Spring 25 - Farm Test 3 Flashcards
Locals and opioids
What is the structure of local anesthetics?
A lipophilic benzene ring connected to a hydrophilic amine group via either an ester or amide linkage.
Name five amide local anesthetics.
- Lidocaine
- Prilocaine
- Mepivacaine
- Ropivacaine
- Bupivacaine
Name five ester local anesthetics.
- Cocaine
- Procaine
- 2-chloroprocaine
- Tetracaine
- Benzocaine
What type of bases are all local anesthetics?
Weak bases.
What is the significance of pKa in local anesthetics?
pKa is the pH at which 50% of the drug is in ionized and 50% in non-ionized form.
What does a lower pKa indicate regarding the onset of local anesthetics?
Faster onset due to more drug in neutral form at physiological pH.
How does increased lipophilicity affect local anesthetics?
It results in slower onset but longer duration of action.
How does increased protein binding affect the duration of action of local anesthetics?
It leads to a longer duration of action.
Which local anesthetics are not racemic mixtures?
- Lidocaine
- Ropivacaine
- Levobupivacaine
What is the effect of epinephrine when used with local anesthetics?
Prolongs block duration and decreases systemic absorption by inducing vasoconstriction.
What is the common concentration of epinephrine used with local anesthetics?
1:200,000.
What is the purpose of alkalinization in local anesthetic administration?
Raises pH to increase the fraction of drug in lipid-soluble (active) form.
What is the primary route of metabolism for esters?
Metabolized by plasma cholinesterases via hydrolysis.
What is the primary route of metabolism for amides?
Metabolized by the liver’s cytochrome P450 system.
What factors increase the risk of local anesthetic toxicity?
- Young and elderly patients
- Pregnancy
- Hepatic disease
- Low cardiac output
What is the potency ranking of local anesthetics from highest to lowest?
- Bupivacaine = Levobupivacaine
- Etidocaine
- Ropivacaine
- Mepivacaine = Lidocaine = Prilocaine
- Esters
What are the risk factors for CNS toxicity from local anesthetics?
- Decreased protein binding
- Decreased clearance
- Rapid IV administration
- Acidosis
- Increased pCO₂
What are common symptoms of CNS toxicity from local anesthetics?
- CNS depression at low plasma levels
- CNS excitation and seizures at higher levels
What is the maximum single dose for Procaine?
- Pediatric 350 mg (7 mg/kg)
- Adult 600 mg
What is the maximum single dose for Chloroprocaine?
- 800 mg plain (11 mg/kg)
- 1000 mg with epinephrine (14 mg/kg)
What is the maximum single dose for Tetracaine?
20 mg.
What is the maximum single dose for Lidocaine?
- 300 mg plain (4.5 mg/kg)
- 500 mg with epinephrine (7mg/kg)
What is the maximum single dose for Prilocaine?
600 mg.
What is the maximum single dose for Mepivacaine?
- 400 mg (plain)
- 500 mg (with epinephrine)
- 100 mg for spinal use
What is the maximum single dose for Bupivacaine?
- 175 mg plain (2.5 mg/kg)
- 225 mg with epinephrine
What is the maximum single dose for Ropivacaine?
200 mg (3 mg/kg)
What is the maximum single dose for Levobupivacaine?
150 mg (2 mg/kg)
What is the protocol for the Lipid Rescue™ treatment?
Intralipid 20%
* Bolus: 1.5 mL/kg IV over 1 minute
* Infusion: 0.25 mL/kg/min immediately after bolus
* Repeat bolus every 3–5 minutes (max cumulative bolus: 3 mL/kg)
* Continue infusion until hemodynamic stability is restored
Intralipid 20% practical application for 70 kg male
- Use a 500 mL bag of Intralipid 20%
- Draw up 50 mL x2 and give immediate IV push
- Attach bag to IV set (macrodrip) and infuse over 15 minutes
-Repeat bolus up to two more times if circulation does not return
What is the clinical use of Benzocaine?
Commonly used in 20% solution for topical application to mucous membranes.
What are the symptoms of Transient Neurologic Symptoms (TNS)?
Radiating pain from the lower back to buttocks and lower extremities.
What is a treatment option for TNS?
Supportive care: opioids, NSAIDs, muscle relaxants, warm compresses, trigger point injections
What is the incidence of TNS with spinal lidocaine administration?
Up to 40%.
What is the main risk factor for TNS?
Spinal lidocaine administration.
What is the significance of the para-aminobenzoic acid (PABA) derivative in Procaine?
It indicates Procaine’s chemical structure.
What is the onset and duration of action for Tetracaine when used for spinal anesthesia?
Onset: 3–5 minutes, Duration: 2–3 hours.
What is the primary application of Chloroprocaine?
Epidural anesthesia during cesarean section.
What is the mechanism of action for Bupivacaine’s cardiotoxicity?
- Slow dissociation during diastole
- Central inhibition via nucleus tractus solitarius
- Peripheral sympathetic inhibition and direct vasodilation
What are the characteristics of Etidocaine?
Highly lipophilic with rapid onset and long duration.
What is the significance of the S-enantiomer in Levobupivacaine?
Offers similar potency to bupivacaine with 30–40% less systemic toxicity.
What is the risk associated with using Benzocaine at doses of 200–300 mg?
Methemoglobinemia risk.
What is Intralipid 20% used for in emergency treatment?
Used as an IV push and then gtt for immediate treatment in local anesthetic-induced cardiac arrest.
A 500 mL bag is typically used, with doses of 50 mL administered as needed.
When was opium first used by the Ancient Sumerians?
Around 3000 BC for religious rituals.
What significant development in opioid history occurred in 1806?
Serturner isolates morphine.
Define ‘opiates’.
Naturally derived from opium, including morphine, codeine, and related alkaloids.
What are ‘opioids’?
A broad class that includes all agonists and antagonists, natural, semi-synthetic, and synthetic compounds, and all substances that bind to opioid receptors.
What are the three major opioid receptors?
- Mu (μ)
- Kappa (κ)
- Delta (δ)
What is the mechanism of opioid receptor action?
G protein-coupled receptors that inhibit adenylyl cyclase, decrease cAMP, decrease Ca²⁺ channel conduction, and open K⁺ channels.
What is desensitization in the context of opioid receptors?
Prolonged activation of receptors leads to reduced sensitivity.
What is the role of endogenous opioid ligands?
Over 20 peptides from brain, pituitary, adrenal, and immune cells that interact with opioid receptors.
List the effects of the Mu (μ) receptor.
- Analgesia
- Respiratory depression
- Sedation
- Euphoria
- Constipation
- Bradycardia
- Hypothermia
- Urinary retention
- Physical dependence
What are the clinical effects of opioids in the short term?
- Analgesia
- Respiratory depression
- Sedation
- Euphoria
- Vasodilation
- Bradycardia
- Cough suppression
- Miosis
- Nausea/vomiting
- Constipation
- Urinary retention
- Biliary spasm
What factors influence opioid response?
- Pain location & intensity
- Psychological factors
- Drug interactions
- Age
- Pathologic and genetic factors
- Sex differences
Fill in the blank: Most clinically useful opioids are ____ receptor-selective.
mu
What is the primary route of opioid metabolism?
Primarily hepatic.
What are the effects of opioids on the gastrointestinal system?
- Decreased peristalsis
- Constipation
- Delayed gastric emptying
- Postoperative ileus
What symptoms characterize opioid withdrawal syndrome?
- Restlessness
- Mydriasis
- Gooseflesh
- Runny nose
- Diarrhea
- Chills
- Drug-seeking behavior
What is the difference between physical dependence and addiction?
Physical dependence refers to physiological adaptation to a drug, while addiction involves psychological dependence.
What is the mechanism of action for naloxone?
- Opioid antagonist
Blocks opioid receptors for acute reversal of opioid toxicity.
What are the side effects of neuraxial opioids?
- Pruritus
- Nausea/vomiting
True or False: True opioid allergies are common.
False
What is the risk associated with meperidine use in renal failure?
Accumulation of normeperidine, which can cause neurotoxicity and seizures.
What is the effect of opioids on respiratory rate?
Dose-dependent depression of response to hypercapnia and hypoxia.
List the four types of opioid agonists.
- Natural/Semisynthetic
- Synthetic
- Others
- Antitussive agents
What is pruritis in the context of neuraxial opioids?
Generalized itching, worst in face, neck, upper thorax. More common in obstetrical patients due to estrogen interaction with receptors.
Not histamine mediated; involves opioid receptors in the trigeminal nucleus. Naloxone is effective; antihistamines help via sedation.
What triggers nausea and vomiting with neuraxial opioids?
Chemoreceptor trigger zone and depression of vomiting center. Responds well to anti-dopaminergic agents like metoclopramide and promethazine.
These agents help mitigate the effects of opioid-induced nausea.
What causes urinary retention in neuraxial opioid use?
Activation of opioid receptors in the sacral spinal cord, leading to reduced parasympathetic outflow, detrusor relaxation, and increased bladder capacity.
What are the risk factors for ventilatory depression with neuraxial opioids?
High dose, low lipid solubility, concomitant use of sedatives, lack of opioid tolerance, older age, high intrathoracic pressure, patient positioning.
Onset may be delayed (6–12 hours) after neuraxial morphine.
What is the clinical significance of decreased level of consciousness (LOC) in opioid use?
Decreased LOC may be the most sensitive indicator of ventilatory depression.
What is the duration of action for IM injection of morphine?
Onset: 15–30 min, Peak effect: 45–90 min, Duration: ~4 hours.
What are the cardiovascular effects of morphine?
Minimal risk of hypotension or myocardial depression in supine patients; risk of orthostatic hypotension when upright.
Bradycardia may occur from increased vagal tone.
What is the potency of meperidine compared to morphine?
1/10th the potency of morphine.
What is the primary metabolite of meperidine that poses a risk?
Normeperidine, which can cause CNS stimulation, myoclonus, seizures, and hallucinations.
What are the key pharmacokinetics of fentanyl?
Potency: 75–125x more than morphine, Rapid onset, short duration, Hepatic metabolism, Renal excretion.
What are the advantages of using fentanyl?
No direct myocardial depression, no histamine release, suppresses surgical stress response.
What is sufentanil’s potency in relation to fentanyl?
5–10 times more potent than fentanyl.
What is the clinical use of remifentanil?
Ideal for transient painful stimuli and preferred in neuro cases where rapid wake-up is needed.
What is the unique characteristic of remifentanil’s metabolism?
Metabolized by nonspecific plasma/tissue esterases, leading to no cumulative effect.
What is the primary use of naloxone?
Opioid overdose, post-op respiratory depression, neonatal depression, diagnostic for dependency.
What is the side effect of naltrexone?
Not used for acute overdose due to delayed onset.
Fill in the blank: The half-life of codeine is _______.
3–3.5 hours.
What are the side effects associated with butorphanol?
Sedation, nausea, diaphoresis, less dysphoria than morphine, ventilatory depression.
What is the duration of action for buprenorphine?
Long (IM = ~8 hours).
What is the significance of the ceiling effect in nalbuphine?
It has a ceiling effect for respiratory depression, making it safer in some contexts.
What is the primary use of Naltrexone (Revia)?
Long-term treatment for opioid or alcohol dependence
Naltrexone is administered orally and has a duration of up to 24 hours. It is not used for acute overdose due to its delayed onset.
What is the structure of Nalmefene?
6-methylene analog of naltrexone
Nalmefene is used similarly to naloxone and has a dosing of 0.25 mg/kg IV over 2–5 minutes (max 1 mg/kg) with a duration of about 8 hours.
What is the action of Methylnaltrexone (Relistor)?
Peripheral only – does not cross the blood-brain barrier
Methylnaltrexone is a quaternary opioid antagonist indicated for opioid-induced constipation (OIC) in chronic non-cancer pain and advanced illness (short-term, <4 months).
What condition is Alvimopan (Entereg) indicated for?
Post-op ileus; accelerates bowel recovery after bowel resection
Alvimopan is used peri-operatively and has a risk of myocardial infarction with long-term use. It should be avoided in patients recently on chronic opioids.
What is the mechanism of Naloxegol (Movantik)?
PEGylated naloxone derivative; peripherally acting
Naloxegol is indicated for the treatment of opioid-induced constipation.
What are the effects of increased sympathetic tone?
↑HR, ↑BP
Increased sympathetic tone can be a response seen with N/V, especially with rapid IV push.
Fill in the blank: Nalmefene dosing is ______ mg/kg IV over 2–5 minutes.
0.25
The maximum dosing for Nalmefene is 1 mg/kg.
True or False: Methylnaltrexone crosses the blood-brain barrier.
False
Methylnaltrexone is designed to act peripherally and does not affect the central nervous system.
What is the duration of action for Nalmefene?
Approximately 8 hours
Nalmefene is similar in use to naloxone but has a different dosing and duration.
