Local Anesthetics 3-24 (exam 3)

Question 1

What factors determine the rate and extent of systemic absorption of local anesthetics?

Answer 1

• Site of injection
• dose
• physicochemical properties
• addition of epinephrine

Question 2

Decreased absorption leads to ________ systemic toxicity

Answer 2

Decreased absorption leads to decreased systemic toxicity.

Question 3

Greater vascularity leads to __________ than areas with more fat

Answer 3

more rapid uptake

Question 4

Rates of absorption from fastest to slowest?

Answer 4

Interpleural > intercoastal > caudal > epidural > brachial plexus > sciatic/femoral > subcutaneous.

Question 5

What factors affect the increase and decrease of systemic absorption?

Answer 5

–Greater the total dose the greater the absorption
–Higher lipid solubility and protein bound compounds have decreased absorption

Question 6

How are local anesthetics distributed in the body?

Answer 6

Rapidly throughout all body tissues.
–Organ perfusion
–Partition coefficient
–Plasma protein binding

Question 7

Which organs are most vulnerable to local anesthetic toxicity?

Answer 7

Cardiovascular and central nervous systems.

Question 8

How are esters eliminated?

Answer 8

Hydrolysis of ester by plasma cholinesterases.

Question 9

How are amides eliminated?

Answer 9

Mixed function oxidase system of liver (e.g., p450).

Question 10

What factors increase toxicity of local anesthetics?

Answer 10

• young and old
• Pregnancy
• Hepatic disease
• Decreased cardiac output

Question 11

Why do young and old increase toxicity?

Answer 11

due to decreased clearance and increased absorption.

Question 12

How does pregnancy affect local anesthetic clearance?

Answer 12

Decreased clearance

Question 13

Why hepatic disease and decreased cardiac output increase toxicity? (extra)

Answer 13

• ↓ perfusion or liver metabolism → slower clearance.
• Avoid regional blocks in shocky or low perfusion states.

Question 14

What is the relative potency ranking of local anesthetics?

Answer 14

Bupivacaine = levobupivacaine > etidocaine > ropivacaine > mepivacaine = lidocaine = prilocaine > esters.

Question 15

Which local anesthetic is the weakeast?

Answer 15

prilocaine, seen mainly in EMLA cream

Question 16

How do local anesthetics affect the central nervous system?

Answer 16

Most local anesthetics are liphophilic –> They readily cross the blood-brain barrier and toxicity is dose-dependent.

Question 17

What is complex behavior of bupivacaine? (extra)

Answer 17

• 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.

Question 18

What happens at low plasma levels of local anesthetics?

Answer 18

CNS depression/sedation occurs (early sign)

Question 19

What happens at higher plasma levels of local anesthetics?

Answer 19

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

Question 20

Why other Sodium Channel Blockers don’t cause CNS toxicity (quinidine, procainamide)? (extra)

Answer 20

• high protein binding
• lower lipophilicity
• large molecular size

Question 21

How can overt toxicity of local anesthetics be avoided or masked?

Answer 21

By benzodiazepines and barbiturates. They raise the seizure threshold.
(However, SZ may emerge later during recovery b/c GABA drugs wear off).

Question 22

Which one is the strong motor and sensory block? (extra)

Answer 22

Bupivicaine

Question 23

Which one is more favor in labor? (extra)

Answer 23

Ropivacaine: less dense motor block, allows more mobility

Question 24

What factors increase the potential for CNS toxicity in local anesthetics?

Answer 24

• Decreased protein binding
• decreased clearance
• rapid rate of intravenous administration
• acidosis
• increased pCO2.

Question 25

High dose or low dose causes Cardiovascular Toxicity?

Answer 25

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.

Question 26

How does cardiovascular toxicity differ between lidocaine and bupivicaine?

Answer 26

* 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)

Question 27

What is a characteristic of bupivicaine's action?

Answer 27

* 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

Question 28

Bupivacaine = levobupivacaine > etidocaine > ropivacaine > mepivacaine = lidocaine = prilocaine > esters. Which side is more cardio toxic? which side is more neuro toxic?

Answer 28

From ropivicaine to the left : cardio toxic From ropivicaine to the right: neuro toxic

Question 29

How neurotoxicity present in local anesthetics?

Answer 29

* Injury to Schwann cells * inhibition of fast axonal transport * disruption of blood/nerve barrier * decreased blood flow with ischemia

Question 30

Which one is more resistant to damage? peripheral nerves or spinal cord?

Answer 30

peripheral nerves

Question 31

What are transient neurologic symptoms (TNS) after spinal anesthesia?

Answer 31

Pain radiating from lower back to buttocks and lower extremities.

Question 32

What are the risk factors for TNS after spinal anesthesia?

Answer 32

* 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

Question 33

When do transient neurologic symptoms typically occur after surgery?

Answer 33

12-23 hours after surgery, with recovery usually within a week.

Question 34

What is the treatment for transient neurologic symptoms after spinal anesthesia?

Answer 34

Opioids NSAIDs muscle relaxants warm heat and positioning possible trigger point injections.

Question 35

What must be ruled out when diagnosing transient neurologic symptoms?

Answer 35

Other causes such as hematoma, abscess, or cauda equina syndrome.

Question 36

What is procaine? Derivative of? Max single dose?

Answer 36

Aminoester derivative of para-aminobenzoic acid with a max single dose of 7mg/kg, max of 350 - 600 mg, cap at 350mg for children

Question 37

What are procaine's properties? Pka lipophilicity onset duration toxicity?

Answer 37

* 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.

Question 38

What are the clinical uses of Procaine?

Answer 38

* 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).

Question 39

What are the characteristics of Chloroprocaine? Derivative of? Max dose without and with epi, onset? Duration? Half life? Uses?

Answer 39

* 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

Question 40

What are the benefits of using Chloroprocaine?

Answer 40

Chloroprocaine has rapid onset, decreased toxicity, and rapid recovery and discharge.

Question 41

What is the drawback of chloroprocaine?

Answer 41

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.

Question 42

What are the characteristics of Tetracaine?

Answer 42

Tetracaine is a butylaminobenzoic acid derivative of procaine with a max single dose of 20 mg. It is potent and long-acting.

Question 43

How is tetracaine used in spinal?

Answer 43

* 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).