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Flashcards in Local Anesthetics (Kiss) Deck (15):
1

Be able to differentiate between amide and ester local anesthetics.

Esters have 1 "i" / Amides have 2 "i's"

Esters:
- Cocaine
- Tetracacine
- Benzocaine
- Procaine
- Chloroprocaine

Amides:
- Lidocaine
- Mepivacaine
- Prilocaine
- Bupivacaine
- Bupivacaine SR
- Ropivacaine
- EMLA

2

Understand the mechanism of action of LAs.

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

3

Understand the effects of pH on the action of LAs

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

4

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

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

5

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

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

6

What is an LA?

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

7

Be able to describe the clinical usages of LAs.

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)

8

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

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

9

Allergic Reactions to LAs

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

Amides:
- do not form same metabolites and no hapten formation
- allergic reactions => rare

10

Describe the manifestations of LA toxicity and their treatment.

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

11

Understand the concept of methemoglobinemia as it relates to LAs.

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

Chocolate colored blood

Tx = methylene blue

12

Describe the salient features of selected LAs: esters

cocaine
benzocaine
tetracaine
procaine
chloroprocaine

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

13

What is an LA?

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

14

In a neuraxial blockade, the order of loss is:

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

15

Describe the salient features about selected LAs (amides:

lidocaine
mepivacaine
prilocaine
bupivacaine
EMLA

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