Lignocaine: A Guide to Its Uses and Medical Importance

Hi, Matthew here. 

You’re reading this because, like me, you want to understand how medications work—not just what they do, but why they’re used and how to get the best results from them. At National Custom Compounding, we work with doctors, dentists, and other healthcare professionals who rely on precise, tailored medications, and lignocaine is one of the most commonly requested.

Compounded lignocaine preparations are only made when a commercially available alternative is unsuitable for a patient’s specific needs. Compounded medications do not undergo the same TGA approval process as commercially manufactured products.

Lignocaine (lidocaine) is commonly used in medical and dental settings under the guidance of healthcare professionals. But despite its widespread use, many people don’t realise the different ways it can be administered, the precautions needed to use it safely, or the risks of getting it wrong. That’s why I’ve put together this guide.

In this article, you’ll learn about lignocaine’s many applications, how it works in the body, and what to watch out for when using it. Whether you’re a healthcare professional, a patient, or just someone curious about how medicine works, 

This guide provides general information about lignocaine’s properties and clinical considerations. Always consult a healthcare professional before using any medication.

Matthew Bellgrove
Founder, National Custom Compounding

Table Of Contents

What is Lignocaine?

Lignocaine, also known as lidocaine, is a widely used local anaesthetic and antiarrhythmic medication. It is commonly utilised in medical and dental procedures to numb specific areas of the body, allowing for pain-free treatment. Beyond its anaesthetic properties, lignocaine is an important drug in emergency medicine, particularly for managing cardiac arrhythmias such as ventricular tachycardia and ventricular fibrillation.

Medical Applications

Lignocaine is a versatile medication with broad applications in healthcare. Its primary use is in local anaesthesia, where it effectively blocks nerve signals, temporarily preventing the sensation of pain. It can be administered via injection or applied topically as a gel or cream, enabling minor surgical and dental procedures to be performed with minimal discomfort to the patient.

In addition to its anaesthetic capabilities, lignocaine is used in cardiology. As a class Ib antiarrhythmic agent, it helps stabilise irregular heart rhythms, particularly during acute episodes of ventricular tachycardia. This makes it an important part of emergency cardiovascular care, often used in cases of myocardial infarction or during surgical interventions requiring cardiac monitoring.

Lignocaine is also widely employed in pain management, particularly for conditions involving nerve pain, such as diabetic neuropathy and postherpetic neuralgia. Available in various formulations, including intravenous injections and topical applications, it provides both immediate and sustained pain relief. Additionally, it is commonly used to alleviate discomfort from sunburns, insect bites, and minor cuts.

Active Ingredients and Mechanism of Action

Lidocaine hydrochloride, a local anaesthetic belonging to the amide group, is the active component in lignocaine-based medications. It inhibits sodium channels in nerve cells, preventing the conduction of pain signals to the brain. This mechanism is essential for both its anaesthetic effects and its role in cardiac rhythm management, where it suppresses abnormal electrical impulses in the heart.

Different Forms and Methods of Administration

Lignocaine is available in multiple formulations, each designed for specific therapeutic uses:

  • Topical Creams and Ointments: Applied directly to the skin or mucous membranes, these formulations provide localised pain relief for conditions like sunburn, insect bites, and minor cuts.
  • Injectable Solutions: Used for nerve blocks and local anaesthesia in surgical procedures, lignocaine injections deliver rapid pain relief.
  • Intravenous Administration: In emergency cardiac care, intravenous lignocaine stabilises heart rhythms, preventing life-threatening arrhythmias.
  • Transdermal Patches: These patches deliver a controlled dose of lignocaine over time, making them effective for chronic pain conditions.

Allergic Reactions and Dermatological Side Effects

Allergic reactions to lignocaine are uncommon but can occur. Symptoms may include skin rash, itching, swelling, and, in severe cases, anaphylaxis. Patients with a history of allergic reactions to local anaesthetics should exercise caution. Mild dermatological side effects, such as irritation or redness at the application site, are more common and usually resolve without intervention.

Mild Dermatological Reactions

Some individuals experience minor skin irritation at the site of application or injection. Common symptoms include:

  • Redness and swelling – A transient reaction due to local irritation from the medication.
  • Itching (pruritus) – Mild itching is a common response to topical lignocaine, especially in sensitive individuals.
  • Burning or stinging sensation – Some patients report a temporary burning sensation upon application, which usually subsides within a few minutes.

Severe Dermatological Reactions

Although rare, lignocaine may cause more significant dermatological side effects, including:

1. Allergic Contact Dermatitis

  • This occurs when the skin becomes sensitised to lignocaine after repeated exposure.
  • Symptoms include persistent redness, swelling, itching, and in severe cases, blistering.
  • Patients with a history of allergic dermatitis should undergo patch testing before using lignocaine-based creams or gels.

2. Skin Necrosis and Tissue Damage (Rare but Serious)

  • In rare cases, excessive lignocaine concentrations or incorrect administration can lead to local tissue damage.
  • Injection site necrosis – If lignocaine is inadvertently injected into a small blood vessel, it can cause ischaemia (restricted blood supply), leading to tissue death.
  • Blistering or ulceration – Prolonged exposure to high doses of topical lignocaine may result in skin breakdown.

Precautions to Minimise Dermatological Reactions

To reduce the risk of skin-related side effects, patients and healthcare professionals should follow these guidelines:

  • Use recommended dosages – Avoid excessive application of topical lignocaine, as overuse can lead to increased absorption and potential toxicity.
  • Patch testing for suspected allergies – Individuals with sensitive skin or a history of allergic reactions should apply a small amount of lignocaine cream to a small area and monitor for any adverse reactions before full application.
  • Avoid prolonged use on damaged skin – Applying lignocaine to open wounds, cuts, or severely inflamed skin increases systemic absorption, raising the risk of adverse effects.
  • Monitor injection sites – Patients receiving lignocaine injections should be observed for signs of irritation, swelling, or necrosis.

Managing Allergic and Dermatological Reactions

Allergic and dermatological reactions can vary in severity, from mild irritation to severe hypersensitivity. Mild cases may be managed with topical corticosteroids, oral antihistamines, or cold compresses. Severe reactions require immediate medical intervention, including epinephrine injections, intravenous antihistamines and corticosteroids, and supportive treatments such as oxygen therapy and IV fluids.

Treatment of Mild Reactions

For mild skin irritation or allergic reactions, the following treatments can help alleviate symptoms:

  • Topical corticosteroids – Can be used to reduce inflammation and itching associated with allergic dermatitis.
  • Oral antihistamines – Help relieve itching, swelling, and mild allergic responses.
  • Cold compresses – Applying a cold compress can reduce redness and discomfort at the application or injection site.

Emergency Management of Severe Allergic Reactions

In cases of severe hypersensitivity reactions, immediate medical attention is required. Treatment may include:

  • Epinephrine (adrenaline) injection – The first-line treatment for anaphylaxis to rapidly reverse airway constriction and low blood pressure.
  • Intravenous antihistamines and corticosteroids – Used in hospital settings to control severe allergic reactions.
  • Oxygen therapy and intravenous fluids – To support breathing and stabilise blood pressure in anaphylactic patients.

Pharmacokinetics: Absorption, Bioavailability, and Distribution

Lignocaine (lidocaine) is a widely used local anaesthetic and antiarrhythmic drug that can be administered via multiple routes, depending on its intended use. The absorption characteristics of lignocaine vary significantly based on the route of administration, tissue vascularity, presence of vasoconstrictors, and formulation type. Understanding its absorption profile and bioavailability is important for optimising therapeutic effects while minimising systemic toxicity.

Factors Affecting Lignocaine Absorption

The absorption of lignocaine is influenced by several key factors, including:

1. Route of Administration

  • Different routes of administration (topical, injectable, intravenous, transdermal) result in varying levels of systemic absorption and bioavailability.
  • Intravenous administration provides 100% bioavailability, whereas topical application has highly variable absorption depending on skin integrity.

2. Blood Flow and Tissue Vascularity

  • Highly perfused tissues (e.g., mucous membranes, muscle tissue) facilitate faster absorption.
  • Poorly perfused areas (e.g., subcutaneous tissue, intact skin) lead to slower systemic uptake.

3. Presence of Vasoconstrictors

  • When combined with adrenaline (epinephrine), lignocaine’s absorption rate decreases, leading to prolonged local anaesthetic effects and reduced systemic exposure.
  • Adrenaline-induced vasoconstriction minimises blood flow at the injection site, slowing the diffusion of lignocaine into the circulation.

4. pH and Ionisation

  • Lignocaine is a weak base (pKa ~7.9) and is more effective in neutral or alkaline environments.
  • Acidic conditions (e.g., inflamed tissue) reduce the proportion of unionised lignocaine, impairing its ability to penetrate nerve membranes and delaying onset.

5. Lipid Solubility and Protein Binding

  • Lignocaine’s moderate lipid solubility allows for efficient penetration into nerve membranes.
  • Plasma protein binding (~65%), primarily to alpha-1-acid glycoprotein (AAG), influences its systemic distribution and clearance.

Absorption Through Different Routes of Administration

Lignocaine absorption varies depending on the route of administration. IV administration provides 100% bioavailability with rapid onset, making it essential for emergencies but requiring careful monitoring due to toxicity risks. IM absorption is faster than SC due to higher vascularity, offering a systemic option when IV access is unavailable. Topical and transdermal absorption is variable, with increased uptake through broken skin, while mucosal application leads to higher systemic levels, increasing toxicity risk. Epidural and spinal administration provide effective nerve blockade, with adrenaline extending duration and reducing systemic absorption. Oral bioavailability is low due to first-pass metabolism, limiting its use to localised anaesthesia.

Let’s look at each one.

1. Intravenous (IV) Absorption

Bioavailability: 100% (direct systemic entry)
Onset of Action: 30–90 seconds
Peak Plasma Concentration: Within minutes
Duration of Action: 10–20 minutes

  • IV administration ensures immediate absorption, making it the preferred route for emergency cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation).
  • Due to rapid metabolism (half-life ~1.5–2 hours), continuous IV infusion is required for sustained effects.
  • Toxicity risk is higher with IV use, necessitating close monitoring of plasma lignocaine levels.

2. Subcutaneous (SC) and Intramuscular (IM) Absorption

Bioavailability: ~60–80%
Onset of Action: 5–15 minutes
Peak Plasma Concentration: 20–30 minutes (IM), slower for SC
Duration of Action: 1–2 hours

  • IM administration leads to faster absorption than SC injection due to higher muscle vascularity.
  • Used when IV access is unavailable for systemic effects (e.g., arrhythmia management).
  • Systemic absorption is moderate, requiring dose adjustments to prevent toxicity.

3. Topical and Transdermal Absorption

Bioavailability: Highly variable (3–50%)
Onset of Action: 30–60 minutes
Peak Plasma Concentration: Variable (depends on skin integrity and application site)
Duration of Action: Several hours

  • Poor absorption through intact skin, but significantly increased through abraded or inflamed skin.
  • Lignocaine patches (5%) provide sustained release over 12 hours, with minimal systemic absorption, making them ideal for neuropathic pain management (postherpetic neuralgia, diabetic neuropathy).
  • Excessive application over large surface areas or broken skin can lead to systemic toxicity (seizures, confusion, cardiovascular effects).

4. Mucosal and Oropharyngeal Absorption

Bioavailability: 50–70%
Onset of Action: 5–15 minutes
Peak Plasma Concentration: 30–60 minutes
Duration of Action: 30–60 minutes

  • Rapid absorption through mucous membranes, leading to higher systemic levels than topical skin application.
  • Used in endoscopy, bronchoscopy, and intubation for localised anaesthesia.
  • Higher risk of systemic toxicity compared to dermal applications, particularly with frequent or excessive use.

5. Epidural and Spinal Absorption

Bioavailability: 80–100%
Onset of Action: 5–15 minutes (epidural), 1–5 minutes (spinal)
Duration of Action: 1–2 hours (without adrenaline)

  • Epidural administration leads to rapid absorption into systemic circulation, requiring careful dosing to prevent toxicity.
  • Spinal lignocaine provides immediate nerve blockade, commonly used in Caesarean sections and orthopaedic procedures.
  • Adrenaline addition reduces systemic absorption, prolonging local anaesthesia while minimising toxicity risks.

6. Oral Absorption and First-Pass Metabolism

Bioavailability: ~35% (extensive first-pass metabolism)
Onset of Action: 30–60 minutes
Peak Plasma Concentration: 1–2 hours
Duration of Action: 3–4 hours

  • Oral lignocaine has poor bioavailability due to rapid hepatic metabolism (first-pass effect), making it unsuitable for systemic pain relief.
  • Used mainly as lozenges or mouth rinses for localised oropharyngeal anaesthesia.

Bioavailability of Lignocaine

Lignocaine exhibits variable absorption characteristics depending on its route of administration. While intravenous delivery ensures complete systemic absorption, topical applications have minimal bioavailability unless applied to damaged skin. Mucosal and transdermal absorption are higher than dermal applications, whereas epidural and spinal routes provide direct nerve blockade with some systemic uptake.

Understanding these absorption profiles allows clinicians to select the most appropriate route for patient needs while mitigating risks of systemic toxicity, particularly in high-dose applications.

Summary of Bioavailability by Route of Administration:
RouteBioavailability (%)Onset of ActionPeak Plasma ConcentrationDuration
Intravenous (IV)100%30–90 secImmediate10–20 min
Intramuscular (IM)~60–80%5–15 min20–30 min1–2 hours
Subcutaneous (SC)~60%10–20 minVariable1–2 hours
Topical (Intact Skin)3–10%30–60 minVariableSeveral hours
Transdermal Patch~50%30–60 minVariable12 hours
Mucosal (Oral/Nasal)50–70%5–15 min30–60 min30–60 min
Epidural/Spinal80–100%1–15 minVariable1–2 hours
Oral (Systemic)~35%30–60 min1–2 hours3–4 hours

Distribution of Lignocaine in the Body

Lignocaine (lidocaine) is widely used in medical settings as both a local anaesthetic and antiarrhythmic agent. After administration, it undergoes rapid distribution throughout the body, influencing its onset, duration of action, and systemic effects. The distribution of lignocaine is determined by factors such as lipophilicity, plasma protein binding, organ perfusion, and metabolic capacity. Understanding how lignocaine is distributed can help clinicians optimise dosing strategies and minimise the risk of systemic toxicity.

Volume of Distribution (Vd) of Lignocaine

The volume of distribution (Vd) refers to the extent to which a drug disperses beyond the plasma compartment into body tissues. Lignocaine exhibits a relatively large Vd, indicating extensive distribution into tissues beyond the bloodstream.

  • The typical Vd of lignocaine ranges from 0.7 to 1.5 L/kg, with an average of 1.3 L/kg in healthy adults.
  • In critically ill patients, the Vd may increase due to alterations in tissue permeability and fluid balance.
  • In neonates and elderly patients, the Vd may be lower due to differences in metabolic capacity and protein binding.

A higher Vd means that lignocaine is widely distributed in fat, muscle, and organ tissues, reducing its plasma concentration. Conversely, a lower Vd would suggest that the drug remains mostly in the vascular compartment, which is not the case with lignocaine.

Metabolism of Lignocaine (Hepatic Biotransformation)

1. Primary Site of Metabolism: The Liver

Lignocaine is primarily metabolised in the liver, undergoing extensive first-pass metabolism when administered orally. More than 90% of lignocaine is metabolised before excretion, with only a small percentage eliminated unchanged. The liver’s enzymatic system breaks down lignocaine into active and inactive metabolites, which are then processed further before being excreted via the kidneys.

2. Role of Cytochrome P450 Enzymes

Lignocaine metabolism occurs mainly through the cytochrome P450 (CYP) enzyme system, specifically CYP1A2 and CYP3A4. These enzymes facilitate oxidative metabolism, converting lignocaine into its primary metabolites.

The key metabolic pathways include:

  • N-dealkylation of lignocaine to form monoethylglycinexylidide (MEGX).
  • Further metabolism of MEGX to produce glycinexylidide (GX).
  • Both MEGX and GX are active metabolites that retain pharmacological activity but have a weaker effect than lignocaine itself.

3. Phase I Metabolism: Oxidative Biotransformation

Lignocaine undergoes oxidative N-dealkylation, which results in the formation of two primary metabolites:

A. Monoethylglycinexylidide (MEGX)

  • Retains approximately 80% of lignocaine’s activity.
  • Has a longer half-life (2–3 hours) than lignocaine itself (1.5–2 hours).
  • Can accumulate in cases of renal impairment, leading to prolonged toxicity.

B. Glycinexylidide (GX)

  • Has minimal anaesthetic or antiarrhythmic properties.
  • Plays a minor role in lignocaine’s overall pharmacological effect.
  • Primarily excreted via the kidneys.

Both MEGX and GX can accumulate in renal dysfunction, increasing the risk of neurological and cardiovascular side effects due to prolonged systemic circulation.

4. Phase II Metabolism: Conjugation (Glucuronidation)

Following oxidative metabolism, lignocaine’s metabolites undergo glucuronidation, a phase II metabolic reaction that enhances their water solubility, facilitating renal excretion.

  • Glucuronidation occurs in the liver, catalysed by UDP-glucuronosyltransferases (UGTs).
  • The conjugated metabolites are water-soluble, making them easier for the kidneys to eliminate.

Excretion of Lignocaine (Renal Elimination)

1. Primary Route of Excretion: The Kidneys

Lignocaine and its metabolites are mainly excreted through renal clearance, with over 90% of the administered dose eliminated in the urine. However, less than 10% of lignocaine is excreted unchanged, with the majority undergoing hepatic metabolism before renal excretion.

2. Half-Life and Clearance Rate

  • The plasma half-life of lignocaine is approximately 1.5–2 hours in healthy individuals.
  • Renal clearance of lignocaine is approximately 10–20 mL/min/kg.
  • Patients with renal impairment may experience an accumulation of lignocaine metabolites, leading to prolonged sedation, CNS toxicity, and cardiac effects.

3. Role of Urine pH in Excretion

The rate of lignocaine excretion is influenced by the pH of the urine:

  • Acidic urine promotes the ionisation of lignocaine metabolites, enhancing renal excretion.
  • Alkaline urine increases reabsorption, prolonging lignocaine’s half-life.

This factor is clinically relevant, as the alkalinisation of urine (e.g., with sodium bicarbonate) can delay lignocaine clearance, potentially increasing toxicity risks.

Factors Affecting Lignocaine Metabolism and Excretion

1. Hepatic Function and Liver Disease

Since lignocaine is extensively metabolised by the liver, hepatic impairment can significantly alter its clearance.

  • Liver disease (e.g., cirrhosis, hepatitis, alcohol-induced damage) reduces the ability to metabolise lignocaine efficiently.
  • This leads to higher plasma concentrations, increasing the risk of CNS toxicity (seizures, dizziness, confusion) and cardiac complications (bradycardia, hypotension, arrhythmias).
  • In severe liver dysfunction, the half-life of lignocaine can be prolonged to 4–6 hours, requiring dose adjustments to prevent drug accumulation.

2. Renal Function and Kidney Disease

Although lignocaine metabolism primarily occurs in the liver, renal clearance of its active metabolites (MEGX, GX) is essential for complete elimination.

  • In renal failure, MEGX and GX accumulate, leading to prolonged CNS and cardiovascular effects.
  • Chronic kidney disease (CKD) patients may require dose adjustments to prevent toxicity.
  • Monitoring renal function is particularly important in elderly patients, as they are more susceptible to drug accumulation and adverse effects.

3. Drug Interactions Affecting Lignocaine Metabolism

Certain drugs can influence lignocaine’s metabolism by either inducing or inhibiting cytochrome P450 enzymes.

A. CYP3A4 and CYP1A2 Inducers (Increase Metabolism, Reducing Lignocaine Levels)

  • Rifampicin
  • Phenytoin
  • Carbamazepine
  • Phenobarbital

These drugs enhance lignocaine metabolism, leading to reduced therapeutic effects and the need for higher doses in some cases.

B. CYP3A4 and CYP1A2 Inhibitors (Reduce Metabolism, Increasing Toxicity Risk)

  • Amiodarone
  • Cimetidine
  • Erythromycin
  • Fluoroquinolones (e.g., ciprofloxacin)
  • Verapamil

These inhibitors slow lignocaine metabolism, increasing plasma concentrations and the risk of toxicity (seizures, cardiac arrhythmias, hypotension).

4. Age-Related Metabolic Differences

  • Neonates and Infants:
    • Reduced hepatic enzyme activity leads to slower metabolism and prolonged drug effects.
    • Lower protein binding increases the free drug fraction, enhancing both therapeutic and toxic effects.
  • Elderly Patients:
    • Declined hepatic and renal function can lead to drug accumulation.
    • Dose reductions are often necessary to avoid excessive CNS depression and cardiovascular complications.

Lignocaine undergoes extensive hepatic metabolism via the CYP450 enzyme system (CYP1A2, CYP3A4), producing active and inactive metabolites that are subsequently eliminated by the kidneys. The rate of metabolism and excretion is influenced by hepatic function, renal clearance, drug interactions, urine pH, and patient-specific factors (age, disease states).

Understanding the metabolism and excretion of lignocaine is important for optimising its clinical use, ensuring safe dosing, and preventing systemic toxicity, particularly in patients with liver disease, renal impairment, or altered metabolic capacity.

Precautions Before Use

Before applying lignocaine cream or ointment, several factors should be considered:

  • Allergies: Patients should confirm they have no known allergies to lignocaine or other local anaesthetics.
  • Medical History: Those with liver disease, heart conditions, or neurological disorders should consult a healthcare provider before use.
  • Pregnancy and Breastfeeding: Pregnant or breastfeeding women should seek medical advice to assess potential risks.
  • Medication Interactions: Lignocaine may interact with other drugs, including antiarrhythmics and blood pressure medications. This means it’s important to disclose all current prescriptions to a doctor.

Potential Side Effects

While lignocaine is generally safe when used correctly, it can cause some side effects, including:

  • Mild Reactions: Skin redness, swelling, or irritation at the application site.
  • Systemic Effects: If absorbed into the bloodstream in high amounts, it may lead to dizziness, drowsiness, or blurred vision.
  • Severe Reactions: In rare cases, anaphylactic reactions, seizures, or cardiovascular complications such as irregular heartbeats may occur.

For more information, read our fact sheet here: https://customcompounding.com.au/wp-content/uploads/2021/07/NCC-topical-anaesthetic-CMI-2021.pdf

References:

1. Pharmacology & Medical References

  • Brunton, L., Knollmann, B., & Hilal-Dandan, R. (2021). Goodman & Gilman’s: The Pharmacological Basis of Therapeutics (13th Edition). McGraw-Hill Education.
  • Rang, H. P., Dale, M. M., Ritter, J. M., Flower, R. J., & Henderson, G. (2019). Rang & Dale’s Pharmacology (9th Edition). Elsevier.
  • Katzung, B. G. (2018). Basic & Clinical Pharmacology (14th Edition). McGraw-Hill.

2. Drug Information Databases

  • Australian Medicines Handbook (AMH)
  • Therapeutic Guidelines – Australian Prescriber
  • Martindale: The Complete Drug Reference
  • Micromedex Drug Information
  • UpToDate – Lidocaine Monograph
  • DrugBank (www.drugbank.ca) – Provides molecular pharmacology, metabolism, and interactions.

3. Medical and Clinical Guidelines

  • The Australian Therapeutic Goods Administration (TGA) – Safety & Use Guidelines for Lignocaine
  • National Health Service (NHS) – UK Guidelines on Lidocaine Use
  • American Heart Association (AHA) Guidelines for Advanced Cardiac Life Support (ACLS)
  • World Health Organization (WHO) Model List of Essential Medicines
  • The European Medicines Agency (EMA) on Lidocaine Formulations

4. Research & Toxicology Studies

  • PubMed (www.pubmed.ncbi.nlm.nih.gov) – Search for “Lidocaine pharmacokinetics,” “Lidocaine systemic toxicity,” or “Lidocaine bioavailability”
  • National Center for Biotechnology Information (NCBI) – Articles on Lignocaine metabolism and side effects
  • Journal of Clinical Anesthesia – Studies on Lidocaine as an Antiarrhythmic
  • Toxicology Data Network (TOXNET) – Lidocaine Toxicity and Overdose Management

5. Patient & Clinical Safety Information

  • Mayo Clinic – Lidocaine Patient Information
  • Royal Australian College of General Practitioners (RACGP) – Guidelines for Lidocaine in Pain Management
  • U.S. Food and Drug Administration (FDA) – Lidocaine Safety Alerts & Recommendations

This article is for educational purposes only and does not constitute medical advice. Compounded medications are prepared under the guidance of a healthcare professional and do not undergo TGA evaluation for safety and efficacy. Patients should always consult their doctor or pharmacist before using any medication.