Nadolol

Last updated
Nadolol
Nadolol.svg
Clinical data
Trade names Corgard, others
AHFS/Drugs.com Monograph
MedlinePlus a682666
License data
Routes of
administration 		By mouth
Drug class Beta blocker
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding 30%
Metabolism Not metabolised
Elimination half-life 14-24 hours
Excretion Renal and fecal (unchanged)
Identifiers
  • * rel-(2R,3S)-5-{[(2R)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol
    • (2R*,3S*)-5-{[(2R*)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-1,2,3,4-tetrahydronaphthalene-2,3-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.050.625 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H27NO4
Molar mass 309.406 g·mol−1
3D model (JSmol)
  • OC(CNC(C)(C)C)COc1cccc2c1C[C@H](O)[C@H](O)C2
  • InChI=1S/C17H27NO4/c1-17(2,3)18-9-12(19)10-22-16-6-4-5-11-7-14(20)15(21)8-13(11)16/h4-6,12,14-15,18-21H,7-10H2,1-3H3/t12?,14-,15+/m1/s1 Yes check.svgY
  • Key:VWPOSFSPZNDTMJ-UCWKZMIHSA-N Yes check.svgY
   (verify)

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. [1] It has also been used to prevent migraine headaches and complications of cirrhosis. [2] [3] It is taken orally. [2]

Contents

Common side effects include dizziness, feeling tired, a slow heart rate, and Raynaud syndrome. [1] Serious side effects may include heart failure and bronchospasm. [1] Its use in pregnancy and breastfeeding is of unclear safety. [4] It is a non-selective beta blocker and works by blocking β1-adrenergic receptors in the heart and β2-adrenergic receptors in blood vessels. [1]

Nadolol was patented in 1970 and came into medical use in 1978. [5] It is available as a generic medication. [1] In 2020, it was the 340th most commonly prescribed medication in the United States, with more than 700 thousand prescriptions. [6]

Medical uses

Nadolol is used to treat hypertension and for long-term treatment of angina pectoris and is approved by the FDA for these purposes. [7]

It is regularly used off-label [7] for control of heart rate in people with atrial fibrillation, [8] prevention of migraine headaches; [9] prevention of bleeding veins in people with portal hypertension caused by cirrhosis; [3] and to treat people with high levels of thyroid hormone. [10]

Nadolol is the preferred beta-blockers in the management of patients with LQTS for prevention of ventricular arrhythmia. It is more efficacious than selective beta blockers or propranolol in the prevention of breakthrough cardiac events. [11] Similarly, it is the preferred type of beta blocker for treatment of patients with CPVT, as it has been shown to be more efficacious than selective beta blockers, like atenolol or bisoprolol. [12]

Nadolol has the advantage of once daily dosing and thus improved patient compliance. For patients with decreased kidney function, nadolol may be dosed less often. [13] It has also been found to be useful (off-label) for several neurological disorders such as the prevention of migraine attacks, [14] attention deficit/hyperactivity disorder(ADHD) [15] and its use has been explored as a treatment for essential tremor [16] and Parkinson's disease [17] but neither is well established. [18] [19] [20]

Side effects

The most common side effects include dizziness and fatigue. [17]

Contraindications

Nadolol and other beta blockers should be used with cautions in people with heart failure and its use should not be abruptly stopped. It is contraindicated for people with asthma, a slow heart rate and certain severe heart problems. [21]

Pharmacology

Pharmacodynamics

Four stereoisomers of nadolol Nadolol Structural Formulae.svg
Four stereoisomers of nadolol

Nadolol is a non-selective beta blocker; that is, it non-selectively blocks both beta-1 and beta-2 receptors. It has a preference for beta-1 receptors, which are predominantly located in the heart, thereby inhibiting the effects of catecholamines and causing a decrease in heart rate and blood pressure. Its inhibition of beta-2 receptors, which are mainly located in the bronchial smooth muscle of the airways, leads to airway constriction similar to that seen in asthma. Inhibition of beta-1 receptors in the juxtaglomerular apparatus of the kidney inhibits the renin–angiotensin system, causing a decrease in vasoconstriction and a decrease in water retention. Nadolol's inhibition of beta-1 receptors in the heart and kidney leads to its effects on lowering blood pressure.

The drug impairs AV node conduction and decreases sinus rate.

Nadolol may also increase plasma triglycerides and decrease HDL-cholesterol levels. [ citation needed ]

Pharmacokinetics

Nadolol is classified as a beta blocker with low lipophilicity and hence lower potential for crossing the blood–brain barrier. [22] This in turn may result in fewer effects in the central nervous system as well as fewer neuropsychiatric side effects. [22]

Chemistry

Nadolol is a mixture of stereoisomers. It is polar and hydrophilic, with low lipid solubility. [23]

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.

<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">Propranolol</span> Beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.

<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.

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.

<span class="mw-page-title-main">Diltiazem</span> Calcium channel blocker medication

Diltiazem, sold under the brand name Cardizem among others, is a nondihydropyridine calcium channel blocker medication used to treat high blood pressure, angina, and certain heart arrhythmias. It may also be used in hyperthyroidism if beta blockers cannot be used. It is taken by mouth or injection into a vein. When given by injection, effects typically begin within a few minutes and last a few hours.

<span class="mw-page-title-main">Metoprolol</span> Medication of the selective β1 receptor blocker type

Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines. It is a selective β1 receptor blocker medication. It is taken by mouth or is given intravenously.

<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">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">Candesartan</span> Angiotensin II receptor antagonist

Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. Like Olmesartan, the metabolism of the drug is unusual as it is a cascading prodrug. Candesartan has good bioavailibility and is the most potent by weight of the AT-1 receptor antagonists.

<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">Carvedilol</span> Oral blood-pressure medication

Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is generally a second-line treatment. It is taken by mouth.

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

Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.

<span class="mw-page-title-main">Adrenergic antagonist</span>

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

A sympatholytic (sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with guanfacine, they have also shown to be beneficial in the treatment of ADHD.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<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">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.

<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.

<span class="mw-page-title-main">Adrenergic receptor autoantibodies</span>

Adrenergic receptor autoantibodies

References

  1. 1 2 3 4 5 "Nadolol Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
  2. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 148. ISBN   9780857113382.
  3. 1 2 Giannelli V, Lattanzi B, Thalheimer U, Merli M (2014). "Beta-blockers in liver cirrhosis". Annals of Gastroenterology. 27 (1): 20–26. PMC   3959530 . PMID   24714633.
  4. ↑ "Nadolol Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 3 March 2019.
  5. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 460. ISBN   9783527607495.
  6. ↑ "Nadolol - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  7. 1 2 Nadolol entry in AccessMedicine. McGraw-Hill Global Education Holdings, LLC. Accessed 8 November 2014
  8. ↑ January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. (December 2014). "2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society". Circulation. 130 (23): e199–e267. doi:10.1161/CIR.0000000000000041. PMC   4676081 . PMID   24682347.
  9. ↑ Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E (April 2012). "Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 78 (17): 1337–1345. doi:10.1212/WNL.0b013e3182535d20. PMC   3335452 . PMID   22529202.
  10. ↑ Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. (June 2011). "Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists". Thyroid. 21 (6): 593–646. doi:10.1089/thy.2010.0417. PMID   21510801. S2CID   29669311.
  11. ↑ Mazzanti A, Maragna R, Vacanti G, Monteforte N, Bloise R, Marino M, et al. (April 2018). "Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome". Journal of the American College of Cardiology. 71 (15): 1663–1671. doi: 10.1016/j.jacc.2018.01.078 . hdl: 20.500.12105/10498 . PMID   29650123.
  12. ↑ Mazzanti A, Kukavica D, Trancuccio A, Memmi M, Bloise R, Gambelli P, et al. (May 2022). "Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers". JAMA Cardiology. 7 (5): 504–512. doi:10.1001/jamacardio.2022.0219. PMC   8968697 . PMID   35353122. S2CID   247792342.
  13. ↑ "Corgard (nadolol) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 27 May 2017.
  14. ↑ "Nadolol - a beta-blocker - Corgard. High blood pressure drugs". patient.info. Retrieved 27 May 2017.
  15. ↑ Barkley RA, Murphy KR (27 May 2017). Attention-deficit Hyperactivity Disorder: A Clinical Workbook. Guilford Press. ISBN   9781593852276 . Retrieved 27 May 2017– via Google Books.
  16. ↑ Zesiewicz TA, Elble RJ, Louis ED, Gronseth GS, Ondo WG, Dewey RB, et al. (November 2011). "Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology". Neurology. 77 (19): 1752–1755. doi:10.1212/WNL.0b013e318236f0fd. PMC   3208950 . PMID   22013182.
  17. 1 2 U.S. National Library of Medicine Nadolol entry in Medline Plus
  18. ↑ Foster NL, Newman RP, LeWitt PA, Gillespie MM, Larsen TA, Chase TN (October 1984). "Peripheral beta-adrenergic blockade treatment of parkinsonian tremor". Annals of Neurology. 16 (4): 505–508. doi:10.1002/ana.410160412. PMID   6149724. S2CID   24179607.
  19. ↑ "Nadolol: MedlinePlus Drug Information". www.nlm.nih.gov. Retrieved 27 May 2017.
  20. ↑ "Nadolol Dosage Guide with Precautions - Drugs.com". drugs.com. Retrieved 27 May 2017.
  21. ↑ "Corgard Label" (PDF). fda.gov. Retrieved 27 May 2017.
  22. 1 2 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.
  23. ↑ Bragg W, Norton D, Shamsi SA (November 2008). "Optimized separation of beta-blockers with multiple chiral centers using capillary electrochromatography-mass spectrometry". Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 875 (1): 304–316. doi:10.1016/j.jchromb.2008.06.028. PMC   2680439 . PMID   18619928.
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