Local Anesthetics Flashcards
Drug that reversibly blocks impulse conduction along nerve axons and other excitable membranes that utilize voltage gated sodium channels as the primary means of action potential generation
Local Anesthetic
What are the three common structural features of local anesthetics?
Aromatic ring, Intermediate chain (Ester or amide), and ionizable group (usually a tertiary amine)
Are weak bases, therefore, the more acid the pH, the greater the [BH+]; the more basic, the greater the neutral [B] form
Local Anesthetics
Required to diffuse to the site of action
Neutral form of local anesthetic
Required for activity
The charged form of a local anesthetic
The more acidic the extracellular medium, the higher the proportion of the
Charged form
Block Na+ channels in excitable membranes without changing resting potential
Local Anesthetics
By doing this, local anesthetics reduce the aggregate
Inward sodium current
Neutral form of LA required to enter membrane, binding site is on the
Cytoplasmic face of channel
The charged LA is required for binding to the
Channel Site
LA binding is a function of the conformational state of the channel, i.e., different kinetics/affinities for different conformational states. This is called the
Modulated Receptor Hypothesis
In the modulated receptor hypothesis, LA’s have a higher affinity for the receptors in the activated & inactivated states, less affinity for the receptor in the
Resting state
Fibers that fire at a faster rate are more susceptible to the effects of
Local Anesthetics
Repeated depolarizations produce more effective
Anesthetic Binding
Repeated depolarizations produce more effective anesthetic binding. This phenomenon is known as
Frequency Dependent Block
High potency, highly hydrophobic drugs tend to be highly bound to
Serum and Tissue Proteins
The greater the degree of protein binding, the longer the
Duration
In clinical practice, incremental increases in local anesthetic concentration result in progressive interruption of (in order of sensitivity)
Autonomic/pain fibers, Sensory Fibers, and Motor Fibers
This is probably a result of a combination of geographic arrangement of nerve fibers and the intrinsic sensitivity of the nerve fiber types
Nerve Sensitivities to LA’s
In neuraxial blockade, the order of loss is
Autonomic/pain, Sensory, and Motor
In a peripheral blockade
- ) Motor Fibers are
- ) Sensory Fibers are
- ) Peripheral
2. ) Central
Of the sensory fibers:
- ) Proximal are?
- ) Distal are?
- ) Outside
2. ) Inside
In peripheral blockade, motor block occurs before
Proximal sensory loss which occurs before distal sensory loss
The absorption of local anesthetics is
Site dependent
What are the common sites for LA’s?
ICE-BS
-Intercostal, Caudal, Epidural, Brachial Plexus, and Sciatic Nerve
Decrease absorption of LA’s irrespective of site of injection
Vasoconstrictors (epinephrine and phenylephrine)
Particularly effective for short and medium acting drugs. Increase tissue binding responsible for duration of action of long acting drugs
Vasoconstrictors
Vasoconstrictors are intrinsically analgesic in
Neuraxial blockade
Low concentration of epinephrine added to LA; Small dose injected before therapeutic dose; Heart rate increases within 2 minutes (15% increase) if LA is injected
Intravascularly
Usually have a shorter duration of action
LA esters
How are the LA amides excreted?
Liver via cytochrome P450
Low flow states to liver (portal hypertension, CHF, etc.) decreases delivery of LA’s to liver, decreasing amide LA metabolism, increasing
Lifetime and serum concentration
Results from effects of LA on excitable membranes and tissues other than target nerves
Systemic Toxicity
Manifests first as CNS toxicity and then cardiotoxicity
Systemic Toxicity
The range of effects of systemic toxicity are directly proportional to
Serum LA concentration
Tinnitus, perioral numbness, blurred vision, metallic taste, change in MS, and convulsions are signs of
Systemic Toxicity
Systemic acidosis or hypercarbia increase sensitivity to
LA toxicity
Rescue of systemic toxicity is via
IV lipid emulsion
High concentrations of LA’s for extended periods can lead to
Nerve tissue destruction
High concentrations of LA’s for extended periods can lead to nerve tissue destruction via membrane damage, cytoskeletal disruption, etc. but not due to blockade of the
Na Channel
Motor and sensory losses are seen (e.g. cauda equina syndrome) and paralysis and paresis may result from
Local (Neural Tissue) Toxicity
Transient pain syndrome associated with spinally administered Lidocaine and certain surgical positions (e.g. lithotomy)
Transient Neurological Symptoms (TNS) from Local Toxicity
TNS is not associated with
Motor or sensory loss
A self limited neuropathic pain syndrome
TNS
When prilocaine metabolites (O-toluidine) act as an oxidizing agent to convert Hb++ to Hb+++
Methemoglobinemia
Which two LA’s can cause methemoglobinemia?
Prilocaine and Benzocaine
Characterized by chocolate colored blood and a pulse oximeter with 85% saturation
Methemoglobinemia
How do we treat methemoglobinemia?
Methylene Blue
Can cause allergic reactions due to hapten formation via PABA
Ester LA’s
A long duration, potent ester primarily used for spinal anesthesia, toxic at relatively low doses
Tetracaine
The exception to the short acting ester rule
Tetracaine
Quick onset, short duration, hypersensitivity reactions, TNS implication (rarely used)
Procaine (Novocain)
Quick onset, moderate duration and toxicity, TNS implication
Lidocaine
Longer duration than lidocaine, lowest pKa of injectable LA’s, acts as a vasoconstrictor
Mepivacaine
Associated with methemoglobinemia, component of EMLA
Prilocaine
Excellent long duration LA with devastating potential for cardiac toxicity. Sensory block>Motor block
Bupivacaine
Single enantiomer long duration LA with properties similar to bupivacaine but with less cardiotoxicity; vasoconstrictor
Ropivacaine
Eutectic Mixture of Local Anesthetic Prilocaine/Lidocaine for topical anesthesia
EMLA
