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      Drug Interactions in Parkinson’s Disease: Safety of Pharmacotherapy for Arterial Hypertension

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          Abstract

          Background

          Parkinson’s disease (PD) is a progressive neurodegenerative disorder of the central nervous system, observed in patients aged older than 50 years. In this study, we review interactions between therapies used in PD and selected antihypertensive agents. Moreover, in view of the lack of evidence-based recommendations regarding the pharmacotherapy of arterial hypertension in PD patients, we propose effective and safe therapeutic algorithms for these two coexisting conditions.

          Method

          We used the “Drug interactions” database affiliated with the Ministry of Health, which allows for the identification of interactions between compared active compounds. The database is updated on a monthly basis and all data are consistent with current legislation. For information about interactions, we additionally added data from the British National Formulary, a joint publication of the British Medical Association and the Royal Pharmaceutical Society of Great Britain. In this analysis, we also used data from Micromedex ®, Cerner Multum™, Wolters Kluwer™, Lexicomp ® and Stockley’s ®. We analysed the potential interactions between antihypertensive and anti-parkinsonian agents included in respective guidelines on the pharmacotherapy of these conditions.

          Results

          Our analysis revealed the lack of clinically relevant interactions between preparations of levodopa and benserazide (used for the treatment of PD) and angiotensin-converting enzyme inhibitors, antagonists of AT 1 receptor for angiotensin II or antagonists of β-adrenoreceptors (β-adrenolytics).

          Conclusion

          To avoid major drug-to-drug interactions, patients receiving preparations of levodopa and benserazide should be prescribed angiotensin-converting enzyme inhibitors, antagonists of AT 1 receptor for angiotensin II, or antagonists of β-adrenoreceptors (β-adrenolytics) as the first-line agents of antihypertensive treatment.

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          Most cited references29

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          Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.

          Establishing relative benefit or harm from specific antihypertensive agents is limited by the complex array of studies that compare treatments. Network meta-analysis combines direct and indirect evidence to better define risk or benefit. To summarize the available clinical trial evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major cardiovascular disease end points and all-cause mortality. We used previous meta-analyses, MEDLINE searches, and journal reviews from January 1995 through December 2002. We identified long-term randomized controlled trials that assessed major cardiovascular disease end points as an outcome. Eligible studies included both those with placebo-treated or untreated controls and those with actively treated controls. Network meta-analysis was used to combine direct within-trial between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which preserve the within-trial randomized findings, were constructed from trials that had one treatment in common. Data were combined from 42 clinical trials that included 192 478 patients randomized to 7 major treatment strategies, including placebo. For all outcomes, low-dose diuretics were superior to placebo: coronary heart disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81); cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR, 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies-beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers-was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR, 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. Low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality. Clinical practice and treatment guidelines should reflect this evidence, and future trials should use low-dose diuretics as the standard for clinically useful comparisons.
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            Angiotensin-converting enzyme inhibitors.

            ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
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              Management of hypertension: summary of NICE guidance.

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                Author and article information

                Contributors
                +48 52 585-36-16 , aniab@doktornat.umk.pl
                Journal
                Drugs Real World Outcomes
                Drugs Real World Outcomes
                Drugs - Real World Outcomes
                Springer International Publishing (Cham )
                2199-1154
                2198-9788
                27 January 2015
                27 January 2015
                March 2015
                : 2
                : 1
                : 1-12
                Affiliations
                [1 ]Chair and Department of Hygiene and Epidemiology, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, The Nicolaus Copernicus University in Toruń, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland
                [2 ]Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH Great Britain
                Article
                8
                10.1007/s40801-015-0008-7
                4883207
                27747611
                f9b46cb7-2478-469e-86e0-616f6ee64434
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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                © The Author(s) 2015

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