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Cardiovascular medicine
Published in Shibley Rahman, Avinash Sharma, A Complete MRCP(UK) Parts 1 and 2 Written Examination Revision Guide, 2018
Shibley Rahman, Avinash Sharma
Examples of centrally acting anti-hypertensives include: methyldopa: used in the management of hypertension during pregnancymoxonidine: used in the management of essential hypertension when conventional anti-hypertensives have failed to control blood pressureclonidine: the anti-hypertensive effect is mediated through stimulating alpha-2 adrenoceptors in the vasomotor centre
Is too much neurohormonal blockade harmful?
Published in ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP, The Year in Heart Failure, 2005
Beta blockers reduce mortality in patients with New York Heart Association class II-IV heart failure by 34-35% 116,17,231. The association between the degree of sympathetic activation and mortality 13,131, and dose-dependent favourable effects of 13 blockers on heart failure mortality and morbidity 1241 raised the possibility that 'more complete' adrenergic blockade might produce even greater benefit on outcomes. Moxonidine, a centrally acting a agonist that greatly reduces circulating catecholamines 1251, was used to test this hypothesis in the Moxonidine in Congestive Heart Failure (MOXCON) triall26l. The study had to be terminated early, with only 1934 of the 4533 patients randomized, because of a 38o/o higher mortality in the moxonidine group. Hospitalizations for heart failure and myocardial infarctions were also increased. The increase in mortality and morbidity was accompanied by a significant decrease in plasma norepinephrine by moxonidine (-18.8%) as compared with placebo ( +6.9o/o) 1261. An earlier study had shown that moxonidine produced marked sympatholytic effects in the target dose of the MOXCON trial, and that this was accompanied by serious adverse effects 1251. Although the mechanisms for the increase in mortality and morbidity in the MOXCON trial are not entirely clear, the marked sympatholytic effects of moxonidine could have produced severe myocardial depression, bradycardia or hypotension. However, these effects could not be documented in the patients who died. Alternatively, premature discontinuation of the drug or non-compliance with the use of higher doses of moxonidine could have resulted in rebound excessive sympathetic discharge that might have been responsible for the serious adverse effects observed in the MOXCON trial. Again, evidence to support this possibility is also not available. Another example of the association between marked sympatholytic effect and adverse outcomes was seen in a subgroup of patients in the Beta-blocker Evaluation of Survival Trial (BEST) 1211. BEST was the only 13 blocker heart failure trial that did not show a mortality benefit. This might be related to the marked sympatholytic effects of bucindolol, not seen with carvedilol or metoprolol. In the BEST trial, patients (n = 153) receiving the sympatholytic 13 blocker bucindolol who had a decrease in norepinephrine of >224 pg/ml from baseline to 3 months, had a 169o/o increase in mortality as compared with patients who had no significant change in norepinephrine (relative risk 1.69; 95o/o confidence interval [CI]l.22-2.34) 1281. These two examples underscore the fact that a severe decrease in adrenergic support may render the body devoid of any compensatory mechanisms, resulting in adverse outcomes.
Adherence and blood pressure control in patients with primary aldosteronism
Published in Blood Pressure, 2022
Thi Minh Phuong Nikrýnová Nguyen, Branislav Štrauch, Ondřej Petrák, Zuzana Krátká, Robert Holaj, Ivana Kurcová, Věra Marešová, Alena Pilková, Jan Hartinger, Petr Waldauf, Tomáš Zelinka, Jiří Widimský
During the visit, we performed unanticipated blood sampling (10 ml of venous blood with subsequent transport to the Department of Toxicology) to measure serum antihypertensive drug concentrations in PA patients (with their informed consent). The time interval between ABPM and measurement of serum drug concentrations did not exceed 3 d. The timing of sampling was at least 3 h after the drug intake. Measurement of amlodipine, verapamil, nitrendipine, lercanidipine, betaxolol, bisoprolol, metoprolol, doxazosin, losartan, telmisartan, candesartan, hydrochlorothiazide, indapamide, chlorthalidone, perindoprilat, ramiprilat, rilmenidine, moxonidine, eplerenone and spironolactone along with its metabolite canrenone was performed. The drug concentration analysis was performed in the Toxicology Laboratory of the Institute of Forensic Medicine and Toxicology by means of liquid chromatography–tandem mass spectrometry (LC–MS/MS) [18,19]. The chromatographic separation was performed on a 1200 RRLC (Agilent, Waldbronn, Germany), consisting of a degasser, binary pump, autosampler and column compartment with controlled temperature. The mass spectrometry analysis was performed using a 3200 Q-trap triple quadrupole/linear ion trap mass spectrometer with a TurboIonSpray source (MDS Sciex, Ontario, Canada). LC–MS/MS with electrospray ionisation method was used for the simultaneous determination of spironolactone and its active metabolite canrenone in human serum [20]. LC–MS/MS with electrospray ionisation method was used for the determination of eplerenone in human serum [21].
Pharmacotherapeutic strategies for treating hypertension in patients with obesity
Published in Expert Opinion on Pharmacotherapy, 2018
Revathy Carnagarin, Vance Matthews, Cynthia Gregory, Markus P. Schlaich
Given the important role of increased sympathetic outflow in the pathogenesis of OHT, it is perhaps surprising that central sympatholytic blockade with imidazoline I1-receptor agonists is not used more frequently in the management of OHT. Some misconceptions may exist relating to the adverse effects of older central sympatholytic agents such as clonidine or α-methyldopa, which were commonly associated with tiredness, sedation, and rebound hypertension when ceased (clonidine). The newer imidazoline I1-receptor agonists such as moxonidine and rilmenidine have been demonstrated to be well tolerated and effective in lowering BP. In contrast to clonidine which binds to central α2 receptors, the newer agents bind to the Imidazoline I1-receptor thereby largely avoiding the clonidine like side effects [66,67]. However, a dry mouth sensation can occur in up to 10% of patients on moxonidine due to its inhibitory effect on salivary flow [68]. From a metabolic perspective, moxonidine has been demonstrated to enhance insulin sensitivity, as shown with an insulin clamp technique in obese spontaneously hypertensive rats [69]. In addition to BP lowering, moxonidine treatment improves insulin sensitivity in patients with obesity hypertension [70]. The BP-lowering effect of moxonidine was comparable to amlodipine, but with additional effects such as the improvement of insulin resistance, reduction of plasma leptin levels and attenuation of sympathetic overdrive [71].
Emerging pharmacotherapies for the treatment of atrial fibrillation
Published in Expert Opinion on Emerging Drugs, 2018
Alessandro Capucci, Laura Cipolletta, Federico Guerra, Irene Giannini
A sympathetic or vagal overactivity leads to AF in some patients. Therefore, the most common cause of AF triggering is a combined sympathovagal activation [16]. Modulation of the autonomic system and, in particular, the sympathetic part could be an interesting therapeutic target in AF. A prospective, double-blinded, single-group, crossover study enrolled 56 hypertensive patients with paroxysmal AF receiving sequential treatment with placebo and moxonidine, a centrally acting sympathoinhibitory factor, for two 6-week periods, respectively [77]. The primary outcome was the change in AF burden, calculated as minutes of AF per day in three 48-hour Holter recordings, between the two treatment periods. During moxonidine treatment, EHRA symptom scale decreased from a median of 2.0–1.0, and AF burden was lowered from 28 to 16.5 min/d. During moxonidine treatment, diastolic blood pressure lowered, whereas systolic blood pressure levels were unchanged (p < 0.01).