Carvedilol

Last updated

Carvedilol
Carvedilol.svg
Carvedilol-I-3D-balls.png
Clinical data
Trade names Coreg, others
Other namesBM-14190
AHFS/Drugs.com Monograph
MedlinePlus a697042
License data
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 25–35%
Protein binding 98%
Metabolism Liver (CYP2D6, CYP2C9)
Elimination half-life 7–10 hours
Excretion Urine (16%), feces (60%)
Identifiers
  • (±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.117.236 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H26N2O4
Molar mass 406.482 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • COc1ccccc1OCCNCC(O)COc3cccc4[nH]c2ccccc2c34
  • InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3 Yes check.svgY
  • Key:OGHNVEJMJSYVRP-UHFFFAOYSA-N Yes check.svgY
   (verify)

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. [1] For high blood pressure, it is generally a second-line treatment. [1] It is taken by mouth. [1]

Contents

Common side effects include dizziness, tiredness, joint pain, low blood pressure, nausea, and shortness of breath. [1] Severe side effects may include bronchospasm. [1] Safety during pregnancy or breastfeeding is unclear. [2] Use is not recommended in those with liver problems. [3] Carvedilol is a nonselective beta blocker and alpha-1 blocker. [1] How it improves outcomes is not entirely clear but may involve dilation of blood vessels. [1]

Carvedilol was patented in 1978 and approved for medical use in the United States in 1995. [1] [4] It is on the World Health Organization's List of Essential Medicines. [5] It is available as a generic medication. [1] In 2021, it was the 26th most commonly prescribed medication in the United States, with more than 21 million prescriptions. [6] [7]

Medical uses

Carvedilol is indicated in the management of congestive heart failure (CHF), commonly as an adjunct to angiotensin-converting-enzyme inhibitor (ACE inhibitors) and diuretics. It has been clinically shown to reduce mortality and hospitalizations in people with CHF. [8] The mechanism behind its positive effect when used long-term in clinically stable CHF patients is not fully understood, but is thought to contribute to remodeling of the heart, improving upon its structure and function. [9] [10]

Carvedilol reduces the risk of death, hospitalizations, and recurring heart attacks for patients with reduced heart function following a heart attack. [11] [12] Carvedilol has also been proven to reduce death and hospitalization in patients with severe heart failure. [13]

In practice, carvedilol has been used in the treatment of uncomplicated hypertension, yet studies suggest it has relatively ineffective blood pressure-lowering effects when compared with other blood pressure-lowering therapies or other beta blockers. [14]

Carvedilol has also shown efficacy in the prevention of bleeding from esophageal varices in patients with cirrhosis. [15]

Available forms

Carvedilol is available in the following forms:

Contraindications

Carvedilol should not be used in patients with bronchial asthma or bronchospastic conditions due to increased risk of bronchoconstriction. [18] [19] It should not be used in people with second- or third-degree atrioventricular block, sick sinus syndrome, severe bradycardia (unless a permanent pacemaker is in place), or a decompensated heart condition. People with severe hepatic impairment should use carvedilol with caution. [20] [21] [22]

Side effects

The most common side effects (>10% incidence) of carvedilol include: [16]

Carvedilol is not recommended for people with uncontrolled bronchospastic disease (e.g. current asthma symptoms) as it can block receptors that assist in opening the airways. [16]

Carvedilol may mask symptoms of low blood sugar, [16] resulting in hypoglycemia unawareness. This is termed beta blocker induced hypoglycemia unawareness.

Pharmacology

Pharmacodynamics

Carvedilol
SiteKi (nM)Action
5-HT1A 3.4Antagonist
5-HT2 207Antagonist
D2 213Antagonist
α1 3.4Antagonist
α2 2,168Antagonist
β1 0.24–0.43Antagonist
β2 0.19–0.25Antagonist
M 2 ?Antagonist [23]

Carvedilol is both a non-selective β-adrenergic receptor antagonist (β1, β2) and an α-adrenergic receptor antagonist (α1). The S(–) enantiomer accounts for the beta-blocking activity whereas the S(–) and R(+) enantiomers have alpha-blocking activity. [16] The affinity (Ki) of carvedilol for the β-adrenergic receptors is 0.32 nM for the human β1-adrenergic receptor and 0.13 to 0.40 nM for the β2-adrenergic receptor. [24]

Using rat proteins, carvedilol has shown affinity for a variety of targets including the β1-adrenergic receptor (Ki = 0.24–0.43 nM), β2-adrenergic receptor (Ki = 0.19–0.25 nM), α1-adrenergic receptor (Ki = 3.4 nM), α2-adrenergic receptor (Ki = 2,168 nM), 5-HT1A receptor (Ki = 3.4 nM), 5-HT2 receptor (Ki = 207 nM), H1 receptor (Ki = 3,034 nM), D2 receptor (Ki = 213 nM), μ-opioid receptor (Ki = 2,700 nM), veratridine site of voltage-gated sodium channels (IC50 = 1,260 nM), serotonin transporter (Ki = 528 nM), norepinephrine transporter (Ki = 2,406 nM), and dopamine transporter (Ki = 627 nM). [25] It is an antagonist of the human 5-HT2A receptors with moderate affinity (Ki = 547 nM), although it is unclear if this is significant for its pharmacological actions given its much stronger activity at adrenergic receptors. [26]

Carvedilol reversibly binds to β-adrenergic receptors on cardiac myocytes. Inhibition of these receptors prevents a response to the sympathetic nervous system, leading to decreased heart rate and contractility. This action is beneficial in heart failure patients where the sympathetic nervous system is activated as a compensatory mechanism. [27] Carvedilol blockade of α1-adrenergic receptors causes vasodilation of blood vessels. This inhibition leads to decreased peripheral vascular resistance and an antihypertensive effect. There is no reflex tachycardia response due to carvedilol blockade of β1-adrenergic receptors on the heart. [28]

Pharmacokinetics

Carvedilol is about 25% to 35% bioavailable following oral administration due to extensive first-pass metabolism. Absorption is slowed when administered with food, however, it does not show a significant difference in bioavailability. Taking carvedilol with food decreases the risk of orthostatic hypotension. [16]

The majority of carvedilol is bound to plasma proteins (98%), mainly to albumin. Carvedilol is a basic, hydrophobic compound with a steady-state volume of distribution of 115 L. Plasma clearance ranges from 500 to 700 mL/min. [16] Carvedilol is lipophilic and easily crosses the blood–brain barrier in animals, and hence is not thought to be peripherally selective. [29] [30]

The compound is metabolized by liver enzymes, CYP2D6 and CYP2C9 via aromatic ring oxidation and glucuronidation, then further conjugated by glucuronidation and sulfation. The three active metabolites exhibit only one-tenth of the vasodilating effect of the parent compound. However, the 4'-hydroxyphenyl metabolite is about 13-fold more potent in β-blockade than the parent. [16]

The mean elimination half-life of carvedilol following oral administration ranges from 7 to 10 hours. The pharmaceutical product is a mix of two enantiomorphs, R(+)-carvedilol and S(–)-carvedilol, with differing metabolic properties. R(+)-Carvedilol undergoes preferential selection for metabolism, which results in a fractional half-life of about 5 to 9 hours, compared with 7 to 11 hours for the S(-)-carvedilol fraction. [16]

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">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">Adrenergic receptor</span> Class of G protein-coupled receptors

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

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">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, angina, 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">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">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">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Bisoprolol</span> Beta-1 selective adrenenergic blocker medication used to treat cardiovascular diseases

Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

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

Penbutolol is a medication in the class of beta blockers, used in the treatment of high blood pressure. Penbutolol is able to bind to both beta-1 adrenergic receptors and beta-2 adrenergic receptors, thus making it a non-selective β blocker. Penbutolol is a sympathomimetic drug with properties allowing it to act as a partial agonist at β adrenergic receptors.

<span class="mw-page-title-main">Beta-1 adrenergic receptor</span> Protein-coding gene in the species Homo sapiens

The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.

<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.

<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">Beta-adrenergic agonist</span> Medications that relax muscles of the airways

Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers: beta-adrenoreceptor agonist ligands mimic the actions of both epinephrine- and norepinephrine- signaling, in the heart and lungs, and in smooth muscle tissue; epinephrine expresses the higher affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP); cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.

<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">Olodaterol</span> Chemical compound

Olodaterol is an ultra-long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating people with chronic obstructive pulmonary disease (COPD). It is manufactured by Boehringer Ingelheim.

<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.

References

  1. 1 2 3 4 5 6 7 8 9 "Carvedilol Monograph for Professionals". Drugs.com. AHFS. Retrieved 24 December 2018.
  2. ↑ "Carvedilol Use During Pregnancy". Drugs.com. Retrieved 24 December 2018.
  3. ↑ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 147. ISBN   9780857113382.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 463. ISBN   9783527607495.
  5. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  6. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ↑ "Carvedilol - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. ↑ Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. (American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines) (15 October 2013). "2013 AHA Guidelines for the Management of Heart Failure" (PDF). Circulation. 128 (16): e240-327. doi:10.1161/CIR.0b013e31829e8776. PMID   23741058.
  9. ↑ Biaggioni I (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw-Hill Medical Publishing Division. p. 189. ISBN   9780071604055.
  10. ↑ Reis Filho JR, Cardoso JN, Cardoso CM, Pereira-Barretto AC (June 2015). "Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure". Arquivos Brasileiros de Cardiologia. 104 (6): 502–6. doi:10.5935/abc.20150025. PMC   4484683 . PMID   26131706.
  11. ↑ Dargie HJ (May 2001). "Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial". Lancet. 357 (9266): 1385–1390. doi:10.1016/s0140-6736(00)04560-8. PMID   11356434. S2CID   1840228.
  12. ↑ Huang BT, Huang FY, Zuo ZL, Liao YB, Heng Y, Wang PJ, et al. (June 2015). "Meta-Analysis of Relation Between Oral β-Blocker Therapy and Outcomes in Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention". The American Journal of Cardiology. 115 (11): 1529–1538. doi:10.1016/j.amjcard.2015.02.057. PMID   25862157.
  13. ↑ Cleland JG, Bunting KV, Flather MD, Altman DG, Holmes J, Coats AJ, et al. (January 2018). "Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials". European Heart Journal. 39 (1): 26–35. doi:10.1093/eurheartj/ehx564. PMC   5837435 . PMID   29040525.
  14. ↑ Wong GW, Laugerotte A, Wright JM (August 2015). "Blood pressure lowering efficacy of dual alpha and beta blockers for primary hypertension". The Cochrane Database of Systematic Reviews. 2015 (8): CD007449. doi:10.1002/14651858.cd007449.pub2. PMC   6486308 . PMID   26306578.
  15. ↑ Reiberg, T, Ulbrich, G, et al. (November 2013). "Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol". Gut. 62 (11): 1634–1641. doi: 10.1136/gutjnl-2012-304038 . PMID   23250049.
  16. 1 2 3 4 5 6 7 8 9 "Coreg - Food and Drug Administration" (PDF).
  17. ↑ "Drug Approval Package". www.accessdata.fda.gov. Retrieved 5 November 2015.
  18. ↑ Morales DR, Lipworth BJ, Donnan PT, Jackson C, Guthrie B (January 2017). "Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study". BMC Medicine. 15 (1): 18. doi: 10.1186/s12916-017-0781-0 . PMC   5270217 . PMID   28126029.
  19. ↑ Kotlyar E, Keogh AM, Macdonald PS, Arnold RH, McCaffrey DJ, Glanville AR (December 2002). "Tolerability of carvedilol in patients with heart failure and concomitant chronic obstructive pulmonary disease or asthma". The Journal of Heart and Lung Transplantation. 21 (12): 1290–5. doi:10.1016/s1053-2498(02)00459-x. PMID   12490274.
  20. ↑ Sinha R, Lockman KA, Mallawaarachchi N, Robertson M, Plevris JN, Hayes PC (July 2017). "Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites" (PDF). Journal of Hepatology. 67 (1): 40–46. doi:10.1016/j.jhep.2017.02.005. hdl:20.500.11820/7afe3b88-1064-4da1-927e-4d4e867387eb. PMID   28213164.
  21. ↑ Zacharias AP, Jeyaraj R, Hobolth L, Bendtsen F, Gluud LL, Morgan MY (October 2018). "Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices". The Cochrane Database of Systematic Reviews. 2018 (10): CD011510. doi:10.1002/14651858.CD011510.pub2. PMC   6517039 . PMID   30372514.
  22. ↑ Lo GH, Chen WC, Wang HM, Yu HC (November 2012). "Randomized, controlled trial of carvedilol versus nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding". Journal of Gastroenterology and Hepatology. 27 (11): 1681–7. doi:10.1111/j.1440-1746.2012.07244.x. PMID   22849337. S2CID   23494154.
  23. ↑ Xu XL, Zang WJ, Lu J, Kang XQ, Li M, Yu XJ (December 2006). "Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart". Autonomic Neuroscience. 130 (1–2): 6–16. doi:10.1016/j.autneu.2006.04.005. PMID   16798104. S2CID   22480332.
  24. ↑ "Carvedilol | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY".
  25. ↑ Pauwels PJ, Gommeren W, Van Lommen G, Janssen PA, Leysen JE (December 1988). "The receptor binding profile of the new antihypertensive agent nebivolol and its stereoisomers compared with various beta-adrenergic blockers". Mol Pharmacol. 34 (6): 843–51. PMID   2462161.
  26. ↑ Murnane KS, Guner OF, Bowen JP, Rambacher KM, Moniri NH, Murphy TJ, et al. (June 2019). "The adrenergic receptor antagonist carvedilol interacts with serotonin 2A receptors both in vitro and in vivo". Pharmacology, Biochemistry, and Behavior. 181: 37–45. doi:10.1016/j.pbb.2019.04.003. PMC   6570414 . PMID   30998954.
  27. ↑ Manurung D, Trisnohadi HB (2007). "Beta blockers for congestive heart failure" (PDF). Acta Medica Indonesiana. 39 (1): 44–8. PMID   17297209. Archived from the original (PDF) on 4 March 2016. Retrieved 12 November 2015.
  28. ↑ Ruffolo RR, Gellai M, Hieble JP, Willette RN, Nichols AJ (1990). "The pharmacology of carvedilol". European Journal of Clinical Pharmacology. 38 (Suppl 2): S82–S88. doi:10.1007/BF01409471. PMID   1974511. S2CID   2901620.
  29. ↑ Wang J, Ono K, Dickstein DL, Arrieta-Cruz I, Zhao W, Qian X, et al. (December 2011). "Carvedilol as a potential novel agent for the treatment of Alzheimer's disease". Neurobiol Aging. 32 (12): 2321.e1–12. doi:10.1016/j.neurobiolaging.2010.05.004. PMC   2966505 . PMID   20579773.
  30. ↑ Bart J, Dijkers EC, Wegman TD, de Vries EG, van der Graaf WT, Groen HJ, et al. (August 2005). "New positron emission tomography tracer [(11)C]carvedilol reveals P-glycoprotein modulation kinetics". Br J Pharmacol. 145 (8): 1045–51. doi:10.1038/sj.bjp.0706283. PMC   1576233 . PMID   15951832.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.