Local Anesthetics Flashcards
How does local anesthetics inhibits the pain stimulus propagation?
Local anesthetics act on a wide range of molecular targets, but they exert their predominant desired clinical effects by blocking sodium ion flux through voltage-gated sodium channels.
From an electrophysiologic standpoint, local anesthetics block conduction of impulses by decreasing the rate of depolarization in response to excitation, preventing achievement of the threshold potential. They do not alter the resting transmembrane potential, and they have little effect on the threshold potential
The lower the pKa, the greater the percentage of … fraction at a given pH
unionized
How many Ranvier nodes need to be blocked to prevent the action potential from propagate?
At the limit of short lengths of nerve exposed to local anesthetic, conduction blockade requires exposure of at least three successive nodes of Ranvier to prevent the action potential from “skipping over” the region of local anesthetic exposure
When a nerve block is performed, why the anatomical proximal areas are affect before than distal areas?
With large nerve trunks, local anesthetics diffuse from the outer surface (mantle) toward the center (core) of the nerve along a concentration gradient. As a result, nerve fibers located in the mantle of the mixed nerve are blocked first. These mantle fibers are generally distributed to more proximal anatomic structures, whereas distal structures are innervated by fibers near the core
Local anesthetics metabolism
The amino-ester local anesthetics undergo hydrolysis by plasma esterases, whereas the amino-amide local anesthetics undergo metabolism by hepatic microsomal enzymes. The lungs are also capable of extracting local anesthetics such as lidocaine, bupivacaine, and prilocaine from the circulation. The rate of this metabolism and first-pass pulmonary extraction may influence toxicity
Systemic absorption of local anesthetic is greatest after injection for … , intermediate after …, and least after …
intercostal nerve blocks and caudal anesthesia
epidural anesthesia
brachial plexus and lower extremity blocks
How high systemic doses of local anesthetics affect the cardiovascular system?
High plasma concentrations of local anesthetics can produce profound hypotension caused by relaxation of arteriolar vascular smooth muscle and direct myocardial depression. The cardiac toxicity, in part, reflects the ability of local anesthetics to block cardiac sodium ion channels in addition to other ion channels, including calcium channels. As a result, cardiac automaticity and conduction of cardiac impulses are impaired, manifesting on the electro- cardiogram as prolongation of the PR interval and widen- ing of the QRS complex. Local anesthetics may profoundly depress myocardial contractility to varying degrees
Lipid emulsion dose for systemic toxicity of local anesthetics
intravenous bolus dose of 20% lipid emulsion starts with a bolus of 1.5mL/kg over 2 to 3 minutes (100 mL if greater than 70 kg) followed by a continuous infusion at 0.25 mL/kg/min
Why lidocaine is avoided for spinel anesthesia?
doses of lidocaine routinely used for single-injection spinal anesthesia (75–100 mg) have been associated with neurotoxicity
What are the transient neurological symptoms (TNS)?
TNS is pain of the lower extremities after spinal anesthesia. Symptoms of TNS generally manifest within the first 12 to 24 hours after surgery, most often resolve within 3 days, and rarely persist beyond a week. Nonsteroidal antiinflammatory drugs are often effective and should be used as first-line treatment. TNS is not associated with sensory loss, motor weakness, or bowel and bladder dysfunction. Additionally, magnetic resonance imaging (MRI) and electrophysiologic examinations are normal. The cause and significance of TNS symptoms remain to be established
Which local anesthetics can cause TNS?
All local anesthetics can cause TNS; however, the risk is 5-to 10-fold higher when patients receive intrathecal doses of lidocaine or mepivacaine compared with bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine
Negative feature of prilocaine’s metabolism
administration of large doses (>600 mg) may result in clinically significant accumulation of the metabolite ortho-toluidine, an oxidizing compound capable of converting hemoglobin to methemoglobin
What is the mechanism associate with the cardio toxicity of bupivacaine
The most likely mechanism for bupivacaine’s cardiotoxicity relates to the nature of its interaction with cardiac sodium ion channels. When electrophysiologic differences between anesthetics are compared, lidocaine enters the sodium ion channel quickly and leaves quickly. In contrast, recovery from bupivacaine blockade during diastole is relatively prolonged, making it far more potent with respect to depressing the maximum upstroke velocity of the cardiac action potential (Vmax) in ventricular cardiac muscle. As a result, bupivacaine has been labeled a “fast-in, slow-out” local anesthetic. This characteristic likely creates conditions favorable for unidirectional block and reentry. Other mechanisms may contribute to bupivacaine’s cardiotoxicity, including disruption of atrio- ventricular nodal conduction, depression of myocardial contractility, and indirect effects mediated by the central nervous system
