Local Anesthetics: Mechanisms and Clinical Use

<p>Voltage-gated Na channels (C)</p> Signup and view all the answers

<p>LA inhibition of Na currents increases with repetitive depolarizations (B)</p> Signup and view all the answers

<p>Higher molecular weight and higher lipid solubility increase potency (A)</p> Signup and view all the answers

<p>They are less readily removed from nerve membranes by the bloodstream (B)</p> Signup and view all the answers

<p>Smaller volumes of more concentrated LAs produce blocks with greater depth and longer duration (C)</p> Signup and view all the answers

<p>It decreases the uncharged portion. (C)</p> Signup and view all the answers

<p>Higher diffusion rates speed up onset. (A)</p> Signup and view all the answers

<p>General Anesthetics (B)</p> Signup and view all the answers

<p>Increase in pKa leads to rapid onset of action. (B)</p> Signup and view all the answers

<p>Bupivacaine (A)</p> Signup and view all the answers

<p>Smaller fibers are blocked at lower concentrations than larger fibers. (B)</p> Signup and view all the answers

<p>Prolonging and increasing intraneural concentrations of local anesthetics through vasoconstriction. (B)</p> Signup and view all the answers

<p>Basic pH increases the potency of local anesthetics. (A)</p> Signup and view all the answers

<p>The effect may depend on whether the local anesthetic solution contains epinephrine or not. (A)</p> Signup and view all the answers

<p>Pregnant individuals and animals show an increase neural susceptibility to local anesthetics. (A)</p> Signup and view all the answers

<p>Intercostal blocks consistently produce higher peak LA concentrations than epidural or plexus blocks. (D)</p> Signup and view all the answers

<p>α1-acid glycoprotein (B)</p> Signup and view all the answers

<p>Greater levels of toxicity may be seen at lower doses due to reduced first-pass uptake by the lungs. (A)</p> Signup and view all the answers

<p>Hydrolysis in the blood via non-specific esterases. (A)</p> Signup and view all the answers

<p>Breakdown to PABA (para-aminobenzoic acid). (D)</p> Signup and view all the answers

<p>o-toluidine (A)</p> Signup and view all the answers

<p>Hepatic blood flow and enzyme function (C)</p> Signup and view all the answers

<p>Increased cardiac output and hepatic blood flow and decreased protein binding. (D)</p> Signup and view all the answers

<p>Renal failure tends to increase the distribution volume and increases the accumulation of metabolic byproducts. (C)</p> Signup and view all the answers

<p>Its association with cauda equina syndrome following large intrathecal doses. (B)</p> Signup and view all the answers

<p>By inducing an increase in intracellular calcium levels. (D)</p> Signup and view all the answers

<p>Use of smaller, incremental doses. (B)</p> Signup and view all the answers

<p>Lipid infusion (A)</p> Signup and view all the answers

<p>Improved treatments and safer practices, including ultrasound guidance. (C)</p> Signup and view all the answers

<p>Inhibition of voltage-gated sodium channels. (A)</p> Signup and view all the answers

<p>Chloroprocaine and mepivacaine (D)</p> Signup and view all the answers

<p>They remain incompletely defined (D)</p> Signup and view all the answers

<p>Delayed-release local anesthetic formulations. (B)</p> Signup and view all the answers

<p>It may result in transient neurologic symptoms and persistent sacral deficits. (B)</p> Signup and view all the answers

<p>Theoretically, cholinesterase deficiency and inhibitors should increase the risk of toxicity from ester LAs, but clinical reports are lacking. (A)</p> Signup and view all the answers

<p>It is inhibited by β-blockers and H2-receptor blockers, potentially reducing the metabolism of amide LAs. (D)</p> Signup and view all the answers

<p>It significantly reduces ropivacaine clearance by inhibiting CYP 1A2. (D)</p> Signup and view all the answers

<p>LAs can bind to a wide range of targets besides sodium channels, including voltage-gated K and Ca channels, enzymes, and various receptors. (A)</p> Signup and view all the answers

<p>Gradual CNS excitation leading to seizures, then progressing to CNS depression and eventual respiratory arrest. (C)</p> Signup and view all the answers

<p>More potent local anesthetics tend to produce seizures at lower blood concentrations and doses than less potent ones. (B)</p> Signup and view all the answers

<p>Acidosis decreases the convulsive dose of lidocaine by increasing CNS excitability. (A)</p> Signup and view all the answers

<p>Most LAs will not produce CV toxicity until the blood concentration exceeds three times that necessary to produce seizures. (C)</p> Signup and view all the answers

<p>Bupivacaine binds more avidly and for longer time than lidocaine to cardiac Na channels. (D)</p> Signup and view all the answers

<p>bupivacaine &gt; levobupivacaine &gt; ropivacaine (A)</p> Signup and view all the answers

<p>They induce dilation of vascular smooth muscle. (D)</p> Signup and view all the answers

<p>True anaphylaxis is more common with ester LAs due to their metabolites. (B)</p> Signup and view all the answers

<p>LA skin testing has an excellent negative predictive value. (A)</p> Signup and view all the answers

<p>True anaphylactic reaction due to metabolic byproducts. (B)</p> Signup and view all the answers

<p>It reduces ropivacaine-induced changes in ST segments and left ventricular contractility. (C)</p> Signup and view all the answers

The study of how local anesthetics work and their potential side effects.

A drug that temporarily blocks pain signals by affecting nerve function, used in regional anesthesia.

The place where a local anesthetic binds to a nerve to block pain signals.

A traditional Andean practice of chewing coca leaves, often with alkaline substances like ash, to release cocaine.

The form of cocaine that is readily absorbed through the body, often produced by adding alkaline substances.

The process of extracting and crystallizing pure cocaine from coca leaves.

The initial exploration and use of cocaine by physicians, including Sigmund Freud.

A monograph written by Sigmund Freud documenting his research on cocaine, detailing its effects and potential for medical use.

The process of inhibiting nerve function by blocking the transmission of electrical signals along nerve fibers.

The region of the sodium channel where local anesthetics bind, preventing sodium ions from flowing through the channel.

The ability of an LA to bind to a sodium channel increases as the channel is repeatedly used or activated.

The degree to which a drug dissolves in lipids (fats).

A measure of the relative acidity of a substance.

The duration of time over which an LA produces its effect.

The time it takes for an LA to start producing its effect.

A type of nerve block that targets specific sensory nerves, reducing pain without affecting motor function.

The ability of an LA to block nerve transmission, with higher potency drugs requiring lower concentrations.

The chemical structure of LAs typically contains an aromatic ring, an amine, a hydrocarbon chain, and an ester or amide bond.

The natural form of cocaine is an ester local anesthetic.

LAs become more potent and have a longer duration of action with increased lipid solubility.

The rate of onset of LAs is influenced by factors including lipid solubility and molecular weight, but is not always predictable.

Sodium channels are integral membrane proteins that play a key role in electrical signaling.

Local anesthetics (LAs) preferentially block smaller diameter fibers at lower concentrations compared to larger fibers of the same type. This means that sensory fibers are blocked before motor fibers, achieving a more selective anesthetic effect.

LAs like bupivacaine and ropivacaine exhibit a higher affinity for sensory fibers, leading to a faster onset of sensory block compared to motor block.

The addition of epinephrine to LA solutions enhances the duration of anesthesia by constricting blood vessels and increasing the LA concentration at the nerve site. This prolongs the time LA stays near the nerves.

Uncharged LA molecules (bases) readily cross nerve sheaths and membranes, allowing for faster onset of anesthesia compared to charged LA molecules.

Sodium bicarbonate can increase the pH of LA solutions, which increases the proportion of uncharged LA molecules and potentially accelerates the onset of anesthesia. However, its effectiveness in clinical practice is inconsistent.

The concentration of LAs at the injection site varies depending on the location of injection. Intercostal blocks tend to have higher peak LA concentrations compared to epidural or plexus blocks.

Local anesthetics bind to plasma proteins, primarily α1-acid glycoprotein and albumin. This binding reduces the concentration of free LA in the bloodstream.

Ester-type local anesthetics are broken down rapidly in the blood by esterases, producing inactive metabolites. Procaine and benzocaine are examples of ester-type LAs.

Amide-type local anesthetics are primarily metabolized in the liver, undergoing various breakdown processes. Lidocaine, bupivacaine, and ropivacaine are examples of amide-type LAs.

Prilocaine, an amide-type LA, undergoes metabolism to o-toluidine, which can lead to methemoglobinemia, a condition where the blood's oxygen-carrying capacity is reduced. This can occur with doses as low as 400mg.

Factors reducing hepatic blood flow, such as β-blockers, H2 blockers, heart or liver failure, can also affect amide LA clearance. This means they stay in the body longer.

During pregnancy, the increased cardiac output and hepatic blood flow lead to faster clearance of amide LAs. Additionally, reduced protein binding allows more free LA to circulate.

Renal failure can result in a larger volume of distribution and accumulation of both ester and amide LA metabolites, potentially causing adverse effects.

LAs, once inside nerve cells, can be significantly affected by changes in pH, with greater potency and effectiveness occurring at more alkaline pH values.

Pregnant women and pregnant animals display enhanced susceptibility to LAs, possibly due to changes in nerve membrane properties or reduced blood flow.

Local anesthetics (LAs) can bind to various targets in the body, including voltage-gated sodium channels, potassium and calcium channels, and other receptors. This binding can lead to different effects, including analgesia and toxic side effects.

Local anesthetic CNS toxicity typically involves a stereotypical progression of signs and symptoms. It starts with CNS excitation, leading to seizures, followed by CNS depression, and ultimately respiratory arrest.

Stronger local anesthetics produce seizures at lower blood concentrations and doses compared to weaker ones.

Metabolic and respiratory acidosis can lower the convulsive dose of lidocaine, increasing the risk of seizures.

Bupivacaine, a longer-acting LA, commonly causes arrhythmias at high doses compared to ropivacaine and lidocaine.

LAs can produce cardiovascular signs of CNS excitation, like increased heart rate and blood pressure, before causing cardiac depression.

Hypocapnia, a decrease in CO2 levels, can reduce ropivacaine-induced changes in cardiac electrical activity and contractility.

Local anesthetics bind to and inhibit cardiac sodium channels, particularly the Nav1.5 isoform.

Bupivacaine has a higher affinity and longer binding duration compared to lidocaine when interacting with cardiac sodium channels.

The R(+) optical isomer of some local anesthetics binds more avidly to cardiac sodium channels than the S(-) optical isomer.

Local anesthetics can inhibit conduction in the heart, producing a dose-dependent effect on myocardial depression.

Local anesthetics bind and inhibit cardiac voltage-gated calcium and potassium channels at concentrations higher than those needed to block sodium channels.

Local anesthetics can bind to β-adrenergic receptors and inhibit the formation of cyclic adenosine monophosphate (cAMP), a key molecule in heart function.

The rank order for cardiac toxicity in rats seems to be bupivacaine > levobupivacaine > ropivacaine.

Cocaine is the only local anesthetic that consistently produces local vasoconstriction.

A condition caused by accidental large-dose intrathecal injection of 2-chloroprocaine, potentially leading to serious nerve damage.

A local anesthetic commonly used for spinal anesthesia, but known to cause concerns about neurotoxicity.

A local anesthetic that was initially formulated with sodium metabisulfite, but later replaced due to concerns about toxicity.

A chemical agent used in the initial formulation of 2-chloroprocaine, now considered a potential contributor to neurotoxicity.

The ability of a local anesthetic to suppress nerve signals for an extended duration.

The harmful effects of local anesthetics on the heart and blood vessels.

A severe adverse reaction to local anesthetics, causing a drop in blood pressure and potential cardiovascular collapse.

A medication used to manage seizures during local anesthetic overdose.

A medication used to manage seizures and provide sedation during local anesthetic overdose.

A medication used to stop muscle spasms and facilitate ventilation during local anesthetic overdose.

An approach to managing local anesthetic toxicity, involving infusing lipid solutions to help with resuscitation.

A medical procedure used to diagnose and treat certain heart conditions, potentially used during severe LAST.

A technique used to guide needles during peripheral nerve blocks, potentially enhancing safety.