Carvedilol

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Carvedilol
Clinical data
Trade namesCoreg, others
Other namesBM-14190
AHFS/Drugs.comMonograph
MedlinePlusa697042
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability25–35%
Protein binding98%
MetabolismLiver (CYP2D6, CYP2C9)
Elimination half-life7–10 hours
ExcretionUrine (16%), feces (60%)
Identifiers
  • (±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
JSmol)
ChiralityRacemic 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 checkY
  • Key:OGHNVEJMJSYVRP-UHFFFAOYSA-N checkY
  (verify)

Carvedilol, sold under the brand name Coreg among others, is a

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]

Common

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.

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.

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

Carvedilol is both a

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),

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

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%

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

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

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]

References

  1. ^ a b c d e f g h i "Carvedilol Monograph for Professionals". Drugs.com. AHFS. Retrieved 24 December 2018.
  2. ^ "Carvedilol Use During Pregnancy". Drugs.com. Retrieved 24 December 2018.
  3. ISBN 9780857113382
    .
  4. ISBN 9783527607495
    .
  5. 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. PMID 23741058
    .
  9. ISBN 9780071604055
    .
  10. PMID 26131706
    .
  11. S2CID 1840228
    .
  12. PMID 25862157
    .
  13. PMID 29040525
    .
  14. PMID 26306578
    .
  15. PMID 23250049
    .
  16. ^ a b c d e f g h i "Coreg - Food and Drug Administration" (PDF).
  17. ^ "Drug Approval Package". www.accessdata.fda.gov. Retrieved 5 November 2015.
  18. PMID 28126029
    .
  19. PMID 12490274
    .
  20. PMID 28213164
    .
  21. PMID 30372514
    .
  22. S2CID 23494154
    .
  23. S2CID 22480332
    .
  24. ^ "Carvedilol | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY".
  25. PMID 2462161
    .
  26. PMID 30998954
    .
  27. PMID 17297209. Archived from the original
    (PDF) on 4 March 2016. Retrieved 12 November 2015.
  28. S2CID 2901620
    .
  29. PMID 20579773
    .
  30. PMID 15951832
    .

Further reading

External links

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