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- Properties
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- Related Drugs
- Related Diseases
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Overview
| Generic Names: | Carvedilolum [Latin]; carvedilol |
|---|---|
| IUPAC Name: | 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol |
| Trade Names: | Coreg |
| PharmGKB Accession Id: | PA448817 |
Description
Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors.
Indication
For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.
ATC Therapeutic Category
- C07AG:Alpha and beta blocking agents
Pharmacology and Interactions
Mechanism Of Action
Carvedilol is a racemic mixture in which nonselective beta-adrenoreceptor blocking activity is present in the S(-) enantiomer and alpha-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol's beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Carvedilol also decreases systemic vascular resistance via its alpha adrenergic receptor blocking properties. Carvedilol and its metabolite BM-910228 (a less potent beta blocker, but more potent antioxidant) have been shown to restore the inotropic responsiveness to Ca2+ in OH- free radical-treated myocardium. Carvedilol and its metabolites also prevent OH- radical-induced decrease in sarcoplasmic reticulum Ca2+-ATPase activity. Therefore, carvedilol and its metabolites may be beneficial in chronic heart failure by preventing free radical damage.
Pharmacology
Carvedilol is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity and is indicated for the treatment of hypertension and mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin. Carvedilol is a racemic mixture in which nonselective b-adrenoreceptor blocking activity is present in the S(-) enantiomer and a-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. The effect of carvedilol's b-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that carvedilol (1) reduces cardiac output in normal subjects; (2) reduces exercise-and/or isoproterenol-induced tachycardia and (3) reduces reflex orthostatic tachycardia.
Food Interactions
Take with food, food slows the absorption rate and reduces the incidence of adverse effects (extent of absorption is not affected).
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Hepatic. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with b-receptor blocking activity. The 4'-hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for b-blockade.
Protein Binding
98%
Absorption
Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.
Half Life
7-10 hours
Toxicity
Not expected to be toxic following ingestion.
Chemical Properties
Chemical Formula:
C24H26N2O4
SMILES Code:
COC1=CC=CC=C1OCCNC[C@H](COC2=CC=CC3=C2C4=CC=CC=C4N3)O
(Format: OpenEye Isomeric)
Molecular Weight ( average / monoisotopic )
406.4742 / 406.1893
Curated Annotations (
)
-
rs1042714
at chr5:148186666
in
ADRB2
Heart failure patients homozygous for Gln27 were less likely to have improved left ventricular ejection fraction after carvedilol treatment compared to Glu27 carriers. However, in another study of heart failure patients, Gln27Glu polymorphism was not associated with the improvement of left ventricular ejection fraction or decrease in heart rate to a beta blocker in stable congestive heart failure.- Variant Name:
- ADRB2: Gln27Glu; 318C>G ; Gln27
- Related Drugs:
- carvedilol
- Related Diseases:
- Heart Failure
- Evidence:
-
PMID:12835612
PMID:15861037
Curated Information
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
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ABCB1 |
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Publications |
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ADRB1 |
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Publications |
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ADRB2 |
|
Publications, Variants |
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CYP2D6 |
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Publications |
|
|
GRK5 |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other genes is available.
Metabolizing Enzymes
Drug Targets
Non-Curated Information
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| acetohexamide | The beta-blocker decreases the symptoms of hypoglycemia |
| chlorpropamide | The beta-blocker decreases the symptoms of hypoglycemia |
| citalopram | The SSRI increases the effect of the beta-blocker |
| clonidine | Increased hypertension when clonidine stopped |
| cyclosporine | Increases the effect and toxicity of cyclosporine |
| digoxin | Increases levels/effect of digoxin |
| dihydroergotamine | Ischemia with risk of gangrene |
| dihydroergotoxine | Ischemia with risk of gangrene |
| disopyramide | The beta-blocker increases toxicity of disopyramide |
| epinephrine | Hypertension, then bradycardia |
| ergonovine | Ischemia with risk of gangrene |
| ergotamine | Ischemia with risk of gangrene |
| escitalopram | The SSRI increases the effect of the beta-blocker |
| fenoterol | Antagonism |
| fluoxetine | The SSRI increases the effect of the beta-blocker |
| formoterol | Antagonism |
| glibenclamide | The beta-blocker decreases the symptoms of hypoglycemia |
| gliclazide | The beta-blocker decreases the symptoms of hypoglycemia |
| glipizide | The beta-blocker decreases the symptoms of hypoglycemia |
| glisoxepide | The beta-blocker decreases the symptoms of hypoglycemia |
| glycodiazine | The beta-blocker decreases the symptoms of hypoglycemia |
| ibuprofen | Risk of inhibition of renal prostaglandins |
| indomethacin | Risk of inhibition of renal prostaglandins |
| insulin | The beta-blocker decreases the symptoms of hypoglycemia |
| insulin-aspart | The beta-blocker decreases the symptoms of hypoglycemia |
| insulin-detemir | The beta-blocker decreases the symptoms of hypoglycemia |
| insulin-glargine | The beta-blocker decreases the symptoms of hypoglycemia |
| insulin-glulisine | The beta-blocker decreases the symptoms of hypoglycemia |
| insulin-lispro | The beta-blocker decreases the symptoms of hypoglycemia |
| isoproterenol | Antagonism |
| lidocaine | The beta-blocker increases the effect and toxicity of lidocaine |
| methysergide | Ischemia with risk of gangrene |
| orciprenaline | Antagonism |
| paroxetine | The SSRI increases the effect of the beta-blocker |
| pirbuterol | Antagonism |
| piroxicam | Risk of inhibition of renal prostaglandins |
| prazosin | Risk of hypotension at the beginning of therapy |
| procaterol | Antagonism |
| repaglinide | The beta-blocker decreases the symptoms of hypoglycemia |
| salbutamol | Antagonism |
| salmeterol | Antagonism |
| sertraline | The SSRI increases the effect of the beta-blocker |
| terbutaline | Antagonism |
| tolazamide | The beta-blocker decreases the symptoms of hypoglycemia |
| tolbutamide | The beta-blocker decreases the symptoms of hypoglycemia |
| verapamil | Increased effect of both drugs |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Cardiomyopathies |
|
Publications |
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Cardiomyopathy, Dilated |
|
Publications |
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Cardiomyopathy, Hypertrophic |
|
Publications |
|
|
Diabetes Mellitus |
|
Publications |
|
|
Heart Failure |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
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Non-Curated Publications
A list of non-curated publications that mention this drug is available.
