Amiodarone vs Lidocaine

Amiodarone (Cordarone, Nextrone, Pacerone) and Lidocaine (Lignocaine, Xylocaine) are medical drugs used for treatment of various heart conditions, such as ventricular tachycardia, cardiac arrest and abnormal hearth rhythms. This post features a detailed comparison of their indications, uses, mechanisms of action, side effects, etc.

Amiodarone

Amiodarone belongs to the class III antiarrhythmic agent which is used for treatment of various types of cardiac dysrhythmias which are both atrial and ventricular. This drug was first discovered in 1961. It has some side effects but still it is used for in arrhythmias which are quite difficult to treat with medication and drugs.

The main observation about this drug was made by a Russian physiologist Gleb Von Anrep. He discovered that this drug has cardiovascular properties. He found that the most important molecule in amiodarone called khellin is a common plant found in North Africa. Arnep observed that one of his patients was cured from the angina symptoms after taking khellin.

This observation intrigued many researchers and industrialists and they sought a method to separate the active compound. Amiodarone was formed by chemists Tondeur and Binon when they were finding a method to prepare khellin.

An Indian researcher from Oxford University discovered that amiodarone has antiarrhythmic properties and was a part of a new class of agents. It has been seen that both these drugs elongate the duration action potential when they interact with cellular functions with K+ channels.

The FDA was initially reluctant to recommend the official use of this drug because initial reports had shown that it increases the incidence of pulmonary side effects.

The European pharmacists threatened the FDA to approve the status of the drug and said that they would cut the supply of the drug to America if the drug isn’t approved.

The FDA approved the use of this drug for the treatment of arrhythmias in 1985. This makes this drug a unique drug to be approved by the FDA without many clinical trials (1, 2).

Medical appplications

Amiodarone is used for the treatment of life threatening arrhythmias and the chronic suppression of arrhythmias because it has a low incident of pro-arrhythmic effects. This drug is useful for both ventricular arrhythmias and supraventricular arrhythmias. The following are some medical applications of amiodarone:

Amiodarone can be used in the treatment of ventricular tachycardia in many cases. People who have unstable ventricular tachycardia should initially avoid using amiodarone. They should convert from their unstable rhythm. People who have stable ventricular tachycardia should use amiodarone.

Amiodarone can be used in such cases regardless of the heart functioning of the individual. But it shouldn’t be used in patients with polymorphic tachycardia because the effect will be made worse by anti-arrhythmic drugs. The appropriate dosage for this drug is 300 mg to be taken as a bolus.

This drug is also used in the treatment of ventricular fibrillation. This drug can be used in shock-refractory VF. A clinical trial showed that amiodarone improved the survival when cardiac heart patients were given amiodarone (3).

Amiodarone has more effectiveness than iodine in treating VF or pulseless ventricular tachycardia (4).

Amiodarone is also helpful in the treatment of atrial fibrillation. Mostly people who go through open heart surgery are at risk of developing atrial fibrillation. A trail showed that the use of amiodarone reduced the incidence of atrial fibrillation when used in the open heart surgery (5).

But current clinical studies have been unable to show the efficacy of this drug and have shown to produce some side effects like pulmonary toxicities.

The FDA hasn’t recommended amiodarone for the treatment of atrial fibrillation but it is still recommended by the doctors and experts because no better alternatives are present. The main benefit of amiodarone in the critical care population hasn’t yet been found but it may prove to be the first choice of the doctors.

This drug has been recommended by the UK government’s National Institute For Health and Clinical Excellence (NICE).

Dosage and intake methods

Amiodarone is available in the oral and intravenous formulations. The trade names in oral forms are Pacerone present in 200 mg and Cordarone present in 400 mg tablet forms. This drug is also present under the trade name Aratac in 100 and 200 mg tablets. The brand name used for this drug in India is Tachyra in 100mg and 200mg tablets. This drug is also available in intravenous ampules and vials mostly of 150 mg increments.

The dosage of amiodarone depends upon the individual being treated. The dosage varies to a great degree when the drug is administered orally. The absorption rate of this drug is from 22% to 95% with better absorption when taken with food.

Amiodarone is fat soluble and it gets concentrated in the tissues including liver, fat, lungs, muscles and skin. This gives it a high volume of distribution and a good half-life. The overloading usually takes up to weeks due to the long half-life of the drug.

The over loading dosage for this drug is about 10 mg which is divided over one or two weeks The maintenance dosage after loading is about 100 mg to 200 mg taken either once or twice a day.

The intravenous dosage is about 300 mg in 20-30 mL 5% dextrose solution. The loading for dysrhythmias is about 150 mg in 100 mL bag of 5% dextrose solution. Both these dosages need to be followed by 360 mg slow infusion over 6 hours.

Intake methods

There are two intake methods of amiodarone. It can be taken in tablet form or in the injection form:

• Amiodarone comes in tablet form which needs to be taken though the mouth. It should be taken once or twice a day. Make sure to take the tablet with water. This tablet can be taken with or without food but you should take this tablet at the same time every day. Take this medicine according to the instructions of the doctor. Don’t increase or decrease the dosage by yourself.
• This drug is also available in the injection form. All you have to do is to buy a syringe and take the injection to a doctor and get the injection.

Mechanism of action

Amiodarone comes under the class III antiarrhythmic agent and it makes the phase 3 of the cardiac action potential a long process which is the repolarization phase in which there is decreased calcium permeability and increased potassium permeability (6). There are many other effects which include actions which are similar to antiarrhythmic class la, II and IV.

The Amiodarone shows a kind of beta blocker and calcium channel blocker-like actions on the SA and AV nodes which increases the overall refractory period through sodium and potassium-channel effects. This slows down the intra-cardiac conduction of the cardiac action potential through sodium channel-effects. Amiodarone is chemically just like thyroxine and its binding action to the nuclear thyroid receptor might contribute to pharmacological and toxic actions.

Actions after intake – pharmacokinetics

The following steps taken place after the intake of amiodarone (7, 8):

1. Absorption

Amiodarone show complex disposition characteristics after intake. The maximum serum concentrations in healthy individuals after a single 5 mg/kg intravenous infusion in healthy subjects is between 5 and 41 mg/L. The maximum concentration after ten minutes of intake in patients suffering from ventricular fibrillation (VF) or ventricular tachycardia (VT) is between 7 and 26 mg/L. The serum concentration declines to 10% of peak values within 30 to 45 minutes after infusion. It was seen that after 48 hour of continued infusions amiodarone mean serum concentrations ranged between 0.7 to 1.4 mg/L.

2. Distribution

The half-life of amiodarone is quite long and the chronic oral dosage can range from 14 to 110 days. But mostly the half-life ranges from 14 to 59 days. Desethylamiodarone is the main metabolite which has been detected in the plasma and other tissues.

This metabolite has a longer half-life as compared to amiodarone which is 10 hours after a single dosing of amiodarone and elongates to 60-90 days after chronic dosing.  Amiodarone is protein bound and it is thought that it binds itself to concentrations of 10 mg/L.

The distribution after the oral intake of amiodarone is 6.31 +-4.93 L/kg. Amiodarone is present in the adipose tissues and in high perfused organs. The concentration of amiodarone in red blood cells is about 60% to that of plasma.

3. Metabolism

The major metabolite of amiodarone in humans is N-desethylamiodarone (DEA). The DEA serum concentrations which are above 0.05 mg/L are not seen until after many days of continuous infusion. The prolonged therapy makes it reach the same level as amiodarone. Amiodarone metabolizes into desethylamiodarone by the cytochrome P450 enzyme group. CYP3A4 enzyme is present in both the liver and intestines. The variable systematic availability of oral amiodarone is attributed to interindividual variability in CYP3A4 activity.

4. Elimination

Amiadarone gets eliminated from the body through hepatic metabolism and biliary excretion but there is almost negligible excretion of amiodarone in the urine. Both amiodarone and DEA are undialyzable. Both amiodarone and DEA cross placenta and appear in breast milk.

Overdosage

Recently there have been some cases of amiodarone Overdosage. Amiodarone Overdosage happens when a person accidentally or intentionally intakes more than the recommended dosage. An overdose of amiodarone can lead to fatal conditions. Some major effects of amiodarone Overdosage include cardiogenic shock, hypertension, hepatotoxicity and AV block.

Standard therapy should be used for the treatment of cardiogenic shock and hypotension. These health problems can also be treated by slowing the rate of infusion, positive inotropic agents and volume expansion. AV block and Bradycardia need temporary pacing. The concentration of hepatic enzymes should be monitored closely. Amiodarone isn’t dialyzable.

Side effects

Some major side effects of the intake of amiodarone are vomiting, constipation, nausea, tiredness, shaking and fatigue. You should immediately tell the doctor if any of these side effects worsen (9).

You should keep in mind that the doctor has prescribed this medicine for you because he thinks that its benefits are greater than its side effects. Most people using this drug don’t suffer from any serious side effects.

You should inform your doctor if you suffer from any serious side effects like loss of coordination, tingling or numbing in hands and feet, uncontrolled movements, increased tiredness, increased shortness of breath when lying down and symptoms of heart failure. Some other serious side effects include fast and irregular heartbeats, fainting and dizziness.

Sometimes amiodarone can create thyroid problems. You may either have low thyroid function or overactive thyroid function. You should inform the doctor right away if you feel the symptoms of low or overactive thyroid including cold or heat tolerance, thinning of hair, unexplained weight loss, irritability, restlessness, swelling or growth in the front of neck (goiter).

Your skin may become sensitive to the sun due to the intake of this drug. You may develop blue-gray color of the skin. This isn’t harmful and the color returns to the skin as soon as the drug is stopped. You should avoid exposure to the sun for longer durations of time to get rid of this side effect.

Sometimes vision changes can be caused due to the intake of this drug. A few cases have been reported in which patients taking this drug have suffered from permanent blindness. You should inform your doctor right away if you suffer from any kind of vision changes.

A serious allergic reactions occurs in rare cases. You should inform the doctor right away if you notice the effects of serious allergic reaction like rashes, itching and swelling, trouble breathing and severe dizziness.

Cases of serious liver problems have also been reported due to the intake of this drug. Some liver toxicity side effects include necrosis, hepatitis, hepatocellular damage and cirrhosis. There are also about 15 reported cases of liver enzyme disturbance.

Moderate side effects

Some less severe side effects of this drug have been mentioned below:

• Low blood pressure
• Dizziness
• Memory loss
• Restlessness
• Awkward stance when walking
• Sensitivity to sun
• Low thyroid levels
• Increased levels of cholesterol including the triglycerides and low-density lipoproteins
• Severe cough
• Loss of appetite
• Indigestion
• Fever
• Itching
• Loss in sexual ability and desire
• Loss of heat from body
• Lower back pain

You should inform your doctor if you suffer from any of these side effects. People living in the US can call FDA for medical advice at 1-800-FDA-1088 and people living in Canada can call FDA for medical advice at 1-866-234-2345.

Decreased efficiency causes

The following things reduce the efficiency of amiodarone:

• The efficiency of amiodarone is reduced when it interacts with other drugs. Some common drugs which can interact with amiodarone are aspirin, Coumadin, crestor, Lasix, synthroid, Vitamin D3, Lipitor and many others.
• You should avoid eating grapefruit or grapefruit juice when taking amiodarone. The reason is that grape fruit can increase the amount of drug in your bloodstream. You should consult your doctor for details.
• Allergic people should avoid taking amiodarone because its efficiency is reduced when allergic people take this drug. Tell your doctor if you have allergies to food, medicines and other substances.

Lidocaine

The scientific name for this drug is lignocaine or xylocaine. It is a drug which is used to numb the tissues in a specific area of the body and for treating tachycardia. This drug is also used for nerve blocks. Lidocaine is mixed with a small amount of epinephrine and is available in larger doses to numb areas and make them look larger. In injectable form the medicine begins within four minutes and lasts for about half an hour to three hours. This drug can be applied directly to the skin to numb it.

Some common side effects of the consumption of this drug include muscle twitching, sleepiness, vision changes, confusion and vomiting. Other common side effects are causing blood pressure and an irregular heartbeat. Some people are concerned that injecting this drug can cause problems with the cartilage.

This drug is usually considered safe for pregnancy. People with liver problems should take lower doses of this medicine. People who are allergic to tetracaine and benzocaine can take this drug freely. Lidocaine is a class lb type antiarrhythmic medication. It blocks the sodium channels and decreases the heart rate concentrations. The local neurons can’t get signals to the brain when this medicine is used as a numbing agent.

This drug was first discovered in 1946 and was put on sale in 1948. This drug is on the WHO model List of Essential Medicines and is considered as one of the most important medicine in the basic health care system (10). This drug is also available as a generic medicine but it isn’t that much expensive.

Medical uses

There are several medical uses of lidocaine. Some are well known while others are quite surprising:

1. Numbing agent

Lidocaine is used as a local anesthetic. There is a rapid onset of action and intermediate duration of efficacy. This drug is therefore, useful for blocking, infiltration and surface anesthesia. Sometimes the long lasting substances like bupivacaine are given preference for epidural anesthesia but lidocaine has the advantage of rapid action. Epinephrine vasoconstricts (constriction of blood vessels which increases the overall blood pressure) the arteries which reduces the bleeding and delays the reabsorption of lidocaine and thus, doubles the duration of anesthesia. Different other formulations are used for surface anesthesia. The local numbing is made less painful through the buffering of lidocaine.

2. Heart arrhythmia

Lidocaine is an important class 1-b antiarrhythmic drug. It is used for the treatment of ventricular arrhythmias if amiodarone isn’t available. Lidocaine can be given after CPR, defibrillation and vasopressors have been initiated. The routine dosage isn’t recommended because the overall benefits aren’t that much convincing (11).

3. Other uses

Lidocaine can be used as an antitussive to reduce the cough reflex. It can be implemented as a safety measure for patients who have been intubated because it reduces coughing and any tracheal damage which is caused during the emergence from anesthesia.

Lidocaine can also be used with ethanol, ammonia and acetic acid and treat jellyfish stings. It numbs the affected area and prevents nematocyst discharge.

Dosage and intake methods

The dosage of lidocaine is divided according to the type of health problem of a certain person. The dosage of lidocaine according to the specific diseases has been mentioned below:

• Dose for arrhythmias – the initial dosage for arrhythmias is about 1 to 1.5 mg/kg to be given over 2 to 3 minutes. The dose can be repeated with 0.5 to 0.75mg/kg/dose IV to be given over 2 to 3 minutes in 5 to 10 minutes till a total of 3 mg/kg.
• Dose for ventricular fibrillation – the other name for ventricular fibrillation is ventricular tachycardia. The initial dose is about 1 to 1.5 mg/kg/ dose to be taken intravenously. The dose can repeated with 0.5 to 0.75 mg/kg/dose for 5 to 10 minutes interval.
• Dose for anesthesia – anesthesia local injectable should be given to the patient. The dose varies according to the degree of anesthesia needed, duration of anesthesia and physical condition of the patient. The maximum dose shouldn’t exceed more than 4.5 mg/kg and shouldn’t be repeated within 2 hours.
• Dose adjustments – the dose should be decreased in patients with shock or hepatic disease. The initial dose for patients with impaired cardiac function should be 0.5 to 0.75 mg/kg/dose. The dose can be repeated every 5 to 10 minutes. The maximum dose shouldn’t exceed than 3 mg/kg.

Intake methods

The following are the intake methods of lidocaine:

1. Lidocaine cream

Lidocaine comes in cream form. You should apply a thin layer of this medication on the affected area 2 or 3 times or as directed by the doctor. You should apply this medication gently around the anus. Apply a small amount on the affected area and rub it gently. Don’t apply the medication inside the anus. You should wash hands quickly after applying the cream. You shouldn’t use the cream on large areas of the body. You should apply heat or waterproof the area with plastic and bandages.

You shouldn’t use the cream longer than the recommendations of the doctor. Don’t stop the medicine at once if you are using it for a long period of time. Your health condition might worsen if the drug is stopped immediately.

2. Lidocaine tablets

This drug also comes in the form of tablets. You should always take the tablets with water. It is your choice to take the tablet with or without food.

3. Liquid form

This drug also comes in syrup form. You should carefully measure the dosage strength of the medicine. Don’t use an ordinary spoon. Use a measuring spoon for exact dosage.

Mechanism of lidocaine

Lidocaine blocks the fast voltage-gated Na+ channels and thus alters the signals of the neurons in the neuronal cell membrane (12). The membrane of postsynaptic neuron doesn’t polarize when there is sufficient blockage and thus an action potential isn’t transmitted. This creates an anaesthetic effect which blocks the signal reaching the brain and stops them even before they begin. A high degree of selectivity is done by careful blocking of sensory neurons. The higher concentrations also affect the neuron signaling.

This principle is the same for the drug’s action in the heart. The depolarization threshold is increased when the sodium channels in the conduction system is blocked. This doesn’t allow the heart to initiate early action potentials which can cause an arrhythmia (13).

Pharmacokinetics – actions after intake

The following steps take place after the intake of lidocaine (14, 15):

1. Absorption

Different formulations have showed that the lidocaine HCL is absorbed completely through parenteral administration. The rate of absorption depends upon a number of factors such as the absence or presence of a vasoconstrictor agent. The high blood levels are reached through intercostal nerve block.

The plasma binding of HCL depends upon drug concentration. The fraction bound decreases as the concentration increases. The percentage of lidocaine HCL is protein bound at concentrations 1 to 4 mcg. The binding also depends upon the plasma concentration of alpha-1 acid glycoprotein.

2. Distribution

Lidocaine is distributed throughout the body through passive diffusion and crosses the blood-brain and placental barriers.

3. Metabolism

The liver rapidly metabolizes lidocaine and the unchanged drugs are metabolized by the kidneys. The steps included in the biotransformation are ring hydroxylation, oxidative N-dealkylation and conjugation. The metabolites glyinexilidide and monoethylglycinexylidide are produced through N-dealkylation.

4. Elimination

About 90% of the lidocaine HCL is excreted from the body in the form of different metabolites. Less than 10% is excreted unchanged through the urine. The main metabolite in urine is a conjugate of 4-hydroxy-2, 6 dimethylaniline.

The elimination half-life of lidocaine ranges from 1.5 to 2 hours. Lidocaine HCL is metabolized rapidly and any condition which affects the liver functioning can change the working of lidocaine HCL. The half-life may be longer in patients with liver dysfunction. The lidocaine HCL function isn’t affected by the renal dysfunction but it can increase the accumulation of metabolites.

Overdosage

The overdose of lidocaine is quite rare but it can occur. You should check your blood concentrations if you think you have overdosed on lidocaine.

The following steps are involved in the management of overdose:

• Supportive care
• Close monitoring
• Symptomatic treatment (Treating the symptoms of overdose)
• Dialysis

When there isn’t massive overdose then the symptoms of toxicity include consideration of other etiologies for the clinical effects from other sources of lidocaine or other local anesthetics.

Side effects of lidocaine

You should tell your doctor immediately if you suffer from any of the following symptoms after injection:

• Numbness or pain in the lower leg
• Difficulty in controlling your bowel movements
• Light-headedness
• Having trouble walking
• Slow pulse or heart rate

Sometimes an allergic reaction can also be caused due to the intake of this drug. You should seek medical care if this happens. Some major symptoms of an allergic reaction include rashes, dizziness, itching, swelling and difficulty in breathing (16).

Some more severe side effects of this drug include drowsiness, head pain, heart block, quivering, seizures, slow heartbeat, overexcitement, unconsciousness, allergic reactions, loss of breath and reaction due to allergies.

Moderate side effects

Some less severe side effects of lidocaine have been mentioned below:

• Confusion
• Dizziness
• Blurred vision
• Ringing in ears
• Throwing up
• Twitching
• Feeling warm
• Feeling cold
• Heightened sense of well being

You should always consult a doctor if you suffer from any of these side effects.

Decreased efficiency causes

The following things reduce the overall efficiency of lidocaine:

• The efficiency of lidocaine is reduced when it reacts with other drugs. About 231 drugs are known to interact with lidocaine. Some common medications which can interact with lidocaine include Nexium, Ambien, Vitamin B12, Vitamin C, Vitamin D3, Xanax, Colace, MiraLax, Lasix and many others.
• You should never swallow lidocaine cream because it can cause life threatening issues. It can cause poisoning if large quantity is consumed.

Clinical trials of amiodarone vs lidocaine

Lidocaine and amiodarone are both helpful for ventricular fibrillation patients. But the question arises that which of the two is more beneficial. Luckily there is a study which compares lidocaine and amiodarone for ventricular fibrillation. The details of the study are mentioned below (17):

About one hundred and fifty patients were chosen for first time elective coronary artery graft surgery. The patients were all of about the same age and the average was 67 years. More than 75% people in the study were male and had a history of heart diseases and some had suffered from heart attack. The patients were given either single doses of lidocaine, amiodarone or given saline about 3 minutes before aortic clamp release. The results were compared through chi-square, Student’s t-test and One-Way Anova.

The study found that ventricular fibrillation was higher in the placebo group than the other two groups. The ventricular fibrillation in the placebo group was 15.9%. The ventricular fibrillation in people taking lidocaine was about 11.8% and those taking amiodarone was 8.9%. The researchers didn’t find any statistical data to show which of the two drugs is better but still the researchers preferred amiodarone over lidocaine because it had lower incidence of ventricular fibrillation.

Conclusion

The study clearly shows that amiodarone is a better drug than lidocaine for the treatment of ventricular fibrillation. The reason is that there are less chances of developing ventricular fibrillation if amiodarone is taken. Amiodarone also has lesser side effects as compared to lidocaine. So amiodarone should be your first choice if you suffer from ventricular fibrillation.