Local anesthetics - Dersh

Question 1

When are tertiary amines charged?

Answer 1

They are charged at low pH (active form of the local anesthetic)

They are uncharged at high pH

Question 2

At what pH are quaternary amines charged?

Answer 2

THey are always charged (active form of the local anesthetic molecule)

Question 3

What conclusions where made about the active form of the local anesthetic molecule?

Answer 3

It is the protonated amine (which is charged)

The local anesthetic molecule blocks conduction from inside the axon

The local anesthetic molecule traverses the axonal membrane in the unprotonated (uncharged) form

Question 4

What is the target for the action of local anesthetics?

Answer 4

The voltage gated Na channel

This transmembrane protein consists of four subunits surrounding a central pore

An action potential causes depolarization of hte nerve membrane and a conformational change that results in the pore opening and permitting Na ions to pass.

Within a few milliseconds after opening, a polypeptide chain between two of the subunits moves to occlude the central pore and prevent further ion conductance

Question 5

At what point of the Na channel activation/deactivation cycle do local anesthetics block it?

What determines the degree of block?

Answer 5

They block the Na channel during the open state

The degree of blockade depends on both the resting potential of the nerve and the rapidity with which it has been stimulated

A resting nerve is less sensitive to local anesthetic blockade

A higher stimulation frequency and a more positive resting potential cause a greater degree of block

Question 6

When a local anesthetic is injected near a compound nerve containing many fiber types, what is the first modality to be blocked?

2nd blocked?

3rd blocked?

Answer 6

First to be blocked is the efferent sympathetic activity fibers

First objective sign of block is –> vasodilation and increase in skin temperature

Second blocked - pain and temperature so there is loss of these sensations

Third blocked - motor strength and the senses of proprioception and light touch (these are the slowest in onset)

Question 7

As local anesthetic wears off, list the functions you gain back first to last.

Answer 7

You get back motor strength, proprioception and light touch

Second to come back - sensations of pain and temperature

Last to come back - sympathetic tone

Question 8

What type of nerve fibers are most easily blocked?

Answer 8

Generally, smaller nonmyelinated nerve fibers are more easily blocked than larger, myelinated fibers.

Question 9

What is a differential block?

Answer 9

This is when you use concentration levels of local anesthetics to block nerve fibers

A low concentration of a local anesthetic solution may block only the sympathetic nerves. A slightly higher concentration may also block the sensations of pain and temperature. Motor blockade is usually achieved only with the highest concentration of the local anesthetic that is clinically available.

Question 10

Many chemical species have local anesthetic effects. Give examples of these

Answer 10

Phenothiazines - used to treat major psychiatric illnesses

Histamine H1 antagonists - used to treat allergies

Question 11

Local anesthetics used clinically are all similar in structure, describe this structure

Answer 11

One end has a substituted aromatic ring, the other end has a substituted amine (with one exception)

These ends are linked by an ester or an amide linkage

Question 12

What are the ester local anesthetics?

Answer 12

BP-PT (Blood pressure physical therapy)

Benzocaine

Procaine

Proparacaine

Tetracaine

Ester anesthetics have higher hypersensitivy reaction in patients due to the high prevalence of hypersensitivity to PABA (product of metabolism of such drugs) in the general population

Methylparaben and/or propylparaben are preservatives that demonstrate cross-reactance with PABA in many people

Question 13

What are the amide local anesthetics?

Answer 13

L-BMR

Lidocaine

Bupivacaine

Mepivacaine

Ropivacaine

Question 14

Procaine

Onset and duration?

Metabolised to what?

Answer 14

First synthetic local anesthetic, rarely used today

Not used because of slow onset and short duration

It is metabolized to p-aminobenzoic acid (PABA) - causes allergic reaction in many people

PABA is commonly found in many skin lotions (includig sunscreens) and creams

Question 15

Lidocaine

Onset and duration?

AE?

Use?

How long is the blockade with a spinal block?

What’s the only site it is not used as a local anesthetic?

Metabolism?

Answer 15

Commonly used anesthetic

Fast onse, short duration and low toxicity

Use:

• Local infiltration
• Nerve blocks IV regional anesthesia - Bier block
• Spinal and epidural anesthesia
• Topically on mucous membranes

Blockade is 1-3 hours

Not used on the cornea

Metabolized by hepatic cytochrome P450 system and subsequently by hepatic amidases:

The tertiary amine is first N-dealkylated to a secondary
amine, and then the amide linkage is hydrolyzed yielding ethylglycine and xylidide. Most of the xylidide thus formed is oxidized by cytochrome P450 to 4-hydroxy-2,6-dimethylaniline which is excreted in the urine

Question 16

How do you prolong the duration of lidocaine?

Answer 16

By giving epinephrine which will cause vasoconstriction and therefore decreases local blood flow and absorption of lidocaine

Question 17

Bupivacaine

Onset and duration?

AE?

What is the use of Epinephrine simultaneously with this drug?

Use?

How long is the blockade with a spinal block?

Answer 17

Amide local anesthetic

Compared to lidocaine, it is slower in onset, much longer in duration (due to its very slow dissociation from its binding site in the sodium channel. Epinephrine does not prolong its duration), and much more toxic (correlated to its higher lipid solubility as compared to lidocaine –> “Bupivacaine is Bad”

Epinephrine (vasoconstrictor) decreases its toxicity by slowing down absorption of Bupivacaine, decreasing the peak blood concentration, and decreasing bleeding at the surgical site.

AE: cardiotoxic local anesthetic and ventricular fibrillation.

It dissociates so slowly from the sodium channel, once severe cardiotoxicity is manifested, a prolonged period of cardiopulmonary resuscitation is often required until a normal rhythm is restored.

Use:

• local infiltration
• nerve blocks
• spinal and epidural anesthesia

Blockade is 8-24 hours

Question 18

Mepivacaine

Onset, duration

AE?

Use?

How long is the blockade with a spinal block?

Answer 18

Similar to lidocaine in that it has fast onset and low toxicity

Longer duration than lidocaine and shorter duration than bupivacaine

Use:

• Local infiltration
• Nerve blocks
• Epidedural anesthesia

Blockade is 4-6 hours

Question 19

Ropivacaine

What is it used for?

Answer 19

The only local anesthetic that is formulated containing one optical isomer

Its primary advantage over bupivacaine is its lower toxicity when used in nerve and plexus blocks in which a large dose needs to be injected (use).

It achieves its lower toxicity primarily by excluding the more cardio- and neurotoxic isomer from the preparation.

It is also slightly less lipid soluble than bupivacaine (compare the length of the side chains on the piperidine nitrogens).

Question 20

Tetracaine

Duration

Toxicity

Use

Answer 20

It is an ester local anesthetic

Longerst duration of any available local anesthetics and also the most toxic (great lipid solubility because of hte four-carbon free alkyl chain - like bupivacaine) –> its “TetraToxic”

Systemic toxicity is rare due to small doses used in local anesthesia

Use: spinal anesthesia

Question 21

Proparacaine

Use?

Answer 21

Used for topical anesthesia of the cornea

It causes the least pitting of the cornea

Can be used to anesthesize the cornea for:

• measurement of intraocular pressure
• removal of a foreign body
• surgical procedures

*** Proparacaine should never be given to a patient with ocular pain for self administration –> repeated or chronic use damages that cornea and masks the underlying disease process

Question 22

Benzocaine

Use?

AE?

Answer 22

Only used topically

Lacks the amino group at the end of the molecule opposite the aromatic ring

Poorly soluble in water

Because the nucleus of benzocaine is aniline (aminobenzene), systemic absorption causes the stoichiometric oxidation of hemoglobin to methemoglobin.

Since benzocaine is typically administered topically on mucous membrane (e.g., mouth, airway), the large doses that may be used to facilitate upper endoscopy or bronchoscopy may cause significant methemoglobinemia.

Other local anesthetics that have a free aromatic amino group (procaine, proparacaine) are not used in sufficient doses to cause a meaningful degree of
methemoglobinemia.

In the lidocaine metabolite with an aromatic animo group (2,6- dimethylaniline), the amino group is sterically hindered from acting as an efficient
oxidizer of hemoglobin.

Question 23

Systemic adverse effects are common with local anesthetic use when?

Answer 23

Large doses are used

Local anesthetic is injected in well perfused tissues or applied to well-perfused surfaces or mucous membranes

*** There is an excellent correlation between the blood concetration of the local anesthetic and the magnitude of the untorward effects

Question 24

On what systems are the side effects of local anesthetics?

Rank the loca anesthetics from least to most toxic

Answer 24

Primarily the central nervous and cardiovascular systems

There is a relation between adverse effects and local anesthetic’s duration and lipid solubility

procaine < lidocaine ~ mepivacaine << bupivacaine < tetracaine

The “bad one” and the “tetratoxic one” are obviously on atop the list

Question 25

What is the initial effect of local anesthetics on the nervous sytem?

Answer 25

Although they inhibit nerve conduction, their initial effect is excitation –> This action may result from a selective effect of local anesthetics upon inhibitory neurons.

The initial CNS effects are:

• restlessness
• tremor
• altered visual perception.

As the blood concentration increases, seizures may result.

Local anesthetic-induced seizures are most often self-limited and followed by a period of CNS depression that may be accompanied by apnea and hypotension.

The appropriate therapy is to administer oxygen by mask and ensure adequate ventilation. If the seizure is prolonged, it may be treated with an intravenous barbiturate or benzodiazepine.

Question 26

Besides the initial effects of local anesthetics, what are the other effects?

Which spefic ones cause these effects?

Answer 26

Local anesthetics can also cause:

• decreased excitability
• conduction rate
• force of contraction in the heart

Bupivacaine is the most cardiotoxic local anesthetic

Question 27

What preservatives used in local anesthetic mixtures have demonstrated cross-reactance with PABA?

Answer 27

methylparaben

propylparaben

Question 28

A patient describes manifestation of local anesthetic “allergy” with symtoms of sweating and tachycardia after a local anesthetic dose. What could this be a result of?

Answer 28

This could be attributable to epinephrine

When a patient gives a history of local anesthetic “allergy,” the patient should be questioned carefully. Even when the symptoms were those of a true hypersensitivity reaction and the local anesthetic was an amide, the overwhelming probability was that the reaction was due
to the preservative!!

Question 29

What is local infiltration?

Advantage?

Disadvantage

Answer 29

The process by which the local anesthetic is injected into the tissue in the area in which numbness is desired

Dilute solutions are used since there is no need to block motor neurons

Epinephrine is often used as a vasoconstrictor except at end arteries like toes ears, nose and penis

Advantage - it requires no knowledge of the anatomic course of any nerves and that it usually does not disrupt any physiological functions

Disadvantage

• the impracticality of anesthetizing large areas
• difficulty in anesthetizing certain tissues by local infiltration (e.g. periosteum, peritoneum)
• difficulty in anesthetizing the viscera by this method

Question 30

What is a peripheral nerve block?

How do you locate the nerve?

Answer 30

Local anesthetic solution is injected in very close proximity to the nerve

Location of nerve:

• Some nerves are known to have very little variation eg median nerve
• Intentionally touch a nerve to induce parasthesia - to prevent intraneural injection which is very painful eg femoral nerve
• Needle connected to motor stimulator an invoke motor activity - only useful for mixed (sensory and motor nerves) eg sciatic nerve
• Needle is visualized in proximity to the nerve via ultrasound

Question 31

What is a plexus block?

Answer 31

Its similar to a peripheral nerve block but in this case the plexus is blocked proximal to where the peripheral nerves seperate from each other

Question 32

What is a spinal anesthetic?

How can you anesthesize high thoracic nerves with this method?

What’s the possible AE of spinal anesthesia?

Answer 32

This consists of injecting the local anesthetic solution into CSF after performing an lumbar puncture

Since the spinal cord ends at L1 in about 90% of people and at L2 in the remaining 10%, spinal anesthetics are administered at the L2-L3, L3-L4, L4-L5, or L5-S1 interspaces.

Typically a spinal anesthetic causes a temporary and reversible pharmacological transection of the spinal cord; autonomic, sensory, and motor nerves are blocked below the level of the anesthetic solution.

Even though no injection can be made above L2-L3, blockade of higher thoracic nerves is done by making the local anesthetic solution hyperbaric (having a higher specific gravity that SCF- by adding glucose) then tilting the patient into a head down position. This method can be used in intraabdominal surgery

AE - hypotension due to sympathetic blockade

• hydrate the patient prior to spinal injection

IV administration of vascontrictor - phenylephrine

Question 33

What is an epidural anesthetic?

Answer 33

The injection of local anesthetic solution into the epidural space - usually through a catheter allowing bolus injections or continuous infusions

Its a segmental block, localized to the dermatomes above and below the site of the catheter insertion

Concentration of the local anesthetic goes along with the degree of block

Question 34

Intravenous regional (or Bier) block

What is the technique of block?

Answer 34

This is a method of produces anesthesia of the arm (or much less commonly the leg)

Technique of block:

1. An intravenous catheter is inserted distally in the extremity.
2. The extremity is wrapped tightly, distally to proximally, with an Esmarch bandage to exsanguinate the limb.
3. A pneumatic tourniquet is placed proximally on the limb and inflated to a pressure approximately twice the systolic pressure.
4. A dilute (usually 0.5%) solution of lidocaine is injected into the i.v. catheter.

This type of block doesnt require much expertise. Limited to procedures less than 1.5 to 2 hours in duration. Pain from the tourniquet usually limits the overal duration of the block

The block dissipates rapidly after the tourniquet is deflated. As long as the tourniquet has been inflated for at least 15 min following lidocaine injection, the risk of
systemic toxicity is low. Conversely, tourniquet failure shortly after lidocaine injection is likely to be associated with systemic toxicity.

Question 35

What is topical anesthesia?

Answer 35

Most commonly used today to facilitate endoscopic procedures. The pharynx, nares, trachea, and esophagus are all readily anesthetized by topically-applied anesthetics.

Systemic absorption of local anesthetic solution from
mucous membranes is very efficient. Coupled with the fact that high concentrations of
local anesthetic solution are used topically (e.g. 4% lidocaine), it is important to limit the
total volume of local anesthetic solution used to minimize systemic toxicity.

Also recall
that topical benzocaine is associated with methemoglobinemia.