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]] [[ar:ليدوكائين]] [[cs:Lidokain]] [[da:Lidokain]] [[de:Lidocain]] [[es:Lidocaína]] [[fr:Lidocaïne]] [[hr:Lidokain]] [[it:Lidocaina]] [[he:לידוקאין]] [[hu:Lidokain]] [[nl:Lidocaïne]] [[ja:リドカイン]] [[pl:Lidokaina]] [[pt:Lidocaína]] [[ro:Lidocaină]] [[sr:Лидокаин]] [[fi:Lidokaiini]] [[sv:Lidokain]] [[tr:Lidocaine]] [[ur:Lignocaine]] [[zh:利多卡因]]