Ibutilide

Last updated
Ibutilide
Ibutilide.svg
Clinical data
Trade names Corvert
AHFS/Drugs.com Monograph
MedlinePlus a601248
Pregnancy
category
  • C
Routes of
administration
Intravenous
ATC code
Pharmacokinetic data
Bioavailability N/A
Protein binding 40%
Metabolism Hepatic oxidation
Elimination half-life 6 hours (2-12 hours)
Excretion Renal (82%), fecal
Identifiers
  • N-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C20H36N2O3S
Molar mass 384.58 g·mol−1
3D model (JSmol)
  • O=S(=O)(Nc1ccc(cc1)C(O)CCCN(CC)CCCCCCC)C
  • InChI=1S/C20H36N2O3S/c1-4-6-7-8-9-16-22(5-2)17-10-11-20(23)18-12-14-19(15-13-18)21-26(3,24)25/h12-15,20-21,23H,4-11,16-17H2,1-3H3 Yes check.svgY
  • Key:ALOBUEHUHMBRLE-UHFFFAOYSA-N Yes check.svgY
   (verify)

Ibutilide is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. It exerts its antiarrhythmic effect by induction of slow inward sodium current, which prolongs action potential and refractory period of myocardial cells. Because of its Class III antiarrhythmic activity, there should not be concomitant administration of Class Ia and Class III agents.

Contents

Ibutilide is marketed as Corvert by Pfizer. Administration resulted in successful heart rhythm control in 31-44% of patients within 90 minutes, with sustained polymorphic ventricular tachycardia in 0.9-2.5% of patients. It appears to show better results in atrial flutter as compared to atrial fibrillation. [1]

Mechanism of action

Ibutilide, like other class III antiarrhythmic drugs, blocks delayed rectified potassium current. [2]

It does have action on the slow sodium channel and promotes the influx of sodium through these slow channels.

Although potassium current seems to play a role, their interactions are complex and not well understood. [3] Ibutilide's unique mechanism works by an activation of a specific inward sodium current, thus producing its therapeutic response in which a prolonged action potential increases myocytes’ cardiac refractoriness in case of atrial fibrillation and flutter.

Pharmacokinetics

Absorption

Ibutilide is intravenously administered. It has a high first-pass metabolism, which results in a poor bioavailability when taken orally. Individual pharmacokinetic properties are highly viable during the clinical trial. [3] [4]

Distribution

Ibutilide has a relatively large volume of distribution among individual subjects, which is about 11L/kg. Approximately 40% of the drug is bound with plasma albumin of healthy volunteers in a trial. This is also approximately close to patients with atrial fibrillation and flutter. [4]

Metabolism

Ibutilide has a high systemic plasma clearance that closes to the hepatic blood flow (29mL/min/kg). Its metabolic pathway is via liver's cytochrome P450 system by isoenzymes other than CYP3A4 and CYP2D6 by which the heptyl side chain of ibutilide is oxidized. [3] [4] With eight metabolites are detected in the urine, however, only one is an active metabolite that shares the similar electrophysiologic property of the Class III antiarrhythmic agents. [3] [4] [5] The plasma concentration of this metabolite is only less than 10% of ibutilide. [4]

Excretion

After administration of ibutilide, it is quickly excreted by renal pathway with a half-life of approximately 6 hours. Approximately 82% of a 0.01 mg/kg dose is excreted in the urine during the trial. Among those, around 7% is excreted as unchanged drug. The remainder of the drug is excreted in feces (about 19%). [3]

Adverse effects and contraindications

Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to develop abnormal heart rhythms; this includes persons that have had polymorphic ventricular tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial infarction, among others. [6]

Patient Information

This medication will be given intravenously for your heart disease. You will have continuously ECG monitoring during the infusion and 4 hours after your infusion. Some of the minor side effects are headache and irregular heartbeat. If you experience chest pain and respiratory difficulties, you should report to your doctors immediately. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Cardioversion</span> Conversion of a cardiac arrhythmia to a normal rhythm using an electrical shock or medications

Cardioversion is a medical procedure by which an abnormally fast heart rate (tachycardia) or other cardiac arrhythmia is converted to a normal rhythm using electricity or drugs. Synchronized electrical cardioversion uses a therapeutic dose of electric current to the heart at a specific moment in the cardiac cycle, restoring the activity of the electrical conduction system of the heart. Pharmacologic cardioversion, also called chemical cardioversion, uses antiarrhythmia medication instead of an electrical shock.


Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia.

<span class="mw-page-title-main">Atrial flutter</span> Medical condition

Atrial flutter (AFL) is a common abnormal heart rhythm that starts in the atrial chambers of the heart. When it first occurs, it is usually associated with a fast heart rate and is classified as a type of supraventricular tachycardia. Atrial flutter is characterized by a sudden-onset (usually) regular abnormal heart rhythm on an electrocardiogram (ECG) in which the heart rate is fast. Symptoms may include a feeling of the heart beating too fast, too hard, or skipping beats, chest discomfort, difficulty breathing, a feeling as if one's stomach has dropped, a feeling of being light-headed, or loss of consciousness.

<span class="mw-page-title-main">Dofetilide</span> Antiarrhythmic medication

Dofetilide is a class III antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. It is not available in Europe or Australia.

<span class="mw-page-title-main">Amiodarone</span> Antiarrhythmic medication used for various types of irregular heartbeats

Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia (VT), ventricular fibrillation (VF), and wide complex tachycardia, as well as atrial fibrillation and paroxysmal supraventricular tachycardia. Evidence in cardiac arrest, however, is poor. It can be given by mouth, intravenously, or intraosseously. When used by mouth, it can take a few weeks for effects to begin.

<span class="mw-page-title-main">Torsades de pointes</span> Type of abnormal heart rhythm

Torsades de pointes, torsade de pointes or torsades des pointes is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram (ECG). It was described by French physician François Dessertenne in 1966. Prolongation of the QT interval can increase a person's risk of developing this abnormal heart rhythm, occurring in between 1% and 10% of patients who receive QT-prolonging antiarrhythmic drugs.

<span class="mw-page-title-main">Ventricular tachycardia</span> Medical condition of the heart

Ventricular tachycardia is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period of time are referred to as an electrical storm. Short periods may occur without symptoms, or present with lightheadedness, palpitations, or chest pain. Ventricular tachycardia may result in ventricular fibrillation (VF) and turn into cardiac arrest. This conversion of the VT into VF is called the degeneration of the VT. It is found initially in about 7% of people in cardiac arrest.

<span class="mw-page-title-main">Sotalol</span> Medication

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.

<span class="mw-page-title-main">Procainamide</span> Medication to treat cardiac arrhythmias

Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is a sodium channel blocker of cardiomyocytes; thus it is classified by the Vaughan Williams classification system as class Ia. In addition to blocking the INa current, it inhibits the IKr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin (BTX)-activated sodium channels in cardiomyocytes.

Proarrhythmia is a new or more frequent occurrence of pre-existing arrhythmias, paradoxically precipitated by antiarrhythmic therapy, which means it is a side effect associated with the administration of some existing antiarrhythmic drugs, as well as drugs for other indications. In other words, it is a tendency of antiarrhythmic drugs to facilitate emergence of new arrhythmias.

<span class="mw-page-title-main">Azimilide</span> Chemical compound

Azimilide is a class ΙΙΙ antiarrhythmic drug. The agents from this heterogeneous group have an effect on the repolarization, they prolong the duration of the action potential and the refractory period. Also they slow down the spontaneous discharge frequency of automatic pacemakers by depressing the slope of diastolic depolarization. They shift the threshold towards zero or hyperpolarize the membrane potential. Although each agent has its own properties and will have thus a different function.

<span class="mw-page-title-main">Lorcainide</span> Antiarrythmic agent

Lorcainide is a Class 1c antiarrhythmic agent that is used to help restore normal heart rhythm and conduction in patients with premature ventricular contractions, ventricular tachycardiac and Wolff–Parkinson–White syndrome. Lorcainide was developed by Janssen Pharmaceutica (Belgium) in 1968 under the commercial name Remivox and is designated by code numbers R-15889 or Ro 13-1042/001. It has a half-life of 8.9 +- 2.3 hrs which may be prolonged to 66 hrs in people with cardiac disease.

<span class="mw-page-title-main">Dronedarone</span> Drug

Dronedarone, sold under the brand name Multaq, is a class III antiarrhythmic medication developed by Sanofi-Aventis. It was approved by the FDA on July 2, 2009. Besides being indicated in arrhythmias, it was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.

<span class="mw-page-title-main">Multifocal atrial tachycardia</span> Fast heart rhythm associated with exacerbations of COPD

Multifocal atrial tachycardia (MAT) is an abnormal heart rhythm, specifically a type of supraventricular tachycardia, that is particularly common in older people and is associated with exacerbations of chronic obstructive pulmonary disease (COPD). Normally, the heart rate is controlled by a cluster of cells called the sinoatrial node. When a number of different clusters of cells outside the SA node take over control of the heart rate, and the rate exceeds 100 beats per minute, this is called multifocal atrial tachycardia.

<span class="mw-page-title-main">Vernakalant</span> Medication for the acute treatment of atrial fibrillation

Vernakalant is a class III antiarrhythmic drug for the acute conversion of atrial fibrillation, a kind of irregular heartbeat, in form of an intravenous infusion. It has been approved for use in the European Union and the UK since 2010. The US Food and Drug Administration denied approval in 2008 and 2019.

<span class="mw-page-title-main">Pilsicainide</span> Chemical compound

Pilsicainide (INN) is an antiarrhythmic agent. It is marketed in Japan as サンリズム (Sunrythm). It was developed by Suntory Holdings Limited and first released in 1991. The JAN applies to the hydrochloride salt, pilsicainide hydrochloride.

Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels.

<span class="mw-page-title-main">Landiolol</span> Chemical compound

Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparison to other beta blockers, landiolol has the shortest elimination half-life, ultra-rapid onset of effect, and predictable effectiveness with inactive metabolites. The pure S-enantiomer structure of landiolol is believed to develop less hypotensive side effects in comparison to other β-blockers. This has a positive impact on the treatment of patients when reduction of heart rate without decrease in arterial blood pressure is desired. Landiolol was developed by modifying the chemical structure of esmolol to produce a compound with a higher rate of cardioselectivity and a greater potency without increasing its duration of action. It is sold as landiolol hydrochloride. Based on its positive benefit risk profile, landiolol has been granted the marketing authorization and introduced to the European markets under the brand names Rapibloc, Raploc, Runrapiq, Landibloc mid 2016. Landiolol is available in Japan under the brand names Onoact (50 mg) and Corbeta.

<span class="mw-page-title-main">Arrhythmia</span> Group of medical conditions characterized by irregular heartbeat

Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be lightheadedness, passing out, shortness of breath, chest pain, or decreased level of consciousness. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in sudden death.

<span class="mw-page-title-main">Celivarone</span> Experimental drug being tested for use in pharmacological antiarrhythmic therapy

Celivarone is an experimental drug being tested for use in pharmacological antiarrhythmic therapy. Cardiac arrhythmia is any abnormality in the electrical activity of the heart. Arrhythmias range from mild to severe, sometimes causing symptoms like palpitations, dizziness, fainting, and even death. They can manifest as slow (bradycardia) or fast (tachycardia) heart rate, and may have a regular or irregular rhythm.

References

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  2. Murray KT (February 1998). "Ibutilide". Circulation. 97 (5): 493–7. doi: 10.1161/01.CIR.97.5.493 . PMID   9490245.
  3. 1 2 3 4 5 Howard PA (January 1999). "Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter". The Annals of Pharmacotherapy. 33 (1): 38–47. doi:10.1345/aph.18097. PMID   9972384. S2CID   44431471.
  4. 1 2 3 4 5 Pharmacia-Upjohn, Corvert (ibutilide fumarate) injection package insert. July 2002: Kalamazoo, MI.
  5. Rogers KC, Wolfe DA (January 2001). "Ibutilide: a class III rapidly acting antidysrhythmic for atrial fibrillation or atrial flutter". The Journal of Emergency Medicine. 20 (1): 67–71. doi:10.1016/s0736-4679(00)00274-2. PMID   11165840.
  6. Jasek W, ed. (2007). Austria-Codex (in German). Vol. 1 (2007/2008 ed.). Vienna: Österreichischer Apothekerverlag. pp. 1768–71. ISBN   978-3-85200-181-4.
  7. Lexi-Comp, Lexi-Drugs Online : Ibutilide.