving this prior to surgery seems counterproductive, given that there is a better alternative.
What are some common characteristics of opioid partial agonists?
Produce analgesia with a reduced risk of respiratory depression
Having a ceiling effect beyond which additional analgesia is not possible
Reduce the efficacy of previously administered opioids
Can cause acute opioid withdrawal in the opioid-dependent patient
Can cause dysphoric reactions
Carry a low risk of dependence
Are used in patients who cannot tolerate a full opioid agonist
What are some examples of partial opioid agonists?
“-ocine”
- Pentazocine
- Nalorphine
- Bremazocine
- Dezocine
- Meptazinol
What is Naloxone, and what are some indications for it?
Answer: NALOXONE is the prototype opioid antagonist. It competitively antagonizes the Mu, Kappa and Delta opioid receptors. However, it has the greatest affinity at the Mu-Receptor
Some common indications for naloxone include:
- Acute reversal of opioid-induced respiratory depression
- Reversal of respiratory depression in the neonate whose mother received an opioid
- Treatment of opioid overdose
What must you be careful of with the administration of Naloxone?
Answer: analgesic reversal activates the SNS. This can cause neurogenic pulmonary edema, tachycardia, cardiac dysrhythmias, and sudden death. Slow titration minimizes these effects.
It can also cause nausea and vomiting. Slow titration over 2-3 minutes causes less N/V.
Can cross placenta and precipitate acute opioid withdrawal in the neonate.
What is Methylnaltrexone and what are some key facts about it?
Answer: It has a quaternary amino group that prohibits the passage across the BBB. It does not cause respiratory depression. It is useful for mitigating the peripheral effects of opioids, such as opioid-induced bowel dysfunction.
What is Nalmefene and how is it dosed?
Nalmefene is similar to naloxone except its duration of action is much longer (10H).
It is dosed as 0.1-0.5 mcg/kg.
How does naltrexone differ from Naloxone?
Unlike Naloxone, Naltrexone does not undergo significant first-pass metabolism.
It can be given orally and has a DOA of up to 24H
An extended-release may be used for alcohol withdrawal treatment
It can also be used to maintain recovering opioid abusers.
