Sotalol

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Sotalol
Sotalol.svg
Sotalol-based-on-HCl-xtal-3D-bs-17.png
Clinical data
Trade names Betapace, Sorine, Sotylize, others [1]
AHFS/Drugs.com Monograph
MedlinePlus a693010
License data
Pregnancy
category
  • AU:C
Routes of
administration 		By mouth
Drug class Beta blocker
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 90–100% [2]
Metabolism Not metabolized [2]
Elimination half-life 12 hours [2]
Excretion Kidney
Mammary gland (In lactating individuals) [2]
Identifiers
  • (RS)-N-{4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl}methanesulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C12H20N2O3S
Molar mass 272.36 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • O=S(=O)(Nc1ccc(cc1)C(O)CNC(C)C)C
  • InChI=1S/C12H20N2O3S/c1-9(2)13-8-12(15)10-4-6-11(7-5-10)14-18(3,16)17/h4-7,9,12-15H,8H2,1-3H3 Yes check.svgY
  • Key:ZBMZVLHSJCTVON-UHFFFAOYSA-N Yes check.svgY
   (verify)

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. [1] Evidence does not support a decreased risk of death with long term use. [1] It is taken by mouth or given by injection into a vein. [1]

Contents

Common side effects include a slow heart rate, chest pain, low blood pressure, feeling tired, dizziness, shortness of breath, problems seeing, vomiting, and swelling. [1] Other serious side effects may include QT prolongation, heart failure, or bronchospasm. [3] Sotalol is a non-selective β-adrenergic receptor blocker which has both class II and class III antiarrhythmic properties. [1]

Sotalol was first described in 1964 and came into medical use in 1974. [4] It is available as a generic medication. [3] In 2020, it was the 296th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [5] [6]

Medical uses

According to the U.S. Food and Drug Administration (FDA), sotalol can be validly used to maintain a normal heart rhythm in people with life-threatening ventricular arrhythmias (e.g., ventricular tachycardia), or very symptomatic atrial fibrillation or flutter. [7] Due to the risk of serious side effects, the FDA states that sotalol should generally be reserved for people whose ventricular arrhythmias are life-threatening, or whose fibrillation/flutter cannot be resolved using the Valsalva maneuver or another simple method. [7] Sotalol has shown some potential efficacy against symptoms of essential tremor due to its binding to the β2-adrenergic receptor but this remains an off-label use. [8]

Contraindications

According to the FDA, sotalol should not be used in people with a waking heart rate lower than 50 beats per minute. [7] It should not be used in people with sick sinus syndrome, long QT syndrome, cardiogenic shock, uncontrolled heart failure, asthma or a related bronchospastic condition, or people with serum potassium below 4 meq/L. [7] It should only be used in people with a second and third degree AV block if a functioning pacemaker is present. [7]

Since sotalol is removed from the body through the kidneys, it should not be used in people with a creatinine clearance rate below 40 mL/min. [7] It is also excreted in breast milk, so mothers should not breastfeed while taking sotalol. [7]

Since sotalol prolongs the QT interval, the FDA recommends against using it in conjunction with other medications that prolong the QT interval. [7] Studies have found serious side effects to be more common in individuals also taking digoxin, possibly because of pre-existing heart failure in those people. [7] As with other beta blockers, it may interact with calcium channel blockers, catecholamine-depleting drugs, insulin or antidiabetic drugs, β2-adrenergic receptor agonists, and clonidine. [7]

Some evidence suggests that sotalol should be avoided in the setting of heart failure with a reduced ejection fraction (resulting in the heart squeezing little blood out into the circulation with each pump) due to an increased risk of death. [9]

Adverse effects

Over 10% of oral sotalol users experience fatigue, dizziness, lightheadedness, headache, weakness, nausea, shortness of breath, bradycardia (slow heart rate), a sensation of the heart beating too hard, fast, or irregularly, or chest pain. Higher doses of sotalol increase the risk for all of these possible side effects. [2]

In rare cases, the QT prolongation caused by sotalol can lead to the development of life-threatening torsade de pointes (TdP) polymorphic ventricular tachycardia. Across several clinical trials, 0.6% of oral sotalol patients with supraventricular abnormal heart rhythms (such as atrial fibrillation) developed TdP. [2] For patients who had a history of sustained ventricular tachycardia (abnormal rhythm lasting more than 30 seconds), 4% developed TdP. Risk increases with dosage, female sex, or having a history of an enlarged heart or congestive heart failure. [2] The incidence of TdP for sustained ventricular tachycardia patients was 0% with an 80 mg daily dose, 0.5% at 160 mg, 1.6% at 320 mg, 4.4% at 480 mg, 3.7% at 640 mg, and 5.8% at doses greater than 640 mg. [2] Due to this risk, the U.S. Food and Drug Administration requires affected individuals to be hospitalized for at least three days in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring upon starting or restarting sotalol. [2]

Pharmacology

Mechanisms of action

Beta-blocker action

Sotalol is a beta blocker and non-selectively binds to both β1- and β2-adrenergic receptors preventing activation of the receptors by their stimulatory ligand (catecholamines). [10] [11] It has no intrinsic sympathomimetic activity. [11]

Without the binding of catecholamines to the β-adrenergic receptor, the G protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels. [12] A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium. In heart cells, calcium is important in generating electrical signals for heart muscle contraction, as well as generating force for this contraction. [13] In consideration of these important properties of calcium, two conclusions can be drawn. First, with less calcium in the cell, there is a decrease in electrical signals for contraction, thus allowing time for the heart's natural pacemaker to rectify arrhythmic contractions. [14] Secondly, lower calcium means a decrease in strength and rate of the contractions, which can be helpful in treatment of abnormally fast heart rates. [14]

Type III antiarrhythmic action

Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles. [15] By blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an increase in the time before another electrical signal can be generated in ventricular myocytes. [13] This increase in the period before a new signal for contraction is generated, helps to correct arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles but also prolongs the frequency of ventricular contraction to help treat tachycardia.[ medical citation needed ]

Pharmacokinetics

Sotalol is classified as a beta blocker with low lipophilicity and hence lower potential for crossing the blood–brain barrier. [11] This in turn may result in fewer effects in the central nervous system as well as a lower risk of neuropsychiatric side effects. [11]

History

Sotalol was first synthesized in 1960 by A. A. Larsen of Mead-Johnson Pharmaceutical. [16] It was originally recognized for its blood pressure lowering effects and its ability to reduce the symptoms of angina. [17] It was made available in the United Kingdom and France in 1974, Germany in 1975, and Sweden in 1979. [17] It became widely used in the 1980s. [14] In the 1980s, its antiarrhythmic properties were discovered. [17] The United States approved the drug in 1992. [18]

Society and culture

Brand names

Trade names for Sotalol include Betapace and Betapace AF (Berlex Laboratories), [19] Sotalex and Sotacor (Bristol-Myers Squibb), and Sotylize (Arbor Pharmaceuticals). [7]

Related Research Articles

<span class="mw-page-title-main">Beta blocker</span> Class of medications used to manage abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<span class="mw-page-title-main">Premature ventricular contraction</span> Skipped beat with ventricular origin

A premature ventricular contraction (PVC) is a common event where the heartbeat is initiated by Purkinje fibers in the ventricles rather than by the sinoatrial node. PVCs may cause no symptoms or may be perceived as a "skipped beat" or felt as palpitations in the chest. PVCs do not usually pose any danger.


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

<span class="mw-page-title-main">Short QT syndrome</span> Medical condition

Short QT syndrome (SQT) is a very rare genetic disease of the electrical system of the heart, and is associated with an increased risk of abnormal heart rhythms and sudden cardiac death. The syndrome gets its name from a characteristic feature seen on an electrocardiogram (ECG) – a shortening of the QT interval. It is caused by mutations in genes encoding ion channels that shorten the cardiac action potential, and appears to be inherited in an autosomal dominant pattern. The condition is diagnosed using a 12-lead ECG. Short QT syndrome can be treated using an implantable cardioverter-defibrillator or medications including quinidine. Short QT syndrome was first described in 2000, and the first genetic mutation associated with the condition was identified in 2004.

<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 (TdP) 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 fast heart rate arising from the lower chambers 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">Nadolol</span> Non-selective beta blocker used in the treatment of high blood pressure and chest pain

Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, atrial fibrillation, and some inherited arrhythmic syndromes. It has also been used to prevent migraine headaches and complications of cirrhosis. It is taken orally.

<span class="mw-page-title-main">Esmolol</span> Class II antiarrhythmic drug

Esmolol, sold under the brand name Brevibloc, is a cardio selective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages.

<span class="mw-page-title-main">Andersen–Tawil syndrome</span> Rare autosomal dominant genetic disorder

Andersen–Tawil syndrome, also called Andersen syndrome and long QT syndrome 7, is a rare genetic disorder affecting several parts of the body. The three predominant features of Andersen–Tawil syndrome include disturbances of the electrical function of the heart characterised by an abnormality seen on an electrocardiogram and a tendency to abnormal heart rhythms, physical characteristics including low-set ears and a small lower jaw, and intermittent periods of muscle weakness known as hypokalaemic periodic paralysis.

<span class="mw-page-title-main">Isoprenaline</span> Medication for slow heart rate

Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).

<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">Catecholaminergic polymorphic ventricular tachycardia</span> Medical condition

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death.

<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.

<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.

QT prolongation is a measure of delayed ventricular repolarisation, which means the heart muscle takes longer than normal to recharge between beats. It is an electrical disturbance which can be seen on an electrocardiogram (ECG). Excessive QT prolongation can trigger tachycardias such as torsades de pointes (TdP). QT prolongation is an established side effect of antiarrhythmics, but can also be caused by a wide range of non-cardiac medicines, including antibiotics, antidepressants, antihistamines, opioids, and complementary medicines. On an ECG, the QT interval represents the summation of action potentials in cardiac muscle cells, which can be caused by an increase in inward current through sodium or calcium channels, or a decrease in outward current through potassium channels. By binding to and inhibiting the “rapid” delayed rectifier potassium current protein, certain drugs are able to decrease the outward flow of potassium ions and extend the length of phase 3 myocardial repolarization, resulting in QT prolongation.

<span class="mw-page-title-main">Discovery and development of beta-blockers</span>

β adrenergic receptor antagonists were initially developed in the 1960s, for the treatment of angina pectoris but are now also used for hypertension, congestive heart failure and certain arrhythmias. In the 1950s, dichloroisoproterenol (DCI) was discovered to be a β-antagonist that blocked the effects of sympathomimetic amines on bronchodilation, uterine relaxation and heart stimulation. Although DCI had no clinical utility, a change in the compound did provide a clinical candidate, pronethalol, which was introduced in 1962.

Adrenergic neurone blockers, commonly known as adrenergic antagonists, are a group of drugs that inhibit the sympathetic nervous system by blocking the activity of adrenergic neurones. They prevent the action or release of catecholamines such as norepinephrine and epinephrine. They are located throughout the body, causing various physiological reactions including bronchodilation, accelerated heartbeat, and vasoconstriction. They work by inhibiting the synthesis, release, or reuptake of the neurotransmitters or by antagonising the receptors on postsynaptic neurones. Their medical uses, mechanisms of action, adverse effects, and contraindications depend on the specific types of adrenergic blockers used, including alpha 1, alpha 2, beta 1, and beta 2.

References

  1. 1 2 3 4 5 6 "Sotalol Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 18 March 2019.
  2. 1 2 3 4 5 6 7 8 9 U.S. Food and Drug Administration (July 2009). "Sotalol: Full Prescribing Information" (PDF). Retrieved 23 April 2015.
  3. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 108. ISBN   9780857113382.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 460. ISBN   9783527607495.
  5. ↑ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  6. ↑ "Sotalol - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  7. 1 2 3 4 5 6 7 8 9 10 11 "Sotylize- sotalol hydrochloride solution". DailyMed. 3 December 2018. Retrieved 1 June 2020.
  8. ↑ Leigh PN, Jefferson D, Twomey A, Marsden CD (1983). "Beta-adrenoreceptor mechanisms in essential tremor; a double-blind placebo controlled trial of metoprolol, sotalol and atenolol". Journal of Neurology, Neurosurgery & Psychiatry. 46 (8): 710–715. doi:10.1136/jnnp.46.8.710. PMC   1027523 . PMID   6310053.
  9. ↑ Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, et al. (July 1996). "Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol". Lancet. 348 (9019): 7–12. doi:10.1016/S0140-6736(96)02149-6. PMID   8691967. S2CID   21284044.
  10. ↑ Bertrix L, Timour-Chah Q, Lang J, Lakhal M, Faucon G (May 1986). "Protection against ventricular and atrial fibrillation by sotalol". Cardiovascular Research. 20 (5): 358–63. doi:10.1093/cvr/20.5.358. PMID   3756977.
  11. 1 2 3 4 Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin MM (February 2021). "Neuropsychiatric Consequences of Lipophilic Beta-Blockers". Medicina (Kaunas). 57 (2): 155. doi: 10.3390/medicina57020155 . PMC   7914867 . PMID   33572109.
  12. ↑ Charnet P, Lory P, Bourinet E, Collin T, Nargeot J (1995). "cAMP-dependent phosphorylation of the cardiac L-type Ca channel: a missing link?". Biochimie. 77 (12): 957–62. doi:10.1016/0300-9084(95)80008-5. PMID   8834778.
  13. 1 2 Kassotis J, Sauberman RB, Cabo C, Wit AL, Coromilas J (November 2003). "Beta receptor blockade potentiates the antiarrhythmic actions of d-sotalol on reentrant ventricular tachycardia in a canine model of myocardial infarction". Journal of Cardiovascular Electrophysiology. 14 (11): 1233–44. doi:10.1046/j.1540-8167.2003.02413.x. PMID   14678141. S2CID   24561848.
  14. 1 2 3 Antonaccio MJ, Gomoll A (August 1993). "Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol". The American Journal of Cardiology. 72 (4): 27A–37A. doi:10.1016/0002-9149(93)90022-5. PMID   8346723.
  15. ↑ Edvardsson N, Hirsch I, Emanuelsson H, Pontén J, Olsson SB (October 1980). "Sotalol-induced delayed ventricular repolarization in man". European Heart Journal. 1 (5): 335–43. doi:10.1093/eurheartj/1.5.335. PMID   7274246.
  16. ↑ Hara T (2003). Innovation in the Pharmaceutical Industry: The Process of Drug Discovery and Development. Edward Elgar Publishing. p. 47. ISBN   9781843765660.
  17. 1 2 3 Anderson JL, Askins JC, Gilbert EM, Miller RH, Keefe DL, Somberg JC, et al. (October 1986). "Multicenter trial of sotalol for suppression of frequent, complex ventricular arrhythmias: a double-blind, randomized, placebo-controlled evaluation of two doses". Journal of the American College of Cardiology. 8 (4): 752–62. doi:10.1016/S0735-1097(86)80414-4. PMID   2428852.
  18. ↑ Fernandes CM, Daya MR (April 1995). "Sotalol-induced bradycardia reversed by glucagon". Canadian Family Physician. 41: 659–60, 663–5. PMC   2146520 . PMID   7787496.
  19. ↑ "Betapace- sotalol hydrochloride tablet Betapace AF- sotalol hydrochloride tablet". DailyMed. 10 August 2018. Retrieved 1 June 2020.
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