Local Anesthetics 3-24 (exam 3) Flashcards
What factors determine the rate and extent of systemic absorption of local anesthetics?
- Site of injection
- dose
- physicochemical properties
- addition of epinephrine
Decreased absorption leads to ________ systemic toxicity
Decreased absorption leads to decreased systemic toxicity.
Greater vascularity leads to __________ than areas with more fat
more rapid uptake
Rates of absorption from fastest to slowest?
Interpleural > intercoastal > caudal > epidural > brachial plexus > sciatic/femoral > subcutaneous.
What factors affect the increase and decrease of systemic absorption?
–Greater the total dose the greater the absorption
–Higher lipid solubility and protein bound compounds have decreased absorption
How are local anesthetics distributed in the body?
Rapidly throughout all body tissues.
–Organ perfusion
–Partition coefficient
–Plasma protein binding
Which organs are most vulnerable to local anesthetic toxicity?
Cardiovascular and central nervous systems.
How are esters eliminated?
Hydrolysis of ester by plasma cholinesterases.
How are amides eliminated?
Mixed function oxidase system of liver (e.g., p450).
What factors increase toxicity of local anesthetics?
- young and old
- Pregnancy
- Hepatic disease
- Decreased cardiac output
Why do young and old increase toxicity?
due to decreased clearance and increased absorption.
How does pregnancy affect local anesthetic clearance?
Decreased clearance
Why hepatic disease and decreased cardiac output increase toxicity? (extra)
- ↓ perfusion or liver metabolism → slower clearance.
- Avoid regional blocks in shocky or low perfusion states.
What is the relative potency ranking of local anesthetics?
Bupivacaine = levobupivacaine > etidocaine > ropivacaine > mepivacaine = lidocaine = prilocaine > esters.
Which local anesthetic is the weakeast?
prilocaine, seen mainly in EMLA cream
How do local anesthetics affect the central nervous system?
Most local anesthetics are liphophilic –> They readily cross the blood-brain barrier and toxicity is dose-dependent.
What is complex behavior of bupivacaine? (extra)
- Highly lipid-soluble → crosses BBB.
- Also highly protein-bound, which limits free drug in circulation.
- May cause cardiac toxicity before CNS symptoms, or vice versa — depends on dose and patient factors.
What happens at low plasma levels of local anesthetics?
CNS depression/sedation occurs (early sign)
What happens at higher plasma levels of local anesthetics?
CNS excitation progressing to SZ.
Example: Patient with recurrent V-tach was stabilized on lidocaine drip, gradually increased up to 6 mg/min →Developed CNS signs (sedation, tics, agitation) → classic signs of lidocaine toxicity
Why other Sodium Channel Blockers don’t cause CNS toxicity (quinidine, procainamide)? (extra)
- high protein binding
- lower lipophilicity
- large molecular size
How can overt toxicity of local anesthetics be avoided or masked?
By benzodiazepines and barbiturates. They raise the seizure threshold.
(However, SZ may emerge later during recovery b/c GABA drugs wear off).
Which one is the strong motor and sensory block? (extra)
Bupivicaine
Which one is more favor in labor? (extra)
Ropivacaine: less dense motor block, allows more mobility
What factors increase the potential for CNS toxicity in local anesthetics?
- Decreased protein binding
- decreased clearance
- rapid rate of intravenous administration
- acidosis
- increased pCO2.
High dose or low dose causes Cardiovascular Toxicity?
Requires higher doses, unless using a high-potency agent (e.g., bupivacaine).
For example: Lidocaine: relatively safe unless dosed excessively will cause cardiovascular toxicity (bradycardia, hypotension, or smoldering arrhythmias).
Except: the higher potency drugs don’t need much to cause CV toxicity. For example, bupivacaine: more likely to cause cardiac arrest (VT/VF, asystole) at lower doses.
All drugs though, on the other hand, CNS toxicity doesn’t require higher dose of local anesthetics.
How does cardiovascular toxicity differ between lidocaine and bupivicaine?
- Lidocaine (lower potency) typically exhibits CV toxicity as hypotension, bradycardia, hypoxia
- whereas bupivicaine (higher potency) demonstrates sudden CV collapse secondary to ventricular arrhythmias that are resistant to treatment (QRS width/duration widened)
What is a characteristic of bupivicaine’s action?
- Bupivicaine dissociates slower during diastole (prolonged blockade at Na channels)
- Crosses BBB → inhibits vasomotor center (NTS) → hypotension and loss of autonomic tone.
- peripheral sympathetic inhibition → direct vasodilation → worsen perfusion during CPR
Bupivacaine = levobupivacaine > etidocaine > ropivacaine > mepivacaine = lidocaine = prilocaine > esters.
Which side is more cardio toxic? which side is more neuro toxic?
From ropivicaine to the left : cardio toxic
From ropivicaine to the right: neuro toxic
How neurotoxicity present in local anesthetics?
- Injury to Schwann cells
- inhibition of fast axonal transport
- disruption of blood/nerve barrier
- decreased blood flow with ischemia
Which one is more resistant to damage? peripheral nerves or spinal cord?
peripheral nerves
What are transient neurologic symptoms (TNS) after spinal anesthesia?
Pain radiating from lower back to buttocks and lower extremities.
What are the risk factors for TNS after spinal anesthesia?
- Spinal administration of lidocaine (up to 40%, except in OB, OB population immuned to lidocaine induced TNS)
- lithotomy position
- ambulatory surgical status
- arthroscopic knee surgery
- obesity
When do transient neurologic symptoms typically occur after surgery?
12-23 hours after surgery, with recovery usually within a week.
What is the treatment for transient neurologic symptoms after spinal anesthesia?
Opioids
NSAIDs
muscle relaxants
warm heat and positioning
possible trigger point injections.
What must be ruled out when diagnosing transient neurologic symptoms?
Other causes such as hematoma, abscess, or cauda equina syndrome.
What is procaine? Derivative of? Max single dose?
Aminoester derivative of para-aminobenzoic acid with a max single dose of 7mg/kg, max of 350 - 600 mg, cap at 350mg for children
What are procaine’s properties? Pka lipophilicity onset duration toxicity?
- has a high pKa and poor lipid solubility → make it a relatively weak local anesthetic with a slow onset and short duration of action (30-60 minutes).
- Toxicity is limited by rapid hydrolysis.
What are the clinical uses of Procaine?
- used for infiltration (0.25-1%) and spinal anesthesia (50-200 mg).
- not used topically and has very limited use in epidural, peripheral block, and intravenous regional anesthesia (IVRA).
What are the characteristics of Chloroprocaine?
Derivative of? Max dose without and with epi, onset? Duration? Half life? Uses?
- derivative of procaine
- max single dose of 11 mg/kg or 800 mg (14 mg/kg or 1000 mg with epinephrine)
- has a rapid onset of action with more rapid metabolism than procaine (plasma half-life 30 seconds).
- Used as Infiltration—1%
- Used in Epidural and peripheral nerve block—2-3%
- Intravenous—inhibits sympathetic response to laryngoscopy
- and intubation
- Used primarily for epidural anesthesia during c-section
What are the benefits of using Chloroprocaine?
Chloroprocaine has rapid onset, decreased toxicity, and rapid recovery and discharge.
What is the drawback of chloroprocaine?
EDTA as a preservative (>40 ml) can cause severe paravertebral muscle spasm after resolution of the epidural block; this can be avoided by using <25 ml of preservative-free formulation.
What are the characteristics of Tetracaine?
Tetracaine is a butylaminobenzoic acid derivative of procaine with a max single dose of 20 mg.
It is potent and long-acting.
How is tetracaine used in spinal?
- For spinal use, it is administered at 0.5-1% concentration with a 3-5 minute onset and a duration of 2-3 hours (duration increased to 4-6 hours if co-administered with epinephrine).
