Kalsiyum Kanal Blokerlerinin Pleiotropik Etkileri

Yıl 2019, Cilt: 9 Sayı: 2, 125 - 131, 01.08.2019

Şerife Canbolat Kısmet Esra Nurullahoğlu Atalık

Öz

Kalsiyum kanal blokerleri, hipertansiyon, angina, periferik vasküler bozukluklar ve bazı aritmiler gibi kardiyovasküler hastalıkların tedavisinde yaygın olarak kullanılan bir ilaç grubudur. Kalsiyum kanal blokerlerinden özellikle daha yeni, daha uzun etkili olanlar, daha düşük yan etki profilleri ile hipertansiyon tedavisinde oldukça etkilidir. Bu
ilaçlar, damar düz kası ve kalp hücrelerinde, sitoplazma membranındaki voltaj-bağımlı kalsiyum kanallarına veya reseptörlere yüksek afinite ile bağlanarak kalsiyum girişini azaltırlar, özellikle arteriyollerde düz kasları gevşeterek güçlü vazodilatasyon yaparlar. Voltaj-bağımlı kalsiyum kanallarının çoğunlukla L-tipine bağlanırlar. Yakın zamanda yapılan çalışmalar, bazı kalsiyum kanal blokerlerinin N- ve T-tipi kanallara da bağlandığını göstermiştir. Bunlardan N-tipi kanallar sempatik sinir uçlarında, T-tipi kanallar ise kardiyak sinus nodu ile afferent ve efferent arteriyollerde bulunur. Bu iki tip kanalın blokajı, glomerüler kapiller basıncın azalmasına, renin-anjiotensin-aldosteron sisteminin ve sempatik sinir sisteminin stabilizasyonuna neden olur. Sonuçta, özellikle yeni jenerasyon kalsiyum kanal blokerleri, renoprotektif, vasküler endotel koruyucu etki ve kardiyoprotektif etkiler gibi pleiotropik etkiler olarak tanımlananan etkilere sahiptirler.

Anahtar Kelimeler

kalsiyum; blokör; pleiotropik etkiler

Kaynakça

• 1. Dolphin AC. A short history of voltage-gated calcium channels. Br J Pharmacol 2006;147:56–62.
• 2. Edraki N, Mehdipour AR, Khoshneviszadeh M, Min R. Dihydropyridines: evaluation of their current and future pharmacological applications. Drug Discovery Today 2009;14(21–22):1058–66.
• 3. Hess EJ, Jen JC, Jinnah HA, Benarroch EE. Neuronal voltagegated calcium channels: brief overview of their function and clinical implications in neurology. Neurology 2010;75:937–8.
• 4. Tsien RW, Lipscombe D, Madison DV, Bley KR, Fox AP. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci 1988;11:431–8.
• 5. Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 2005;57:411–25.
• 6. Errington AC, Stohr T, Lees G. Voltage gated ion channels: targets for anticonvulsant drugs. Current Ttopics Med Chem 2005;5(1):15–30.
• 7. Ishibashi H, Rhee JS, Akaike N. Regional defference of high voltage-activated Ca2+ channels in rat CNS neurones. NeuroReport 1995;6:1621–4.
• 8. Richard S. Vascular effects of calcium channel antagonists: new evidence. Drugs 2005;65 Suppl 2:1–10.
• 9. Wang AL, Wang IC. New generations of dihydropyridines for treatment of hypertension. J Geriatr Cardiol 2017;14(1):67–2.
• 10. Pedrinelli R, Dell’Omo G, Mariani M. Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension. J Hum Hypertens 2001;15:455.
• 11. Elliott WJ, Ram CV. Calcium channel blockers. J Clin Hypertens (Greenwich)2011 Sep; 13(9):687–9.
• 12. Pisoschi CG, Stănciulescu CE, Andrei AM, BerbecaruIovan A, Munteanu C, Popescu F, et al. Role of transforming growth factor β-connective tissue growth factor pathway in dihydropyridine calcium channel blockers-induced gingival overgrowth. Rom J Morphol Embryol 2014;55(2):285–90.
• 13. Coca A, Mazon P, Aranda P, Redón J, Divisón JA, Martínez J et al. Role of dihydropyridinic calcium channel blockers in the management of hypertension. Expert Rev Cardiovasc Ther 2013;11:91–105.
• 14. Leenen FH. Clinical relevance of 24 h blood pressure control by 1, 4-dihydropyridines. Am J Hypertens 1996;9:97–104.
• 15. Koike H, Kimura T, Kawasaki T, Sada T, Ikeda T, Sanbuissho A et al. Azelnidipine, long-acting calcium channel blocker with slow onset and high vascular affinity. Annu Rep Sankyo Res Lab 2002;54:1–64.
• 16. Malhotra HS, Plosker GL. Barnidipine. Drugs 2001;61:989–96.
• 17. Sugiyama A, Satoh Y, Takahara A, Itomine T, Sakanashi M. Comparison of the direct negative dromotropic effect of a new calcium channel blocker, cilnidipine, with that of nicardipine. Heart Vessels 2005;20:112–5.
• 18. Herbette LG, Vecchiarelli M, Sartani A, Leonardi A. Lercanidipine: short plasma half-life, long duration of action and high cholesterol tolerance: updated molecular model to rationalize its pharmacokinetic properties. Blood Press Suppl 1998;2:10–7.
• 19. Soma MR, Natali M, Donetti E et al. Effect of lercanidipine and its ®-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits. Br J Pharmacol 1998;125(7):1471–6.
• 20. Canavesi M, Baldini N, Leonardi A, Baetta R, Farina P, Leonardi A et al. In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages. J Cardiovasc Pharmacol 2004;44(4):416–22.
• 21. Bang LM, Chapman TM, Goa KL. Lercanidipine: a review of its efficacy in the management of hypertension. Drugs 2003;63(22):2449–72.
• 22. Sabbatini M, Leonardi A, Testa R, Vitaioli L, Amenta F. Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats. Hypertension 2000;35(3):775–9.
• 23. Berkels R, Taubert D, Rosenkranz A, Rosen R. Vascular protective effects of dihydropyridine calcium antagonists. Involvement of endothelial nitric oxide. Pharmacology 2003;69(4):171–6.
• 24. Grassi G, Robles NR, Seravalle G, Fici F. Lercanidipine in the management of hypertension: An Update. J Pharmacol Pharmacother 2017;8(4):155–5.
• 25. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med 1999;341:1447–57.
• 26. Kearney PM, Whelton M, Reynolds K, Whelton PK, He J. Worldwide prevalence of hypertension: a systematic review. J Hypertens 2004;22:11–9.
• 27. Cramer JA, Benedict A, Muszbek N, Keskinaslan A, Khan ZM. The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review. Int J Clin Pract 2008;62:76–87.
• 28. Taira N. Differences in cardiovascular profile among calcium antagonists. Am J Cardiol 1987;30:24–9.
• 29. Minami J, Kawano Y, Makino Y, Matsuoka H, Takishita S. . Effects of cilnidipine, a novel dihydropyridine calcium antagonist, on autonomic function, ambulatory blood pressure and heart rate in patients with essential hypertension. Br J Clin Pharmacol 2000;50:615–20.
• 30. Prabhakar HS, Somashekar PK, Mohammed R, Umar D, Basheer B, Baroudi K. Comparison of amlodipine with cilnidipine on antihypertensive efficacy and incidence of pedal edema in mild to moderate hypertensive individuals: A prospective study. J Adv Pharm Technol Res 2015;6(2):81–5.
• 31. Akizuki O, Inayoshi A, Kitayama T, Yao K, Shirakura S, Sasaki K et al. Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R. Eur J Pharmacol 2008;584(2–3):424–34.
• 32. Rirash F, Tingey PC, Harding SE, Maxwell LJ, Tanjong Ghogomu E, Wells GA, et al. Calcium channel blockers for primary and secondary Raynaud’s phenomenon. Cochrane Database Syst Rev 2017;13:1–115.
• 33. Visentin S, Rolando B, Di Stilo A, Fruttero R, Novara M, Carbone E et al. New 1, 4-dihydropyridines endowed with NOdonor and calcium channel agonist properties. J Med Chem 2004;47(10):2688–93.
• 34. Sun J, Xie J, Kang L, Ferro A, Dong L, Xu B. Amlodipine Ameliorates Ischemia-Induced Neovascularization in Diabetic Rats through Endothelial Progenitor Cell Mobilization. Biomed Res Int 2016;3:1–13.
• 35. Tabrizchi R. Amlodipine and endothelial nitric oxide synthase activity. Cardiovasc Res 2003;59(4):807–9.
• 36. Taddei S, Virdis A, Ghiadoni L, Magagna A, Favilla S, Pompella A, et al. Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. . Hypertension 2001;37(3):943–8.
• 37. Derosa G, Mugellini A, Pesce RM, D’Angelo A, Maffioli P. Barnidipine compared to lercanidipine in addition to losartan on endothelial damage and oxidative stress parameters in patients with hypertension and type 2 diabetes mellitus. BMC Cardiovasc Disord 2016;12:1–7.
• 38. Fukuo K, Yang J, Yasuda O, Mogi M, Suhara T, Sato N et al. Nifedipine indirectly upregulates superoxide dismutase expression in endothelial cells via vascular smooth muscle celldependent pathways. Circulation 2002;106(3):356–61.
• 39. De Ciuceis C, Rossini C, Tincani A, Airò P, Scarsi M, AgabitiRosei C et al. Effect of antihypertensive treatment with lercanidipine on endothelial progenitor cells and inflammation in patients with mild to moderate essential hypertension. Blood Press 2016;25(6):337–43.
• 40. Spirou A, Rizos E, Liberopoulos EN, Kolaitis N, Achimastos A, Tselepis AD, et al. Effect of barnidipine on blood pressure and serum metabolic parameters in patients with essential hypertension: a pilot study. J Cardiovasc Pharmacol Ther 2006;11(4):256–61.
• 41. Manabe S, Okura T, Fukuoka T, Higaki J. Antioxidative effects of azelnidipine on mesangial cell proliferation induced by highly concentrated insulin. Eur J Pharmacol 2007;567(3):252–7.
• 42. Komoda H, Shiraki A, Oyama JI, Nishikido T, Node K. Azelnidipine inhibits the differentiation and zctivation of THP-1 macrophages through the L-type calcium channel. J Atheroscler Thromb 2018;25:1–8.
• 43. Kyselovic J, Martinka P, Batova Z, Gazova A, Godfraind T. Calcium channel blocker inhibits Western-type diet-evoked atherosclerosis development in ApoE-deficient mice. J Pharmacol Exp Ther 2005;315(1):320–8.
• 44. Zanchetti A, Bond MG, Hennig M, Neiss A, Mancia G, Dal Palù C et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation 2002;106(19):2422–7.
• 45. Ishii N, Matsumura T, Kinoshita H, Fukuda K, Motoshima H, Senokuchi T et al. Nifedipine induces peroxisome proliferator-activated receptor-gamma activation in macrophages and suppresses the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2010;30(8):1598–605.
• 46. Kojima T, Miyauchi K, Yokoyama T, et al. Azelnidipine and amlodipine anti-coronary atherosclerosis trial in hypertensive patients undergoing coronary intervention by serial volumetric intravascular ultrasound analysis in Juntendo University (ALPS-J). Circ J 2011;75(5):1071–9.
• 47. Schampel A, Kuerten S. Danger: High Voltage-The Role of Voltage-Gated Calcium Channels in Central Nervous SystemPathology. Cells 2017;15:1–8.
• 48. Pope JE, Deer TR. Ziconotide: a clinical update and pharmacologic review. Journal Expert Opinion on Pharmacotherapy 2013;14(7):957–66.
• 49. Wallace MS, Kosek PS, Staats P, Fisher R, Schultz DM, Leong M. Phase II, open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of ziconotide in patients receiving intrathecal morphine for severe chronic pain. Pain Med 2008;9(3):271–81.
• 50. Takahara A, Konda T, Enomoto A, Kondo N. Neuroprotective effects of a dual L/N-type Ca2+ channel blocker cilnidipine in the rat focal brain ischemia model. Biol Pharm Bull 2004;27:1388–91.
• 51. Aslan A, Gurelik M, Cemek M, et al. Nimodipine can improve cerebral metabolism and outcome in patients with severe head trauma. Pharmacol Res 2009;59:120–4.
• 52. Kim HA, Miller AA, Drummond GR, Goksel HM, Buyukokuroglu ME. Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol 2012;385(10):953–9.
• 53. Egan CG, Pontremoli R. Role of the fixed-dose combination lercanidipine-enalapril in renal protection. J Nephrol 2011;24(4):428–37.
• 54. Tomino Y. Renoprotective effects of the L-/T-type calcium channel blocker benidipine in patients with hypertension. Curr Hypertens Rev 2013;9(2):108–14.
• 55. Rinker B, Fink BF, Barry NG, Fife JA, Milan ME. The effect of calcium channel blockers on smoking-induced skin flap necrosis. Plast Reconstr Surg 2010;125(3):866-71.
• 56. Huby M, Rem K, Moris V, Guillier D, Revol M, Cristofari S. Are prostaglandins or calcium channel blockers efficient for free flap salvage? A review of the literature. J Stomatol Oral Maxillofac Surg 2018;1:1–4.
• 57. Baker JS, Miranpuri S. Perniosis A Case Report with Literature Review. J Am Pediatr Med Assoc 2016;106(2):138–40.
• 58. Wang R, Mao Y, Zhang Z, Li Z, Chen J, Cen Y. Role of verapamil in preventing and treating hypertrophic scars and keloids. Int Wound J 2016;13(4):461–8.
• 59. Golfam F, Golfam P, Golfam B, Pahlevani P. Comparison of topical nifedipine with oral nifedipine for treatment of anal fissure: a randomized controlled trial. Iran Red Crescent Med J 2014;16(8):1–3.
• 60. Innocenti M, Ramoni S, Doria C, Antropoli C, Garbagna N, Grossi E et al. Treatment of periocular wrinkles with topical nifedipine. J Dermatolog Treat 2010;21:282–5.
• 61. Lepcha A, Amalanathan S, Augustine AM, Tyagi AK, Balraj A. Flunarizine in the prophylaxis of migrainous vertigo: a randomized controlled trial. Eur Arch Otorhinolaryngol 2014;271(11):2931–6.
• 62. Paul IA. Antidepressant activity and calcium signalingcascades. Hum Psychopharmacol 2001;16:71–80.
• 63. Galeotti N, Bartolini A, Ghelardini C. Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test. Neuropharmacol 2006;50(3):309–16.
• 64. Tully PJ, Peters R, Pérès K, Anstey KJ, Tzourio C. Effect of SSRI and calcium channel blockers on depression symptoms and cognitive function in elderly persons treated for hypertension: three city cohort study. Int Psychogeriatr 2018;21:1–10.
• 65. Rajakulendran S, Hanna MG. The Role of Calcium Channels in Epilepsy. Cold Spring Harb Perspect Med 2016;6(1):1–22.
• 66. Sathyanarayana Rao KN, Subbalakshmi NK. An experimental study of the anticonvulsant effect of amlodipine in mice. Singapore Med J 2010;51(5):424–8.
• 67. Selvaraj N, Adhimoolam M, Perumal DK, Rajamohammed MA. Neuroprotective Effect of Lercanidipine- A Novel Calcium Channel Blocker in Albino Mice. J Clin Diagn Res 2015;9(11):1–5. 68. Baunack AR, Weihrauch TR. Clinical efficacy of nifedipine and other calcium antagonists in patients with primary esophageal motor dysfunctions. Arzneimittelforschung 1991;41(6):595–602.
• 69. Dziegielewska B, Gray LS, Dziegielewski J. T–type calcium channels blockers as new tools in cancer therapies. Pflugers Arch 2014;466(4):801–10.