Lidocaine
298762
225280818
2008-07-12T21:27:56Z
Lionelbrits
226319
/* Clinical use */
{{Drugbox|
| image = Lidocaine.png
| image2 = Lidocaine_spin.gif
| IUPAC_name = 2-(diethylamino)-<br />''N''-(2,6-dimethylphenyl)acetamide
| ATC_prefix=N01
| ATC_suffix=BB02
| ATC_supplemental={{ATC|C01|BB01}} {{ATC|D04|AB01}} {{ATC|S02|DA01}} {{ATC|C05|AD01}}
| PubChem=3676
| DrugBank=APRD00479
| CAS_number = 137-58-6
| C = 14 | H = 22 | N = 2 | O = 1
| molecular_weight = 234.34 g/mol
| smiles = CCN(CC)CC(=O)Nc1c(C)cccc1C
| melting_point = 68
| bioavailability = 35% (oral) <br /> 3% (topical)
| metabolism = [[Liver|Hepatic]], 90% [[CYP1A2]]-mediated
| elimination_half-life = 1.5–2 hours
| excretion = [[renal]]
| pregnancy_AU = A
| legal_AU = S4
| legal_US = unregulated
| routes_of_administration = [[Intravenous therapy|IV]], [[subcutaneous]], [[topical]]
}}
'''Lidocaine''' ([[International Nonproprietary Name|INN]]) ({{pronEng|ˈlaɪdoʊkeɪn}}) or '''lignocaine''' (former [[British Approved Name|BAN]]) ({{IPA|/ˈlɪgnoʊkeɪn/}}) is a common [[local anesthetic]] and [[antiarrhythmic agent|antiarrhythmic]] drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic, and in minor surgery. The most commonly encountered{{Fact|date=October 2007}} lidocaine preparations are marketed by [[Abraxis Pharmaceutical Products]] under the brand names '''Xylocaine''' and '''Xylocard''', and as 'Lanacane' topical ointment in the UK, though lidocaine is also found in many other proprietary preparations.
==History==
Lidocaine, the first [[amino]] [[amide]]-type local anesthetic, was first synthesized under the name xylocaine by [[Nils Löfgren]] in 1943.<ref name="lofgren_1948">{{cite book|author=Nils Löfgren|title=Xylocaine: a new synthetic drug|address=Stockholm|year=1948|note=Inaugural Dissertation May 24th 1948}}</ref>
His colleague Bengt Lundqvist made the first injection anesthesia experiments on himself.<ref name="lofgren_1948"/>It was first marketed in [[1948]].
==Pharmacokinetics==
Lidocaine has a more rapid onset of action and longer duration of action than [[amino]] [[ester]]-type local anesthetics such as [[procaine]].{{Fact|date=October 2007}} It is approximately 90% metabolized in the [[liver]] by [[CYP1A2]] (and to a minor extent [[CYP3A4]]) to the pharmacologically-active [[Metabolomics#metabolites|metabolites]] [[monoethylglycinexylidide]] and [[glycinexylidide]].
The elimination [[half-life]] of lidocaine is approximately 1.5–2 hours in most patients. This may be prolonged in patients with [[liver failure|hepatic impairment]] (average 343 minutes) or [[heart failure|congestive heart failure]] (average 136 minutes). (Thomson ''et al.'', 1973)
==Pharmacodynamics==
===Anesthesia===
Lidocaine alters depolarization in [[neuron]]s, by blocking the fast [[sodium channel|voltage gated sodium (Na<sup>+</sup>) channels]] in the cell membrane<ref name="novartis">{{cite journal |author= Cattterall WA |title= Molecular mechanisms of gating and drug block of sodium channels |journal= Novartis Found Symp |volume=241 |pages=206–32 |year=2002 |pmid=11771647 |doi= 10.1002/0470846682.ch14}}</ref>. With sufficient blockade, the membrane of the presynaptic neuron will not depolarize and so fail to transmit an [[action potential]], leading to its anesthetic effects.
Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling.
==Clinical use==
===Indications===
[[Topical]] lidocaine has been shown to relieve [[postherpetic neuralgia]] in some patients, although there is not enough study evidence to recommend it as a [[first-line treatment]]. (Khaliq ''et al.'', 2007)
[[Intravenous]] or [[intraosseous]] lidocaine is used to blunt the effects of [[laryngoscopy]] during rapid sequence intubation procedures, especially in cases of head injury.{{Fact|date=June 2008}}
===Contraindications===
Contraindications for the use of lidocaine include:
*[[Heart block]], second or third degree (without pacemaker)
*Severe [[sinoatrial block]] (without pacemaker)
*Serious [[adverse drug reaction]] to lidocaine or amide local anaesthetics
*Concurrent treatment with [[quinidine]], [[flecainide]], [[disopyramide]], [[procainamide]] (Class I [[antiarrhythmic agents]])
*Prior use of [[Amiodarone hydrochloride]]
*[[Hypotension]] not due to [[Arrhythmia]]
*[[Bradycardia]]
*[[Accelerated idioventricular rhythm]]
=== Adverse drug reactions ===
[[Adverse drug reaction]]s (ADRs) are rare when lidocaine is used as a local anesthetic and is administered correctly. Most ADRs associated with lidocaine for anesthesia relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, but [[allergy|allergic]] reactions can rarely occur.{{Fact|date=October 2007}}.
Systemic exposure to excessive quantities of lidocaine mainly result in [[central nervous system]] (CNS) and [[cardiovascular]] effects – CNS effects usually occur at lower [[blood plasma]] concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, [[tinnitus]], tremor, dizziness, blurred vision, [[seizure]]s) followed by depression, and with increasingly heavier exposure: drowsiness, loss of consciousness, [[respiratory depression]] and [[apnea]]). Cardiovascular effects include [[hypotension]], [[bradycardia]], [[arrhythmia]]s, and/or [[cardiac arrest]] – some of which may be due to [[Hypoxia (medical)|hypoxemia]] secondary to respiratory depression. (Rossi, 2006)
ADRs associated with the use of intravenous lidocaine are similar to toxic effects from systemic exposure above. These are dose-related and more frequent at high infusion rates (≥3 mg/minute). Common ADRs include: headache, dizziness, drowsiness, confusion, visual disturbances, [[tinnitus]], tremor, and/or [[paraesthesia]]. Infrequent ADRs associated with the use of lidocaine include: [[hypotension]], [[bradycardia]], [[arrhythmia]]s, [[cardiac arrest]], muscle twitching, [[seizure]]s, [[coma]], and/or respiratory depression. (Rossi, 2006)
===Insensitivity to lidocaine===
Relative insensitivity to lidocaine runs in families. In [[hypokalemic sensory overstimulation]], relative insensitivity to lidocaine has been described in people who also have [[attention deficit hyperactivity disorder]]. In dental anesthesia, a relative insensitivity to lidocaine can occur for anatomical reasons due to unexpected positions of nerves.
===Dosage forms===
Lidocaine, usually in the form of '''lidocaine hydrochloride''', is available in various forms including:
*Injected local anesthetic (sometimes combined with [[epinephrine]])
*Dermal patch (sometimes combined with [[prilocaine]])
*Intravenous injection (sometimes combined with [[epinephrine]])
*Intravenous infusion
*Nasal instillation/spray (combined with [[phenylephrine]])
*Oral gel (often referred to as "viscous lidocaine" or abbreviated "lidocaine visc" or "lidocaine hcl visc" in pharmacology; used as teething gel)
*Oral liquid
*Topical gel (as with [[Aloe Vera]] gels that include Lidocaine)
*Topical liquid
*Topical patch (Lidocaine 5% patch is marketed as "Lidoderm" in the US (since 1999) and "Versatis" in the UK (since 2007 by Grünenthal))
==Additive in cocaine==
Lidocaine is often added to [[cocaine]] as a [[diluent]].<ref>{{cite journal |author=Naissa Prévide Bernardo, Maria Elisa Pereira Bastos Siqueira, Maria José Nunes de Paiva, Patrícia Penido Maia |title=Caffeine and other adulterants in seizures of street cocaine in Brazil |journal= International Journal of Drug Policy |volume=14 |issue=4 |pages=331–334 |year=2003|doi=10.1016/S0955-3959(03)00083-5 |url=http://www.sciencedirect.com/science/article/B6VJX-497HGRX-5/2/3b5f81654f1e907ceb3095b4b5207362}}
</ref> Cocaine numbs the [[gums]] when applied, and since lidocaine causes stronger gingival numbness, customers get the impression of high-quality cocaine when in actuality, the user is receiving a diluted product.{{Fact|date=January 2008}}<ref>http://bulk.resource.org/courts.gov/c/F2/599/599.F2d.635.78-5314.html</ref>
==Notes==
<references/>
==References==
*{{cite journal |author=Khaliq W, Alam S, Puri N |title=Topical lidocaine for the treatment of postherpetic neuralgia |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD004846 |year=2007 |pmid=17443559 |doi=10.1002/14651858.CD004846.pub2 |url=http://www.cochrane.org/reviews/en/ab004846.html}}
*Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
* {{cite journal |author=Thomson PD, Melmon KL, Richardson JA, ''et al'' |title=Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans |journal=Ann. Intern. Med. |volume=78 |issue=4 |pages=499–508 |year=1973 |pmid=4694036 |doi=}}
{{Antiarrhythmic agents}}
{{Vasoprotectives}}
{{Antipruritics}}
{{Local anesthetics}}
{{Throat preparations}}
{{Otologicals}}
[[Category:Antiarrhythmic agents]]
[[Category:Local anesthetics]]
[[Category:Amides]]
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