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Chapter 11 (Local anesthetics)
Terms in this set (25)
What is the prototype local anesthetic? Explain its structure.
The procaine molecule is derived from an aromatic acid (para-aminobenzoic acid) and an amino alcohol, yielding a structure with three distinct regions: an aromatic head, which imparts lipophilicity; a terminal amine tail, a proton acceptor that imparts hydrophobicity; and a hydrocarbon chain attached to the aromatic acid by an ester
Explain the development of lidocaine, and why its lower risk for allergic rxn?
lidocaine was introduced, and it was the first departure from the amino-ester series. Being derived from an aromatic amine (i.e., xylidine) and an amino acid, the hydrocarbon chain and the aromatic head of the lidocaine molecule are linked by an amide bond (rather than an ester), imparting greater stability. This molecular structure also averts the allergic reactions
commonly associated with ester anesthetics (which result from sensitivity to the cleaved aromatic acid).
Mneumonic to remember topical anesthestics.
The word 'amide' has a letter I in it and the amides have TWO I's in their name:
lidocaine, prilocaine, bupivacaine, mepivacaine, ropivacaine, etidocaine, and dibucaine.
Ester anesthetics contain only ONE I in their name:
cocaine, chloroprocaine, tetracaine, and benzocaine.
How do the newer regional anesthetics differ from the first generation topicals?
Xylidine, including mepivacaine, bupivacaine, ropivacaine,
In contrast to lidocaine, the terminal amino portion of these newer compounds is contained within a piperidine ring.
What is the advantage for using Ropivacaine and levobupivacaine?
These are single enantomers that take advantage of the sterio-selectivity of neuronal sodium channels thereby reducing cardiotoxicity.
What influence do these drugs have on the resting membrane potential?
None, they simply decrease the likelihood of ion transmission during depolarization.
How does the Quaternary form and the tertiary form of these compounds relate to the mechanism of action?
Most likely these compounds exert their anti-conductive effects with the positively charged tertiary amine form which interferes with the sodium channel. However the compound can't penetrate the hydrophillic neuron membrane in this form thus the quaternary form allows the drug to penetrate the membrane and reach the sodium ion channel. However this doesn't explain the MOA of procaine for example which is an uncharged structure and not affected by pH.
What confirmational states does local anesthetics bind to Na Channels and how does this result in functional anesthesia?
They bind to both the inactivated and activated states but not the resting state, thus the drugs effect is enhanced when depolarization occurs leading to enhanced blockade, thus nerves with increased AP frequencies are subject to enhanced blockage.
How does acid affect the efficacy of local anesthetics?
Local anesthetics are more effective they they are ionized form since this is the confirmation that allows them to exert their action. Thus acidic environments such as localized acidosis due to infection can decrease the efficacy of these drugs. Acid is used to store these compounds since it makes them more stable as a uncharged base, however, bicarb is commonly added to these drugs to increased the ionized fraction.
When injecting anesthesia, how would you expect the anatomical effect to occur?
Proximal to distal due to the outer nerves in the bundle usually representing proximal distribution while the core nerves are usually more peripheral.
Vasoactive properties of most locals?
In general they cause vaso-dilation, ropivicaine may cause constriction.
CNS toxicity syndrome? Tx?
Circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, and slurred speech, culminating in tonic-clonic seizures (inhibition of inhibitory neurons), though marked variation from this pattern is quite common. Even larger doses lead to coma and CNS depression. Acidosis during such an even from hypoxemia can potentiate toxicity.
Neuromuscular blockade can be helpful, but this wont affect underlying CNS issues. Propofol and benzos can also help.
Cardio toxiciy w/ locals?
Produce profound hypotension due to relaxation of arteriolar vascular smooth muscle and direct myocardial depression.
Cardiac automaticity and conduction of cardiac impulses are impaired,
manifesting on the electrocardiogram as prolongation of the PR interval and widening of the QRS complex.
New method for addressing local anesthetic cardiovascular collapse and systemic toxicity?
Injection of lipid emulsions essentially scavange local anesthetic into the lipid fraction injected thus decreasing concentration of active product affecting tissue. Usually a bag of 20% lipid emulsion can do the trick.
Which type of anesthetic has more potential for allergic rxn?
The ester local class is more likely due to the byproduct of para-aminobenzoic acid.
Mostly used for spinal anesthesia. Tetracaine is rarely used for epidural
anesthesia or peripheral nerve blocks because of its slow onset, profound motor blockade, and potential toxicity when administered at high doses. Much slower breakdown even though it is an ester.
Chloroprocaine initially gained popularity as an epidural anesthetic, particularly in obstetrics because its rapid hydrolysis virtually eliminated concern about systemic toxicity and fetal exposure to the local anesthetic. Unfortunately, neurotoxic injury, presumed to occur from accidental intrathecal injection of high doses intended for the epidural space, tempered enthusiasm.
Chloroprocaine produces epidural anesthesia of a relatively short duration. Epidural administration of chloroprocaine is sometimes avoided because it impairs the anesthetic or analgesic action of epidural bupivacaine and of opioids used concurrently or sequentially.
Lidocaine is the most commonly used local anesthetic. It is used for local topical and regional intravenous applications, peripheral nerve block, and spinal and epidural anesthesia. Although recent issues have led to restricted use of lidocaine for spinal anesthesia, this local anesthetic
remains popular for all other applications, including epidural anesthesia.
Potential neurotox has been ID'd w/ risk for cauda equina syndrome w/ neurotoxic doses injected.
Transient Neurologic Symptoms (TNS) decribed by pain and dysesthesia can occur. Presents w/i 12-24hrs often resolve by 3 day usually no longer than a week. Tx w/ NSAIDs. No functional loss is seen.
Compared to lidocaine has less vasodilation, slightly longer duration of action. Clinical use parallels lidocaine except not topically used. Lower incidence of TNS than lidocaine when used spinally.
Rapid metabolism, and low CNS toxicity, however metabolite ortho-toluidine can cause methemoglobinemia which can be reversed w/ methylene blue 1-2 mg/kg IV.
Not approved in US but currently being looked at for spinal anesthesia in Europe.
Congener of mepivicaine. It has a high proportion of sensory block versus motor w/ longer duration of action, makes it the most commonly used epidural anesthetic for labor and posoperative pain. Also effective for peripheral nevers and spinal anesthesia.
Cardiotoxicity mediated by its relatively fastidious nature to adhere to sodium channels, thus far more depressing. Thus max amount injected is an important consideration for this anesthetic.
Similar to both mepivicaine and buvivacaine this is an (S) enantiomer with an added propyl group. This drug has a more favorable interaction with sodium channels of the heart providing less cardiotoxicity and vasoconstriction which also most likely contibutes to its ability to be cardiac safe. Also though to have less motor block.
Interestingly it is less potent compared to bupivicaine so its cardiotoxicty profile is called into affect when comparisons of equieffective analgesia are put into consideration.
The (S) enantiomer of bupivicaine is less cardiotoxic with a similar blockade profile. May only be beneficial when considering larger doses of anesthetc
Lidocaine prilocaine cream
Best for topical anesthesia 2.5% for both compounds. Can take 1 hour to take effect.
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