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Basic pharmacology of cardiac drugs
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
Continuous administration of organic nitrates leads to rapid development of drug tolerance in most patients. In the case of intravenous administration of nitrates, this can generally be overcome simply by increasing the infusion rate. There is good evidence that development of tolerance to transcutaneous nitrate can be largely prevented by the practice of a nitrate-free interval of 10–12 hours per day, most commonly during the night. Similarly, it has been shown that tolerance to the clinical effects of isosorbide mononitrate develops with twice daily dosage but not when the drug is given once daily as recommended.
Angina pectoris in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Wilbert S. Aronow, William H. Frishman
An isosorbide mononitrate is also available for the prevention of angina. The major advantage of the mononitrate preparation is that it is completely bioavailable because it does not undergo first-pass hepatic metabolism. To avoid drug tolerance, it is recommended that the 20–40 mg tablets be given twice daily with 7 hours between doses. A sustained-release formulation of isosorbide mononitrate is also available that provides therapeutic plasma drug concentrations for up to 12 hours each day and low concentrations during the latter part of the 24-hour period. The drug dose range is 30–240 mg given once daily.
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Isosorbide dinitrate undergoes extensive first-pass metabolism in the liver. It is taken up by smooth muscle cells of blood vessels and the nitrate group is cleaved to inorganic nitrite and then to nitric oxide. It is also rapidly metabolised in the liver to the major active metabolites isosorbide 2-mononitrate and isosorbide 5-mononitrate. Isosorbide mononitrate is metabolised to inactive metabolites, including isosorbide and isosorbide glucuronide. Only about 2% of isosorbide mononitrate is excreted unchanged in the urine.
Vericiguat for the treatment of heart failure with reduced ejection fraction
Published in Expert Review of Cardiovascular Therapy, 2023
Ahmed K. Siddiqi, Stephen J. Greene, Marat Fudim, Robert J Mentz, Javed Butler, Muhammad Shahzeb Khan
In another randomized, phase-Ib, Vericiguat-Isosorbide Mononitrate Interaction (VISOR) study [27], the hemodynamic effects of co-administration of vericiguat with long-acting nitrates was evaluated. Since both these medications interact with the same NO-sGC-cGMP pathway, it was important to establish any potential PD interactions. Altogether, concomitant therapy with isosorbide mononitrate and vericiguat led to reductions in SBP and DBP, and an increase in HR [27]. Vericiguat had a slightly extra BP lowering effect, mean maximum DBP decrease of (18.4–22.3 mmHg) and (14.0–20.0 mmHg) in the vericiguat and placebo arms; mean maximum seated SBP decrease of (25.7–32.2 mmHg) and (21.0–30.2 mmHg) in the vericiguat and placebo arms, respectively. The isosorbide mononitrate and vericiguat combination was also well tolerated, with no major adverse effects (AEs) [27].
Evaluating the efficacy of outpatient use of isosorbide mononitrate on cervical ripening in pregnant women with unfavourable cervix
Published in Journal of Obstetrics and Gynaecology, 2021
Maryam Kashanian, Solmaz Jangjoo, Narges Sheikhansari, Tayyebeh KaramiAbd
Most studies to date (Thomson et al. 1997; Ekerhovd et al. 2003; Väisänen-Tommiska et al. 2003; Bullarbo et al. 2007; Rameez and Goonewardene 2007; Habib et al. 2008; Bollapragada et al. 2009; Agarwal et al. 2012; Yazdizadeh et al. 2013; Ghosh et al. 2016; Abotorabi et al. 2019) proposed isosorbide mononitrate as a suitable method for cervical ripening which is in agreement with the present study, however, some reported an improvement in different stages of labour (Yazdizadeh et al. 2013), and shorter admission-delivery interval (Habib et al. 2008; Yazdizadeh et al. 2013). In the present study, intervention to delivery interval and the duration of different stages of labour did not show a significant difference in the two groups. Collingham et al. (2010) reported that the addition of vaginal isosorbide mononitrate to oral misoprostol did not reduce time to vaginal delivery and Chanrachakul et al. (2002) found that it was less effective than misoprostol for cervical ripening. Schmitz et al. 2014, showed that isosorbide mononitrate does not reduce caesarean delivery rates, which is in accordance with the present study. Some studies (Bollapragada et al. 2009) found that isosorbide mononitrate does not shorten the admission to delivery interval in comparison to placebo. All of these studies are in agreement with the present study. However, additional data is needed to assess the real impact of NO donors on different stages of labour and its implications. Due to the contradictory results of various studies, more studies should be performed with greater sample size to evaluate its effect on labour duration and reducing caesarean deliveries.
The effects of cardiac drugs on human erythrocyte carbonic anhydrase I and II isozymes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Onur Argan, Kübra Çıkrıkçı, Aybike Baltacı, Nahit Gencer
Isosorbide mononitrate is a drug mainly used to treat angina pectoris. It relaxes the coronary arteries, thereby increasing the circulation in the ischaemic zone. Isosorbide mononitrate relaxes vascular smooth muscles through the formation of nitric oxide (NO). NO activates guanylyl cyclase, resulting in decreased blood pressure and relaxation of the veins and arteries. In our study, this drug inhibited CA isoenzymes at the micromolar level.