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The Evolution of Anticancer Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Agents capable of blocking any of these drug resistance pathways should not only enhance the action of the relevant anticancer drugs but also allow them to be used for longer periods of time before resistance develops. An early lead in this therapeutic strategy came from the observation that co-administration of verapamil (a calcium channel antagonist) can enhance the activity of some anticancer drugs. Verapamil, a viscous, pale yellow oil (also known as dexverapamil hydrochloride), was first patented by Knoll in the early 1960s (Figure 2.9). It was the prototype calcium antagonist and was developed for use as an antihypertensive, antianginal, and antiarrhythmic agent.Structure of verapamil.
Basic pharmacology of cardiac drugs
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
A common fallacy concerning these important drugs is to think of them as a homogeneous group with only minor differences in dosage, kinetics, and side effects. There are in fact quite major differences between the calcium antagonist drugs. By far the most important distinction from a clinical point of view is between the dihydropyridines (nifedipine and related compounds) and the other two pharmacological groups, represented by verapamil and diltiazem (see below). It is therefore potentially quite misleading to refer to calcium antagonists as being useful or not being useful for a given clinical condition, without specifying the particular family of calcium antagonists indicated.
Magnesium in obstetrics
Published in Kupetsky A. Erine, Magnesium, 2019
David N. Hackney, Alison Bauer
Why does the intravenous administration of magnesium not impact term or preterm labor despite being a calcium antagonist? The answer is likely that increasing magnesium serum concentrations is not in any way specific to the uterine myometrium and thus, clinically meaningful reductions in uterine contractions cannot be obtained without broader muscular inhibitions and thus toxicity. Likewise, one of the contemporaneous categories of tocolytic agents is oxytocin-receptor antagonists45 which are obviously much more specific to the myometrium. However, if intravenous magnesium does not inhibit labor, then what would explain the clinical observation that many women in spontaneous preterm labor stop contracting and their pregnancies remain undelivered after receiving it? The answer is that, for reasons that are incompletely understood, many patients who present in spontaneous preterm labor will stop contracting and their pregnancies remain undelivered even with no treatment or the administration of a placebo. In a systematic review of all published subjects with spontaneous preterm labor who did not receive tocolysis, a majority (62.8%) remained undelivered at 48 hours and 40.4% actually still delivered at term.46 Explanations for these observations include the fact that preterm labor remains clinically, and thus imperfectly, diagnosed. Even for patients in “true” preterm labor, however, the progression to delivery may not be as linear or uniform as one may intuitively believe.
Time trends of coronary procedures, guideline-based drugs and all-cause mortality following acute coronary syndrome in patients with bipolar disorder
Published in Nordic Journal of Psychiatry, 2023
Line Philipsen, Nanna Würtz, Christoffer Polcwiartek, Kristian Hay Kragholm, Christian Torp-Pedersen, Rene Ernst Nielsen, Svend Eggert Jensen, Rubina Attar
A decreased difference was seen between patients with BD and PHCs regarding redeemed prescriptions of beta blockers (p=0.016; Supplemental Appendix Figure 3A). The respective cumulative incidences of redeemed prescriptions of beta blockers in the three time periods were 36.2, 53.3 and 65.1% for patients with BD and 59.4, 64.1 and 66.1% for PHCs (Table A1). Prescription redemption of nitrates decreased throughout the study period for both patients with BD and PHCs (Supplemental Appendix Figure 3A). Patients with BD redeemed fewer calcium antagonist prescriptions compared to PHCs (Supplemental Appendix Figure 3A). For both nitrates and calcium antagonists, no significant time trends were observed in use between the two groups. A more detailed depiction over the redemption of all the guideline-based drugs can be seen in Supplemental Appendix Table 1A.
Smoking and overweight associated with masked uncontrolled hypertension: a Hypertension Optimal Treatment (HOT) Sub-Study
Published in Blood Pressure, 2021
Magnus Holanger, Sverre E. Kjeldsen, Kenneth Jamerson, Stevo Julius
The Hypertension Optimal Treatment (HOT) Study included patients in 26 countries. The rationale was described in detail [1] and HOT was conducted in accordance with the Prospective Randomised Open Blinded Endpoint (PROBE) design [2]. The main aim was to evaluate the relationship between three levels of target diastolic blood pressure (BP) (≤80, ≤85 or ≤90 mmHg) and cardiovascular morbidity (CV) and mortality in hypertensive patients. In addition, the study examined the effects of a low dose (75 mg daily) of acetylsalicylic acid vs. placebo. 18,790 patients between 50 and 80 years of age participated. Antihypertensive treatment commenced with a calcium antagonist. Additional antihypertensive therapy was given in accordance with a set protocol to reach target BPs. Details of the patient characteristics at randomisation, cardiovascular risk profiles, early BP results and CV outcomes were published [1,3,4].
A case of anti-MDA5 antibody-positive dermatomyositis developing reversible cerebral vasospasm syndrome successfully treated by multi-immunosuppressant combination including mycophenolate mofetil
Published in Modern Rheumatology Case Reports, 2021
Takumi Muramatsu, Toshihiro Tono, Yoshiro Kanayama, Yasuhiro Hasegawa, Junichi Kondo, Takayuki Hoshiyama, Tatsuhiko Wada, Yoshiyuki Arinuma, Sumiaki Tanaka, Kunihiro Yamaoka
Diagnostic criteria for RCVS have been proposed [6]. We did not examine her cerebrospinal fluid because she could not stay still. However, RCVS was a suitable diagnosis based on acute headache, single course temporary symptom for 1 month, brain MRI finding of arterial narrowing without aneurysmal subarachnoid haemorrhage, and the improvement of headache and cerebrovascular narrowing lesion within 12 weeks. A previous report suggested that immunosuppressant use is one of the causes of RCVS development [11]. When development is suspected, physicians are initially required to investigate potential inducers, including medicines, and should eliminate as many as possible [6]. However, no established therapies for RCVS exist. Some reports describe the effectiveness of the calcium antagonist nimodipine for RCVS, but another reports that symptoms were exacerbated by nimodipine [7]. There also exist reports about the use of diltiazem in challenging situations [12,13]. In these reports, verapamil was ineffective against cerebrovascular narrowing, but diltiazem was effective. However, the efficacy of diltiazem through cerebral vasorelaxation cannot be concluded because other medicines causing cerebral vasospasm were discontinued in this report.