Week 2-Specific Opioid Agonists/Antagonists Flashcards
What type of pain is morphine more effective in relieving?
Continuous, dull pain is relieved by Morphine more effectively than is sharp, intermittent pain
Rank the following medications from lowest to highest potency: Morphine Merperidine Hydromorphine Methadone Fentanyl Sufentanil
Merperidine (0.1) Methadone and morphine (1) Hydromorphone (5-8) Fentanyl (100) Sufentanil (1000)
The effect of an opioid (as in peak effect) is proportional to the concentration at ______, not the plasma concentration.
the effect site
What effects drug onset?
Drug onset will depend on the effect being measured (e.g., incisional vs. postoperative pain, etc.), the opioid dose administered, and any pre-existing opioid concentrations.
What effects the absorption of a drug?
its lipid solubility and inversely on its polarity or degree of ionization
What is produced from morphine metabolism?
5-10% results in active metabolite: morphine-6-glucuronide (M6G)
What is elimination half life?
Elimination half-time is time necessary forplasmaconcentration of a drug to fall to 50% during the elimination phase
… is independent of the dose administered
Review opioid agonists. ``
Slide 62
What is context-sensitive half-time?
Context-sensitive half-time is time necessary for plasma concentration of a drug to fall to 50% aftera continuous infusion of a specific duration
What is effect site equalibration time?
Effect-site equilibration time is the half-time of equilibration between the drug concentration in plasma and the drug effect
Review peak effect slide.
Slide 73
What is codeine used for?
Used mainly for antitussive effects
What is the PK of codeine?
PRO-drug converted to Morphine (10%) in the liver
What impact does the liver have on codeine?
Limited first pass hepatic effect
What effect does liver failure and opioids have on one another?
Even though the liver is the metabolic organ primarily responsible for the biotransformation of most opioids, the degree of liver failure typically seen in perioperative patients is not severe enough to have a major impact on opioid pharmacokinetics
Alfentanil affected by _________.
CYP enzyme alterations
How is morphine metabolized?
Morphine 3-glucuronide and morphine 6-glucuronide are excreted via the kidney
What is important to know about meriperidine’s active metabolite, normeperidine?
excitatory CNS effects that can cause seizures
What is the relation between remifentanil and renal failure?
it is not impacted by renal failure
What is the relationship between morphine and gender?
- Evidence that Morphine is more potent in women than in men
- A lower concentration of morphine is required to produce comparable analgesia
- May be related to cyclic gonadal hormones
Fentanyl congeners are more potent in _________
older patients
What are the pharmokinetic differences associated with older patients?
decreases in clearance and Vd, in older patients
Pharmacodynamic differences are primarily responsible for _______________ in patients greater than 65 years of age
decreased dose requirements
What is an important factor influencing the clinical pharmacology of opioids?
Body weight
Morbidly obese patients require _________ doses than lean patients to achieve target concentrations
Higher
What is the response from partial agonists?
Bind to mu receptors, and activates it with a smaller shape change which leads to only a partial receptor response.
What are the effects of competitive antagonists?
Bind to mu receptors= Produce no effect
Also exert partial agonist actions at ______ & ______ receptors
kappa and delta
What effect can opioid agonist-antagonists have on opioid agonists?
Antagonistic properties of these drugs can attenuate the efficacy of subsequently administered opioid agonists
What are the side effects of opioid agonist-antagonists similar to?
Side effects are similar to those of opioid agonists
Opioid agonist-antagonists can cause ____________ reactions
dysphoric
What are some advantages to Opioid agonist-antagonist (3)?
- Ability to produce analgesia with limited depression of ventilation
- Reduced potential to produce physical dependence
- No Ceiling effect
What should the class of Opioid Agonists-Antagonists be reserved for?
be reserved for those patients who cannot tolerate a pure agonist
What is a ceiling effect?
increased doses do not produce additional side effects
Naloxone, Naltrexone, and Nalmefene are _________ opioid receptor antagonists with no agonist activity
pure mu opioid receptor
What effect do opioid antagonists have on the mu receptors?
- Displaces the opioid agonist from mu receptors
- Following this displacement, the binding of the pure antagonist does not activate mu receptors, and antagonism occurs
What is the effects of naltrexone?
- Highly effective, given orally
- Produces sustained antagonism of opioids for as long as 24 hours
True opioid allergy is ______
rare
What is true about opioid allergy?
-Predictable side effects are often misinterpreted as an allergic reaction
-Localized histamine release
-Orthostatic hypotension
N&V
What is minimum alveolar concentration?
is the concentration of a vapor in the alveoli of thelungsthat is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus
What is MAC used to compare?
the strengths, orpotency, of anesthetic inhalational agents
What effect does morphine have on MAC?
Morphine decreases the MAC of volatile anesthetics in a dose-dependent manner
What effect does MAC have on fentanyl in relationship to forane & desflurane?
A single dose of Fentanyl 3 ug/kg IV 25-30 minutes prior to surgical incision reduces MAC of Forane and Desflurane by 50%
Sufentanil and Alfentanil also produce a ___________ until a plateau is reached
dose-dependent reduction in MAC
What is the effect of MAC on remifentanil?
The decrease in MAC produced by Remifentanil is similar to that produced by other opioids and ranges from 50-91% depending upon the plasma concentration of Remifentanil
Opioid agonists do not provide ________, even at extremely high doses
reliable amnesia
What is less effective in decreasing the MAC?
- Opioid agonists-antagonists are less effective than opioid agonists in decreasing MAC
- Even large doses of opioid agonists-antagonists do not produce unconsciousness or prevent patient movement in response to surgical stimulation
- Intraoperative role of these drugs is minimal
What is the rationale for using PCA?
Rationale: by using frequent, small doses of opioid, patients will have better control of their pain by keeping effect-site concentrations in the therapeutic range for a longer period of time
What are the two important characteristics of PCA?
Increases patient satisfaction & Lowers opioid consumption
Neuraxial approach: What is the most reliable clinical sign of respiratory depression?
Most reliable clinical sign of respiratory depression is a depressed level of consciousness, possibly caused by hypercarbia
Neuraxial approach: What is the most reliable clinical sign of hypoventilation in those with supplemental oxygen?
arterial hypoxemia is a late sign of hypoventilation
Neuraxial opioids: What is the single dose for an epidural morphine dose? Infusion?
2-5 mg; infusion 0.1-1 mg/h
Neuraxial opioids: What is the single dose for an epidural Fentanyl dose? Infusion?
50-100 mcg; infusion 25-100 mcg hr
Neuraxial opioids: What is the single dose for an subarachnoid Fentanyl dose? Infusion?
10-20 mcg
Neuraxial opioids: What is the single dose for an subarachnoid Morphine dose? Infusion?
0.25-0.3 mg
What is the goal of Central Acting Nonopioid Analgesics (2)?
- Minimize the adverse effects of opioids (Goal)
- Provide a multimodal approach for relieving pain
Neuraxial approach to bypass ________
blood-brain barrier
What are some disadvantages to the neuraxial drug/approach (4)?
- Damage to structures of the CNS (dura, nerves) by needles and catheters
- Neurotoxic effects from the drugs (preservatives, antioxidants)
- ? adequate testing for drug for neuraxial route (novel approach for many medications)
- Infection
What does neostigimine increase?
Increase Ach levels
What neostigimine side effects can be seen?
Muscarinic side effects (N/V) limit its use despite analgesic effects
What are the advantages to ketamine?
Advantages include lack of CV and respiratory depression
What are some side effects of ketamine?
Neurotoxicity, psychomimetic issues, inadequate motor blockage, short duration of action- concerns
What is midazolam being investigated for?
Investigated for use in postop and chronic pain (Used with opioids and clonidine for additive effects).
What have animal trials shown about midazolam?
Serious risk: neurotoxicity in animal models that manifested after human use
What is the MOA of ketorolac?
COX inhibitor to ⬇️ prostaglandin after cell injury.
What do the theoretical implications say about ketorolac?
Despite theoretical implications, especially for chronic pain, limited effect with neuraxial route
