Rational Pharmacotherapy in Cardiology

Advanced search

Peculiarities of Adverse Events Manifested by Injury of Skin and Skin Derivatives and Associated with Beta-blockers Use

Full Text:


More than 50 years after Propranolol was introduced to the pharmaceutical market as a drug that can lower the heart rate, beta-blockers (BAB) are still widely used in the pharmacotherapy of cardiovascular diseases. However, the use of BAB has a number of limitations, first of all, due to adverse drug events (AE) that develop during their use. The purpose of our review was to study the features of the BAB AE manifested by injuries of the skin and its appendages. The clinical manifestations of them are the development or exacerbation of psoriasis, lichen planus, contact dermatitis, acrocyanosis, Raynaud's disease, alopecia, hyperhidrosis, vitiligo, anaphylaxis, and allergic skin reactions. True medicinal psoriasis occurs in patients taking BAB with no family or previous history and most often mimics erythrodermic psoriasis and palmar-plantar pustular psoriasis. Systemic use of BAB can also be accompanied by exacerbation of vitiligo. In patients with segmental vitiligo, the results of Doppler flowmetry and iontophoresis showed increased blood flow in vitiligo foci compared with normal skin. The development of anaphylactic reactions against the background of BAB therapy may be due to the modulation of adenylate cyclase, which can affect the release of anaphylactogenic mediators, as well as a decrease in the severity of cardiovascular compensatory changes. The peculiarities of the development of such reactions may be the resistance of patients to traditional treatment, which is due to the development of paradoxical reflex vagotonic effects when using adrenaline. Some of the mentioned AE may pose a potential threat to the life and health of the patient and therefore require additional discussion.

About the Authors

A. V. Matveev
Medical Academy named after S. I. Georgievsky, V.I. Vernadsky Crimean Federal University; Russian Medical Academy of Continuing Professional Education
Russian Federation

Aleksandr V. Matveev

Simferopol, Moscow

E. A. Egorova
Medical Academy named after S. I. Georgievsky, V.I. Vernadsky Crimean Federal University
Russian Federation

Elena A. Egorova


E. I. Konyaeva
Medical Academy named after S. I. Georgievsky, V.I. Vernadsky Crimean Federal University
Russian Federation

Elena I. Konyaeva


A. G. Dormidor
Center of the Blood Circulation Pathology
Russian Federation

Artur G. Dormidor


E. Yu. Bekirova
Medical Academy named after S. I. Georgievsky, V.I. Vernadsky Crimean Federal University
Russian Federation

Elvira Y. Bekirova



1. Prichard BN, Gillam PM. Use of propranolol (Inderal) in treatment of hypertension. Br Med J. 1964;2(5411):725-27. DOI:10.1136/bmj.2.5411.725.

2. Ogrodowczyk M, Dettlaff K, Jelinska A. Beta-Blockers: Current State of Knowledge and Perspectives. Mini Rev Med Chem. 2016;16(1):40-54. DOI:10.2174/1389557515666151016125948.

3. Wiysonge CS, Opie LH. β-Blockers as initial therapy for hypertension. JAMA. 2013;310(17):1851-2. DOI:10.1001/jama.2013.277510.

4. do Vale GT, Ceron CS, Gonzaga NA, et al. Three Generations of β-blockers: History, Class Differences and Clinical Applicability. Curr Hypertens Rev. 2019;15(1):22-31. DOI:10.2174/1573402114666180918102735.

5. Laurent S. Antihypertensive drugs. Pharmacol Res. 2017;124:116-25. DOI:10.1016/j.phrs.2017.07.026.

6. Wong GW, Boyda HN, Wright JM. Blood pressure lowering efficacy of beta-1 selective beta blockers for primary hypertension. Cochrane Database Syst Rev. 2016;3(3):CD007451. DOI:10.1002/14651858.CD007451.pub2.

7. Mann SJ. Redefining beta-blocker use in hypertension: selecting the right beta-blocker and the right patient. J Am Soc Hypertens. 2017;11(1):54-65. DOI:10.1016/j.jash.2016.11.007.

8. Kendall MJ, Beeley L. Beta-adrenoceptor blocking drugs: adverse reactions and drug interactions. Pharmacol Ther. 1983;21(3):351-69. DOI:10.1016/0163-7258(83)90060-8.

9. Martimyanova LA, Makienko NV, Usan NYu. Beta-adrenoblockers in a therapeutic clinic. Bulletin of KhNU im. V.N. Karazin. Medicine series. 2008;16(831):95-103. (In Russ.)

10. Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidence-based assessment. Am J Ophthalmol. 2002;134(5):749-60. DOI:10.1016/s0002-9394(02)01699-9.

11. Frishman WH. Beta-adrenergic receptor blockers. Adverse effects and drug interactions. Hypertension. 1988;11(3):II21-II29. DOI:10.1161/01.hyp.11.3_pt_2.ii21.

12. O'Brien M, Koo J. The mechanism of lithium and beta-blocking agents in inducing and exacerbating psoriasis. J Drugs Dermatol. 2006;5(5):426-32.

13. Yilmaz MB, Turhan H, Akin Y, et al. Beta-blocker-induced psoriasis: a rare side effect--a case report. Angiology. 2002;53(6):737-9. DOI:10.1177/000331970205300617.

14. Balak DM, Hajdarbegovic E. Drug-induced psoriasis: clinical perspectives. Psoriasis (Auckl). 2017;7:87-94. DOI:10.2147/PTT.S126727.

15. Tsankov N, Angelova I, Kazandjieva J. Drug-induced psoriasis. Recognition and management. Am J Clin Dermatol. 2000;1(3):159-65. DOI:10.2165/00128071-200001030-00003.

16. Dika E, Varotti C, Bardazzi F, et al. Drug-induced psoriasis: an evidence-based overview and the introduction of psoriatic drug eruption probability score. Cutan Ocul Toxicol. 2006;25(1):1-11. DOI:10.1080/15569520500536568.

17. Stanford CW, Kollipara R, Melookaran AM, et al. Palmoplantar pustular psoriasis following initiation of a beta-blocker: disease control with low-dose methotrexate. Cutis. 2014;94(3):153-5.

18. Sehgal VN, Dogra S, Srivastava G, et al. Psoriasiform dermatoses. Indian J Dermatol Venereol Leprol. 2008;74(2):94-9. DOI:10.4103/0378-6323.39688.

19. Glass LR, Nguyen M, Winn BJ, et al. Timolol drops causing reversible psoriatic fingernail changes. JAMA Ophthalmol. 2013;131(9):1134. DOI:10.1001/jamaophthalmol.2013.1579.

20. Heng MC, Heng MK. Beta-adrenoceptor antagonist-induced psoriasiform eruption. Clinical and pathogenetic aspects. Int J Dermatol. 1988 ;27(9):619-27. DOI:10.1111/j.1365-4362.1988.tb02419.x.

21. Armstrong AW. Psoriasis Provoked or Exacerbated by Medications: Identifying Culprit Drugs. JAMA Dermatol. 2014;150(9):963. DOI:10.1001/jamadermatol.2014.1019.

22. Wu S, Han J, Li WQ, et al. Hypertension, antihypertensive medication use, and risk of psoriasis. JAMA Dermatol. 2014;150(9):957-63. DOI:10.1001/jamadermatol.2013.9957.

23. Halevy S, Livni E. Psoriasis and psoriasiform eruptions associated with propranolol—the role of an immunological mechanism. Arch Dermatol Res. 1991;283(7):472-3. DOI:10.1007/BF00371785.

24. Wu S, Han J, Li WQ, et al. Hypertension, antihypertensive medication use, and risk of psoriasis. JAMA Dermatol. 2014;150(9):957-63. DOI:10.1001/jamadermatol.2013.9957.

25. Levin A, Gottlieb AB. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014;70(3):555-61. DOI:10.1016/j.jaad.2013.10.043.

26. McGeachy MJ, Chen Y, Tato CM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol. 2009;10(3):314-24. DOI:10.1038/ni.1698.

27. Awad VM, Sakhamuru S, Kambampati S, et al. Mechanisms of Beta-Blocker Induced Psoriasis, and Psoriasis De Novo at the Cellular Level. Cureus. 2020;12(7):e8964. DOI:10.7759/cureus.8964.

28. Herrick AL. Pathogenesis of Raynaud's phenomenon. Rheumatol (Oxford). 2005;44(5):587-96. DOI:10.1093/rheumatology/keh552.

29. Roustit M, Khouri C, Blaise S, et al. Pharmacology of Raynaud's phenomenon. (in French). [Pharmacologie du phenomene de Raunald]. Therapie. 2014;69(2):115-28. DOI:10.2515/therapie/2013068.

30. Suter LG, Murabito JM, Felson DT, et al. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis Rheum. 2005;52(4):1259-63. DOI:10.1002/art.20988.

31. De Angelis R, Salaffi F, Grassi W. Raynaud's phenomenon: prevalence in an Italian population sample. Clin Rheumatol. 2006;25(4):506-10. DOI:10.1007/s10067-005-0077-1.

32. Khouri C, Jouve T, Blaise S, Carpentier P, et al. Peripheral vasoconstriction induced by β-adrenoceptor blockers: a systematic review and a network meta-analysis. Br J Clin Pharmacol. 2016;82(2):549-60. DOI:10.1111/bcp.12980.

33. Heintzen MP, Strauer BE. Peripheral vascular effects of beta‐blockers. Eur Heart J. 1994;15(C):2-7. DOI:10.1093/eurheartj/15.suppl_c.2.

34. VandenBurg MJ, Evans SJW, Cooper WD, et al. Is the feeling of cold extremities experienced by hypertensive patients due to their disease or their treatment? Eur J Clin Pharmacol. 1984;27(1):47-9.

35. Rolfes L, de Swart-Ruijter I, van Hunsel F. Labetalol for hypertension during pregnancy and nipple pain. Eur J Obstet Gynecol Reprod Biol. 2014;182:254-5. DOI:10.1016/j.ejogrb.2014.09.041.

36. Avila-Vega J, Urrea-Mendoza E, Lee C. Raynaud's phenomenon of the nipple as a side-effect of labetalol: Case report and literature review. Case Rep Womens Health. 2019;23:e00135. DOI: 10.1016/j.crwh.2019.e00135.

37. Mcguinness N, Cording V. Raynaud's phenomenon of the nipple associated with labetalol use. J Hum Lact. 2012;29(1):17-9. DOI:10.1177/0890334412467509.

38. Schallreuter KU. Beta-adrenergic blocking drugs may exacerbate vitiligo. Br J Dermatol. 1995;132:168-9. DOI:10.1111/j.1365-2133.1995.tb08660.x.

39. Wu CS, Yu HS, Chang HR, et al. Cutaneous blood flow and adrenoceptor response increase in segmental-type vitiligo lesions. J Dermatol Sci. 2000;23(1):53-62. DOI:10.1016/S0923-1811(99)00090-0.

40. Tatu AL, Elisei AM, Chioncel V, et al. Immunologic adverse reactions of β-blockers and the skin. Exp Ther Med. 2019;18(2):955-9. DOI:10.3892/etm.2019.7504.

41. Choi ME, Yoo H, Lee HR, et al. Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture. Int J Mol Sci. 2020;21(22):8796. DOI:10.3390/ijms21228796.

42. Lang DM. Anaphylactoid and Anaphylactic Reactions. Hazards of beta-blockers. Drug-Safety. 1995;12(5):299-304. DOI:10.2165/00002018-199512050-00002.

43. Goddet NS, Descatha A, Liberge O, et al. Paradoxical reaction to epinephrine induced by beta-blockers in an anaphylactic shock induced by penicillin. Eur J Emerg Med. 2006;13(6):358-60. DOI:10.1097/01.mej.0000217993.09364.35.

44. Toogood JH. Beta-blocker therapy and the risk of anaphylaxis. CMAJ. 1987;137(7):587-8.

45. Jacobs RL, Rake GW, Fournier DC, et al. Potentiated anaphylaxis in patients with drug-induced betaadrenergic blockade. J Allergy Clin Immunol. 1981;68(2):125-7. DOI:10.1016/0091-6749(81)90170-6.

46. Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371-6. DOI:10.1016/j.jaci.2004.04.029.

47. Lee S, Hess EP, Nestler DM, et al. Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis. J Allergy Clin Immunol. 2013;131(4):1103-8. DOI:10.1016/j.jaci.2013.01.011.

48. Coop CA, Schapira RS, Freeman TM. Are ACE Inhibitors and Beta-blockers Dangerous in Patients at Risk for Anaphylaxis? J Allergy Clin Immunol Pract. 2017;5(5):1207-11. DOI:10.1016/j.jaip.2017.04.033.

49. Francuzik W, Dölle-Bierke S, Knop M, et al. Refractory Anaphylaxis: Data From the European Anaphylaxis Registry. Front Immunol. 2019;10:2482. DOI:10.3389/fimmu.2019.02482.

50. Francuzik W, Ruёff F, Bauer A, et al. Phenotype and risk factors of venom-induced anaphylaxis: A case-control study of the European Anaphylaxis Registry. J Allergy Clin Immunol. 2021;147(2):653-62. DOI:10.1016/j.jaci.2020.06.008.

51. Pathak A, Mrabeti S. beta-Blockade for Patients with Hypertension, Ischemic Heart Disease or Heart Failure: Where are We Now? Vasc Health Risk Manag. 2021;17:337-348. DOI:10.2147/VHRM.S285907.

For citation:

Matveev A.V., Egorova E.A., Konyaeva E.I., Dormidor A.G., Bekirova E.Yu. Peculiarities of Adverse Events Manifested by Injury of Skin and Skin Derivatives and Associated with Beta-blockers Use. Rational Pharmacotherapy in Cardiology. 2021;17(5):779-784. (In Russ.)

Views: 75

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)