Interactions between magnesium and drugs in the treatment of .hypertension W. P. Leary Zusammenfassung Summary Resume Der Herzmuskel kann ungi.instig durch The heart may be adversely affected by Les medicaments antihypertenseurs peu­ eine antihypertensive Medikation beein­ antihypertensive medications causing vent avoir un effet prejudiciable sur le fluBt werden, die Magnesium (Mg2+) magnesium (Mg2+) depletion or reduced creur en provoquant une depletion en -Verarmung verursacht oder den Influx inflow of the ion across the sarcolemma. magnesium (Mg++) ou une diminution dieses Ions durch das Sarcolemma redu­ Common diuretics cause hypermagnesi­ de !'influx de !'ion a travers le sarcolem­ ziert. Die iiblichen Diuretika fi.ihren zu uresis as may the angiotensin converting me. Les diuretiques usuels, de meme que Hypermagnesiurie, die auch durch den enzyme (ACE) inhibitor captopril. Some le captopril, un inhibiteur de !'enzyme de Hemmer von ACE (angiotensin conver­ calcium antagonists interfere with Mg2+. conversion de l'angiotensine, provoquent ting enzyme), das Gaptopril, verursacht entry to the myocardium. Single doses of une hypermagnesiurie. Certains inhibi­ werden kann. Einige Calcium-Antagoni­ various diuretics including clopamide teurs calciques interferent dans la pene­ tration de Mg++ dans sten interferieren mit der Mg2+-Aufnah­ 5 mg, chlorthalidone 100 mg, hydrochlo­ le myocarde. Des doses uniques de divers diuretiques - me ins Myocard. Die einmalige Gabe rothiazide 25, 50 mg, xipamide 5, 10, verschiedener Diuretika, eingeschlossen par exemple 5 mg de clopamide, I 00 mg 20 mg, and furosemide 40 mg significant­ de chlortalidone, 25 ou 50 mg d'hydro­ Clopamid 5 mg, Chlorthalidon 100 mg, ly increase 24 hour urinary excretion of Hydrochlorothiazid 25 und 50 mg, Xipa­ chlorothiazide, 5, I 0 ou 20 mg de xipami­ Mg2+. The loop diuretics muzolimine 30, de et 40 mg de furosemide- augmentent mid 5, 10 und 20 mg, und Furosemid 40 mg and torasemide 5, 10 mg and the 40 mg steigert signifikant die Mg2+.Aus­ significativement !'excretion urinaire de postassium-retaining diuretic amiloride 5, Mg+ + sur 24 heures. En revanche, 30 ou scheidung im 24-Stunden-Urin. Die 10 mg do not affect Mg2+ excretion ad­ Schleifendiuretika Muzolimin 30 und 40 mg de muzolimine et 5 ou I 0 mg de to­ versely. Mechanisms whereby common rasemide (diuretiques de l'anse), de meme 40 mg, und Torasemid 5 und l 0 mg sowie diuretics induce MgZ+ excretion are com­ das kaliumretinierende Diuretikum Ami­ que 5 ou 10 mg d'amiloride, un diureti­ plex and may involve" parathyroid hor­ que d'epargne potassique, n'ont pas d'ef­ lorid, 5 und 10 mg, haben keinen negati­ mone and the renin-angiotensin-aldo­ ven Effekt auf die Mg2:t-Ausscheidung. fet prejudicilible sur !'excretion de Mg+ +. sterone system. The beta blocker p,indol­ Les mecanismes Die Mechanismen, iiber die die iiblichen de I'hypermagnesiurie ol, amiloride and the ACE-inhibitor indiuite par les Diuretika die Mg2+-Exkretion induzie­ cap­ diuretiques courants sont topril' all reduce urinary complexes et peuv'ent impliquer la 'parat­ ren, sind komplex und kOnnen Parathor­ losses of Mg2+ which occur in response to acute doses of hormone et le systeme renine-angiotensi­ mon und das Renin-Angiotensin-Aldo­ ne-aldosterone. Le pindolol (beta-blo­ steron-System einschlieBen. Der Beta­ distal tubular diuretics. Some experimen­ tal evidence suggests that Mg2+ deficien­ quant), l'amiloride"et le captopril (un in­ blocker Pindolol, Amilorid und der hibiteur de l'enzyme, de conversion de ACE-Inhibitor Captopril mindern jeweils cy might contribute to the pathogenesis of essential hypertension. Studies in hy­ l'angiotensine) reduisent to us 1es fuites Mg2+-Verluste i.iber den Harn, die nach urinaires de Mg+ + induites par les doses akuter Gabe von Diuretika erfolgen, wel· pertensive patients do not provide con­ vincing support for this postulate. Mg2+ aigutls des diuretiques d'effet tubulaire che am distalen Tubulus angreifen. Eini­ distal. Certaines donnees experimentales ge experimentelle Oaten lassen vermuten, deficiency may he a coronary risk factor. Accordingly MgZ+ depletion should be plaident en faveur d'un role du deficit en daB Mg2+-Mangel an der Pathogenese Mg+ + dans la pathogenie de !'hyperten­ der essentiellen Hypertonie beteiligt ist. avoided during prolonged treatment of arterial hypertension. J'he clinical presen­ sion essentielle, mais les etudes menees Studien an Hochdruckpatienten stiitzen chez des malades hypertendus tation of MgZ+ deficiency is non-specific n'etayent diese Annahme aber nicht i.iberzeugend. pas cette hypothese de fayon convaincan­ but the condition Mg2+-Mangel kann einen koronaren Ri­ should be suspected te. Le deficit en Mg+ + peut constituer un sikofaktor beinhalten. Entsprechend soll­ whenever therapy with magnesiuretics facteur de risque coronarien. 11 faut done te eine Verarmung an MgZ+ wahrend der has been prolonged, particularly when prevenir un deficit en Mg+ + pendant le Langzeit-Behandlung der arteriellen Hy­ other factors favouring the development traitement au long cours de !'hyperten­ pertension vermieden werden. Das klini­ of Mg2+ deficiency are present. · sion arterielle. Le tableau clinique du de­ sche Bild des Mg2+-Mangels ist unspezi­ ficit en Mg++ n'est pas specifique, mais fisch; der Verdacht sollte aber immer be­ un tel deficit doit etre suspecte en cas de stehen bei Langzeit-Behandlung mit traitement prolonge par des medicaments MgZ+-ausscheidenden Diuretika und ins­ magnesiuretiques, surtout s'il existe en besondere dann, wenn andere Faktoren meme temps d'autres facteurs suscepti­ vorhanden ,sind, die die Entwicklung ei­ University of Natal, Durban/South Af­ bles de favoriser le developpement d'une nes Mg2+-Mangels begiinstigen. rica carence en magnesium. 62 . Mag.~Bull. 9 {1987) Interaetions 'betweell magnesium and drugs in .the treatment of hypertension The to le of magnesium (Mg2+) van der By!, K.;: unpublished)~ Diuretics in the three main in both the healthy and malfunc­ Some ca.z+ antagonists may also groups are not interchangeable in tioning cardiov·ascular system interfere with Mg~ + entry in the the management of hypertension has recently become the focus of myocardium [22, 23]. [69]. Loop diuretics do not con­ increasing research and interest form to the strict definition of [8, 20, 28, 29, 30, 39, 73, 79, 85, antihypertensive diuretics [76] 86, 94, 96, 98]. The magnesium Effects of diuretics on and should not be used as mono­ ion appears necessary for opti­ magnesium turnover therapy for uncomplicated hy­ mal regulation of electrical phen­ pertension; they are useful when omena at the sarcolemma and hypertension and renal insuffi­ also, in certain circumstances, for Diuretics and the treatment of ciency coexist, in treatment of the maintenance of an appro­ hypertension hypertensive crises and when the priately low tone in the coronary The diuretics most commonly coadministration of Na +-retain­ arterial musculature. Magnesium used at present are divisible into ing antihypertensives such as va­ deficiency may be complicated three groups in accordance with sodilators and some sympathetic by clinically important cardiac their principal sites of action blockers has caused a syndrome arrhythmias and has also been within the kidney. Loop diuretics of pseudo-resistant hypertension identified as an important risk such as furosemide, muzolimine, [76]. Early distal tubular diuret­ factor for cardiac ischaemic epi­ piretanide and bumetanide exer­ ics are widely employed as drugs sodes including myocardial in­ cise their main renal effect at a of ftrst-choice for the monother­ farction [3, 20, 28, 94]. Most of common site located in the thick apy of uncomplicated essential the adverse cardiovascular ef­ ascending segment'1of the loop of hypertension and their use in fects associated with Mg2+ defi­ Henle. Early distal tubular di­ combination with other antihy­ ciency may be accounted for by uretics, including the thiazides, pertensive substances is also ac­ the induction of significant intra­ chlorthalidone, clopamide, inda­ cepted practice in many coun­ cellular electrolyte imbalances pamide and xipamide, act at spe­ tries [50, I 00]. The K +-retaining including increases in cytosolic cific acceptors for each substance diuretics are not used as monoth­ Ca2+ and Na+ and a decrease in erapy but in the first portion of the distal are sometimes admin­ cytosolic K + [3, 39, 64, 95]. istered with convoluted tubule. The K +-re­ antihypertensive di­ The heart may be adversely af­ uretics in order to limit the taining diuretics spironolactone, sever­ fected by antihypertensive for­ ity of electrolyte imbalances as­ amiloride and triamterene act mulations which promote Mg2+ in sociated with the prolonged use the terminal depletion or reduce the inflow of part of the distal of these substances. the ion across the sarcolemma convoluted tubule where they in­ and the antihypertensive efficacy hibit transparietal exchange be­ Diuretics of these substances could also be tween Na +, which is normally and magnesium deple­ unfavourably affected by der­ reabsorbed from the pre-urine, tion anged Mg2+ turnover within vas­ and K+ and H+ which are ex­ Potassium deftciency secondary cular tissues. Common antihy­ creted fromthe milieu interieur. to increased urinary losses of the pertensive diuretics are known to In view of their widespread clini• ion has usually been identifted as augment urinary Mg2+ excretion cal use, loop and tubular diuret­ the most important cause of car­ and may