Exam 3 Local Anesthetics Flashcards
What is pharmacokinetics?
The study of how drugs are absorbed, distributed, metabolized, and excreted in the body.
What factors determine the rate and extent of systemic absorption?
Site of injection, dose, physicochemical properties, and addition of epinephrine.
How does decreased absorption affect systemic toxicity?
Decreased absorption leads to decreased systemic toxicity.
How does vascularity affect drug uptake?
Greater vascularity leads to more rapid uptake than areas with more fat.
What is the order of rates of absorption from fastest to slowest?
Interpleural > intercoastal > caudal > epidural > brachial plexus > sciatic/femoral > subcutaneous.
What is the relationship between total dose and systemic absorption?
Greater the total dose, the greater the absorption.
How does lipid solubility affect absorption?
Higher lipid solubility and protein-bound compounds have decreased absorption.
How does distribution occur in the body?
Distribution occurs rapidly throughout all body tissues.
What factors influence drug distribution?
Organ perfusion, partition coefficient, and plasma protein binding.
Which systems are most vulnerable during drug distribution?
The cardiovascular and central nervous systems are most vulnerable.
What is the elimination process for esters?
Hydrolysis of ester by plasma cholinesterases.
What is the elimination process for amides?
Mixed function oxidase system of liver (i.e., p450).
Who is at increased risk for toxicity?
Young and old individuals due to decreased clearance and increased absorption.
How does pregnancy affect drug clearance?
Decreased clearance in pregnancy increases potential for toxicity.
What conditions lead to decreased clearance?
Hepatic disease and decreased cardiac output.
What is the relative potency of local anesthetics?
Bupivacaine = levobupivacaine > etidocaine > ropivicaine > mepivacaine = lidocaine = prilocaine > esters
How do local anesthetics affect the Central Nervous System?
They readily cross the blood-brain barrier.
What is the relationship between toxicity and dosage in local anesthetics?
Toxicity is dose dependent; CNS depression occurs at low plasma levels, while CNS excitation can progress to seizures at higher concentrations.
What substances may mask overt toxicity of local anesthetics?
Benzodiazepines and barbiturates may raise the seizure threshold, potentially avoiding or masking overt toxicity.
What factors increase the potential for CNS toxicity?
Decreased protein binding, decreased clearance, rapid rate of intravenous administration, acidosis, increased pCO2
How does cardiovascular system toxicity compare to CNS toxicity?
Generally higher doses lead to toxicity when compared to CNS toxicity.
What increases the risk for cardiovascular toxicity?
Higher relative potency (lipophilicity) increases risk for toxicity.
What cardiovascular toxicity does lidocaine exhibit?
Lidocaine typically exhibits cardiovascular toxicity as hypotension, bradycardia, and hypoxia.
What cardiovascular toxicity does bupivicaine exhibit?
Bupivicaine demonstrates sudden cardiovascular collapse secondary to ventricular arrhythmias that are resistant to treatment (QRS width/duration widened).
How does bupivicaine dissociate during diastole?
Bupivicaine dissociates slower during diastole.
What central effects does bupivicaine have?
Bupivicaine has central effects on the nucleus tractus solitarius.
What peripheral effects does bupivicaine cause?
Bupivicaine causes peripheral sympathetic inhibition and direct vasodilation.
What is neurotoxicity (peripheral)?
Neurotoxicity (peripheral) refers to damage to peripheral nerves.
Causes include injury to Schwann cells, inhibition of fast axonal transport, disruption of blood/nerve barrier, and decreased blood flow with ischemia.
How do peripheral nerves compare to spinal cord in terms of damage resistance?
Typically, peripheral nerves are more resistant to damage than the spinal cord.
What are transient neurologic symptoms (TNS) after spinal anesthesia?
TNS includes pain radiating from the lower back to the buttocks and lower extremities.
What are the risk factors for Transient Neurologic Symptoms (TNS) after spinal anesthesia?
- Spinal administration of lidocaine (up to 40%)
- Lithotomy position
- Ambulatory surgical status
- Arthroscopic knee surgery
- Obesity
- Lowest incidence in obstetrical patients undergoing c-section
When do Transient Neurologic Symptoms (TNS) typically occur after surgery?
12-23 hours after surgery
What is the usual recovery time for Transient Neurologic Symptoms (TNS)?
Recovery is usually within a week
What are Transient Neurologic Symptoms after Spinal Anesthesia (TNS)?
TNS are symptoms that may occur after spinal anesthesia.
What is the treatment for TNS?
Treatment consists of opioids, NSAIDs, muscle relaxants, warm heat and positioning, and possible trigger point injections.
What must be ruled out when diagnosing TNS?
Other causes such as hematoma, abscess, or cauda equina syndrome must be ruled out.
What is Procaine?
Procaine is a derivative of para-aminobenzoic acid.
What is the maximum single dose of Procaine?
The maximum single dose of Procaine is 7 mg/kg or 350-600 mg
What is Procaine?
Procaine is an aminoester local anesthetic with high pKa and poor lipid solubility, making it relatively weak.
What is the onset and duration of action for Procaine?
Procaine has a slow onset and a short duration of action, lasting 30-60 minutes.
How is the toxicity of Procaine limited?
The toxicity of Procaine is limited by rapid hydrolysis.
What are the common clinical uses of Procaine?
Procaine is used for infiltration (0.25-1%) and spinal anesthesia (50-200 mg).
Is Procaine used topically?
No, Procaine is not used topically.
What are the limitations of Procaine in anesthesia?
Procaine has very limited use in epidural, peripheral block, and intravenous regional anesthesia (IVRA).
What is Chloroprocaine?
Chloroprocaine is a derivative of procaine.
What is the maximum single dose of Chloroprocaine?
The max single dose is 11mg/kg or 800 mg (14mg/kg or 1000 mg with epinephrine).
What is the onset of action for Chloroprocaine?
Chloroprocaine has a rapid onset of action with more rapid metabolism than procaine.
What is the plasma half-life of Chloroprocaine?
The plasma half-life of Chloroprocaine is 30 seconds.
What concentration of Chloroprocaine is used for infiltration?
For infiltration, a concentration of 1% is used.
What concentrations of Chloroprocaine are used for epidural and peripheral nerve blocks?
For epidural and peripheral nerve blocks, concentrations of 2-3% are used.
What is the use of Chloroprocaine in intravenous administration?
Intravenous Chloroprocaine inhibits sympathetic response to laryngoscopy and intubation.
What is the primary clinical use of Chloroprocaine?
Chloroprocaine is primarily used for epidural anesthesia during c-section.
What are the clinical uses of Chloroprocaine?
Chloroprocaine has a rapid onset, decreased toxicity, and allows for rapid recovery and discharge.
What can EDTA as a preservative cause when used in Chloroprocaine?
EDTA as a preservative (>40 ml) can cause severe paravertebral muscle spasm after resolution of epidural block.
How can the muscle spasm caused by EDTA be avoided?
This can be avoided by using <25 ml of preservative-free formulation.
What is Tetracaine?
Tetracaine is a butylaminobenzoic acid derivative of procaine.
What is the maximum single dose of Tetracaine?
The maximum single dose of Tetracaine is 20 mg.
Often used in topical and ophthalmic work. See it often in drops
What are the characteristics of Tetracaine?
Tetracaine is potent and long-acting.
What is the onset and duration of Tetracaine when used in spinal anesthesia?
In spinal anesthesia (0.5-1%), Tetracaine has a 3-5 minute onset with a duration of 2-3 hours.
How does the duration of Tetracaine change with epinephrine?
The duration increases to 4-6 hours if co-administered with epinephrine.
What is the hydrolysis rate of Tetracaine?
Tetracaine has the slowest rate of hydrolysis, but its half-life is still shorter than any of the amides.
What are the clinical uses of Tetracaine?
Tetracaine has excellent topical properties, particularly for topical ophthalmologic anesthesia.
What limits the use of Tetracaine in clinical settings?
Toxicity concerns limit the use of Tetracaine by epidural, peripheral nerve, or IVRA.
What is cocaine classified as?
Local anesthetic with intense vasoconstriction
What is the maximum single dose of cocaine?
150 mg
What concentration of cocaine solution is used prior to nasopharyngeal or otolaryngologic manipulation?
4-10% solution
What limits the use of cocaine?
Low therapeutic index and abuse potential limit its use to topical only
What is unique about Benzocaine compared to other aminoesters?
Benzocaine possesses a secondary amine and is a weak acid with a pKa of 3.5.
What is the form of Benzocaine at physiologic pH?
Benzocaine is in unchanged form at physiologic pH.
What is the maximum single dose of Benzocaine?
The maximum single dose of Benzocaine is 200 mg.
What is the ideal use of Benzocaine?
Benzocaine is ideal for topical application to mucous membranes prior to endoscopy or bronchoscopy (20% solution).
What is the onset and duration of action for Benzocaine?
Benzocaine has a rapid onset of action with a duration of 30-60 minutes.
What adverse effect can occur with doses of 200-300 mg of Benzocaine?
Doses of 200-300 mg can cause methemoglobinemia, leading to cyanosis and decreased oxygen carrying capacity.
Who is at the most risk for methemoglobinemia when using Benzocaine?
Neonates are at the most risk for methemoglobinemia.
How can methemoglobinemia caused by Benzocaine be treated?
It can be treated with 1% methylene blue at a dose of 1-2 mg/kg over 20 minutes.
What is the max single dose of Lidocaine?
4.5 mg/kg or 300 mg (7mg/kg or 500 mg with epi)
This is the maximum single dose for administration.
What concentration of Lidocaine provides rapid onset anesthesia?
0.5-1% provides anesthesia of rapid onset with duration of 60-120 minutes.
What is the topical concentration of Lidocaine?
4%.
What is Tumescent Lidocaine?
Large volumes of dilute lidocaine/epinephrine combination injected into subcutaneous tissue; useful for liposuction. Peak effects may not occur for 10-12 hours.
What is the IVRA dosage for Lidocaine?
50 ml of 0.5% provides 45-60 minutes of anesthesia for upper extremity surgery.
What is the use of Spinal/Epidural Lidocaine?
Popular for dense sensory anesthesia and motor block for surgery of trunk and lower extremities.
Controversial neurotoxicity with spinal use; max single dose 100 mg.
What is the intravenous or laryngotracheal administration dosage of Lidocaine?
2-2.5 mg/kg to blunt effects of tracheal intubation; prevents elevations in IOP, ICP, and IAP.
What is a clinical use of Lidocaine?
Suppresses ventricular ectopy; 100-200 mg bolus followed by 1-4 mg/min infusion.
What dosage of Lidocaine may be used as a systemic analgesic?
1-5 mg/kg may be used as a systemic analgesic for acute postoperative and chronic neuropathic pain.
How effective is Lidocaine when used transdermally?
Transdermal very effective.
What is Prilocaine similar to?
Prilocaine is similar to lidocaine but has less vasodilation.
What is the maximum single dose of Prilocaine?
The maximum single dose of Prilocaine is 600 mg.
What is a common use for Prilocaine?
Prilocaine is commonly used topically in a prilocaine/lidocaine combination.
What is the clinical use of Prilocaine?
Anesthesia for painful procedures is realized after 60-90 minutes under occlusive dressing.
Examples include vascular cannulation or spinal puncture.
What is a key characteristic of Prilocaine’s metabolism?
It has rapid metabolism and is the least toxic of the aminoamides.
What metabolite of Prilocaine is implicated in methemoglobinemia?
o-toluidine.
How does Mepivicaine compare to Lidocaine?
It is similar to lidocaine but has a slightly longer duration.
What is the maximum single dose of Mepivicaine?
400 mg, or 500 mg with epinephrine
What is the onset and duration of epidural anesthesia with Mepivicaine?
1.5-2% provides surgical anesthesia within 10-15 minutes with a duration of 70-90 minutes.
What is the duration of peripheral block anesthesia with Mepivicaine?
1-1.5% provides anesthesia for 2-4 hours.
What is the risk associated with Mepivicaine in obstetrics?
There is an increased toxicity risk due to poor metabolism in the fetus.
What is Bupivicaine?
A long-acting aminoamide local anesthetic with a slow onset, except for infiltration and spinal use.
What is a drawback of Bupivicaine?
It has an increased risk of toxicity despite being a very potent local anesthetic.
What is the maximum single dose of Bupivicaine?
175 mg (225 mg with epinephrine).
What concentration of Bupivicaine is used for infiltration into surgical wounds?
0.25%.
What is the onset and duration of Bupivicaine for spinal use?
Fast onset within 5 minutes, lasting 1-4 hours.
What is Bupivicaine ideal for?
Continuous epidural use in labor and post-operatively.
What happens to the degree of motor block with Bupivicaine below 0.25% concentration?
The degree of motor block decreases, while 0.1% provides sensory analgesia with minimal motor block.
What is the duration of peripheral block with Bupivicaine?
4-12 hours (may last up to 24 hours).
What is Etidocaine?
A potent, highly lipophilic aminoamide local anesthetic with rapid onset and duration similar to Bupivicaine.
What is Levobupivicaine?
S-enantiomer of racemic bupivicaine with similar potency
30-40% less systemic toxicity
What is the maximum single dose of Levobupivicaine?
150 mg
What concentration of Levobupivicaine is used for epidural labor analgesia?
0.125-0.25%
What is the current focus in local anesthesia research?
Emphasis on delivery systems including ambulatory pumps, encapsulation with liposomes, microspheres, or polymers with slow degradation and release
What is Exparel?
Liposomal bupivacaine
What is a key characteristic of Etidocaine?
Selective more potent motor blockade than sensory anesthesia.
What is the max single dose of Ropivicaine?
200 mg
Used in epidural—0.1-0.25% for labor analgesia.
How does Ropivicaine compare to Bupivicaine?
Decreased lipid solubility over bupivicaine with less motor block.
What is the cardiotoxicity of Ropivicaine compared to Bupivicaine?
30-40% less cardiotoxic than bupivicaine.
What effect does Ropivicaine have on blood vessels?
Causes vasoconstriction.
What three local anesthetics have their own vasoconstriction?
Cocaine, levobupivicaine, ropivicaine
What is Lipid Rescue™ used for?
Treatment for local anesthetic-induced cardiac arrest.
What should be done in addition to standard CPR during local anesthetic-induced cardiac arrest?
Administer Intralipid 20% intravenously.
What is the initial bolus dose of Intralipid 20%?
1.5 mL/kg over 1 minute.
What is the infusion rate of Intralipid 20% after the initial bolus?
0.25 mL/kg/min.
What should be continued while administering Intralipid?
Continue chest compressions (lipid must circulate).
How often should the bolus of Intralipid be repeated?
Every 3-5 minutes up to a total of 3 mL/kg until circulation is restored.
What should be done after circulation is restored?
Continue the infusion until hemodynamic stability is restored.
What should be done if blood pressure declines during infusion?
Increase the infusion rate to 0.5 mL/kg/min.
What is the maximum total dose of Intralipid recommended?
10 mL/kg.
What is the first step in resuscitating an adult weighing 70kg using LipidRescue™?
Take a 500ml bag of Intralipid 20% and a 50ml syringe.
How much Intralipid should be drawn up for the initial bolus?
Draw up 50ml and give stat i.v., X2.
What should be done after the initial bolus of Intralipid?
Attach the Intralipid bag to an iv administration set (macrodrip) and run it i.v. over the next 15 minutes.
What should be repeated if spontaneous circulation has not returned?
Repeat the initial bolus up to twice more.
