Lidocaine

Lidocaine is an antiarrhythmic Class 1 B agent belonging to Sodium channel blocker.

Lidocaine is used in the treatment of ventricular arrhythmias. It is also used as an local anesthetic and nerve blocking agent.

Lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin . The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream. And although Lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism Volume of distribution: 0.7 to 1.5 L/kg and Plasma protein binding: 60-80%.Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys . Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation.

The common side effects are Arrhythmia, bradycardia, arterial spasms, CV collapse, oedema, flushing, heart block, hypotension, sinus node suppression, agitation, anxiety, coma, confusion, drowsiness, hallucinations, euphoria, headache, hyperaesthesia, hypoaesthesia, lightheadedness, lethargy, nervousness, psychosis, seizure, slurred speech, unconsciousness, somnolence, nausea, vomiting, metallic taste, tinnitus, disorientation, dizziness, paraesthesia, resp depression and convulsions, etc.

Lidocaine is available in the form of a dosage form such as injection, topical solutions like gel cream, jelly, ointment, spray, solution, lotion ,and patches.

Lidocaine is available in Switzerland, Europe, India, U.S

Lidocaine is sodium channel blocker.ln 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.

Lidocaine is a class 1 b antiarrhythmic. 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.

The onset of Action of Lidocaine was within 45-90 sec (IV); approx 4 hr (transdermal); 20 sec to 5 min (ophth).

The Duration of Action of Lidocaine was within 10-20 min (IV); 5-30 min (ophth).

The Tmax was about 1.8 - 2 hr and Cmax was about nine h, respectively

Lidocaine is available in the form of a dosage form such as injection and topicals.

Lidocaine is an anesthetic of the amide group indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks.

Lidocaine is a class 1b antiarrhythmic. Through direct cardiac effects, 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.

Lidocaine is available in various dosage strengths :

Infusion solution in D5W

100mg/100mL

200mg/100mL

400mg/100mL

800mg/100mL

Injectable solution

10mg/mL

20mg/mL

Transdermal Patch

5%; 700mg/patch

1.8%; 36mg/patch

4%

Topical jelly

2%

Topical gel

0.5%

0.8%

3%

4%

Topical cream

2%

4%

5%

Topical ointment

5%

Topical lotion

3%

Topical spray

2%

4%

10mg/spray

Topical solution, mouth/throat

2%

4%

Lidocaine is available in the form of a dosage form such as injection, topical solutions like gel cream, jelly, ointment, spray, solution, lotion ,and patches.

Lidocaine is used in the treatment of ventricular arrhythmias. It is also used in the treatment of Stable Ventricular Tachycardia, Ventricular Arrhythmia Associated with Myocardial Infarction, Atrial Fibrillation, and AV Junctional Tachycardia.

Ventricular arrhythmias: Diets high in processed foods, such as fast food, and items high in added sugar, like soda and sugary baked goods, have been linked to increased heart disease risk.

Drinking too much alcohol can increase the risk of developing AFib.It may also trigger AFib episodes in people who already have AFib, especially if patient have existing cardiovascular disease or diabetes.

Ventricular Tachycardia: High blood pressure can lead to an abnormally fast heartbeat. The DASH diet encourages the inclusion of fruits, vegetables, low fat dairy, protein, and whole grains to keep your blood pressure at normal levels and to reduce your risk of heart disease and stroke.

The dietary restriction should be individualized as per the patient's requirements.

Lidocaine may be contraindicated in the following

• Use with caution in patients with heart failure, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), myasthenia gravis patients, and in hepatic or renal impairment. Lidocaine also crosses the placenta and may be present in the milk of breastfeeding mothers, and as such, chronic use requires caution in this population.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

In order to manage possible adverse reactions, resuscitative equipment, oxygen and other resuscitative drugs should be immediately available when lidocaine is used.

Systemic toxicity may result in manifestations of central nervous system depression (sedation) or irritability (twitching), which may progress to frank convulsions accompanied by respiratory depression and/or arrest. Early recognition of premonitory signs, assurance of adequate oxygenation and, where necessary, establishment of artificial airway with ventilatory support are essential to management of this problem. Should convulsions persist despite ventilatory therapy with oxygen, small increments of anticonvulsant drugs may be used intravenously. Examples of such agents include benzodiazepines (eg, diazepam), ultrashort-acting barbiturates (eg, thiopental or thiamylal), or a short-acting barbiturate (eg, pentobarbital or secobarbital). If the patient is under anesthesia, a short-acting muscle relaxant (eg, succinylcholine) may be used. Longer-acting drugs should be used only when recurrent convulsions are evidenced.

Should circulatory depression occur, vasopressors may be used.

Constant electrocardiographic monitoring is essential to the proper administration of lidocaine. Signs of excessive depression of cardiac electrical activity such as sinus node dysfunction, prolongation of the P-R interval and QRS complex or the appearance or aggravation of arrhythmias, should be followed by flow adjustment and, if necessary, prompt cessation of the intravenous infusion of this agent. Occasionally, acceleration of ventricular rate may occur when lidocaine is administered to patients with atrial flutter or fibrillation.

Precautions

General

• Caution should be employed in the use of lidocaine in patients with severe liver or kidney disease because accumulation of the drug or metabolites may occur. lidocaine should be used with caution in the treatment of patients with hypovolemia, severe congestive heart failure, shock, and all forms of heart block. In patients with sinus bradycardia or incomplete heart block, the administration of lidocaine intravenously for the elimination of ventricular ectopic beats, without prior acceleration in heart rate (eg, by atropine, isoproterenol or electric pacing), may promote more frequent and serious ventricular arrhythmias or complete heart block.
• Dosage should be reduced for pediatric patients and for debilitated and/or elderly patients, commensurate with their age and physical status.
• The safety of amide local anesthetic agents in patients with genetic predisposition to malignant hyperthermia has not been fully assessed; therefore, lidocaine should be used with caution in such patients.
• In hospital environments where drugs known to be triggering agents for malignant hyperthermia (fulminant hypermetabolism) are administered, it is suggested that a standard protocol for management should be available.

• It is not known whether lidocaine may trigger this reaction; however, large doses resulting in significant plasma concentrations, as may be achieved by intravenous infusion, pose potential risk to these individuals. Recognition of early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the triggering agent and institution of treatment including oxygen therapy, supportive measures and dantrolene (for details see dantrolene package insert).

● Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term studies in animals have not been performed.

● Teratogenic Effects: Pregnancy Category C

Animal reproduction studies have not been conducted with PA. It also is not known whether PA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PA should be given to a pregnant woman only if clearly needed.

Alcohol consumption with Lidocaine may increase the risk of low blood pressure and cause adverse effects, such as Dizziness, fainting, light-headedness, or headache.

Lidocaine use in breastfeeding patients is not recommended.

Pregnancy Category C

Animal reproduction studies have not been conducted with PA. It also is not known whether PA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PA should be given to a pregnant woman only if clearly needed.

Tobacco: Using tobacco may interfere with the action of Lidocaine and as a result of this, may alter the effectiveness of the drug.

The adverse reactions related to molecule Lidocaine can be categorized as

• Common Adverse effects:

Hemodynamic compromise, Dizziness, peripheral ischemia, dry mouth,asthenia, and somnolence.

• Less Common adverse effects:

Asymptomatic and symptomatic hypotension, burning, crawling, itching, numbness.

• Rare adverse effects:

Bradycardia, decompensated heart failure, cardiac arrest, and heart block.

The clinically relevant drug interactions of Lidocaine is briefly summarized here.

• May cause a potentiated prolongation of conduction or diminished contractility and hypotension with other group IA antiarrhythmic agents (e.g. Lidocaine, disopyramide).
• The risk or severity of adverse effects can be increased when Lidocaine is combined with 1,2-Benzodiazepine.
• May cause additive antiviral effects on A-V nodal conduction with anticholinergic agents.
• The metabolism of Acetaminophen can be decreased when combined with Lidocaine.
• May enhance the therapeutic efficacy of neuromuscular blocking agents.
• Cimetidine or trimethoprim may increase the plasma concentration of Lidocaine.
• The risk or severity of adverse effects can be increased when Lidocaine is combined with Alprazolam

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Symptoms:

Hypotension, oliguria, lethargy, nausea, vomiting, confusion; continuous widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves; increasing AV block, ventricular extrasystoles, ventricular Tachycardia or fibrillation; delayed intraventricular conduction.

Management:

Symptomatic and supportive treatment. Monitor ECG, blood pressure, and vital signs. Administer vasopressors after adequate fluid volume replacement. Ensure mechanical cardiorespiratory support. May perform haemodialysis to remove from the circulation.

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 .

Pharmacokinetics:

• Absorption:

In general, Lidocaine is readily absorbed across mucous membranes and damaged skin but poorly through intact skin. The agent is quickly absorbed from the upper airway, tracheobronchial tree, and alveoli into the bloodstream. And although Lidocaine is also well absorbed across the gastrointestinal tract the oral bioavailability is only about 35% as a result of a high degree of first-pass metabolism.

• Distribution:

The volume of distribution determined for Lidocaine is 0.7 to 1.5 L/kg. In particular, Lidocaine is distributed throughout the total body water

• Metabolism:

Lidocaine is metabolized predominantly and rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys

• Excretion:

The excretion of unchanged Lidocaine and its metabolites occurs predominantly via the kidney with less than 5% in the unchanged form appearing in the urine . The renal clearance is inversely related to its protein binding affinity and the pH of the urine. This suggests by the latter that excretion of Lidocaine occurs by non-ionic diffusion.

• https://reference.medscape.com/drug/xylocaine-zingo-lidocaine-anesthetic-343363
• https://go.drugbank.com/drugs/DB00281
• https://www.rxlist.com/consumer_lidocaine_lidopen/drugs-condition.htm
• https://www.webmd.com/drugs/2/drug-8532-9170/lidocaine-topical/lidocaine-topical/details
• https://my.clevelandclinic.org/health/drugs/19854-lidocaine-skin-cream-or-ointment