Pharmacology I: Lecture 5 - LAs and Nerve Blocks

Question 1

What is the primary mechanism of action of local anesthetics?

Answer 1

Local anesthetics prevent conduction of nerve impulses by blocking sodium ion influx through voltage-gated sodium channels

Prevents the propagation of the depolarization down the length of the nerve

Voltage- gated Sodium Channels
Complex transmembrane proteins
3 states: Open (activated), inactivated and resting
LA have a higher affinity for open and inactivated states

This action prevents the propagation of depolarization along the nerve.

Question 2

Mechanism of Action of LA

Answer 2

LA binds reversibly in concentration dependent manner

Unionized/unprotonated base
Lipophilic - permeates through phospholipid membrane

Ionized/protonated charged form
Hydrophilic – binds with greater affinity to open sodium channels
Ionized form is the active species

Question 3

Local Anesthetic Properties

Answer 3

Potency and Onset Time
LOWER the pKA greater potency (WHAT IS pKA and pH relationship)
Lower the onset time

Duration of Action
Greater the % Protein Bound > DOA

Question 4

Progression of Signs and Symptoms

Answer 4

Vertigo
Tinnitus
Circumoral numbness
Tremors
Myoclonic jerks
Convulsions
Coma
Cardiovascular collapse

Question 5

LA Toxicity Treatment

Answer 5

BDZ
Seizures

ETT
Aspiration & Hypoventilation

Fluids & Vasoactive agents
Hypotension & Bradycardia

Cardiopulmonary Bypass for cardiovascular collapse

Lipid Emulsion (Intralipid)
MOA – Lipids sequester the LA
20% intralipid 1.5 ml/kg bolus followed by 0.25ml/kg/min

Question 6

What are the three states of voltage-gated sodium channels?

Answer 6

Open (activated), inactivated, resting

Local anesthetics have a higher affinity for the open and inactivated states.

Question 7

What form of local anesthetic is the active species?

Answer 7

Ionized/protonated charged form

This form binds with greater affinity to open sodium channels.

Question 8

How does pKa affect the potency and onset time of local anesthetics?

Answer 8

Lower the pKa, greater potency and lower onset time

This relationship indicates that the chemical properties of the anesthetic influence its effectiveness.

Question 9

What is the relationship between protein binding and the duration of action of local anesthetics?

Answer 9

Greater the % protein bound, greater the duration of action

This indicates that local anesthetics that bind more to proteins tend to last longer.

Question 10

What are the early signs of local anesthetic toxicity?

Answer 10

Vertigo, tinnitus, circumoral numbness, tremors, myoclonic jerks

These symptoms indicate the progression of toxicity and should be monitored closely.

Question 11

What is the treatment for seizures caused by local anesthetic toxicity?

Answer 11

Benzodiazepines (BDZ)

This is a common first-line treatment to manage seizures.

Question 12

Sequence of Nerve Blockade

Answer 12

Loss of Temperature
First to be lost last to come back
Meditated by unmyelinated c fibers (regulate temperature) and A lamda small myelinated

Sensory Sharp Pain

Pressure

Proprioception

Motor paralysis
Last to be blocked first to “come back” (ex. as the spinal wears off, patient will be able to move legs before regaining sensation)
Large myelinated nerve structure

Question 13

Fill in the blank: Loss of _______ is the first sensation to be lost and last to return during nerve blockade.

Answer 13

Temperature

Question 14

What are the clinical uses of local anesthetics?

Answer 14

Topical

IV

Neuraxial (epidural and spinal blocks)

Peripheral nerve blocks
Upper Extremity
Lower Extremity
Truncal Blocks

Each application serves different surgical and pain management needs.

Question 15

Which local anesthetic has the longest duration of action?

Answer 15

Liposomal Bupivacaine

It has a duration of action of about 72 hours.

Question 16

The Most Common Local Anesthetics Used Clinically

Answer 16

Plasma esters LA are less toxic
Less Toxic = Quicker Onset

Liposomal Bupivacaine is time released why DOA is so long

*** This numbers are for topical and regional block, not spinal/epidural

Question 17

What is the typical dose and duration of action for Mepivacaine used in spinal anesthesia?

Answer 17

Typical dose is 45-60 mg, duration is ~70 minutes

Mepivacaine is often used in shorter orthopedic cases.

Question 18

Epidural Anesthesia (Thoracic)

Answer 18

Thoracic epidural
Based on base of scapula (T7) - upper limit (Dr. Hurley’s limit)

Remember iliac crest landmark (L3-4) (DOUBLE CHECK THIS and where spinal cord ends!!)

Question 19

Epidural Anesthesia

Answer 19

Focus on the Mechanism of Action block…

Onset first = come back first
Onset last = come back last

Know the fibers - big take away is size and myelinated vs unmyelinated

The only true absolute contraindications is patient refusal
However, sepsis is big as a general rule never want to put an indwelling catheter in a sepsis patient in

KNOW the Relative contraindications as well

Question 20

Anatomy

Answer 20

Question 21

Landmarks

Answer 21

T4 loss of cardioaccelerator fibers

Question 22

Physiological Effects

Answer 22

Neurologic
Order of nerve blockade leads to small sympathetic c fibers leads to small sensory A fibers (pain and temp) leads to large sensory AB fibers (proprioception and touch) leads to large motor fibers Aa

Cardiovascular
Sympathectomy (spinal>epidural)
Loss of vascular tone leads to hypotension and reflex tachycardia (can use pressors to hit A1)
Above T4 loss of cardioaccelerator fibers

GI
Sympathectomy (caused by epidural)
Hyperperistalsis

Question 23

What are the three most important factors affecting anesthetic spread in the intrathecal space?

Answer 23

Most common given a single shot…
* Baricity
Solution density in relation to CSF
Isobaric (density = CSF) get block at level of injection
Hyperbaric ( density > CSF, dextrose added) spread of medication with gravity
Hypobaric (density < CSF) get spread of medication against gravity

(LOOK UP WHAT CAN ADD TO CHANGE BARICITIES!!!)

• Position of patient after injection
• Dose of local anesthetic

Question 24

Choice of Local Anesthetic

Answer 24

Clinically used a continuous infusion

Labor Epidural Infusions for Analgesia
0.065% Bupivacaine with an opioid added at 6-14cc/hour

Conversion of epidural to surgical anesthesia for C-section
2% Lidocaine or 3% Chloroprocaine given in 5cc increments

(LOOK UP WHY USING EACH FOR EACH BLOCK CASES??? Want a denser block/more concentrated LA???)

Question 25

Spinal Anesthesia

Answer 25

Rapid and reliable onset of lower body anesthesia by injection local anesthetic into the intrathecal space Peripheral nerves covered by myelin nerve sheath CNS are encased in three layers of meninges: Pia matter – adherent to the nerve itself Arachnoid – separated from the pia matter by CSF Space between pia matter and arachnoid makes up the intrathecal space with “naked” nerves reside Requires 10 times less LA to block the naked nerves compared to epidural administration Dura matter

Question 26

What are the common additives to local anesthetics for peripheral nerve blocks?

Answer 26

* Epinephrine * Glucocorticoids

Question 27

What is the typical infusion rate for Ropivacaine in continuous infusion peripheral nerve blocks?

Answer 27

0.2% infusions at 6-8 ml/hr for 3-4 days ## Footnote This method helps maintain analgesia over an extended period.

Question 28

What is the effect of adding epinephrine to local anesthetics?

Answer 28

Decreases systemic absorption, increases duration of action ## Footnote This property is particularly beneficial in prolonging the effects of Bupivacaine, Lidocaine, and Ropivacaine.

Question 29

Most Common LA for Spinal Anesthesia

Answer 29

Mepivacaine 1.5% Gives duration of block ~70 minutes Typical dose is 45-60 mg Used in shorter orthopedic cases If you are doing a lower limb, spinal at L3-4 and want to keep it right there to hit the nerves that run to leg, so want it isobaric Bupivacaine 0.75 % in 8.25% dextrose (hyperbaric) Duration of anesthesia is 90-150 minutes Typical dose is 10-15 mg Used primarily in C-sections 0.5% isobaric Duration of anesthesia is ~ 90minutes Used in total joints procedures Ropivacaine 0.5% isobaric Duration ~ 75 minutes Typical dose is 10-15 mg Outpatient procedures Lidocaine is typically not used for Spinals due to transient neurologic symptoms (TNS) Present as low back pain and lower extremity burning/tingling after spinal has worn off

Question 30

Upper Extremity Peripheral Nerve Blocks

Answer 30

Get a pneumonic to remember it!!

Question 31

Brachial Plexus

Answer 31

Arises from the C5-C8 and TI Can be used a primary anesthetic as well as for post operative analgesia Peripheral Nerve Blocks of the Brachial Plexus: Interscalene Block – used for shoulder surgery; spares C8,T1 (ulnar nerve - be mindful that will be able to feel pinky and medial portion of ring finger) Takes phrenic nerve = 100% of time (never do bilate!) Supraclavicular Block – “Spinal of the Arm” (captures everything) Takes phrenic nerve = 50% of time Infraclavicular Block – Forearm, elbow and hand procedures (spares shoulder) Does not take phrenic, as branched by then (LOOK AT INTRO SLIDE ABOUT THE COMPLICATIONS!!)

Question 32

Lower Extremity Peripheral Nerve Blocks

Answer 32

Femoral Nerve Block – anterior thigh, anterior knee, medial malleolus Sciatic Nerve Block – ankle minus medial malleolus

Question 33

Local Anesthetics for Single Shot Peripheral Nerve Blocks

Answer 33

Bupivacaine 0.5% Typical dose 15-30 ml Duration of Action is ~24 hours Increased risk of toxicity More common for lower extremity blocks, lower limbs have more defined vasculature to make sure not to injecting Ropivacaine 0.5 % Typical dose 15-30 ml Duration of Action is 16-24 hours Less cardiotoxic than Bupivacaine Typically used for upper extremity blocks, upper has less defined vasculature, so with higher safety profile not as worried about intravascularly injection as much Liposomal Bupivacaine Duration of action ~ 72 hours

Question 34

Common Additives to LA for PNB’s

Answer 34

Epinephrine Vasoconstrictive properties decrease systemic absorption Dose 1:200,000 Increases duration of Bupivacaine, Lidocaine and Ropivacaine A lot of times an "Epi Wash" is used Glucocorticoids Prolongation thought to be related to membrane stabilization 4-8mg added to LA has been shown to increase duration of Bupivacaine and Ropivacaine by 4-8 hours (KNOW HOW TO ADD to ROPIVACAINE to get same DOA as Bupivacaine but more safety!!!)

Question 35

Continuous Infusion PNB

Answer 35

Ropivacaine 0.2% infusions at 6-8 ml/hr for 3-4 days If have an indwelling cath, want that safety profile to be maintained