Lidocaine

from Wikipedia, the free encyclopedia
Structural formula
Structure of lidocaine
General
Non-proprietary name Lidocaine
other names

2-Diethylamino- N - (2,6-dimethylphenyl) acetamide ( IUPAC )

Molecular formula C 14 H 22 N 2 O
Brief description

White to almost white, crystalline powder

External identifiers / databases
CAS number
  • 137-58-6 (lidocaine)
  • 73-78-9 (lidocaine hydrochloride)
  • 6108-05-0 (lidocaine hydrochloride monohydrate)
EC number 205-302-8
ECHA InfoCard 100,004,821
PubChem 3676
ChemSpider 3548
DrugBank DB00281
Wikidata Q216935
Drug information
ATC code
Drug class
Mechanism of action

Blockade of voltage-dependent sodium channels

properties
Molar mass 234.34 g mol −1
Physical state

firmly

Melting point

68.5 ° C

pK s value

8.01

solubility
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lidocaine is a topical anesthetic ( local anesthetic ) of the amide type . It also acts as a class Ib antiarrhythmic in tachycardiac (accelerated pulse) ventricular arrhythmias .

history

Lidocaine was the first amino-amide local anesthetic and was synthesized in 1943 by the Swedish chemists Nils Löfgren (1913-1967) and Bengt Lundqvist . They sold the patent rights for lidocaine to the Swedish pharmaceutical company AstraZeneca . Lidocaine was used worldwide from 1947.

presentation

Synthesis of lidocaine from 2,6-xylidine

Lidocaine is synthesized from 2,6-xylidine in several stages . The salt form lidocaine hydrochloride is often used medicinally .

Working principle

Lidocaine blocks voltage-dependent sodium channels in the cell membranes of the nerve cell . Lidocaine reduces the membrane permeability for cations , especially for sodium ions , and in higher concentrations also for potassium ions . Depending on the concentration, this leads to a reduced excitability of the nerve fiber, since the sudden increase in sodium permeability necessary for the development of the action potential is reduced. Lidocaine penetrates from the inside of the cell into the opened Na channel of the cell membrane and blocks its conductivity by occupying a specific binding site. If sensitive receptors on the skin are supposed to transmit the sensation of pressure, pain, warmth, cold, etc. to the brain, the transmission of excitation is blocked, since no sodium can flow into the nerve cell, which makes it difficult for an action potential to develop. When injected under the skin or when applied as an ointment, lidocaine only works on the nerve cells located there. Thin nerve fibers are blocked earlier in their transmission than thick ones. This results in the following order of loss of sensation: pain - temperature - touch - pressure. Finally, the innervation of the muscles, the efferents , is inhibited. Efferents are nerve fibers that come from the central nervous system and innervate muscles, for example. As a result, the motor skills (muscle movement) in the effective area of ​​the lidocaine fail.

Another active principle is the inhibition of the inflammation of the skin caused by staphylococcal toxin in atopic dermatitis , which could be demonstrated in vitro .

Analytics

The reliable qualitative and quantitative detection of lidocaine in body fluids is possible after appropriate sample preparation by coupling chromatographic methods such as HPLC or gas chromatography with mass spectrometry . These analytical methods are also used for forensic questions and drug control. Lidocaine is also an object of research in wastewater analysis.

application areas

Local anesthesia

Lidocaine is widely used in human and veterinary medicine as a good and fast-acting local anesthetic. The drug is listed three times in the list of essential drugs of the WHO , which shows its importance.

For this purpose, lidocaine is either injected into the tissue ( infiltration anesthesia ) in order to numb a smaller area, as is necessary for suturing a laceration or similar smaller operations. Alternatively, it is injected into the area of ​​a nerve in order to numb its supply area ( conduction anesthesia ). The drug should act for one to three minutes, then adequate local anesthesia is given. The duration of action is dose-dependent and is one to three hours.

Since lidocaine is well absorbed through the mucous membrane , this active ingredient is available in the form of sprays or ointments for surface anesthesia .

The combination of lidocaine with the anesthetic prilocaine in a ratio of 1: 1 creates a eutectic mixture ("Eutectic Mixture of Local Anesthetic", EMLA), which is liquid at skin temperature and penetrates well into the skin. The mixture is used as an active ingredient in surface anesthesia of the skin. A eutectic mixture with tetracaine is also used ( Pliaglis ). Another pharmaceutical development is liposomal encapsulation of lidocaine ( LMX4 ), which has been therapeutically available since 1998. This form of formulation should have a favorable effect on the application properties, since the duration of action on the skin should be shortened, the duration of action should be lengthened and side effects should be reduced.

Lidocaine is also an active ingredient in sprays and lubricants to facilitate endotracheal intubation and the insertion of a urinary catheter .

Lidocaine requires a prescription for parenteral use, with a few exceptions, as well as for use on the eye and the external auditory canal . For subcutaneous or intramuscular regional anesthesia in obstetrics (performing perineal incisions , suturing perineal incisions and tears), lidocaine in Germany may be given to midwives and obstetricians in a limited dose and in concentrations of up to 1% without a doctor's prescription .

Lidocaine has been available in various European countries since 2007 in the form of a transdermal patch with five percent by weight lidocaine, which is approved under the trade name Versatis for the treatment of neuropathic pain after herpes zoster infection.

In the context of major abdominal surgery, intravenous lidocaine leads to less pain, less nausea and better bowel function. In addition to the suppression of pain stimuli in the surgical area, an inhibiting effect on granulocytes is also held responsible for this effect. Therefore, intravenous lidocaine can be used for certain operations if a peridural catheter , which is the gold standard , is not available. This off-label use requires the consent of the patient before the operation. The dosage regimens usually start with an initial short infusion of 1.5 mg / kg followed by a continuous infusion of 1.5 mg / kg / h during the operation and a postoperative dose of 1.33 mg / kg / h for about 4 hours.

Local anesthesia in dentistry

Lidocaine is used in the form of an injection solution by dentists for local anesthesia. Epinephrine ( adrenaline ) is usually added to the finished medicinal products used in dentistry , which extends the duration of the lidocaine action. This happens through a narrowing of the vessels caused by the epinephrine, which means that it is transported more slowly into the patient's bloodstream. This means that the dentist seldom - usually not at all - has to re-inject, which makes work easier and shortens the session. However, undesirable effects are also known in which patients have had an allergic reaction to the added epinephrine. Injection solutions without added adrenaline are available for these patients. In practice, incidents are rare, as the drug is usually well tolerated.

Lidocaine is also used as an active ingredient in a teething aid for babies.

Lidocaine is also used in combination with chamomile flower extract as a mild drug for the treatment of painful inflammation of the gums and the oral mucosa .

Lidocaine has the nickname "dentist cocaine", especially in the southern German and Swiss-speaking regions.

Premature Ejaculation Control

Lidocaine is available to men in the form of ointments, sprays or creams to suppress premature ejaculation . The lidocaine-containing "long-term ointments" or "delay creams" or "delay spray solutions" are available without a prescription and are applied thinly to the glans when the foreskin is pulled back . Depending on the dosage, lidocaine often only reduces the sensitivity of the glans after 30 minutes and can take effect for 60 minutes.

Antiarrhythmic

Lidocaine slows down the spread of excitation in the heart muscle between the bundle of His and Purkinje fibers and thus has a stabilizing effect on the heart rhythm . As a class Ib antiarrhythmic , it suppresses cardiac arrhythmias that have their origin in the heart chambers (ventricular extrasystoles / tachycardia ) and is mainly used for tachycardiac arrhythmias. The earlier frequent use as an emergency medication has since declined sharply, since lidocaine itself can cause cardiac arrhythmias and limit the contraction force of the heart ( negative inotropic effect).

Lidocaine must be administered intravenously as an (Ib) antiarrhythmic. The first dose (1 to 1.5 mg / kg) is given as a “bolus” , then lidocaine should be given continuously by infusion or by a syringe pump (1 to 5 mg / min). It is indicated for all types of ventricular arrhythmias, including poisoning with antidepressants or glycosides and torsade de pointes tachycardia. Before interventions that cause irritation to the heart muscle (e.g. ablation or coronary angiography ), lidocaine can be given preventively in order to reduce the risk of ventricular arrhythmias.

In an AV block grade II lidocaine may not be given. Also, heart failure or hypotension represent contraindications as lidocaine - like other antiarrhythmic drugs - also has a negative inotropic effect.

Lidocaine slows down the steep rise in the action potential of the heart muscle cell, which occurs due to the rapid influx of sodium into the heart muscle cell. As with nerve cells, lidocaine inhibits the sodium channels in the heart muscle, and the influx of sodium into the heart muscle cell when excited slows down.

The binding of lidocaine to a sodium channel and influencing it is only possible if the sodium channel is in the open or inactivated state - i.e. during or at the end of a heart action. When the sodium channel is closed, i.e. H. in the resting phase, the lidocaine gradually dissociates from the sodium channel. During this period between two action potentials , the inhibitory effect of lidocaine therefore constantly decreases. Therefore, the inhibitory effect of lidocaine depends on the heart rate ( use-dependence block ).

At a high heart rate, lidocaine only partially dissociates from the sodium channel until a new action potential arises. With a slow heart rate, the lidocaine has enough time between two action potentials to completely dissociate from the sodium channel. As a result, the slowing down of the action potential at a low heart rate is less effective or not at all, while the effect on the sodium channels is more pronounced at high heart rates. This is a key benefit in treating tachycardiac arrhythmias with lidocaine.

Another advantage is that lidocaine can almost only work on already damaged myocardial cells, since these are already "pre-polarized" and the resting phase, in which the lidocaine cannot bind to the sodium channel, is shortened, although the time between the action potentials is not shortened have to be.

Cluster headache

To treat the acute cluster headache attack, lidocaine is given into the nostril on the affected side of the headache. Another use is to inject lidocaine near a nerve pathway to create a nerve block. Nasal application of 1 ml of 4 to 10% lidocaine solution can lead to an attack clipping within minutes. The presumed mechanism of action is an anesthetic of the nerve tracts in the area of ​​the palatine fossa ( fossa pterygopalatina ).

Experimental areas of application

Lidocaine was significantly superior to placebo in placebo-controlled studies for the treatment of tinnitus . However, since lidocaine can cause significant side effects, the substance was largely discarded for this area of ​​application.

Contraindications

If methyl 4-hydroxybenzoate is added to lidocaine as a preservative, it must not be used for intrathecal, intracisternal, intra- or retrobulbar injection.

In addition, lidocaine must not be used:

  • with severe disorders of the cardiac conduction system,
  • in acute decompensated heart failure,
  • in cardiogenic or hypovolemic shock,
  • if you have known allergies to the components

unwanted effects

Like all local anesthetics, lidocaine can cause the typical side effects and (if overdosed) poisoning symptoms; these include effects in the area of ​​the central nervous system (such as restlessness, seizures, etc.), the heart (arrhythmia), drop in blood pressure and allergic reactions .

Precautions

In patients with a reduced general condition or altered plasma protein binding ( e.g. renal insufficiency , liver insufficiency , carcinoma diseases , pregnancy ), smaller doses must always be used. In Melkersson-Rosenthal syndrome , allergic and toxic reactions of the nervous system can occur more frequently. The dose should be reduced in patients with signs of heart failure or clinically relevant disorders of cardiac excitation formation and spread. Caution is advised with myasthenia gravis and in patients with partial or complete heart block .

Trade names (selection)

Lidocaine is available as a monopreparation and a combination preparation .

Monopreparations

Dynexan (D, A, CH), Kenergon (CH), Licain (D), Acoin (D), LidoPosterine (D), Lignocaine (D), Posterisan akut (D), Sedagul (CH), Solarcaine (CH), Trachisan (D), Versatis (D), Xylocaine (D, A, CH), Xylocitin-loc (D), Xyloneural (CH, A) numerous generics (D, CH)

Combination preparations

Anaesthecomp (D), Anginazol (CH), Dentinox (D, A), Doloproct (D), Doxiproct (CH), Emla (D, A), Faktu akut (D), Fenipic (CH), Instillagel (D, A ), Kamistad (D), Lemocin (D, A, CH), Lidocain / Prilocain Plethora (EU), LMX4 (UK), Locastad (D), Neo-angin (CH), Parodontal (D), Pliaglis (D) , Rapydan (A), Sangerol (CH), Wick Sulagil (D)

Web links

Wiktionary: Lidocaine  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b European Pharmacopoeia Commission (Ed.): European Pharmacopoeia . 5th edition. tape 5.0-5.8 , 2006.
  2. ↑ E. Mutschler, G. Geisslinger, HK Kroemer, M. Schäfer-Korting: Mutschler drug effects. 8th edition. 2001, ISBN 3-8047-1763-2 , p. 267 ff.
  3. ↑ a b c d e Entry on lidocaine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. ↑ a b Lidocaine data sheet from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
  5. ↑ Raymond S. Sinatra, Jonathan S. Jahr, J. Michael Watkins-Pitchford: The Essence of Analgesia and Analgesics - Sinatra / year / Watkins-Pitc . ISBN 1-139-49198-9 , pp. 280 ( limited preview in Google Book search).
  6. ^ Nils Löfgren: Studies on local anesthetics: Xylocaine: a new synthetic drug . Ivar Heggstroms, Stockholm 1948.
  7. ↑ Qingqing Jiao et al .: Lidocaine inhibits staphylococcal enterotoxin-stimulated activation of peripheral blood mononuclear cells from patients with atopic dermatitis. In: Archives of Dermatological Research . 2013, pp. 1–8.
  8. ↑ A. Grigoriev, A. Nikitina, I. Yaroshenko, A. Sidorova: Development of a HPLC-MS / MS method for the simultaneous determination of nifedipine and lidocaine in human plasma. In: J Pharm Biomed Anal. 131, Nov 30, 2016, pp. 13-19. PMID 27521985
  9. ↑ A. Abdel-Rehim, M. Abdel-Rehim: Dried saliva spot as a sampling technique for saliva samples. In: Biomed Chromatogr. 28 (6), Jun 2014, pp. 875-877. PMID 24861757
  10. ↑ CE Hignite, C. Tschanz, J. Steiner, DH Huffman, DL Azarnoff: Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography. In: J Chromatogr. 161, Nov 21, 1978, pp. 243-249. PMID 730798
  11. ^ RT Coutts, GA Torok-Both, LV Chu, YK Tam, FM Pasutto: In vivo metabolism of lidocaine in the rat. Isolation of urinary metabolites as pentafluorobenzoyl derivatives and their identification by combined gas chromatography-mass spectrometry. In: J Chromatogr. 421 (2), Oct 30, 1987, pp. 267-280. PMID 3429583
  12. ↑ SF Lapachinske, GG Okai, A. dos Santos, AV de Bairros, M. Yonamine: Analysis of cocaine and its adulterants in drugs for international trafficking seized by the Brazilian Federal Police. In: Forensic Sci Int. 247, Feb 2015, pp. 48-53. PMID 25544694
  13. ^ R. Oertel, N. Arenz, SG Zeitz, J. Pietsch: Investigations into distribution of lidocaine in human autopsy material. In: Biomed Chromatogr. 29 (8), Aug 2015, pp. 1290-1296. PMID 25619956
  14. ^ R. Bad, JM White, C. Gerber: Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry. In: Anal Bioanal Chem. 410 (2), Jan 2018, pp. 529-542. PMID 29214532
  15. ↑ H. Lutz: Anesthesiological Practice . Springer-Verlag, 2013, ISBN 978-3-642-70974-6 , pp. 408- ( google.com ).
  16. ↑ Rolf H. Eichenauer: Clinic Guide Urology . Elsevier, Urban & FischerVerlag, 2003, ISBN 978-3-437-22790-5 , pp. 53- ( google.com ).
  17. ↑ Yellow list: Xylocaine gel 2% .
  18. ↑ Product information in the drug information system (AMIS) of the federal and state governments .
  19. ^ A. Herminghaus, M. Wachowiak, W. Wilhelm, A. Gottschalk, K. Eggert, A. Gottschalk: Intravenous lidocaine for perioperative pain therapy. In: The anesthesiologist. 60, 2011, p. 152, doi: 10.1007 / s00101-010-1829-0 .
  20. ↑ Xylocitin 2% with epinephrine (adrenaline) 0.001% (1: 100000) - Instructions for use. Retrieved on August 3, 2018 (German).
  21. ↑ Local anesthesia in old age . In: zm-online . ( zm-online.de [accessed on August 3, 2018]).
  22. ↑ Lidocaine for premature ejaculation .
  23. ↑ Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , pp. 73-76.
  24. ↑ May A, Evers S, Straube A, Pfaffenrath V, Diener HC: Therapy and prophylaxis of cluster headaches and other trigeminal autonomic headaches. Revised recommendations of the German Migraine and Headache Society . In: pain . 19, No. 3, June 2005, pp. 225-41. doi : 10.1007 / s00482-005-0397-8 . PMID 15887001 . DMKG: PDF file
  25. ↑ C. Rudack, M. Hillebrandt, M. van man, U. Hauser: Tinnitus treatment with lidocaine? A clinical experience report. In: ENT. 45 (2), Feb 1997, pp. 69-73. PMID 9173072 .
  26. ^ Technical information on xylocaine . Accessed July 31, 2019.