Lidocaine

Lidocaine
Systematic (IUPAC) name
2-(diethylamino)- N-(2,6-dimethylphenyl)acetamide
Identifiers
CAS number	137-58-6
ATC code	N01BB02 C01BB01 D04AB01 S02DA01 C05AD01
PubChem	3676
DrugBank	APRD00479
ChemSpider	3548
Chemical data
Formula	C14H22N2O
Mol. mass	234.34 g/mol
SMILES	eMolecules & PubChem
Physical data
Melt. point	68 °C (154 °F)
Pharmacokinetic data
Bioavailability	35% (oral) 3% (topical)
Metabolism	Hepatic, 90% CYP1A2-mediated
Half life	1.5–2 hours
Excretion	renal
Therapeutic considerations
Pregnancy cat.	A(AU)
Legal status	Prescription Only (S4)(AU) ?(US)
Routes	IV, subcutaneous, topical

Lidocaine (INN) (pronounced /ˈlaɪdoʊkeɪn/) or lignocaine (former BAN) (/ˈlɪgnoʊkeɪn/) is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic, and in minor surgery.

History

Lidocaine, the first amino amide-type local anesthetic, was first synthesized under the name xylocaine by Nils Löfgren in 1943.^[1] His colleague Bengt Lundqvist made the first injection anesthesia experiments on himself.^[1]It was first marketed in 1948.

Pharmacokinetics

Lidocaine is approximately 90% metabolized in the liver by CYP1A2 (and to a minor extent CYP3A4) to the pharmacologically-active 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 hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes). (Thomson et al., 1973)

Pharmacodynamics

Anesthesia

Lidocaine alters depolarization in neurons, by blocking the fast voltage gated sodium (Na⁺) channels in the cell membrane^[2]. With sufficient blockade, the membrane of the presynaptic neuron will not depolarize and so fail to transmit an action potential, leading to its anaesthetic 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.

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 reactions (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 allergic reactions can rarely occur..

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, seizures) followed by depression, and with increasingly heavier exposure: drowsiness, loss of consciousness, respiratory depression and apnoea). Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest – some of which may be due to 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, arrhythmias, cardiac arrest, muscle twitching, seizures, 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))
• Topical aerosol Spray

Additive in cocaine

Lidocaine is often added to cocaine as a diluent.^[3] Cocaine numbs the gums when applied, and since lidocaine causes stronger gingival numbness, users get the impression of high-quality cocaine when in actuality, the user is receiving a diluted product.^[4]

Notes

1. ↑ ^{1.0 1.1} Nils Löfgren (1948). Xylocaine: a new synthetic drug. 
2. ↑ Cattterall WA (2002). "Molecular mechanisms of gating and drug block of sodium channels". Novartis Found Symp 241: 206–32. doi:10.1002/0470846682.ch14. PMID 11771647. 
3. ↑ Naissa Prévide Bernardo, Maria Elisa Pereira Bastos Siqueira, Maria José Nunes de Paiva, Patrícia Penido Maia (2003). "Caffeine and other adulterants in seizures of street cocaine in Brazil". International Journal of Drug Policy 14 (4): 331–334. doi:10.1016/S0955-3959(03)00083-5. http://www.sciencedirect.com/science/article/B6VJX-497HGRX-5/2/3b5f81654f1e907ceb3095b4b5207362. 
4. ↑ 599 F.2d 635

References

• Khaliq W, Alam S, Puri N (2007). "Topical lidocaine for the treatment of postherpetic neuralgia". Cochrane Database Syst Rev (2): CD004846. doi:10.1002/14651858.CD004846.pub2. PMID 17443559. 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
• Thomson PD, Melmon KL, Richardson JA, et al (1973). "Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans". Ann. Intern. Med. 78 (4): 499–508. PMID 4694036.