Local Anesthetics (Kiss)

Question 1

Be able to differentiate between amide and ester local anesthetics.

Answer 1

Esters have 1 “i” / Amides have 2 “i’s”

Esters:

• Cocaine
• Tetracacine
• Benzocaine
• Procaine
• Chloroprocaine

Amides:

• Lidocaine
• Mepivacaine
• Prilocaine
• Bupivacaine
• Bupivacaine SR
• Ropivacaine
• EMLA

Question 2

Understand the mechanism of action of LAs.

Answer 2

Neutral form diffuses through lipid bilayer and then charged form binds channel on cytoplasmic side

LA + H+ LAH+

Block NA+ channels in excitable membranes without changing resting potential

Reduce aggregate inward Na+ current

Question 3

Understand the effects of pH on the action of LAs

Answer 3

LAs are weak bases… need both of both species (ionized and neutral)

The more acidic the extracellular medium, the higher the proportion of the charged form

Question 4

Be able to explain the concept of the Modulated Receptor Hypothesis.

Answer 4

LA binding is a function of conformational state of the channel, i.e., different kinetics/affinities for different conformational states

LAs have higher affinity for receptors in activated and inactivated states, less affinity for receptor in resting state

Question 5

Understand the concepts of lipophilicity, pKa, and protein binding as they relate to potency, onset of action, and duration of LAs.

Answer 5

Inc. lipophilicity (the fattier the LA, the longer it lasts)

• inc. potency
• inc. duration
• slower onset of action

Inc. pKa = slower onset of action
- more “base-ier” the LA is, the more it will become charged in an acidic medium - you want to keep pKa and ambient pH as close as possible

Inc. protein binding = inc. duration
- Harder to metabolize -> therefore, lasts longer

Question 6

What is an LA?

Answer 6

A drug that reversibly blocks impulse conduction along nerve axons and other excitable membranes that utilize voltage gated sodium channels as primary means for AP generation

Question 7

Be able to describe the clinical usages of LAs.

Answer 7

Topical (benzocaine)

Infiltration (take a small gauge needle, go subcutaneously and inject LA - works fro small areas, not whole arm)

Regional anesthesia and analgesia

• Peripheral blocks (plexus anesthesia, individual nerve blocks)
• Neuraxial blocks (spinal, epidural)

Question 8

Understand the use of vasoconstrictors as it relates to absorption and duration of LAs.

Answer 8

epinephrine, phenylephrine

vasoconstrictors will prolong the duration of the block

• dec. absorption
• particularly effective for short and medium acting drugs
• inc. tissue binding responsible for duration of action of long acting drugs

Question 9

Allergic Reactions to LAs

Answer 9

Esters:
PABA -> hapten formation -> true IgE mediated allergy

Amides:

• do not form same metabolites and no hapten formation
• allergic reactions => rare

Question 10

Describe the manifestations of LA toxicity and their treatment.

Answer 10

Systemic toxicity

• Results from effects of LA on excitable membranes and tissues other than target nerves
• Manifest first as CNS toxicity then cardiotoxicity

Local (neural tissue) toxicity

• High concentration of LA for extended periods can lead to nerve tissue destruction
• Motor and sensory loss seen
• Paralysis and paresis

Question 11

Understand the concept of methemoglobinemia as it relates to LAs.

Answer 11

Prilocaine metabolites act as oxidizing agent to convert Hb++ to Hb+++

Chocolate colored blood

Tx = methylene blue

Question 12

Describe the salient features of selected LAs: esters

cocaine
benzocaine
tetracaine
procaine
chloroprocaine

Answer 12

cocaine: stimulant, vasoconstrictor
benzocaine: primarily topical, MetHb potential
tetracaine: a long duration, potent ester primarily used for spinal anesthesia, toxic at relatively low doses (exception to short acting ester rule)

procaine (novocain): quick onset, short duration, hypersensitivity rxns, TNS implication (no motor/sensory loss) - rarely used

chloroprocaine: used to have a bad rep, now a commonly used quick onset, short duration LA

Question 13

What is an LA?

Answer 13

A drug that reversibly blocks impulse conduction along nerve axons and other excitable membranes that utilize voltage gated sodium channels as primary means for AP generation

Question 14

In a neuraxial blockade, the order of loss is:

Answer 14

1. autonomic/pain
2. sensory
3. motor (need most concentrated amount of local)

Question 15

Describe the salient features about selected LAs (amides:

lidocaine
mepivacaine
prilocaine
bupivacaine
EMLA

Answer 15

lidocaine: quick onset, moderate duration and toxicity, TNS implication
mepivacaine: longer duration than lidocaine, lowest pKa of injectable LAs, acts as a vasoconstrictor
prilocaine: associated w/ methemoglobinemia, component of EMLA

bupivacaine: excellent long duration LA w/ devastating potential for cardia toxicity
- sensory block > motor block

EMLA: eutectic mixture of LA (prilocaine/lidocaine) for topical anesthesia