COMPOUND LIDOCAINE CREAM

Indications

• Infiltration anesthesia
• Nerve block anesthesia
• Dental procedures
• Regional anesthesia

Dosage

Children: Consult the BNF for Children for specific dosing guidelines, as pediatric doses vary based on age, weight, and the procedure being performed.

Adults: For infiltration anesthesia, the typical adult dose is 100–200 mg/minute, adjusted according to the site of administration and patient response, with a maximum of 400 mg per course. For spinal anesthesia, a usual dose is 40–60 mg (maximum 80 mg).

Mechanism of action

Prilocaine exerts its local anesthetic effects by reversibly binding to and inhibiting voltage-gated sodium channels in the neuronal cell membrane. This action prevents sodium influx during depolarization, thereby interrupting the propagation of action potentials along sensory nerves and leading to a loss of sensation in the targeted area.

Pharmacodynamics

Prilocaine demonstrates a dose-dependent effect on nerve conduction. It has a rapid onset of action, typically occurring within minutes, with a duration of anesthesia that can last from 1 to 2 hours depending on the dose and route of administration. The drug is less likely to induce systemic toxicity compared to other local anesthetics, but high doses can lead to complications such as methaemoglobinaemia.

Pharmacokinetics

Prilocaine is metabolized primarily in the liver by cytochrome P450 enzymes. Its systemic absorption and elimination are influenced by the route of administration, with infiltration anesthesia resulting in slower absorption compared to nerve blocks. The half-life of prilocaine is approximately 1.5 to 2 hours, and the drug is excreted in urine primarily as metabolites.

Contra-indications

• Hypersensitivity to prilocaine or any component of the formulation
• Acquired methaemoglobinaemia
• Congenital methaemoglobinaemia
• Severe cardiac conduction disorders
• Infection at the injection site
• Inflamed tissues

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Paraesthesia
• Hypotension
• Hypertension
• Respiratory depression
• Methaemoglobinaemia
• Cardiac arrest

Interactions

• Other local anaesthetics
• Sympathomimetics
• Vasoconstrictors

Precautions

• Use with caution in elderly or debilitated patients
• Caution in hepatic impairment due to increased risk of toxic plasma concentrations
• Caution in renal impairment due to increased risk of side effects
• Use with caution during early pregnancy
• Only to be administered by trained personnel with resuscitation equipment available

Pregnancy

Use with caution in early pregnancy, large doses during delivery may cause neonatal respiratory depression, hypotonia and bradycardia.

Breast-feeding

Present in milk but not known to be harmful; use with caution.

Storage

Store in a cool, dry place, protected from light. Follow specific storage instructions as per product literature.

Formulations

• Citanest 1% solution for injection (prilocaine hydrochloride 10 mg per 1 ml) available in 50 ml vials

Indications

• Ventricular arrhythmias, especially after myocardial infarction
• Local anesthesia for minor surgical procedures
• Pain relief in conditions such as oral ulceration and inflammation

Dosage

Children: Refer to the BNF for Children

Adults: For ventricular arrhythmias, an initial intravenous bolus of 100 mg is given over a few minutes, followed by a continuous infusion of 4 mg/minute for 30 minutes, then reduced to 2 mg/minute for 2 hours, and finally to 1 mg/minute. The total dose should not exceed 3 mg/kg.

Mechanism of action

Lidocaine hydrochloride exerts its effects by blocking voltage-gated sodium channels in neurons, which inhibits the influx of sodium ions during depolarization. This action prevents the generation and conduction of nerve impulses, resulting in local anesthesia. The drug also stabilizes neuronal membranes and decreases the excitability of both peripheral and central nerves.

Pharmacodynamics

The onset of action for lidocaine is rapid, typically occurring within minutes of administration, with a duration of action that can vary based on the route of administration and the presence of additives such as epinephrine. Lidocaine can be used to manage ventricular arrhythmias by decreasing myocardial excitability and conduction velocity, thus stabilizing the cardiac rhythm.

Pharmacokinetics

Lidocaine is well-absorbed when administered intravenously, with peak plasma concentrations occurring shortly after infusion. It is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP1A2 and CYP3A4, producing active metabolites. The elimination half-life of lidocaine ranges from 1.5 to 2 hours, and it is excreted mainly in urine. Caution is advised in cases of hepatic impairment, as the metabolism of lidocaine may be significantly reduced, leading to increased plasma levels.

Contra-indications

• All grades of atrioventricular block
• Severe myocardial depression
• Sino-atrial disorders

Adverse effects

• Anxiety
• Arrhythmias
• Cardiac arrest
• Circulatory collapse
• Confusion
• Dizziness
• Drowsiness
• Euphoric mood
• Headache
• Hypotension (may lead to cardiac arrest)
• Loss of consciousness
• Methaemoglobinaemia
• Muscle twitching
• Nausea
• Neurological disorders
• Tinnitus
• Tremor
• Blurred vision
• Vomiting

Interactions

• Antiarrhythmics

Precautions

• Acute porphyrias (consider infusion of glucose for its anti-porphyrinogenic effects)
• Congestive cardiac failure (consider lower dose)
• Post cardiac surgery (consider lower dose)
• Monitor serum potassium
• Caution in hepatic impairment (risk of increased exposure)
• Caution in renal impairment (possible accumulation of lidocaine and active metabolites)

Pregnancy

Crosses the placenta but not known to be harmful in animal studies-use if benefit outweighs risk.

Breast-feeding

Present in milk but amount too small to be harmful.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Lidocaine hydrochloride 5 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10% solution for oral use

Indications

• Local anesthesia for surgical and diagnostic procedures
• Management of certain types of arrhythmias
• Topical anesthesia for mucosal surfaces

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Lidocaine acts by diffusing through neural sheaths into the axoplasm, where it is ionized and binds reversibly to sodium ion channels on nerve cell membranes. This binding keeps the channels in an open state, preventing nerve depolarization and thus blocking action potential transmission. This mechanism facilitates its anesthetic effects by aborting pain signal generation and preventing their transmission to the brain.

Pharmacodynamics

Excessive blood levels of lidocaine may lead to changes in cardiac output, total peripheral resistance, and mean arterial pressure. The block of autonomic fibers and the direct depressant effect on the cardiovascular system can cause hypotension when recommended dosages are exceeded. Lidocaine's action on sodium channels affects cardiac myocytes, potentially leading to hypotension, bradycardia, myocardial depression, arrhythmias, or even cardiac arrest.

Pharmacokinetics

Lidocaine is absorbed rapidly and widely distributed throughout the body. It undergoes extensive hepatic metabolism, primarily by cytochrome P450 enzymes, leading to various metabolites. Its elimination half-life is approximately 1.5 to 2 hours, but this can vary based on factors such as hepatic blood flow and enzyme activity.

Contra-indications

• Hypersensitivity to lidocaine or any amide local anesthetics
• Severe degree of heart block
• A history of malignant hyperthermia

Adverse effects

• Hypotension
• Bradycardia
• Myocardial depression
• Cardiac arrhythmias
• CNS stimulation followed by depression
• Dizziness
• Nausea
• Vomiting
• Tinnitus

Interactions

• cimetidine+lidocaine: Moderate (increases exposure)
• cobicistat+lidocaine: Unknown (increases concentration)
• lidocaine+suxamethonium: Unknown (increases effects)
• ciprofloxacin+lidocaine: Unknown (increases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Use with caution in patients with cardiac conditions
• Monitor for signs of systemic toxicity, especially after high doses or rapid administration

Pregnancy

Lidocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as FDA pregnancy category B.

Breast-feeding

Lidocaine is excreted in breast milk, but at therapeutic doses, it is not expected to cause adverse effects in nursing infants. Monitor infants for any signs of sedation.

Storage

Store at room temperature, away from moisture and heat. Protect from light. Do not freeze.

Formulations

• Lidocaine injection solution
• Lidocaine cream
• Lidocaine gel
• Lidocaine patch

Indications

• Local anesthesia for surgical procedures
• Dental anesthesia
• Regional anesthesia techniques

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in pediatric patients.

Adults: Refer to the BNF for specific dosing information as it may vary depending on the procedure and individual patient factors.

Mechanism of action

Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. It blocks conduction in nerves by preventing the large transient increase in permeability of excitable membranes to sodium ions, which is normally triggered by slight depolarization. This action results in reversible inhibition of action potential propagation and nerve function.

Pharmacodynamics

Prilocaine binds to the intracellular surface of sodium channels, effectively blocking the influx of sodium ions into the neuron. This inhibition of sodium channel function prevents the generation and conduction of nerve impulses, leading to a loss of sensation in the targeted area. The effects of prilocaine are dose-dependent and reversible, allowing for restoration of nerve function once the drug is eliminated from the site of action.

Pharmacokinetics

Prilocaine is metabolized primarily in the liver by cytochrome P450 enzymes, with a half-life of approximately 1.5 to 2.5 hours. Its onset of action is typically rapid, occurring within a few minutes when administered via injection. The duration of action can vary based on the specific formulation and site of administration, generally lasting 1 to 2 hours. Excretion occurs mainly via the kidneys, with metabolites being eliminated in urine.

Contra-indications

• Hypersensitivity to prilocaine or any of its components
• Severe liver disease
• History of methaemoglobinaemia

Adverse effects

• Methaemoglobinaemia
• Hypotension
• Cardiovascular collapse
• Respiratory depression
• Nerve damage
• Allergic reactions

Interactions

• metoclopramide: Severe (increases risk of methaemoglobinaemia)
• nitrates: Severe (increases risk of methaemoglobinaemia)
• aminosalicylic acid: Moderate (increases risk of methaemoglobinaemia)
• antiepileptics (fosphenytoin, phenobarbital, phenytoin, primidone): Moderate (increases risk of methaemoglobinaemia)
• dapsone: Moderate (increases risk of methaemoglobinaemia)
• nitrofurantoin: Moderate (increases risk of methaemoglobinaemia)
• paracetamol: Moderate (increases risk of methaemoglobinaemia)
• nitroprusside: Unknown (increases risk of methaemoglobinaemia)

Precautions

• Use with caution in patients with compromised cardiovascular function
• Careful monitoring in patients with respiratory conditions
• Consider alternative anesthetics in patients with history of methaemoglobinaemia
• Administer in a controlled setting where resuscitation equipment is available

Pregnancy

Prilocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines for specific use.

Breast-feeding

Prilocaine is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature (15-25 degrees Celsius). Protect from light and moisture.

Formulations

• Prilocaine hydrochloride injection
• Topical prilocaine cream

Mechanism of action

Lidocaine is a local anesthetic of the amide type. It is used to provide local anesthesia by nerve blockade at various sites in the body. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place. In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction. Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+ channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose-gap method, peptide alpha-toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+ channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5-30 uM lidocaine. Lidocaine caused a rapid, concentration-dependent decay of the plateau, quantitatively consistent with blockade of open Na(+) channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 uM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 hr, showing that lidocaine had not caused dissociation of channel-bound alpha-toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the "abnormal" features of action potentials caused by non-inactivating Na+ channels without affecting the normal spike component. Lidocaine controls ventricular arrhythmias by suppressing automaticity in the His-Purkinje system and by suppressing spontaneous depolarization of the ventricles during diastole. These effects occur at lidocaine concentrations that do not suppress automaticity of the sinoatrial (SA) node. At therapeutic plasma concentrations, lidocaine has little effect on atrioventricular (AV) node conduction and His-Purkinje conduction in the normal heart. Specialized conducting tissues of the atria are less sensitive to the effects of lidocaine than are those of ventricular tissues. Lidocaine has a variable effect on the effective refractory period (ERP) of the AV node; the drug shortens the ERP and the action potential duration of the His-Purkinje system. Lidocaine does not appear to affect excitability of normal cardiac tissue. Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydroly

Pharmacodynamics

Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded. In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse. Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection. Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels.

Mechanism of action

Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. ... BLOCK CONDUCTION IN NERVE PERHAPS BY COMPETING WITH CA @ SOME SITE THAT CONTROLS PERMEABILITY OF MEMBRANE ... CA IS ALSO INVOLVED IN ACTION OF LOCAL ANESTHETICS ON SMOOTH MUSCLE ... & ON ADRENAL MEDULLA ... /LOCAL ANESTHETICS/ ... PREVENT THE GENERATION & THE CONDUCTION OF THE NERVE IMPULSE. THEIR PRIMARY SITE OF ACTION IS THE CELL MEMBRANE. ... BLOCK CONDUCTION BY DECREASING OR PREVENTING THE LARGE TRANSIENT INCREASE IN THE PERMEABILITY OF EXCITABLE MEMBRANES TO NA+ THAT NORMALLY IS PRODUCED BY A SLIGHT DEPOLARIZATION OF THE MEMBRANE. /LOCAL ANESTHETICS/ AS ANESTHETIC ACTION PROGRESSIVELY DEVELOPS IN A NERVE, THRESHOLD FOR ELECTRICAL EXCITABILITY INCR & SAFETY FACTOR FOR CONDUCTION DECR; WHEN THIS ACTION IS SUFFICIENTLY WELL-DEVELOPED, BLOCK OF CONDUCTION IS PRODUCED. /LOCAL ANESTHETICS/ .../2 POSSIBILITIES:/ ACHIEVE BLOCK BY INCR SURFACE PRESSURE OF LIPID LAYER THAT CONSTITUTES NERVE MEMBRANE...CLOSING PORES THROUGH WHICH IONS MOVE. ... /OR:/ AFFECT PERMEABILITY BY INCR DEGREE OF DISORDER OF MEMBRANE. /LOCAL ANESTHETICS/

Pharmacodynamics

Prilocaine binds to the intracellular surface of sodium channels which blocks the subsequent influx of sodium into the cell. Action potential propagation and nerve function is, therefore, prevented. This block is reversible and when the drug diffuses away from the cell, sodium channel function is restored and nerve propagation returns.