Opioid, Opioid agonist/antagonist, antagonist Factoids Flashcards
What is the potency ratio of Sufentanil?
500-1000
How do opioids provide analgesia through the CNS?
Inhibiting the ascending transmission of nociceptive transmission from the spinal cord AND activate pain control pathways from the midbrain
What is the prototype opioid drug?
Morphine
What is the potency ratio of Alfentanil?
10-20
What opioid receptor has the largest concentration?
The Mu receptor has the largest concentration in the cerebral cortex, limbic system, caudate putamen, thalamus, periaqueductal grey matter and pre/post synaptic neurons in the spinal cord.
Where is the highest concentration of Mu receptors?
Periaqueductal Grey Matter
What is the potency ratio of Butorphanol (Stadol)?
5
What cardiovascular effects do opioids have?
Bradycardia with little effect on blood pressure and dose dependent peripheral vasodilation.
What is the most stimulating part of surgery?
Intubation, which means you need more drugs up front.
What is the active metabolite of morphine and in what instance should Morphine use be avoided?
Morphine-6-Glucuronide (M6G) is the active metabolite that prolongs Morphines effects. It should be avoided in renal patients due to decreased elimination.
What is the potency ratio of Codeine?
0.4
What is an undesirable quality of Morphine?
Histamine release, it should be avoided in asthmatics and hemodynamically unstable patients.
What is the metabolite of Meperidine (Demerol) and what’s its disadvantage?
Normeperidine - lowers seizure threshold
What drug potentiates muscle rigidity in Remifentanyl use?
Nitrous Oxide, most significantly seen with chest wall compliance and truncal rigidity.
What is the major benefit to Dilaudid?
There is no known active metabolite, good for use in renal patients.
What opioid receptor reduces shivering, and causes dysphoria, sedation mitosis and analgesia?
Kappa Receptors
What is the potency ratio of Fentanyl and Remifentanyl?
100
What is unique about Fentanyl’s metabolism?
Fentanyl undergoes significant 1st pass effect in the lungs, however clearance is dependent on hepatic blood flow.
Why isn’t Alfentanil widely used?
There is great patient to patient variability, not very predictable.
What is the potency ratio of Buprenorphine?
30
How is Remifentanyl metabolized?
Metabolized by non-specific blood esterases (be aware when giving to patient with cholinesterase deficiency)
What can occur in a chronic drug user when given pain medication?
Down regulation of one receptor causes use of another receptor that isn’t as effective. May have to give more medication to alleviate pain.
What opioid agonist-antagonist has the same potency as Morphine?
Nubaine
How do opioids effect the eyes?
Parasympathetic stimulation of the oculomotor nerve causes vasoconstriction this is known as Miosis (small pupils)
What is the most potent phenylpiperidine?
Sufentanil
Meperidine (Demerol) use is contraindicated with which drug class?
MAOI, significant reaction and possible seretonergic crisis
What is the potency ratio of Meperidine (Demerol)?
0.1
Why aren’t opioids considered anesthetics?
Opioids do not provide amnesia and the patient will have recall if not given another medication
Where are Kappa receptors located in the CNS?
Nucleus raphe mangnus (midbrain)
Hypothalamus
Spinal Cord
Which opioid receptor provides analgesia, mild constipation, urinary retention, and dependence?
Delta Receptors
if a patient is not intubated, how can opioids effect ICP?
Opioids can increase ICP by hypoventilation which causes vasodilation and increased cerebral blood flow
What are the effects of stimulating the Mu opioid receptor?
Analgesia, euphoria, sedation, dependence, respiratory depression, miosis, marked constipation, urinary rentention, bradycardia, pruritus, muscle rigidity and biliary spasm
Where are Delta opioid receptors located in the CNS?
Olfactory centers Cerebral cortex Nucleus accembens Caudate putmen Spinal Cord
True or false, respiratory depression is a very sensitive indicator of opioid effects?
False, respiratory depression is NOT a very sensitive indicator of opioid effects. (the respiratory drive is separate from analgesia)
How do opioids effect the respiratory system?
Opioids produce dose dependent depression of ventilatory response of CO2 by directly affecting the ventilatory centers in the medulla.
What cardiovascular mechanisms are not effected by opioid agents?
Opioids have no effects on myocardial contractility, baroreceptor reflexes and autonomic responsiveness.
What causes generalized hypertonus that is associated with high dose opioids?
Mu receptors and dopamine and GABA pathways
What drugs can relieve the muscle rigidity associated with opioids?
Relieved by muscle relaxants and antagonists (succinylcholine)
What is the least lipophilic opioid agent?
Morphine
Why is Codeine thought to be a weak opioid?
10% is converted to morphine
What opioid is structurally similar to atropine?
Meperidine (Demerol) has antispasmodic properties
What opioid can be given post operatively to reduce shivering?
Meperidine (Demerol), works at the Kappa receptors
What opioid is the most lipid soluble?
Sufentanil
Why shouldn’t we bolus Remifentanil?
Increased risk for muscle rigidity, limits bolus dosing
What opioid can not be used in an epidural?
Remifentanil, it causes glycine neurotoxicity
Define Agonist
Drugs that occupy a receptor and activate them
Define Antagonist
Drugs that occupy receptors but do not activate them, antagonists block receptor activation by agonists.
How do antagonists, agonists and partial agonists effect their receptor sites?
Agonists exhibit unlimited effect
partial agonists reach maximum effect after specific dose
True antagonists never exhibit the clinical effect
What types of drugs have a ceiling effect?
Partial agonists
What does a steep dose response curve indicate?
The drug is more responsive with higher doses, small changes in dose produce large effects
Which drug’s antagonistic affects relates to its ability to displace opioid agonists from their receptors?
Buprenorphine
Which receptor site does Buprenorphine compete for?
Mu
Which antagonist-agonist opioid is an agonist at the Kappa receptor and a weak antagonist at the Mu receptor?
Butorphanol
Why aren’t we as worried about respiratory depression in opioid agonist-antagoinist agents?
Respiratory depression exhibits a ceiling effect in opioid agonist-antagoinist agents
What factors should be considered if you are using an agonist-antagonist as a primary analgesic?
Consider the options for rescue or further treatment of pain
What is a non-selective antagonist at all opioid receptors?
Naloxone, treats opioid induced respiratory depression, pruritus and suspected drug overdose
How should Naloxone be administered?
Naloxone should be given in small incremental doses because it can cause flash pulmonary edema.
Which opioid antagonist has an active metabolite?
Naltrexone
Which agonist antagonist opioid agent causes an increase in cardiovascular effects and why?
Butorphanol causes an increase in circulating catecholamines
Which partial opioid agonist is very slow to dissociate from the opioid receptor?
Buprenorphine, there is not a rescue drug for this, should be used with caution
Where is nociception suppressed in neuraxial opioids?
Lamina II and V cells of the dorsal horn of the spinal cord and Kappa receptors in the substantia gelatinosa
What two side effects are seen more in neuraxial opioids than if the opioid was given IV?
Greater incidence of pruritus and urinary retention
What is the difference between spinal anesthesia and an epidural?
Spinal anesthesia is injected into the CSF on the spinal cord where an epidural is placed in the potential space
What three factors determine opioid uptake from neuraxial anesthesia?
Epidural fat
CSF
Systemic circulation of blood
Why is it beneficial to add epinephrine to a neuraxial opioid?
Epi constricts the vessels decreasing blood flow and keeping the medication in the the affected area longer
What two opioid agents are associated with early respiratory depression in neuraxial anesthesia?
Fentanyl and Sufentanil ( <2 hrs) central circulation
What opioid agent is associate with delayed respiratory depression in neuraxial anesthesia?
Morphine ( >2hrs) ventral medulla
What determines how fast or slow an opioid will take effect in neuraxial anesthesia?
Dependent on the lipid solubility of the drug
What is the major cause of respiratory depression in neuraxial anesthesia?
Additional medication given because time was not allowed for epidural/spinal to work
What is the intrathecal or subarachnoid single dose of Fentanyl?
5-25 mcg
What is the intrathecal or subarachnoid single dose of Morphine?
0.1-0.3 mg
What is the epidural single dose of Fentanyl?
50-100mcg
What is the epidural single dose of Morphine?
1-5mg
What is the epidural continuous infusion of Fentanyl?
25-100mcg/hr
What is the epidural continuous infusion of Morphine?
0.1-1mg/hr
What is the onset and duration of Alfentanil in comparison to fentanyl?
Alfentanil has a more rapid onset and a shorter duration of action than fentanyl.
What type of surgery would warrant the use of Nalbuphene (Nubain) for post-operative pain management?
Brain surgery! Because it reverses sedative qualities.
Why is continuous monitoring important after a dose of Narcan is given?
Because of its short half-life in comparison to opioids, respiratory depression may return once Narcan wears off.
Which opioid agonist-antagonist is useful in the cardiovascular population?
Nalbuphine (Nubian)
What adverse effects does Naloxone have on the body?
Nausea and Vomiting
Increased SNS activity
Pulmonary edema
Sudden death
What drug is often given to drug addicts to prevent the euphoric effects of the drug they abuse?
Naltrexone
Why is the SNS unable to be activated during neuraxial opioid administration?
SNS is inhibited due to blockage of the sympathetic chain ganglia
Where can neuraxial opioids be given?
Can be given via epidural and intrathecal routes
