http://www.druginfosys.com/Drug.aspx?

drugCode=418&DrugName=Lignocaine&type=

http://en.wikipedia.org/wiki/Local_anesthetic

lignocaine 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 or as a local anesthetic for minor surgery.

Preparation Lignocaine is a sodium channel blocking agent, used as a local anesthetic

and antiarrhythmic agent. It stabilizes nerve cell membranes to prevent impulse
conduction. Used topically or by injection for local anaesthesia in minor
operations.Intravenous injection or infusion used to treat abnormal heart rhythms.
Excessive doses also block motor impulses and normal cardiac conduction. It has a
low incidence of toxicity and a high degree of effeciveness in arrhythmias. Lignocaine
is one of the least cardiotoxic drug of the currently used sodium channel blocker.

Lidocaine may be prepared in two steps by the reaction of 2,6-xylidine with chloroacetyl
chloride, followed by the reaction with diethylamine:[2]

Contents
[hide]

• 1 History
• 2 Preparation
• 3 Pharmacokinetics
• 4 Pharmacodynamics
 o 4.1 Anesthesia
o 4.2 Indications
o 4.3 Contraindications
o 4.4 Adverse drug reactions
o 4.5 Overdosage
o 4.6 Insensitivity to lidocaine
o 4.7 Dosage forms
• 5 Additive in cocaine
• 6 Illegal uses
• 7 Compendial status
• 8 See also
• 9 Notes and references

• 10 External links

Pharmacokinetics
Lidocaine is approximately 95% metabolized (dealkylated) in the liver by CYP3A4 to the
pharmacologically-active metabolites monoethylglycinexylidide (MEGX) and then
subsequently to the inactive glycine xylidide. MEGX has a longer half life than lidocaine
but also is a less potent sodium channel blocker. [3]

The elimination half-life of lidocaine is approximately 90–120 minutes in most patients.

This may be prolonged in patients with hepatic impairment (average 343 minutes) or
congestive heart failure (average 136 minutes).[4]

Pharmacodynamics
Anesthesia
Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium
(Na+) channels in the neuronal cell membrane that are responsible for signal
propagation[5]. With sufficient blockage the membrane of the postsynaptic neuron will not
depolarize and will thus fail to transmit an action potential. This creates the anaesthetic
effect by not merely preventing pain signals from propagating to the brain but by aborting
their birth in the first place. 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.
A local anesthetic is a drug that causes reversible local anesthesia and a loss of
nociception. When it is used on specific nerve pathways (nerve block), effects such as
analgesia (loss of pain sensation) and paralysis (loss of muscle power) can be achieved.

Mechanism of action
All local anesthetics are membrane stabilizing drugs; they reversibly decrease the rate of
depolarization and repolarization of excitable membranes (like nociceptors). Though
many other drugs also have membrane stabilizing properties, not all are used as local
anesthetics (propranolol, for example). Local anesthetic drugs act mainly by inhibiting
sodium influx through sodium-specific ion channels in the neuronal cell membrane, in
particular the so-called voltage-gated sodium channels. When the influx of sodium is
interrupted, an action potential cannot arise and signal conduction is inhibited. The
receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium
channel. Local anesthetic drugs bind more readily to sodium channels in activated state,
thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred
to as state dependent blockade.

Local anesthetics are weak bases and are usually formulated as the hydrochloride salt to
render them water-soluble. At the chemical's pKa the protonated (ionized) and
unprotonated (unionized) forms of the molecule exist in an equilibrium but only the
unprotonated molecule diffuses readily across cell membranes. Once inside the cell the
local anesthetic will be in equilibrium, with the formation of the protonated (ionized
form), which does not readily pass back out of the cell. This is referred to as "ion-
trapping". In the protonated form, the molecule binds to the local anesthetic binding site
on the inside of the ion channel near the cytoplasmic end.

Acidosis such as caused by inflammation at a wound partly reduces the action of local
anesthetics. This is partly because most of the anesthetic is ionized and therefore unable
to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium
channel.

All nerve fibers are sensitive to local anesthetics, but generally, those with a smaller
diameter tend to be more sensitive than larger fibers. Local anesthetics block conduction
in the following order: small myelinated axons (e.g. those carrying nociceptive impulses),
non-myelinated axons, then large myelinated axons. Thus, a differential block can be
achieved (i.e. pain sensation is blocked more readily than other sensory modalities).
Indications

Topical lidocaine has been shown to relieve postherpetic neuralgia (arising, for example,
from shingles) in some patients, though there is not enough study evidence to recommend
it as a first-line treatment.[6] It also has uses as a temporary fix for tinnitus. Although not
completely curing the illness, it has been shown to reduce the effects by around two
thirds.[7]

The efficacy profile of lidocaine as a local anesthetic is characterized by a rapid onset of

action and intermediate duration of efficacy. Therefore, lidocaine is suitable for
infiltration, block and surface anesthesia. Longer-acting substances such as bupivacaine
are sometimes given preference for spinal and peridural anesthesias; lidocaine, on the
other hand, has the advantage of a rapid onset of action. Adrenaline vasoconstricts
arteries and hence delays the resorption of Lidocaine, almost doubling the duration of
anaesthesia. For surface anesthesia several formulations are available that can be used
e.g. for endoscopies, before intubations etc.

Lidocaine is also the most important class 1B antiarrhythmic drug: it is used

intravenously for the treatment of ventricular arrhythmias (for acute myocardial
infarction, digitalis poisoning, cardioversion or cardiac catheterization). However, a
routine prophylactic administration is no longer recommended for acute cardiac
infarction; the overall benefit of this measure is not convincing.

Lidocaine has also been efficient in refractory cases of status epilepticus.

Lidocaine has also proved effective in treating jellyfish stings, both numbing the affected
area and preventing further nematocyst discharge [8]

[edit] 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
• Pacemaker
[edit] 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 only rarely occur.[9]

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 (also
known as circumoral paraesthesia), 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.[10]

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.[10]

[edit] Overdosage

Overdosage with lidocaine can be a result of excessive administration via topical or

parenteral routes, accidental oral ingestion of topical preparations by children, accidental
intravenous (rather than subcutaneous, intrathecal or paracervical) injection or prolonged
use of subcutaneous infiltration anesthesia during cosmetic surgical procedures. These
occurrences have often led to severe toxicity or death in both children and adults.
Lidocaine and its two major metabolites may be quantitated in blood, plasma or serum to
confirm the diagnosis in potential poisoning victims or to assist in the forensic
investigation in a case of fatal overdosage. It is important in the interpretation of
analytical results to recognize that lidocaine is often routinely administered intravenously
as an antiarrhthymic agent in critical cardiac care situations.[11]

[edit] Insensitivity to lidocaine

Relative insensitivity to lidocaine is genetic. 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. Some people with
Ehlers-Danlos syndrome are insensitive to lidocaine.[12]
[edit] Dosage forms

Topical lidocaine spray

Lidocaine, usually in the form of lidocaine hydrochloride, is available in various forms

including:

• Injected local anesthetic (sometimes combined with epinephrine to reduce

bleeding)
• Dermal patch (sometimes combined with prilocaine)
• Intravenous injection (sometimes combined with epinephrine to reduce bleeding)
• 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) [13]
• 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
• Inhaled via a nebulizer