PIMOBENDAN EM GATOS
Palavras-chave:
Felino, inodilatador, cardiomiopatiaResumo
As miocardiopatias são as cardiopatias mais comumente diagnosticadas em felinos domésticos. A cardiomiopatia hipertrófica (CMH) soma a maioria dos casos de cardiomiopatias em pacientes atendidos na rotina da medicina interna de felinos. Gatos com doenças cardíacas podem não apresentar manifestações clínicas evidentes podendo apresentar sinais sutis de insuficiência cardíaca (IC) ao longo do tempo de modo que em um dado momento descompensam e evidenciam sinais clínicos. O pimobendan é um fármaco denominado inodilatador devido a sua capacidade de promover inotropismo positivo e vasodilatação. Apesar de escassos, os estudos existentes com a utilização de pimobendan demonstram boa tolerância em gatos saudáveis e com cardiopatias diversas. Atualmente, o uso do pimobendan em gatos é extra bula e a dose baseia-se em estudos realizados com cães. No entanto, sabe-se que as concentrações plasmáticas diferem entre as espécies o que pode requerer possíveis ajustes. A terapia da IC em gatos é bastante discutida e evidências recentes demonstram que o pimobendan pode ser um aliado no tratamento de diversas doenças cardíacas que levem à disfunção sistólica sendo capaz de prover melhora dos sinais clínicos e até aumento da expectativa de vida desses pacientes. Contudo, pesquisas são necessárias para melhor entendimento dos efeitos hemodinâmicos do medicamento em gatos com disfunção diastólica.
Referências
ATKINS, C.E.; GALLO A.M.; KURZMAN I.D.; COWEN P. Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985–1989). Journal of the American Veterinary Medical Association. v.201, n.4, p.613–618, 1992.
BELL, E.T.; DEVI, J.L; CHIU, S.; ZAHRA, P; WHITTEM, T. The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs. Journal of Veterinary Pharmacology and Therapeutics. v.39, n.1, p.54-61, 2015.
BOHM, M.; MORANO, I.; PIESKE, B.; RUËGG.J.C.; WANKERL, M.; ZIMMERMANN, R; ERDMANN, E. Contribution of cAMP phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium. Circulation Research, v.68, n.3, p.689–701, 1991.
BOSWOOD, A. Current Use of Pimobendan in Canine Patients with Heart Disease. Veterinary Clinics of North America: Small Animal Practice, v.40, n.4, p.571–580, 2010.
BOYLE, K.L.; LEECH, E. A review of the pharmacology and clinical uses of pimobendan. Journal of Veterinary Emergency and Critical Care. v.22, n.4, p.398-408, 2012.
FITTON, A.; BROGDEN, R.N. Pimobendan. A Review of its Pharmacology and Therapeutic Potential in Congestive Heart Failure. Drugs & Aging. v.4, n.5, p.417–441, 1994.
FOX, P.R.; LIU, S.K; MARON, B.J. Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. An animal model of human disease. Circulation. v.92, n.9, p.2645–2651, 1995.
FOX, P.R. Hypertrophic cardiopathy. Clinical and pathologic correlates. Journal of Veterinary Cardiology. v.5, n.2, p.39-45, 2003.
FOX, P.R.; KEENE, B.W.; LAMB, K.; SCHOBER, K.A.; CHETBOUL, V.; LUIS FUENTES, V.; WESS G.; PAYNE J.R.; HOGAN D.F.; MOTSINGER-REIF A.; HÄGGSTRÖM J.; TREHIOU-SECHI E.; FINE-FERREIRA D.M.; NAKAMURA R.K.; LEE P.M.; SINGH M.K.; WARE W.A.; ABBOTT J.A.; CULSHAW G.; RIESEN S.; BORGARELLI M.; LESSER M.B.; VAN ISRAËL N.; CÔTÉ E.; RUSH J.E.; BULMER B.; SANTILLI R.A.; VOLLMAR A.C.; BOSSBALY M.J., QUICK N., BUSSADORI C.; BRIGHT J.M., ESTRADA A.H.; OHAD D.G.; FERNÁNDEZ-DEL PALACIO M.J.; LUNNEY BRAYLEY J.; SCHWARTZ D.S.; BOVÉ C.M.; GORDON S.G.; JUNG S.W.; BRAMBILLA P.; MOÏSE N.S.; STAUTHAMMER C.D.; STEPIEN R.L.; QUINTAVALLA C.; AMBERGER C.; MANCZUR F.; HUNG Y.W.; LOBETTI R.; DE SWARTE M.; TAMBORINI A.; MOONEY C.T.; OYAMA M.A.; KOMOLOV A.; FUJII Y.; PARIUT R., UECHI M.; TACHIKA OHARA V.Y. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: the REVEAL Study. Journal of Veterinary Internal Medicine. v.32, n.6, p.930–943, 2018.
FUENTES, V.L; CORCORAN, B.; FRENCH, A.; SCHOBER, K.E.; KLEEMANN, R.; JUSTUS, C. A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy. Journal of Veterinary Internal Medicine, v.16, n.3, p.255-261, 2002.
FUENTES, V.L. Use of pimobendan in the management of heart failure. Veterinary Clinics of North America: Small Animal Practice. v.34, n.5, p.1145-1155, setembro. 2004.
FUJINO, K.; SPERELAKIS, N.; SOLARO, R.J. Sensitization of dog and guinea pig heart myofilaments to Ca2 + activation and the inotropic effect of pimobendan: comparison with milrinone. Circulation Research, v.63, n.5, p.911-922, 1988.
GORDON, S.G.; MILLER, M.W.; SAUNDERS, A.B. Pimobendan in Heart Failure Therapy – A Silver Bullet? Journal of the American Animal Hospital Association, v.42, n.2, p.90-93, 2006.
GORDON, S.G.; CÔTÉ, E. Pharmacotherapy of feline cardiomyopathy: chronic management of heart failure. Journal of Veterinary Cardiology v.17, n.1, p.159-172, 2015.
GORDON, S.G.; SAUNDERS, A.B.; WESSELOWSKI, S.R. Asymptomatic canine degenerative valve disease: current and future therapies. Veterinary Clinics: Small Animal Practice, v. 47, n.5, p.955-975, 2017.
HAGEMEIJER, F. Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. European Heart Journal, v.14, n.4, p.551-566, 1993.
HAGGSTROM, J; BOSWOOD, A; O’GRADY, M; JONS, O; SMITH, S; SWIFT, S.; BORGARELLI, M.; GAVAGHAN, B.; KRESKEN, J.G.; PATTESON, M., ÅBLAD, B.; BUSSADORI, C.M.; GLAUS, T.; KOVAČEVIĆ, A.; RAPP, M.; SANTILLI, R.A.; TIDHOLM, A.; ERIKSSON, A.; BELANGER, M.C.; DEINERT, M., LITTLE, C.J.; KVART, C.; FRENCH, A.; RØNN-LANDBO, M.; WESS, G.; EGGERTSDOTTIR, A.; LYNNE O'SULLIVAN, M.; SCHNEIDER, M.; LOMBARD, C.W.; DUKES-MCEWAN, J.; WILLIS, R.; LOUVET, A.; DIFRUSCIA R. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. Journal of Veterinary Internal Medicine, v.27, n.6, p.1441-1451, 2013.
HAMBROOK, L.E.; BENNETT, P.F. Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy. Journal of Feline Medicine and Surgery, v.14, n.4, p.233-239, 2012.
HANZLICEK, A.S.; GEHRING, R.; KUKANICH, B.; KUKANICH, K.S.; BORGARELLI, M.; SMEE, N.; OLSON, E.E.; MARGIOCCO, M. Pharmacokinetics of oral pimobendan in healthy cats. Journal of Veterinary Cardiology v.14, n.4, p.489–496, 2012.
HOLUBARSCH, C. New inotropic concepts: Rationale for and differences between calcium sensitizers and phosphodiesterase inhibitors. Cardiology, v.88, n.2, p.12-20, 1997.
HONERJÄGER, P. Pharmacology of bipyridine phosphodiesterase III inhibitors. American Heart Journal, v.121, n.6, p.1939-1944, 1991.
HORI, Y; TAIRA, H; NAKAJIMA, Y; ISHIKAWA, Y. YUMOTO, Y; MAEKAWA, Y; OSHIRO, A. Inotropic effects of a single intravenous recommended dose of pimobendan in healthy dogs. The Journal of Veterinary Medical Science, v.81, n.1, p.22–25, 2019.
KENT M.A. Effects of Atenolol, Ivabradine and Pimobendan on Left Atrial and Left Atrial Appendage Function: An Echocardiographic Study in Healthy Cats. Ohio, 2011. 37p. Dissertação de mestrado, The Ohio State Unviersity, 2011.
KITTLESON, M.D.; MEURS K.M.; MUNRO, M.J.; KITTLESON, J.A. et al. Familial hypertrophic cardiomyopathy in Maine Coon cats: an animal model of human disease. Circulation, v..99, n.24, p.3172–3180, 1999.
LUBSEN, J.; JUST, H.; HJALMARSSON A.C; LA FRAMBOISE, D.; REMME, W.J et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the pimobendan in congestive heart failure (PICO) trial. Heart. v.76, n.3, p.223-231, 1996.
MACGREGOR, J.M.; RUSH, J.E.; LASTE, N.J; MALAKOFF, R.L.; CUNNINGHAM, S.M.; ARONOW, N.; HALL, D.J.; WILLIAMS, J.; PRICE L.L. Use of pimobendan in 170 cats (2006-2010). Journal of Veterinary Cardiology. v.13, n.4, p.251-260, 2011.
MANTOVANI, M.M; GIMENES, A.M; CASTRO, J.R; GOLDFEDER, G.T; LARSSON, M.H.M.A; SCHWARTZ, D.S. Tricuspid valve dysplasia in a domestic feline: case report. Semina: Ciências Agrárias, Londrina, v.38, n.2, p.1087-1092, 2017.
MIYAGAWA, Y.; MACHIDA, N.; TODA, N.; TOMINAGA, Y.; TAKEMURA, N. Comparison of the effects of long-term pimobendan and benazepril administration in normal cats. Journal of Veterinary Science, v.78, n.7, p.1099–106, 2016
OLDACH, M.S; UEDA, Y; ONTIVEROS, E.S; FOUSSE, S.L; HARRIS, S.P; STERN, J.A. Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study. Frontiers in Veterinary Science, v.6, n.15, p.1-8, 2019.
PAGEL, P.S; HETTRICK, D.A; WARLTIER, D.C. Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs. British Journal of Pharmacology, v.119, n.3, p.609–615, 1996.
PAYNE, J.R; BRODBELT, D.C; FUENTES, V.L. Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). Journal of Veterinary Cardiology, v.17, n.1, p.244–257, 2015.
POLLESELLO, P.; PAPP, Z.; PAPP, J.G. Calcium sensitizers:What have we learned over the last 25 years? International Journal of Cardiology, v.203, n.1, p.543–548, 2016.
POULEUR, H.; GURNE, O.; HANET, C.; BALASSIM, H.; VAN MECHELEN, H.; CHARLIER, A.A. Effects of pimobendan (UD-CG 115) on the contractile function of the normal and “postischemic” canine myocardium. Journal of Cardiovascular Pharmacology. v.11, n.1, p.100–106, 1988.
PRIETO-RAMOS, J.; MCNAUGHT, K.; FRENCH A.T. The novel use of intravenous pimobendan and oral torasemide in a cat with congestive heart failure secondary to end-stage hypertrophic cardiomyopathy. Veterinary Record Case Reports. v.3, n.2, p.1-5, 2016.
REINA-DORESTE, Y.; STERN, J.A.; KEENE, B.W.; TOU, S.P.; ATKINS, C.E.; DEFRANCESCO, T.C.; AMES, M.K.; HODGE, T.E.; MEURS, K.M. Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. Journal of the American Veterinary Medical Association, v.245, n.5, p.534-539, 2014.
RICHARDSON, P.; MCKENNA, W.; BRISTOW, M.; MAISCH, B.; MAUTNER, B.; O'CONNELL, J.; OLSEN, E.; THIENE, G.; GOODWIN, J.; GYARFAS, I.; MARTIN, I.; NORDET, P. Report of the 1995 World Health Organization/ International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation v.93, n.5, p.841–842, 1996.
RUSH, J.E; FREEMAN L.M; FENOLLOSA N.K; BROWN D.J. Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990–1999). Journal of the American Veterinary Medical Association, v.220, n.2, p.202–207, 2002.
SCHMITZ, W; ESECHENHAGEN, T; MENDE, U; MIILER, F.U; NEUMANN, J; SCHOLZ, H. Phosphodiesterase inhibition and positive inotropy in failing human myocardium. Basic Research in Cardiology, v.87, n.1, p.65-71, 1992.
SUMMERFIELD, N.J; BOSWOOD, A., O’GRADY, M.R; GORDON, S.G; DUKES-MCEWAN, J.; OYAMA, M.A.; SMITH, S.; PATTESON, M.; FRENCH, A.T.; CULSHAW, G.J.; BRAZ-RUIVO, L.; ESTRADA, A.; O'SULLIVAN, M.L.; LOUREIRO, J.; WILLIS, R.; WATSON, P. Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study). Journal of Veterinary Internal Medicine. v.26, n.6, p.1337-1349, 2012.
TISSIER, R.; CHETBOUL, V.; MORAILLON, R.; NICOLLE, A.; CARLOS, C.; ENRIQUEZ, B; POUCHELON, J.L. Increased mitral valve regurgitation and myocardil hypertrophy in two dogs with long-term pimobendan therapy. Cardiovascular Toxicology, v.5, n.1, p.43-51, 2005.
VERDOUW, P.D; HARTOG, J.M; DUNKER, D.J; ROTH, W; SAXENA, P.R. Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. European Journal of Pharmacology, v.126, n.1, p.21–30, 1986.
VON DER LEYEN, H.; MENDE, U.; MEYER, W.; NEUMANN, J.; NOSE, M.; SCHMITZ, W.; SCHOLZ, H.; STARBATTY, J.; STEIN, B.; WENZLAFF, H.; DÖRING, V.; KALMÁR, P.; HAVERICH, A. Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations. Naunyn Schmiedeberg's Archives of Pharmacology, v.344, n.1, p.90-100, 1991.
VON MEEL, J.C. Cardiovascular effects of the positive inotropic agents pimobendan and sulmazole in vivo. Arzneimittelforschung, v.35, n.1, p.284-2888, 1985.
WAINBERG, S. Use of pimobendan in feline congenital heart failure. Canadian Veterinary Journal. v.54, n.3, p.1164–1166, 2013.
WESTFALL, M.V; WAHLER, G.M; SOLARO, R.J. A highly specific benzimidazol pyridazinone reverses phosphate-induced changes in cardiac myofilament activation. Biochemistry, v.32, n.1, p.10464–10470, 1993.
WHITE, A.J.M. End-stage hypertrophic cardiomyopathy in a cat. Canadian Veterinary Journal, v.56, n.5, p.509–511, 2015.
YATA M.; MCLACHLAN, A. J.; FOSTER, D.J; HANZLICEK, A.S.; BEIJERINK, N.J. Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats, Journal of Veterinary Cardiology, v.18, n.4, p.310-325, 2016.
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