Morgan & Mikhail Chap 16(Local Anesthetics) Flashcards
Large vs Small Nerve Fibers
In comparing nerve fibers of the same type (myelinated versus unmyelinated), smaller diameter associates with increased
sensitivity to local anesthetics and with slower conduction velocity. Thus, larger, faster conducting Aα fibers are less sensitive to local anesthetics than smaller, slower conducting Aδ fibers. Larger unmyelinated fibers are less sensitive than smaller unmyelinated fibers. On the other hand, small unmyelinated C fibers are relatively resistant to inhibition by local anesthetics as compared with relatively larger myelinated
fibers. In a human peripheral nerve, the onset of local anesthetic inhibition generally
follows this sequence: autonomic before sensory before motor. But at steady state, if sensory anesthesia is present, usually all modalities are inhibited.
Nerve fiber classification
Pharmacokinetics - Absorption
In regional anesthesia, local anesthetics are typically applied close to their intended site of action; thus, their pharmacokinetic profiles in blood are important determinants of elimination and toxicity and have very little to do with the duration of their desired clinical effect.
Systemic absorption of injected local anesthetics depends on blood flow, which
is determined by the following factors.
1. Site of injection—
The rates of local anesthetic systemic absorption and rise of local anesthetic concentrations in blood are related to the vascularity of the site of injection and generally follow this rank order: intravenous (or intraarterial) > tracheal (transmucosal) > intercostal > paracervical > epidural > brachial plexus > sciatic > subcutaneous.
- Presence of additives—
The addition of epinephrine causes vasoconstriction at the site of administration,
leading to some or all of the following: reduced peak local anesthetic concentration in
blood, facilitated neuronal uptake, enhanced quality of analgesia, prolonged duration of
analgesia, and reduced toxic side effects. - Local anesthetic agent—
More lipid-soluble local anesthetics that are highly tissue bound are also more slowly
absorbed than less lipid-soluble agents. The agents also vary in their intrinsic vasodilator properties.
Pharmacokinetics - Distribution
Distribution depends on organ uptake, which is determined by the following factors.
1. Tissue perfusion—
The highly perfused organs (brain, lung, liver, kidney, and heart) are responsible for the
initial rapid removal of local anesthetics from blood, which is followed by a slower redistribution to a wider range of tissues. In particular, the lung extracts significant amounts of local anesthetic during the “first pass”; consequently, patients with right-to left cardiac shunts are more susceptible to toxic side effects of lidocaine injected as an antiarrhythmic agent.
- Tissue/blood partition coefficient—
Increasing lipid solubility is associated with greater plasma protein binding and also
greater tissue uptake of local anesthetics from an aqueous compartment. - Tissue mass—
Muscle provides the greatest reservoir for the distribution of local anesthetic agents in
the bloodstream because of its large mass.
Pharmacokinetics - Biotransformation and Excretion
The biotransformation and excretion of local anesthetics are defined by their chemical
structure. For all compounds, very little nonmetabolized local anesthetic is excreted by
the kidneys.
- Esters—
Ester local anesthetics are predominantly metabolized by pseudocholinesterase
(also termed butyrylcholinesterase). Ester hydrolysis is rapid, and the water-soluble metabolites are excreted in the urine. - Amides—
Amide local anesthetics are metabolized (N-dealkylation and hydroxylation) by
microsomal P-450 enzymes in the liver.
Benzocaine, a common ingredient in topical local anesthetic sprays,
can also cause dangerous levels of methemoglobinemia
Clinical use of local anesthetic agents
Effects on Organ Systems
Because voltage-gated Na channels underlie action potentials in neurons throughout the body as well as impulse generation and conduction in the heart, it is not surprising that increased circulating concentrations of local anesthetics could produce systemic toxicity. Although organ system effects are discussed for these drugs as a group, individual drugs differ
Effects on Organ Systems - Neuro
The central nervous system is vulnerable to local anesthetic systemic toxicity (LAST); fortunately, there are premonitory signs and symptoms of increasing local
anesthetic concentrations in blood in awake patients. Such symptoms include circumoral
numbness, tongue paresthesia, dizziness, tinnitus, blurred vision, and a feeling of impending doom. Such signs include restlessness, agitation, nervousness, and garrulousness. Muscle twitching precedes tonic–clonic seizures. Still higher blood
concentrations may produce central nervous system depression (eg, coma and
respiratory arrest). The excitatory reactions are thought to be the result of selective
blockade of inhibitory pathways.
In the past, unintentional injection of large volumes of chloroprocaine into the
subarachnoid space (during attempts at epidural anesthesia) produced total spinal
anesthesia, marked hypotension, and prolonged neurological deficits.
Transient neurological symptoms (including
dysesthesias, burning pain, and aching in the lower extremities and buttocks) have been
reported following spinal anesthesia with a variety of local anesthetic agents, but most
commonly after use of lidocaine 5% for male outpatients undergoing surgery in the
lithotomy position.
Effects on Organ Systems - Respiratory
Lidocaine depresses the ventilatory response to low PaO2 (hypoxic drive). Apnea can
result from phrenic and intercostal nerve paralysis (eg, from “high” spinals) or depression of the medullary respiratory center following direct exposure to local
anesthetic agents (eg, after retrobulbar blocks; see Chapter 36). However, apnea after
administration of a “high” spinal or epidural anesthetic is nearly always the result of hypotension and brain ischemia rather than phrenic block. Local anesthetics relax bronchial smooth muscle. Intravenous lidocaine (1.5 mg/kg) may block the reflex
bronchoconstriction sometimes associated with intubation.
Effects on Organ Systems - Cardiovascular
Effects on Organ Systems - Immunological
True hypersensitivity reactions (due to IgG or IgE antibodies) to local anesthetics —as distinct from LAST caused by excessive plasma concentrations—are uncommon.
Esters appear more likely to induce an allergic reaction, especially if the compound is a
derivative (eg, procaine or benzocaine) of PABA, a known allergen.
