TRATAMIENTO

FARMACOLOGICO
DE LA ANGINA DE
PECHO
Dr. Persio López Contreras
PUCMM
Marzo 2011

Sunday, March 20, 2011

 ANGINA DE PECHO

Angina de pecho estable crónica es la

presencia de la sensación de opresión o
ahogo en el pecho o áreas adyacentes,
causada por isquemia miocárdica en
asociación con estrés físico o emocional, y
mejoría rápida de estos síntomas con el
reposo o con nitroglicerina sublingual.

Sunday, March 20, 2011

 ANGINA DE PECHO

✴ Desbalance entre aporte y el

consumo de O2 miocárdico
✴ En la mayoría de los
pacientes hay estenosis
(estrecheces) severas de una
o más arterias coronarias
epicárdicas
✴ Disfunción endotelial con
vasoconstricción inapropiada
durante el ejercicio
✴ La ateroesclerosis es la
principal causa subyacente

Sunday, March 20, 2011

 PERFUSION MIOCARDICA

Sunday, March 20, 2011

 PERFUSION MIOCARDICA

Sunday, March 20, 2011

 PERFUSION CORONARIA

Sunday, March 20, 2011

Sunday, March 20, 2011
 DETERMINANTES DEL CONSUMO DE
OXIGENO MIOCARDICO
✴ Frecuencia cardíaca
✴ Fenómeno de treppe o
Bowditch
✴ Estrés de la pared
✴ Presión x radio ÷ grosor
de la pared
✴ Contractilidad

✴ DOBLE PRODUCTO....

Sunday, March 20, 2011

Sunday, March 20, 2011
 ANGINA DE PECHO
✴ La perfusión miocárdica es diastólica
✴ La extracción de O2 miocárdico es de 75%
✴ Densidad capilar de 2000/mm3, 60-80% funcionales en
reposo
✴ El endocardio tiene mayor extracción que el epicardio:
más susceptible a la hipoxia
✴ Estenosis 25% lo comprometen, 60% trast. metabólicos, 75% trast. de
contractilidad y electrocardiográficos
✴ La resistencia aumenta x 4 con la reducción del radio
(Ley de Poiseuille)
✴ La resistencia aumenta con la longitud de la estenosis o
con estenosis secuenciales

Sunday, March 20, 2011

 Fatty-Streak Formation in Atherosclerosis

Ross R. N Engl J Med 1999;340:115-126

Ross R. N Engl J Med 1999;340:115-126

Sunday, March 20, 2011

 Review Vulnerable Plaque: Scope of the Literature

Figure. Normal arterial segment (A) compared with a vulnerable plaque (B) in longitudinal and cross-sectional views.

Ann Intern Med 2010; 153: 387-395.

Plaque vulnerability features that have been included in the criteria of the vulnerable plaque definition are indicated.

Sunday, March 20, 2011 (ACS), whereas in the remaining studies, experimental pa- proteinases and vascular endothelial growth factor. Study
 1666 Circulation October 7, 2003

Figure 2. Different types of vulnerable plaque as underlying cause of acute coronary events (ACS) and sudden cardiac death (SCD). A,
Rupture-prone plaque with large lipid core and thin fibrous cap infiltrated by macrophages. B, Ruptured plaque with subocclusive
thrombus and early organization. C, Erosion-prone plaque with proteoglycan matrix in a smooth muscle cell-rich plaque. D, Eroded
plaque with subocclusive thrombus. E, Intraplaque hemorrhage secondary to leaking vasa vasorum. F, Calcific nodule protruding into
the vessel lumen. G, Chronically stenotic plaque with severe calcification, old thrombus, and eccentric lumen.

The Challenge of Terminology: Culprit and macrophage-dense inflammation on or beneath its surface
Plaque Versus Vulnerable Plaque (Figure 3).
Over the past several years, “vulnerable plaque” has been
Culprit Plaque, a Retrospective Terminology
used sometimes to denote this concept and at other times to
Interventional cardiologists and cardiovascular pathologists ret-
denote the specific histopathologic appearance of the above-
rospectively describe the plaque responsible for coronary occlu-
described plaque. This dual usage is confusing, particularly as
sion and death as a culprit plaque, regardless of its histopatho-
Sunday, March 20, logic
2011 features. For prospective evaluation, clinicians need a
plaques can have other histologic features (see Figure 2) that
 1286 Arterioscler Thromb Vasc Biol July 2010

Figure 3. Illus
sizes the imp
gen synthesis
in the mainte
integrity of th
Vascular smo
synthesize es
lar matrix pro
lagen and ela
acids. This pr
inhibited by i
secreted by a
thereby disru
synthesis, wh
with the main
repair of colla
supporting th
Importantly, t
CD40 ligand
promote tissu
through the r
tion of matrix-degrading enzymes produced by vascular smooth muscle cells and inflammatory macrophages. Activat
within the fibrous cap can secrete tissue proteases that support the breakdown of collagen and elastin to peptides an
The loss of structural molecules provided by the extracellular matrix can thin and weaken the fibrous cap, rendering it
ceptible to rupture and acute coronary syndromes. Additional factors involved in the activation of macrophages includ
factor-" (TNF-"), macrophage colony-stimulating factor (M-CSF), and macrophage chemoattractant protein-1 (MCP-1
Sunday, March 20, 2011
 Hansson G. N Engl J Med 2005;352:1685-1695

Sunday, March 20, 2011

 ANGINA DE PECHO

Texto

Sunday, March 20, 2011

Sunday, March 20, 2011
 FACTORES CONTRIBUYENTES A LA ANGINA
VARIANTE, DE PRINZMETAL O
VASOSPASTICA
✴ Tabaquismo
✴ Cocaína
✴ Hipomagnesemia
✴ Resistencia a la insulina
✴ Deficiencia de vitamina E
✴ Administración de antimigrañosos: sumatriptán,
ergotamina
✴ Hiperventilación
✴ Exposición al frío

Sunday, March 20, 2011

 ANGINA DE PECHO
METAS DEL TRATAMIENTO
✴ Reducir la frecuencia de aparición de los síntomas y
su severidad
✴ Aumentar la tolerancia a los esfuerzos
✴ Reducir la incidencia de Síndromes Coronarios
Agudos
✴ Angina Inestable
✴ Infarto sin elevación del segmento S-T
✴ Infarto transmural
✴ Reducir la mortalidad

Sunday, March 20, 2011

 ANGINA DE PECHO
TRATAMIENTO
✴ NITRATOS
✴ BETABLOQUEADORES
✴ CALCIOANTAGONISTAS
✴ METABOLICOS
✴ BRADICARDIZANTES (IVABRADINA)
✴ INHIBIDORES DE LA ECA
✴ ESTATINAS
✴ ANTIAGREGANTES PLAQUETARIOS
✴ NICORANDIL

Sunday, March 20, 2011

 NITRATOS
✴ Esteres nítricos y nitrosos de polialcoholes
✴ Metabolizados activamente en hígado
✴ Rápida acción por vía sublingual o inhalados
✴ Nitroglicerina: prototipo
✴ Biodisponibilidad baja por VO (<10-20%)
✴ Metabolitos activos: 2 dinitroglicerinas, 2 mononitros
✴ Dinitrato de isosorbide: VM 4-6 horas
✴ 5-MNIS: metabolito activo de VM larga

Sunday, March 20, 2011

 NITRATOS

Sunday, March 20, 2011

 NITRATOS

✴ Relajan todos los tipos de músculo liso, venoso >

arterial (pulmonar y sistémico)
✴ Efecto antiagregante plaquetario débil (c-GMP)
✴ Aumentan flujo por vasos colaterales
✴ NTG: toxicidad por cianuro (dosis muy altas)
✴ Rápido desarrollo de tolerancia:
✴ Intervalo libre de nitratos, dosis asimétricas
✴ Efectos secundarios: CEFALEA, taquicardia, hipotensión
ortostática (extrema al combinar con sildenafil,
inhibidor de la PDE), retención de Na y agua

Sunday, March 20, 2011

 ANGINA DE PECHO

Sunday, March 20, 2011

 NITRATOS

Sunday, March 20, 2011

 NITRATOS

Sunday, March 20, 2011

 BETABLOQUEADORES

Sunday, March 20, 2011

 BETABLOQUEADORES
✴ Bloqueo competitivo de los receptores β
✴ Muy efectivos en angina de todos tipos, reducción de
mortalidad post-IAM
✴ Reducen la FC y contractilidad
✴ Efectivos en reposo y ejercicio
✴ Efectivos en combinación con nitratos y Ca++
Antagonistas (especialmente dihidropiridinas)
✴ Antihipertensivos
✴ Antiarrítmicos

Sunday, March 20, 2011

 BETABLOQUEADORES
CONTRAINDICACIONES

✴ Asma bronquial, broncoespasmo

✴ Bradicardia severa
✴ Bloqueo A-V
✴ Síndrome del seno enfermo (taquicardia/bradicardia)
✴ Cuidado especial en Insuficiencia Ventricular Izq.
✴ Insuficiencia arterial de MIs descompensada
✴ Cuidado con hipoglucemia
✴ Otros: letargo, depresión, sueños vívidos,
constipación, impotencia

Sunday, March 20, 2011

 BETABLOQUEADORES

Sunday, March 20, 2011

 BETABLOQUEADORES

Sunday, March 20, 2011

 BETABLOQUEADORES

Sunday, March 20, 2011

 MECANISMO DE ACCION DE Ca++
ANTAGONISTAS

Sunday, March 20, 2011

 ANGINA DE PECHO

Sunday, March 20, 2011

 ANGINA DE PECHO

FENILALQUILAMINAS:
•Verapamil BENZOTIAZEPINAS:
•Galopamil ! Diltiazem
•Tiapamil ! Clentiazem
•Anipamil
•Riapamil

Sunday, March 20, 2011

 ANGINA DE PECHO

Sunday, March 20, 2011

 Calcioantagonistas:
Dihidropiridinas
Nifedipina Felodipina
Nisoldipina Clinidipina
Nimodipina Niludipina
Nitrendipina Benidipina
Israpidina Clevidipina
Amlodipina Pranidipina
Lacidipina Elgodipina
Lercanidipina Manidipina

Sunday, March 20, 2011

 Selectividad Vascular de Dihidropiridinas
respecto a miocardio:

Dihidropiridina Relación
Lercanidipina 730
Lacidipina 193
Amlodipina 95
Felodipina 6
Nitrendipina 3

Sunday, March 20, 2011

Sunday, March 20, 2011
Sunday, March 20, 2011
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Sunday, March 20, 2011
Sunday, March 20, 2011
 TRIMETAZIDINA

Basal Dos semanas tto.

Sunday, March 20, 2011

 IVABRADINA
CORRIENTE If
✴ Activada por hiperpolarización celular.
✴ If: funny, chistosa, activada en diástole,
permite el paso de Na al interior y salida
de K
✴ Principal determinante de la corriente de
despolarización diastólica
✴ Mediada por receptores HCN
(hiperpolarization- activated, cyclid
nucleotid-gated)
✴ Cuatro isoformas, expresadas en corazón,
cerebro y retina
✴ HCN4 en nodo sinusal. Escasa en nodo A-
V y Purkinje

Sunday, March 20, 2011

 CORRIENTE If
✴ Estado basal, a -60 mV, 23% canales
activados
✴ 87% canales activos bajo
estimulación beta: aumento del AMP
cíclico
✴ Acetilcolina la inhibe bradicardia
✴ If 20 veces más sensible que otros
canales (Ik, ICaL, ICaT)
✴ Ausencia de HCN4: FC 40% más
lenta
✴ Ausencia de HCN4: No respuesta a
cAMP.
✴ If responsable en parte del
cronotropismo ß
✴ Efecto sólo en fase 4 potencial
acción
Sunday, March 20, 2011
 EFECTO DE LA IVABRADINA EN EL CANAL HCN4

Sunday, March 20, 2011

 EFECTO DE IVABRADINA SOBRE FASE 4

Sunday, March 20, 2011

 IVABRADINA

✴ Bloqueador selectivo de corriente If

✴ Agente bradicardizante puro
✴ Ausencia de efectos inotrópicos o vasculares
✴ Reduce MVO2
✴ Aumenta tiempo de perfusión diastólica
✴ Mejora el balance entre aporte y consumo O2

Sunday, March 20, 2011

 EFECTOS ANTI-ISQUEMICOS DE IVABRADINA

Borer J. Circulation 2003; 107: 817.

Sunday, March 20, 2011

 EFICACIA Y SEGURIDAD DE
IVABRADINA EN ANGINA DE PECHO

Lopez Bescos et al. 2009. Cardiology. 2007; 108: 387.

Sunday, March 20, 2011

 EFICACIA ANTIANGINOSA Y SEGURIDAD DE
IVABRADINA COMPARADA A AMLODIPINA

Ruzyllo W, Tendera M . et al. Drugs 2007; 67: 393

Sunday, March 20, 2011

 MAYOR EFICACIA ANTI-ISQUEMICA DE
IVABRADINA SOBRE ATENOLOL

Tardif JC. Eur Heart J 2005 26:2529.

Sunday, March 20, 2011

 ASSOCIATE
Ivabradina + atenolol

Tardiff JC, et al. Eur Heart J. 2008; 29(suppl): 386.

Sunday, March 20, 2011

 isation, and who also had left- adequately powered controlled trial with relevant
n. Also reported is a subanalysis, endpoints in patients, most of whom were pretreated
e effect of heart rate on the primary
ascular death, hospitalisation for Heart rate↑
+
ction, and new onset or worsening + Atherosclerosis
Oxidative stress↑
UTIFUL addresses the potentially Chronic heart failure Plaque stability↓
+ Arterial stiffness↑
d pathophysiological relevance of Tachycardiomyopathy↑
Oxygen demand↑
Ventricular efficiency↑
+ + Ischaemia
Ventricular relaxation↑
owed the effect of heart rate on Oxygen consumption↑
Diastole length↓
al population4 or in patients with Coronary perfusion↓
ary heart disease,6 myocardial Comorbidities
Remodelling
failure.8 Data have largely been Microalbuminuria↑
Cardiac hypertrophy↑
emiological studies, and have led
at heart rate might be a general
pathophysiological mechanisms
cular complications.9,10 High heart
important comorbidities in high-
s those with microalbuminuria.11
en observed at rather low heart Heart rate↓ Inhibition
n.4–11 Events↓? Ivabradine

ogical studies identified potential

in the development of athero-
remodelling, and chronic heart
morbidities associated with these
he crucial remaining question is
uction by drugs can reverse cardio-
es—an epidemiologically lower
ht be associated with higher levels
s obesity, fewer comorbidities, and
If channel
Figure: Potential role of heart rate in cardiovascular pathology
High heart rate is a risk factor for the development of atherosclerosis. High heart rate leads to ischaemia,
remodelling of heart and vessels, and contributes to comorbidities in hypertension and in chronic heart failure.
Figure shows potential mechanisms with experimental or clinical evidence. If channels are exclusively located in
sinoatrial node and are responsible for inwardly directed current, which accelerates diastolic depolarisation of sinus
node and thus its pacemaker function. The If channel can be inhibited by ivabradine. Green dots=If current.

September 6, 2008 Reil JC, Bohm M. Lancet 2008; 372: 779-781.

779

Sunday, March 20, 2011

 ANGINA DE PECHO
✴ TRATAMIENTO COMPLEMENTARIO:
✴ ANTIAGREGANTES PLAQUETARIOS
✴ ESTATINAS: reducción agresiva de LDL
✴ I-ECAs.
✴ REVASCULARIZACION CORONARIA
✴ Angioplastía + stents
✴ Revascularización coronaria
✴ CONTRAPULSACION EXTERNA

Sunday, March 20, 2011

 ANGINA DE PECHO

Texto

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 ANGINA DE PECHO

Texto

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 ANGINA DE PECHO

Sunday, March 20, 2011