Fármacos Antireninas IECA Antagonistas de angiotensina II

Presentación del tema: "Fármacos Antireninas IECA Antagonistas de angiotensina II"— Transcripción de la presentación:

1 Fármacos Antireninas IECA Antagonistas de angiotensina II
Sistema renina- angiotensina- aldosteona Fármacos Antireninas IECA Antagonistas de angiotensina II Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI) : Advantages In class II-IV heart failure patients treated with diuretics and digitalis, ACE-inhibitors decrease symptoms, improve hemodynamics and functional class, and increase exercise tolerance. Additionally, they reduce left ventricular dimensions, improve the cardiothoracic index, improve renal function, and improve hyponatremia. More importantly, ACE-inhibitors are the best drugs to date for preventing expansion and dilatation of the left ventricle post infarction, thereby decreasing the number and duration of hospitalizations, and improving symptoms and survival. They also retard progression to heart failure in patients with asymptomatic ventricular dysfunction. ACE-inhibitors differ from other vasodilators in that they do not produce neurohormonal activation or reflex tachycardia, and tolerance to these agents does not seem to develop over time. ACE-inhibitors increase plasma renin, bradykinin, and angiotensin I activities, and reduce plasma and tissue levels of angiotensin II, and plasma levels of aldosterone and cortisol. ACE-inhibitors can also decrease plasma norepinephrine levels, especially after long-term therapy, which has been attributed to the suppression of the stimulating effect angiotensin II has on the synthesis and release of norepinephrine. ACE-inhibitors also reduce arginine-vasopressin levels.

2 Agentes inhibidores de la enzima de conversión
Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI) : Advantages In class II-IV heart failure patients treated with diuretics and digitalis, ACE-inhibitors decrease symptoms, improve hemodynamics and functional class, and increase exercise tolerance. Additionally, they reduce left ventricular dimensions, improve the cardiothoracic index, improve renal function, and improve hyponatremia. More importantly, ACE-inhibitors are the best drugs to date for preventing expansion and dilatation of the left ventricle post infarction, thereby decreasing the number and duration of hospitalizations, and improving symptoms and survival. They also retard progression to heart failure in patients with asymptomatic ventricular dysfunction. ACE-inhibitors differ from other vasodilators in that they do not produce neurohormonal activation or reflex tachycardia, and tolerance to these agents does not seem to develop over time. ACE-inhibitors increase plasma renin, bradykinin, and angiotensin I activities, and reduce plasma and tissue levels of angiotensin II, and plasma levels of aldosterone and cortisol. ACE-inhibitors can also decrease plasma norepinephrine levels, especially after long-term therapy, which has been attributed to the suppression of the stimulating effect angiotensin II has on the synthesis and release of norepinephrine. ACE-inhibitors also reduce arginine-vasopressin levels.

3 Introducción 1960: Ferreira: venenos de víboras, factores
que intensificaban las respuestas a bradiquininas. Erdos y col establecieron la identidad de Enzima convertidora y la quininasa II. 1977: Cushman: captopril Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

4 Orígen y Química Sulfidrilo IECA Dicardoxilo IECA Fósforo IECA
COOH enalapril COO C2Hv CHc captopril CH3 COOH H CH2CH2 C N C C N HSCH2 C C N H H O H O quinapril CH3CH2 OOC CH3 COOH H Fósforo IECA CH2CH2C N C C N H H O fosinopril COONa O COOH ramipril COO C2H5 CH3 CH2CH2CH 2CH2 P CH2 C N H CH2CH2C N C C N O O H H H H O CH3CH2COOCHCH(CH3)2 23

5 Mecanismo de acción E.C.A. Kininas II VASOCONSTRICCION VASODILATACION
ALDOSTERONA PROSTAGLANDINAS VASOPRESINA Kininógeno tPA SIMPATICO Kalikreína Angiotensinógeno RENINA BRADIKININAS Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI) :Mechanisms of action ACE-inhibitors competitively block the converting enzyme that transforms angiotensin I into angiotensin II. The reduction in angiotensin II levels explains its arteriovenous vasodilatory actions, as angiotensin II is a potent vasoconstrictor that augments sympathetic tone in the arteriovenous system. Additionally, angiotensin causes vasopressin release and produces sodium and water retention, both through a direct renal effect and through the liberation of aldosterone. Since converting enzyme has a similar structure to kinase II that degrades bradykinin, ACE-inhibitors increase kinin levels that are potent vasodilators (E2 and F2) and increase release of fibrinolytic substances such as tPA. Angiotensina I E.C.A. Kininas II ANGIOTENSINA II Fragmentos Inactivos

6 Acciones de angiotensina II
Acciones renales: a) vasculares: Arteriola aferente: Contricción; arteriola eferente. Constricción Aldosterona b)Glomérulo: Disminuye el flujo sanguíneo Na+ K+ d)TCP: Aumenta reabsorción Na+ Corteza c)Mesangio Constricción Médula externa Na+ Médula interna Acciones suprarenales: aumenta síntesis de aldosterona Acciones vasculares sistémicas: vasoconstricción arterial: aumento RP Acciones cardíacas: vasoconstricción coronaria, potencia catecolaminas, HVI Acciones cerebrales: Aumento sed, estímulación simpática central y aumento ADH

7 Farmacodinamia Angiotensinógeno Péptidos incativos Angiotensina I
Pool Acido Araquidónico RENINA Angiotensinógeno Péptidos incativos Angiotensina I Enz Convertidora angiotensina CAPTOPRIL CAPTOPRIL Kininas Angiotensina II Acido Araquidónico Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%. Aldosterona TA PGE2 PG Retención de Na PGI2

8 Mecanismo de acción E.C.A. Kininas II VASOCONSTRICCION VASODILATACION
ALDOSTERONA PROSTAGLANDINAS VASOPRESINA Kininógeno tPA SIMPATICO Kalikreína Angiotensinógeno RENINA BRADIKININAS Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI) :Mechanisms of action ACE-inhibitors competitively block the converting enzyme that transforms angiotensin I into angiotensin II. The reduction in angiotensin II levels explains its arteriovenous vasodilatory actions, as angiotensin II is a potent vasoconstrictor that augments sympathetic tone in the arteriovenous system. Additionally, angiotensin causes vasopressin release and produces sodium and water retention, both through a direct renal effect and through the liberation of aldosterone. Since converting enzyme has a similar structure to kinase II that degrades bradykinin, ACE-inhibitors increase kinin levels that are potent vasodilators (E2 and F2) and increase release of fibrinolytic substances such as tPA. Angiotensina I E.C.A. Inhibidor Kininas II ANGIOTENSINA II Fragmentos Inactivos

9 Efecto cardioprotector
Angiotensina I Angiotensina II Vasoconstricción (sistémica coronaria) 2. Sistema simpático (central y periférico) Restauración balance entre consumo y demanda de oxígeno Reducción pre y postcarga Reducción masa VI Reducción estimulación simpática Efecto beneficioso en injuria de reperfución* IECA Eva Lonn, et al. Circulation 1994; 90(4): * Not demonstrated conclusively in humans

10 Efecto vasculoprotector
Efecto antiaterogénico * Efecto antiproliferativo y antimigratorio de células del músculo liso, neutrófilo y células mononucleares Mejoría y restauración de la disfunción endotelial Efecto protector de la ruptura de placa * Efecto antiplaquetario Mejora fibrinolísis endógena Efecto antihipertensivo Mejoría del tono arterial Eva Lonn, et al. Circulation 1994; 90(4): * Not demonstrated conclusively in humans

11 Clasificación Prodrogas Tiempo de acción SH2 Captopril Alacepril
Ramipril Enalapril Lisinopril Cilazapril Fosenopril-perindopril Trandolapril Quinapril no sí corta larga sí no Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

12 Farmacocinética Captopril: Absorción oral, biodisponibilidad 65%
- reducida por alimentos - inicio min, efecto máx 1 hora. Vida media 2hs, persisten 8-12hs - Desaparece de sangre 4-5hs. -Metabolismo hepático, Eliminación renal 40% activo - Tabletas: 12.5, 25, 50 y 100mgs Enalapril: prófarmaco, hidrolizado a enalaprilato - Oral y EV. Biodisponibilidad no afectada por alimentos. -Comienza 60 min. Concentración máxima 3-4 hs(VO), 15 min (EV) -VO: 2.5, 5, 10 y 20mgs. Enalaprilato EV. 1.25mg/ml Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

13 Indicaciones Insuficiencia cardíaca clínica
- Todos los pacientes Disfunción ventricular asintomática - FEVI < 35 % Hipertensión arterial Pacientes postinfarto agudo de miocardio Proteinuria del diabético Controlar la sed Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

14 Insuficiencia Cardíaca
Venous Vasodilatation VENOSOS Nitratos Molsidomine MIXTOS Antagonistas cálcicos Bloqueantes a-adrenergicos IECA Inhibidores Angiotensina II Nitroprusiato Arterial Vasodilatation ARTERIAL Minoxidil Hydralazine

15 Insuficiencia Cardíaca
Inhibe la remodelación postinfarto. Modifica la progresión de la ICC crónica Sobrevida Hospitalizaciones Mejora la calidad de vida. En contraste con otros vasodilatadores, no produce activatión neurohormonal o taquicardia refleja. No desarrolla tolerancia a estos efectos. Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI) : Advantages In class II-IV heart failure patients treated with diuretics and digitalis, ACE-inhibitors decrease symptoms, improve hemodynamics and functional class, and increase exercise tolerance. Additionally, they reduce left ventricular dimensions, improve the cardiothoracic index, improve renal function, and improve hyponatremia. More importantly, ACE-inhibitors are the best drugs to date for preventing expansion and dilatation of the left ventricle post infarction, thereby decreasing the number and duration of hospitalizations, and improving symptoms and survival. They also retard progression to heart failure in patients with asymptomatic ventricular dysfunction. ACE-inhibitors differ from other vasodilators in that they do not produce neurohormonal activation or reflex tachycardia, and tolerance to these agents does not seem to develop over time. ACE-inhibitors increase plasma renin, bradykinin, and angiotensin I activities, and reduce plasma and tissue levels of angiotensin II, and plasma levels of aldosterone and cortisol. ACE-inhibitors can also decrease plasma norepinephrine levels, especially after long-term therapy, which has been attributed to the suppression of the stimulating effect angiotensin II has on the synthesis and release of norepinephrine. ACE-inhibitors also reduce arginine-vasopressin levels.

16 Insuficiencia Cardíaca
50 p = 0.30 Placebo n=2117 40 IECA Mortalidad 30 20 Enalapril n=2111 Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival Mortality curves in patients with asymptomatic ventricular dysfunction in the SOLVD study. This study compared the effect of enalapril versus placebo in 4228 asymptomatic patients with EF < 35% who were previously untreated. Overall mortality was similar in both groups (15.8% vs. 14.8%, NS), but in the enalapril arm a reduction in development of clinical symptoms of heart failure or need for hospitalization was seen. Once again, patients with the lowest EF’s were those who benefited the most from therapy. The SOLVD Investigators. N Engl J Med1992;327:685 n = 4228 No CHF symptoms EF < 35 10 6 12 18 24 30 36 42 48 SOLVD (Prevention) N Engl J Med 1992;327:685 Months

17 Insuficiencia Cardíaca
50 40 30 20 10 p = Placebo n=1284 IECA Mortalidad Enalapril n=1285 Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI) : Survival SOLVD study-symptomatic heart failure. Mortality curves in patients with clinical heart failure in the SOLVD treatment study. In this study, 2589 symptomatic heart failure patients with EFs<35% (90% in functional class II – III) were randomized to receive enalapril or placebo. Mortality over a 41 month follow-up period was 39.7% in the enalapril arm and 35.2% in the placebo arm (p<0.004). The mortality reduction was chiefly mediated through less progression of heart failure; deaths due to arrhythmia were not reduced. Additionally, the enalapril group required fewer hospitalizations for heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293 n = 2589 CHF - NYHA II-III - EF < 35 48 6 12 18 24 30 36 42 SOLVD (Treatment) N Engl J M 1991;325:293 Months

18 Insuficiencia Cardíaca
30 Asymptomatic ventricular dysfunction post MI Placebo n=1116 IECA Mortalidad 20 Captopril n=1115 Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival SAVE (Survival and Ventricular Enlargement). Mortality curves in the SAVE study in patients with varying degrees of post-infarct ventricular dysfunction. In this study, 2231 patients with EF < 40% were randomized to receive captopril or placebo between 3 to 16 days after experiencing a transmural infarct. After 42 months, the captopril group had a significant reduction in overall mortality (-19%), number of reinfarctions (-25%), hospitalizations (-22%), and in the number of patients who developed clinical congestive heart failure. The mortality reduction appeared after 1 year of treatment. Pfeffer MA et al. Survival and Ventricular Enlargement (SAVE) Study. NEngl J Med 1992;327:669. 10 n = 2231 days post AMI EF < 40 mg / day ² -19% p=0.019 SAVE N Engl J Med 1992;327:669 1 2 3 4 Years

19 Tratamiento de la Insuficiencia Cardíaca
30 Asymptomatic ventricular dysfunction post MI Placebo n=1116 IECA Mortalidad 20 Captopril n=1115 Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival SAVE (Survival and Ventricular Enlargement). Mortality curves in the SAVE study in patients with varying degrees of post-infarct ventricular dysfunction. In this study, 2231 patients with EF < 40% were randomized to receive captopril or placebo between 3 to 16 days after experiencing a transmural infarct. After 42 months, the captopril group had a significant reduction in overall mortality (-19%), number of reinfarctions (-25%), hospitalizations (-22%), and in the number of patients who developed clinical congestive heart failure. The mortality reduction appeared after 1 year of treatment. Pfeffer MA et al. Survival and Ventricular Enlargement (SAVE) Study. NEngl J Med 1992;327:669. 10 n = 2231 days post AMI EF < 40 mg / day ² -19% p=0.019 SAVE N Engl J Med 1992;327:669 1 2 3 4 Years

20 Efectos colaterales Hipotensión arterial Disfunción hemodinámica renal
(estenosis renal bilateral o estenosis de arteria renal en monorenos) Tos Angioedema Proteinuria Hematológicos: Neutropenia, agranulocitosis Neurológicos: cefalea, ataxia, parestesias, mareos, Depresión psíquica Digestivos Disturbios del gusto, nauseas,diarrea, constipación Renales: glomerulopatías membranosa Disfunción hepática Sexuales, Impotencia sexual Respiratorio: broncoespasmo Alérgicas: Rash cutáneo Osteomusculares: calambres, fatiga, astenia Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

21 Contraindicaciones Precauciones Embarazo Alergia a la droga
Insuficiencia renal con clearence menor 30 ml/h Precauciones Patologías con hipereninemia (estenosis renal bilateral) Asma bronquial Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

22 Interacciones Diuréticos ahorradores de K+ Suplementos de K+
Beta bloqueantes AINEs Probenecid Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

23 Antagonistas de angiotensina II
Treatment of Heart Failure. Angiotensin Converting-Enzyme Inhibitors (ACEI) : Advantages In class II-IV heart failure patients treated with diuretics and digitalis, ACE-inhibitors decrease symptoms, improve hemodynamics and functional class, and increase exercise tolerance. Additionally, they reduce left ventricular dimensions, improve the cardiothoracic index, improve renal function, and improve hyponatremia. More importantly, ACE-inhibitors are the best drugs to date for preventing expansion and dilatation of the left ventricle post infarction, thereby decreasing the number and duration of hospitalizations, and improving symptoms and survival. They also retard progression to heart failure in patients with asymptomatic ventricular dysfunction. ACE-inhibitors differ from other vasodilators in that they do not produce neurohormonal activation or reflex tachycardia, and tolerance to these agents does not seem to develop over time. ACE-inhibitors increase plasma renin, bradykinin, and angiotensin I activities, and reduce plasma and tissue levels of angiotensin II, and plasma levels of aldosterone and cortisol. ACE-inhibitors can also decrease plasma norepinephrine levels, especially after long-term therapy, which has been attributed to the suppression of the stimulating effect angiotensin II has on the synthesis and release of norepinephrine. ACE-inhibitors also reduce arginine-vasopressin levels.

24 Orígen y Química Losartán N CL OH n-Bu N N-Benzilimidazol, derivado
del ácido talamic Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%. K+ N N N N

25 INHIBIDORES DE ANGIOTENSINA II Angiotensina I ANGIOTENSINA II
Farmacodinamia RENINA Angiotensinógeno Angiotensina I ANGIOTENSINA II ECA Otras vías BLOQUEANTES RECEPTORES AT1 Treatment of congestive heart failure. Angiotensin II inhibitors Angiotensin II has different effects mediated via specific receptors. There are two types of tissue receptors for angiotensin: AT1 and AT2. Stimulation of AT1 receptors has a proliferative and vasoconstrictor effect, while stimulation of AT2 receptors has the opposite effects, that is, vasodilatory and antiproliferative. In the treatment of heart failure, specific blockade of the AT1 receptors is desirable. Drugs which create a selective and competitive block of the AT1 receptors include:losartan, valsartan, irbersartan and candersartan. RECEPTORES AT1 AT2 Vasoconstricción Acción Proliferativa Vasodilatación Acción Antiproliferativa

26 Clasificación Losartan (Cozaarex , losacor) 12.5-25-50-100 mgs
Candesartan (Atacand, tyadil, dacten) 8 mg y 16 mg Valsartan (Diovan) 80mg- 160 mg Irbersartan (Aprovel) Telmisartan (Micardis, Gliosartan, Pritor) Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

27 Farmacocinética Losartán: Absorción oral, biodisponibilidad 65%
- No modificación con alimentos - Vida media 2hs, persisten 8-12hs - Eliminación renal 40% activo, resto inactivo. -Efecto antihipertensivo máximo: 3-6 semanas - Dosis: HTA: 50 mgs ICC: mg Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

28 Indicaciones Precauciones
Insuficiencia cardíaca En ptes que no toleran IECA Combinación IECA +Bloq AT1 disminuye hospitalizaciones y calidad de vida Hipertensión arterial Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%. Precauciones Depleción de Na+ o volumen

29 Contraindicaciones Hipersensibilidad Embarazo Lactancia
Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

30 Efectos colaterales Hipotensión arterial Mareos
Alteraciones cutáneas: exantema,prurito Gastrointestinales: diarrea, valores elevados de TGP Músculo-esqueléticas: mialgias SNervioso: migraña Tos Hiperkalemia Descenso ácido úrico Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

31 Interacciones Diuréticos ahorradores de K+ Suplementos de potasio
Sales con K Treatment of Heart Failure Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.

32 Muchas Gracias Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibits (ACEI) Indications. ACE-inhibitors probably constitute the cornerstone of drug therapy for heart failure, in that administration over time leads to amelioration of symptoms, beneficial hemodynamic changes, increased functional capacity, regression of structural changes, and, unequivocally, prolongation of survival. Thus, ACE-inhibitors are first-line therapy, not only in symptomatic heart failure patients, but also in patients with asymptomatic left ventricular dysfunction. The exact degree of ventricular dysfunction below which it is advisable to begin therapy with an ACE-inhibitor has not been defined; however, in general terms they can be helpful in patients with ejection fractions less than 35%.