Outpatient Management of Stable Heart Failure with Reduced Ejection Fraction
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
The overall clinical goal is to achieve the highest tolerated dose, best done by starting with a low dose and increasing the dose over time while being mindful of precipitating fluid retention among those without concurrent diuretic therapy. MERIT-HF11 showed a mortality reduction of over 30% when targeting 200 mg/day. This dose was achieved in 64% of patients; the mean dose was 159 mg/day.5 In the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) trial, four out of five patients reached the target dose of 50 mg daily.12 Furthermore, side effects reported with carvedilol were actually less than those reported with placebo. Importantly, reactive airways disease or asymptomatic bradycardia should not necessarily constrain the use of beta-blockers.13 In most health systems, beta-blocker prescription costs are low, yielding an Incremental Cost Effectiveness Ratio of only $34/quality-adjusted life years in one analysis.14
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Carvedilol is a β-adrenoceptor antagonist with vasodilating activity based on a1-blockade, available for the treatment of hypertension and congestive heart failure. This drug is used clinically as a racemic mixture of R- and S-enantiomers. Carvedilol is extensively metabolized in man, giving products from both oxidation and conjugation pathways (Neugebauer et al. 1990). In human liver microsomes, 4′- and 5′-hydroxyphe-nyl carvedilol, O-desmethylcarvedilol, and 8-hydroxy carbazolyl carvedilol are detected for both the R- and S-enantiomers of carvedilol (Figure 3.66) (Oldham and Clarke 1997). 4′- and 5′-Hydroxylations are mainly catalyzed by CYP2D6, with minor contribution from CYP2E1 and 2C9 (Oldham and Clarke 1997). CYP1A2 is the most significant hepatic enzyme for 8-hydroxylation of carvedilol, with contribution from CYP3A4 and 1A1. In addition, CYP2C9 is the major enzyme for O-demethylation of carvedilol, but CYP2D6 and possibly CYP1A2 and CYP2E1 also contribute to this pathway.
Adrenoceptor Antagonists
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Carvedilol is a selective β1-adrenoceptor antagonist with additional α1-adrenoceptor blocking properties. The latter accounts for most of its vasodilator activity, although at higher concentrations Ca2+ channel blockade may also accur. Carvedilol is an effective antihypertensive agent. It increases exercise capacity of patients with chronic stable angina and reduces their myocardial oxygen consumption. In addition, it has beneficial effects in patients with chronic congestive heart failure (NYHA class II or III) secondary to ischaemic heart disease. It is highly lipophilic and undergoes rapid first-pass hepatic metabolism. It appears to have few adverse effects on lipid metabolism (McTavish et al. 1993). Carvedilol provides marked cardioprotection in models of MI and affords protection against the growth of new vascular intima after balloon angioplasty. This novel action appears to be independent of β-adrenoceptor or L-type Ca2+ channel blockade and indicates a potential use in the treatment of vascular restenosis following balloon angioplasty (Douglas et al. 1994).
New and developing pharmacotherapies for hypertension
Published in Expert Review of Cardiovascular Therapy, 2022
Christian Höcht, Miguel A Allo, Ariel Héctor Polizio, Marcela A Morettón, Andrea Carranza, Diego A Chiappetta, Marcelo Roberto Choi
Another point of great relevance is the lack of adequate formulations for paediatric patients [179]. It is estimated that 4% of the paediatric population is affected by hypertension and is exposed to a greater risk of developing adult hypertension and metabolic syndrome [180]. Adequate screening, diagnosis, and treatment of paediatric hypertension can prevent one of the 10 cases of hypertension in adults [180]. Carvedilol is only available in solid dosage forms, which can be a real problem for those paediatric patients who cannot swallow tablets [181]. For this reason, Wegmann et al. developed a novel carvedilol paediatric liquid formulation based on polymeric nanomicelles [182]. This formulation showed an increase in oral bioavailability of 4.95-fold versus a drug formulation currently employed in a paediatric hospital (Garrahan Paediatric Hospital, Argentina) [181,182].
Oral ivermectin for the treatment of red scrotum syndrome
Published in Journal of Dermatological Treatment, 2022
Jose Dario Martinez, Manuel Soria Orozco, Jesus Alberto Cardenas-de la Garza
To our knowledge this is the first report in literature to examine and describe successful treatment with oral ivermectin. The successful clinical outcome is hypothesized to be due to ivermectin’s profile in reducing the priming and activation of specific T cells, as well as reducing the production of inflammatory cytokines and vascular inflammation (2). Other therapeutic options addressed to the vascular component of RSS have been reported. Indeed, anecdotal case reports have found oral carvedilol, a β-2 adrenergic blocker, to be a therapeutic option in managing red vulva syndrome and RSS (3,4). Carvedilol, besides the β-blocker and vasoconstriction effect, seems to have also antioxidant and anti-inflammatory effects with clinical response 3 weeks after initiation of treatment (4,5). However, carvedilol dose should be adjusted to minimize risks and adverse effects (e.g. orthostatic effects, hypotension, dizziness, and bradycardia) (3). Topical timolol was reported effective in a patient that previously failed oral carvedilol therapy (6).
Blood pressure targets and pharmacotherapy for hypertensive patients on hemodialysis
Published in Expert Opinion on Pharmacotherapy, 2020
Takashi Maruyama, Hiroyuki Takashima, Masanori Abe
The results of the BLOCADE study were recently reported [125]. Seventy-two patients who were undergoing hemodialysis or peritoneal dialysis were treated with carvedilol for a run-in period of 6 weeks, and those who tolerated carvedilol at 6.25 mg twice daily were randomly assigned to receive carvedilol (up to 25 mg twice daily) or placebo. The primary outcome was the proportion of patients who tolerated carvedilol at 6.25 mg twice daily during the run-in period. Forty-nine of 72 patients achieved the primary outcome. Twenty-six of these 49 patients were then allocated to a carvedilol group and 23 to a placebo group. Overall, the withdrawal rate and the incidence of intra-dialytic hypotension were comparable between the two groups. This study could not recruit the intended number of patients because of its narrow inclusion criteria and the high number of dropouts at all stages. Despite the possible therapeutic outcome of β-blockers in patients on dialysis, the evidence from randomized controlled investigations of efficacy is limited to these two trials. Further studies are needed to clarify the potential use of β-blockers to improve cardiovascular mortality before a recommendation can be made. However, β-blockers are prescribed as first-line antihypertensive therapy in patients on hemodialysis in the absence of supporting studies. Table 4 summarizes the clinical studies performed to elucidate the effect of β-blockers on cardiovascular outcomes in patients on dialysis [56,120,125].
Related Knowledge Centers
- Dizziness
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- Hypotension
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- Nausea
- Hypertension
- Medication
- Heart Failure
- Oral Administration
- Side Effect