Local Anesthetics (Kiss) Flashcards
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
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
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
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
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
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
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)
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
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
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
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
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
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
In a neuraxial blockade, the order of loss is:
- autonomic/pain
- sensory
- motor (need most concentrated amount of local)
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
