Metabolic Manipulator Drug – Amiodarone

OVERVIEW

Metabolic manipulators are those agents or factors which manipulate or disturb the metabolic functions of cells, tissues or body organs(Lange,2012).

Metabolic manipulator which we are going to discuss in this assignment is Amiodarone.

It is an antiarrythmic medication use in the treatment of unusual rhythm of heartbeats.

Its molecular formula is C₂₅H₂₉I₂NO_3.

_IUPAC name if this drug is (2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-2,6-diiodophenoxy}ethyl)diethylamine

Molecular mass of this drug is exactly ‎645.32 g/mol.

Structural formula can be written as-

Class of drug in which it falls is Class III Vaughan Williams Antiarrhythmic agent

The main component of this drug is iodine rich benzofurane. This acts as an antiarrhythmic agent.

USES OF DRUG

Amiodarone is used in the treatment of

• acute life-threatening arrhythmias
• acute life-threatening arrhythmias
• acute life-threatening arrhythmias
• Ventricular tachycardia
• Atrial fibrillation

WORKING OF DRUG

Amiodarone is a type of antiarrhythmic drug which help in the treatment of irregular heartbeats by

• Slowing conduction rate of SA node and AV node.
• Increasing the refractory period of ventricles, bundle of HIS and purkinjee fibers
• By acting as beta blockers a calcium channel blockers to increase the refractory period.
• Increase refractory period by sodium potassium channel effect.
• Slowing the intra-cardiac conduction of cardiac action potential.

METHOD OF SYNTHESIS OF DRUG

Amiodarone is synthesized by the following steps:

1. Salicylaldehyde is reacted with2-halogenated hydrocarbyl hexanoate.
2. The product is then reacted with p-methoxybenzoyl chroride.

• Further it is reacted with iodine and 2-diethylaminoethyl chloride.

1. The final product we get is (2-butyl-3-benzofuryl)[4-[2-(diethylamino) ethyoxyl]3,5-diiodine pehyl] ketone hydrochloride, this product obtained is called as Amiodarone.

PHARMACOLOGY AND PHARMACOKINETICS OF AMIODERONE DRUG

Amiodarone consists of 37% of iodine by weight. When we look for its structure, it is similar to the structure of thyroid hormones. Bioavailability of the drug inside the body is about 20% to 25%.

Half life of the drug is about 58 days inside the body. After that it is metabolized in the liver and then excreted out from the body.

METABOLISM OF DRUG IN THE BODY

Inside the body, Amiodarone is metabolized by the liver. Enzyme present in the liver which metabolize it is P450 3A4(Ambesh P,2017). Metabolism of this drug also affects the metabolism of other drugs. It interacts with drugs like digoxin, phenyton, warfarin and others(Freeman,2016). Desethylamiodarone (DEA) is the major metabolite of the drug Amiodarone and (DEA) also have antiarrhythemic properties. When Amiodarone is intake along with the drug simvastin, it leads to rhabdomyosis which further results in the kidney failures and in most of the cases it leads to death of the patients.

All the drugs which are taken for the treatment of heart diseases are affected due to the intake of Amiodarone.

Amiodarone stimulates the action of the drugs warfarin and thus the doses of the warfarin drug are to be halved when taken along with Amiodarone. Similarly, doses of digoxin are halved while taking it along with Amiodarone. It increases the concentration of the calcium channel blocking agents, quinidine a flecainide.  After taking Amiodarone, coagulation property of the blood reduces by 50%

Excretion of this drug is primarily done by the kidneys through hepatic and billiary processes. There is no elimination through renal routes. Eliminaion of the drug is done fully after 58 days after the in taking of last dose. Its active metabolites are remained in body for around 36 days. In pregnant women, 10% of the drugs transferred through the placenta as well from the breast milk. There is also accumulation of the drug in the adipose tissues of the body. Therefore, pregnant ladies and person it chronic level of Amiodarone should stop the in taking of the drug.

As Amiodarone is having a benzene ring, it is highly lipophilic and thus it remained in the body for the long time. Drug doses thus cannot be increased in the few days after the starting of the treatment or it may lead to serious condition of the patient.

CURRENT RESEARCH

Current research was made on the incidence of Amiodarone-mediated aggravation of ventricular tachyarrhythmia(Ambesh P,2016). Another objective of this research was to develop new arrhythmias in patients with cardiac diseases.

In this research, the articles and reports on the use of Amiodarone was collected which were published or recorded from last 20 years. These reports and articles were then divided into three categories-

1. Case reports
2. Uncontrolled retrospective studies

• Prospective control trials

At the end of the study,

• 65 case reports which were dealing with torsade de pointes during Amiodarone therapy were found in the literature.
• 17 studies were on the data from the reports of the 50 patients with the treatment of Amiodarone for the 6 months.
• 57 patients were reported to show proarrhythmic event went they were exposed to the drug.

In none of these, patient did a recurrent episode of torsade de pointes develop, despite of the prolongation of the QTc interval by the action of Amiodarone drug.

From the above study, the conclusion was made that there were very few cases of prorrhythmic cases and the incidence of torsade de pointes is also less than 1%. It is therefore, Amiodarone is given to the patients who are at a very high risk of the arrhythmias and can have a risk of dying at any moment.

Another research was done for the Evaluation of Amiodarone versus metoprolol in treating atrial fibrillation after coronary artery bypass grafting

The atrial fibrillation is a type of arrhythmia which is most commonly occurring in the patients which recently undergone bypass surgery. Many doctors select beta blockers to treat this disease but some doctors prefer drugs like Amiodarone in the treatment of this disease. Therefore, this study was conducted to know which drug is better in the treatment of atrial fibrillation.

For this study, two groups of people were created by choosing randomly. Each group was having 73 patients who were going to be admitted for the bypass surgery. Group A patients were given the treatment with Amiodarone while group M were given metoprolol. The data was then collected an as analyzed via SPSS 19.

At the end of the research, it was found that

1. Amiodarone was successful in treatment of AF in 55 patients, that is, 73%.
2. Metoprolol was success in the treatment of AF in 69 patients, that is, 92%.

The conclusion from this study was that, in the treatment of articular fibrillation, metoprolol I more effective than the Amiodarone drug.

DIAGNOSIS

As the main constituent of the Amiodarone is iodine rich benzofurane, it is used in the diagnosis and investigations related to thyroid glands. One of them is in diagnosing the functional activity of the thyroid stimulating hormone(Freeman,2016).

Although, there are fluctuations in the level of thyroid stimulating hormone in the blood level after the intake of the Amiodarone drug, the rise in the level of hormone is straight forward and thus it can be helpful in the calculation of TSH level.

SIDE EFFECTS

Major side effects of the drug Amiodarone are given below-

It is possible that the patient which is not having any thyroid abnormality before the treatment with Amiodarone to develop the abnormalities and thyroid diseases , but it is not suggested to withdraw the intake of the drug(Lange,2012). It so because, the action of such drug is very useful and more serious problems can be raised if the drug is withdrawn. It is therefore advised that when patients develop any of such abnormalities related to thyroid , it should also take treatment of that disease without the withdrawal of the Amiodarone. Treatment with T4 can also be started without any delay in few cases.

TREATMENTS

Amiodarone is used to treat diseases like atrial fibrillations, pulseless  V-Tach , stable V-Tach  and  supraventricular tachycardia (SVT).

ATRIAL FIBRILLATION

Atrial fibrillation is an abnormality in the rythmof heartbeats. In the beginnings it shows briefs periods of abnormal heartbeats, then after one time it becomes longer and finally it possibly constant overtime.

For the treatment of this disease ,the Amiodarone is given orally . 600 mg to 800 mg of the drug is divided until a total of 10 gm is given. After that , total daily dose of 150 mg can be administered to the patient.

PULSELESS V-TACH

Pulselesss V-Tach or ventricular tachycardia is the disease in which there is fast heart rate which arised due to abnormal electrical activities in the ventricles of the heart. Ventricular tachycardia may result in the cardiac arrest.

For the treatment of this disease ,300 mg of the drug is administered in the form of rapid bolus. It can be repeated with 150 mg dose if patient can take it in one go. In the case if there is return of spontaneous circulation occurs then 1 mg/min IV/IO for 6 hours, then 0.5 mg/min IV/IO thereafter up to 1050 mg can be given with the maximum dose of 2.2 g every day.

STABLE V-TACH

For the treatment of this, 1050 mg of the drug is given for the first few days of the treatments and drug is administered by the infusion regimen. Initial IV load of 150 mg per 100 mL (in 100 mL of D5W) infused over 10 minutes, then 1 mg/min for 6 hours, and then 0.5 mg/min thereafter.

SUPRAVENTRICULAR TACHYCARDIA (SVT)

Supraventricular tachycardia  is the disease in which there is fast heart rhythm which arised due to abnormal electrical activities in the upper chambers of the heart. By infusing technique, 150  mg of the drug Amiodarone is dissolved in 100 ml of D5W and given to the patient .thereafter , daily total dose of 100 mg to 200 mg can be administered to the patients through oral doses.

Dosage forms in which this drug is available in the market are given below-

POLICIES

For the administration of the drug Amiodarone, certain policies which government have made are-

• 01
• 00
• 12
• 05

The statement of the policy is

• The medication can be prescribed by the only license and authorized practitioner or nurse.
• All the prescriptions should be recorded
• Before administration, the prescription to be checked by second nurse also.
• The adverse drug reactions which can occur in the patient are to be reported to the drug officer.
• Medication errors are to be reported via IIMS.
• Amiodarone may be administered via a peripheral cannula or central line.
• Amiodarone must always be administered via a dedicated lumen and never “piggybacked” with other drugs or fluids. Where multiple infusions are required, administer with other compatible drugs, via a three-way tap.
• Infusions must be done by syringes or infusion pumps
• Amiodarone must not be administered via hemodylasis port.
• The patient must be monitored while infusion.

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