Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Bisoprolol is a selective β1-adrenoceptor blocker indicated for hypertension and chronic heart failure (Johns and Lopez 1995; McGavin and Keating 2002). Bisoprolol has a chiral center, with S-(−)-bisoprolol being 30 to 80 times more pharmacologically active than R-(+)-bisoprolol. The oral bioavail-ability of bisoprolol is high (>90%) and the drug has a long t1/2β (11 h), which allows once-daily administration (Lancaster and Sorkin 1988). In humans, 50% of the dose is eliminated renally as unchanged drug and the other 50% is eliminated metabolically, with subsequent renal excretion of the metabolites (Leopold et al. 1986). Bisoprolol is mainly metabolized to M4 via O-deisopropylation by CYP3A4 and 2D6 (Figure 3.63) (Horikiri et al. 1998a,b). CYP2D6 metabolized bisoprolol stereoselectively (R > S), whereas the metabolism of bisoprolol by CYP3A4 is not stereoselective (Horikiri et al. 1998a). In Japanese patients, the genotype of CYP2D6 and 2C9 did not affect the pharmacokinetics of bisoprolol (Taguchi et al. 2005).
Paper 2
Aalia Khan, Ramsey Jabbour, Almas Rehman in nMRCGP Applied Knowledge Test Study Guide, 2021
The following statements are true regarding the use of beta blockers in heart failure, except which one? Beta blockers should be considered in all patients with heart failure who are able to take them.Beta blockers are contraindicated in all patients with chronic obstructive pulmonary disease.Beta blockers of proven benefit in heart failure include carvedilol and bisoprolol.In trials, the use of beta blockers in heart failure resulted in a relative risk reduction in mortality of around 35%.It may take up to 6 months for the beneficial effects of beta blockers on left ventricular function to appear.
Coronary Artery Disease
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
Sublingual nitroglycerin is usually able to quickly relieve variant angina. Symptoms can be prevented by using calcium channel blockers. The most commonly used drugs in this class include sustained-release diltiazem, sustained-release verapamil (though doses must be reduced if there is kidney or liver dysfunction), and amlodipine (though doses must be reduced with liver dysfunction or in elderly patients). These drugs do not appear to change the prognosis, however. Though not proven clinically, it is theorized that beta-blockers can worsen spasms by allowing alpha-adrenergic vasoconstriction to occur. For diabetic patients, bisoprolol must be used carefully since it can mask symptoms of hypoglycemia. However, this is not an issue in nondiabetic patients with variant angina.
Bisoprolol transdermal patch improves orthostatic hypotension in patients with chronic heart failure and hypertension
Published in Clinical and Experimental Hypertension, 2020
Shunsuke Kiuchi, Shinji Hisatake, Takayuki Kabuki, Takashi Oka, Shintaro Dobashi, Takahiro Fujii, Takahide Sano, Takanori Ikeda
The subjects were 45 consecutive stable CHF patients with HT; 33 and 12 patients (73.3% and 26.7%) belonged to NYHA Class I and II, respectively. There were 29 male patients (64.4%), and the average age was 69.6 ± 12.9 years (30–88 years). The height and weight of the patients were 159.1 ± 9.4 cm and 62.7 ± 15.3 kg, respectively. Table 1 show the baseline patients characteristics. Various etiologies of HF were included in the present study. For BB, all of the patients were taking the bisoprolol fumarate tablet. The average dose of the bisoprolol fumarate tablet was 3.89 ± 1.51 mg, and the patients were subsequently switched to the average 6.22 ± 2.42 mg bisoprolol transdermal patch (Table 1). RAAS-I and MRA were administered to 68.9% and 20.0% of the patients, respectively. Diabetic medications were administered to seven (15.6%) patients.
A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension
Published in Current Medical Research and Opinion, 2022
Ulrike Hostalek-Gottwald, Zbigniew Gaciong
FDC bisoprolol and amlodipine was developed to simplify the treatment regimen of patients with hypertension. Prospective data from a large cohort showed a high level of patient adherence with FDC bisoprolol and amlodipine in daily practice, accompanied by striking improvements in BP control versus baseline and an expected reduction in cardiovascular risk factors. The tolerability of the therapy further supports its use to manage hypertension. Results from the Phase 3 clinical trials demonstrated the favorable efficacy and tolerability of the therapy in second line, supporting its use to manage hypertension following monotherapy failure. Lastly, in an indirect treatment comparison, the combination of bisoprolol and amlodipine treatment resulted in a similar influence on SBP and a meaningful reduction in diastolic BP compared with up-titration of amlodipine to 10 mg, further supporting the efficacy of the therapy.
Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy
Published in Expert Opinion on Pharmacotherapy, 2023
Akiva Rosenzveig, Neil Garg, Shiavax J. Rao, Amreen K. Kanwal, Arjun Kanwal, Wilbert S. Aronow, Matthew W. Martinez
Beta blockers have long since been regarded as the mainstay for management of HCM associated LVOTO. Mechanistic reduction in maximum contraction velocity achieved by beta blockers positively affects systolic function as well as decreases the amplitude of LVOTO in HCM patients [15]. A 2022 placebo-controlled double-blind trial found that metoprolol was linked with positive changes to the LVOT gradient, as well as decreased mitral regurgitation and increased stroke volume at rest and during exercise in HCM patients [16]. To combat LVOTO, beta blockers, such as atenolol, nadolol, bisoprolol, and metoprolol, are current treatment standards. Titration of these drugs based on cardiac response, symptoms, and vitals is best practice, as high doses are usually required and well tolerated [17]. A recent retrospective study evaluated 92 adults with obstructive HCM treated with bisoprolol. Seventeen percent of the patients met the primary endpoint (reduction of LVOT gradient to <30 mmHg and ≥1 NYHA class improvement)), 36% of the patients had the LVOT gradient reduced to <30 mmHg, and 62% of the patients had a gradient reduced to <50 mmHg [18]. This study demonstrated both the effectiveness of bisoprolol therapy as well as the need for better therapies.
Related Knowledge Centers
- Angina
- Asthma
- Beta Blocker
- Peripheral Edema
- Tachycardia
- Cardiovascular Disease
- Hypertension
- Heart Failure
- Hypoglycemia
- Oral Administration