Cardiac therapy Beta Blocking Agents- Ettinger Flashcards
(25 cards)
BB can be selective β1 receptor antagonists (e.g., …………., metoprolol, bisoprolol, …………………),
nonselective β1 and β2 antagonists (e.g., ………………..)
or act as a partial β1 agonists (pindolol).
Some newer agents offer more comprehensive adrenergic blockade (β1, β2, α1 antagonism) and additional ancillary properties such as free radical scavenging (e.g., ……………..)
BB can be selective β1 receptor antagonists (e.g., atenolol, metoprolol, bisoprolol, esmolol),
nonselective β1 and β2 antagonists (e.g., propranolol)
or act as a partial β1 agonists (pindolol).
Some newer agents offer more comprehensive adrenergic blockade (β1, β2, α1 antagonism) and additional ancillary properties such as free radical scavenging (e.g., carvedilol)
As a class, BB have multimodal effects and are used alone or in combination with other pharmacologic agents for the treatment of a variety of feline and canine cardiovascular diseases (Box 239-1). Historically, BB were considered indirect positive ………………., class…….antiarrhythmics, and ……………….agents. There is now a large body of literature demonstrating their beneficial role as ………………. modulators in the treatment of heart disease and heart failure
As a class, BB have multimodal effects and are used alone or in combination with other pharmacologic agents for the treatment of a variety of feline and canine cardiovascular diseases (Box 239-1). Historically, BB were considered indirect positive lusiotropes, class II antiarrhythmics, and sympatholytic agents. There is now a large body of literature demonstrating their beneficial role as neuroendocrine modulators in the treatment of heart disease and heart failure
All BB have the potential to improve ventricular ……………… indirectly by slowing heart rate, but unlike diltiazem they do not ………………… improve ventricular relaxation and actually indirectly slow ventricular relaxation.
The indirect positive ………………. properties of BB are primarily useful in the treatment of diseases characterized by ………………… ventricular hypertrophy such as ………………. (feline), and congenital …………..and……………..(canine).
All BB have the potential to improve ventricular relaxation indirectly by slowing heart rate, but unlike diltiazem they do not directly improve ventricular relaxation and actually indirectly slow ventricular relaxation.
The indirect positive lusiotropic properties of BB are primarily useful in the treatment of diseases characterized by concentric ventricular hypertrophy such as hypertrophic cardiomyopathy (feline), and congenital subaortic and pulmonic stenosis (canine).
In some disease conditions such as hypertrophic obstructive cardiomyopathy (feline), congenital subaortic and pulmonic stenosis (canine) and congenital mitral valve dysplasia with dynamic outflow tract obstruction (canine), augmentation (exercise, stress, excitement) of ………………………………. …………. can be deleterious. This effect may be ameliorated by chronic β-blockade.
Some etiologies of systemic arterial hypertension may likewise be exacerbated by elevated …………………system tone and patients may therefore benefit from β-blockade typically in combination with other antihypertensive therapies.
Clinical signs associated with diseases such as …………and ……………………… may be partially palliated by β-blockade alone or by more comprehensive adrenergic blockade respectively. Comprehensive adrenergic blockade may be achieved with ………….or a combination of ……………….. and prazosin (α1-receptor blocker).
In some disease conditions such as hypertrophic obstructive cardiomyopathy (feline), congenital subaortic and pulmonic stenosis (canine) and congenital mitral valve dysplasia with dynamic outflow tract obstruction (canine), augmentation (exercise, stress, excitement) of sympathetic nervous system tone can be deleterious. This effect may be ameliorated by chronic β-blockade.
Some etiologies of systemic arterial hypertension may likewise be exacerbated by elevated sympathetic nervous system tone and patients may therefore benefit from β-blockade typically in combination with other antihypertensive therapies.
Clinical signs associated with diseases such as hyperthyroidism and pheochromocytoma may be partially palliated by β-blockade alone or by more comprehensive adrenergic blockade respectively. Comprehensive adrenergic blockade may be achieved with carvedilol or a combination of propranolol and prazosin (α1-receptor blocker).
Beta blocking agents are Class …..antiarrhythmic drugs and are useful for treatment of both supraventricular (including sinus tachycardia) and ventricular tachyarrhythmias.
Sympathetic nervous system stimulation does not cause the majority of arrhythmias but it can exacerbate preexisting arrhythmias. This can be minimized by β-blockade.
BB are commonly used to slow ventricular response rates in supraventricular tachyarrhythmias (e.g., atrial fibrillation) by slowing …………………. conduction. BB are used most commonly in combination with other antiarrhythmic agents for the treatment of both ventricular and supraventricular tachyarrhythmias. Sinus tachycardia can potentate clinical signs associated with a variety of diseases such as hypertrophic obstructive cardiomyopathy (feline), congenital subaortic and pulmonic stenosis (canine) and congenital mitral valve dysplasia with dynamic outflow tract obstruction (canine). Frequently BB are efficacious as monotherapy in the treatment or prevention of sinus tachycardia.
Beta blocking agents are Class II antiarrhythmic drugs and are useful for treatment of both supraventricular (including sinus tachycardia) and ventricular tachyarrhythmias. Sympathetic nervous system stimulation does not cause the majority of arrhythmias but it can exacerbate preexisting arrhythmias. This can be minimized by β-blockade.
BB are commonly used to slow ventricular response rates in supraventricular tachyarrhythmias (e.g., atrial fibrillation) by slowing atrioventricular conduction. BB are used most commonly in combination with other antiarrhythmic agents for the treatment of both ventricular and supraventricular tachyarrhythmias. Sinus tachycardia can potentate clinical signs associated with a variety of diseases such as hypertrophic obstructive cardiomyopathy (feline), congenital subaortic and pulmonic stenosis (canine) and congenital mitral valve dysplasia with dynamic outflow tract obstruction (canine). Frequently BB are efficacious as monotherapy in the treatment or prevention of sinus tachycardia.
Neuroendocrine modulators address the maladaptive changes in the progression of heart disease and heart failure associated with chronic activation of the renin angiotensin aldosterone and sympathetic nervous systems. The sympatholytic effects of BB confer them membership in this growing class
Neuroendocrine modulators address the maladaptive changes in the progression of heart disease and heart failure associated with chronic activation of the renin angiotensin aldosterone and sympathetic nervous systems. The sympatholytic effects of BB confer them membership in this growing class
Catecholamines have been shown to reduce viability and ……………….. synthesis in isolated adult human cardiomyocytes, offering insight into one potential mechanism for impaired systolic function in both CVD and DCM
Catecholamines have been shown to reduce viability and protein synthesis in isolated adult human cardiomyocytes, offering insight into one potential mechanism for impaired systolic function in both CVD and DCM
The reported beneficial effects of gradual β-blockade are not immediate upon initiation of therapy. In fact in the short-term, the …………..and…………………. properties of these agents make decompensation a relative risk and mandate gradual initiation of therapy in the form of an up-titration protocol. However, improved systolic function and left ventricular remodeling have been demonstrated in every human study greater than 3 months in duration
The reported beneficial effects of gradual β-blockade are not immediate upon initiation of therapy. In fact in the short-term, the negative inotropic and chronotropic properties of these agents make decompensation a relative risk and mandate gradual initiation of therapy in the form of an up-titration protocol. However, improved systolic function and left ventricular remodeling have been demonstrated in every human study greater than 3 months in duration
Early evaluations of β-blockade for the treatment of heart failure focused on second-generation β1-selective agents (metoprolol, atenolol) to avoid increases in ……………….. characteristic of nonselective β-blockade.
However, …… and …….. receptors are present in the myocardium and both are important in mediating adrenergic effects in cardiomyocytes. Additionally, in human heart failure, cardiac …….receptors are down-regulated while …….. receptor numbers remain unchanged. This relative increase in β2 receptors means more comprehensive cardiac adrenergic blockade can be achieved with the use of nonselective β-blockers. Nonselective β-blockade may also be achieved with high-dose ……………agents
Early evaluations of β-blockade for the treatment of heart failure focused on second-generation β1-selective agents (metoprolol, atenolol) to avoid increases in afterload characteristic of nonselective β-blockade.
However, β1 and β2 receptors are present in the myocardium and both are important in mediating adrenergic effects in cardiomyocytes. Additionally, in human heart failure, cardiac β1 receptors are down-regulated while β2 receptor numbers remain unchanged. This relative increase in β2 receptors means more comprehensive cardiac adrenergic blockade can be achieved with the use of nonselective β-blockers. Nonselective β-blockade may also be achieved with high-dose β1 selective agents
Carvedilol is a third generation …………. β-blocker with ……………blocking properties and ancillary …………… effects, and thus combines the potential benefit of a …………………. β-blockade with the …………….. effects of an ………..-blocker. Additionally, the …………………….. properties may reduce the oxidative stress associated with progressive heart failure.
Carvedilol is a third generation nonselective β-blocker with α1-blocking properties and ancillary antioxidant effects, and thus combines the potential benefit of a nonselective β-blockade with the vasodilatory effects of an α1-blocker. Additionally, the antioxidant properties may reduce the oxidative stress associated with progressive heart failure.
High dose atenolol (2 to 5 mg/kg PO q24h), a second generation selective BB, improved left ventricular (LV) function in an experimental canine model of chronic MR. The improvement was associated with enhanced innate contractile function of isolated cardiomyocytes owing to an increase in the absolute number of contractile elements
High dose atenolol (2 to 5 mg/kg PO q24h), a second generation selective BB, improved left ventricular (LV) function in an experimental canine model of chronic MR. The improvement was associated with enhanced innate contractile function of isolated cardiomyocytes owing to an increase in the absolute number of contractile elements
The LV work associated with MR represents a model of pure volume overload because the excess volume is ejected into the relatively low pressure of the left atrium (reduced afterload). In contrast, LV work associated with other forms of volume overload such as aortic insufficiency represents a combination of pressure and volume overload because the LV ejects the excess volume against relatively high aortic diastolic pressures (normal afterload). Although patients with chronic MR develop compensatory LV remodeling in the form of eccentric hypertrophy (dilation), the hypertrophic response is reportedly inadequate. This contributes to increased LV wall stress with commensurate increases in myocardial oxygen consumption. Research suggests that inadequate hypertrophy is the result of the relatively low LV afterload in this condition
The LV work associated with MR represents a model of pure volume overload because the excess volume is ejected into the relatively low pressure of the left atrium (reduced afterload). In contrast, LV work associated with other forms of volume overload such as aortic insufficiency represents a combination of pressure and volume overload because the LV ejects the excess volume against relatively high aortic diastolic pressures (normal afterload). Although patients with chronic MR develop compensatory LV remodeling in the form of eccentric hypertrophy (dilation), the hypertrophic response is reportedly inadequate. This contributes to increased LV wall stress with commensurate increases in myocardial oxygen consumption. Research suggests that inadequate hypertrophy is the result of the relatively low LV afterload in this condition
Gradual chronic β-blockade seems to be well tolerated and may delay the development of overt clinical signs of heart failure in asymptomatic MMVD dogs. The relative risk of decompensation associated with β-blockade in dogs with overt or stable heart failure is much higher.
Gradual chronic β-blockade seems to be well tolerated and may delay the development of overt clinical signs of heart failure in asymptomatic MMVD dogs. The relative risk of decompensation associated with β-blockade in dogs with overt or stable heart failure is much higher.
Recently, the hemodynamic effects of the combination of pimobendan and carvedilol in normal dogs were reported.[12] This study suggested that the positive inotropy of pimobendan was preserved and the vasodilatory actions of both were potentiated with no increase in heart rate. This combination of hemodynamic effects may be particularly advantageous in dogs with CVD. The combination of pimobendan and carvedilol or other BB may be particularly well tolerated and have greater benefit than either individual agent in the setting of both preclinical and clinical CVD. Any definitive recommendations regarding BB for the treatment of CVD await adequately powered prospective clinical trials.
Recently, the hemodynamic effects of the combination of pimobendan and carvedilol in normal dogs were reported.[12] This study suggested that the positive inotropy of pimobendan was preserved and the vasodilatory actions of both were potentiated with no increase in heart rate. This combination of hemodynamic effects may be particularly advantageous in dogs with CVD. The combination of pimobendan and carvedilol or other BB may be particularly well tolerated and have greater benefit than either individual agent in the setting of both preclinical and clinical CVD. Any definitive recommendations regarding BB for the treatment of CVD await adequately powered prospective clinical trials.
Cats with cardiomyopathies characterized by concentric hypertrophy, and in particular dynamic outflow tract obstruction, may benefit from chronic β-blockade. However, cats with active heart failure like dogs may not tolerate BB. Any definitive recommendations regarding BB for the treatment of feline cardiomyopathy await adequately powered prospective clinical trials.
Cats with cardiomyopathies characterized by concentric hypertrophy, and in particular dynamic outflow tract obstruction, may benefit from chronic β-blockade. However, cats with active heart failure like dogs may not tolerate BB. Any definitive recommendations regarding BB for the treatment of feline cardiomyopathy await adequately powered prospective clinical trials.
Acutely, all BB are dose-dependant …………………………… and can therefore result in the occurrence of adverse signs suggestive of heart failure following initiation or during up-titration. If this occurs the dose should be reduced to the last tolerated dose (not abruptly discontinued) and therapy for heart failure should be initiated as required based on clinical signs
Acutely, all BB are dose-dependant negative inotropes and can therefore result in the occurrence of adverse signs suggestive of heart failure following initiation or during up-titration. If this occurs the dose should be reduced to the last tolerated dose (not abruptly discontinued) and therapy for heart failure should be initiated as required based on clinical signs
Preexisting bradycardia is a contraindication to β-blockade.
Preexisting bradycardia is a contraindication to β-blockade.
Do not combine BB with other BB, calcium …………… or sotalol (a Class III antiarrhythmic with β-blocking properties).
Do not combine BB with other BB, calcium channel blockers or sotalol (a Class III antiarrhythmic with β-blocking properties).
Serum concentrations required to produce a beneficial effect depends on the prevailing …………….. and ….-adrenergic receptor density and sensitivity. These variables vary widely from patient to patient and are likely different in normal versus diseased states; however, most pharmacokinetic and pharmacodynamic studies are carried out in normal animals.
Serum concentrations required to produce a beneficial effect depends on the prevailing sympathetic tone and β-adrenergic receptor density and sensitivity. These variables vary widely from patient to patient and are likely different in normal versus diseased states; however, most pharmacokinetic and pharmacodynamic studies are carried out in normal animals.
In one normal dog study, a fivefold difference between dogs administered the same dose of oral carvedilol was reported.[13] As a result of this, BB dosage may need to be titrated to an effective endpoint or maximum tolerated target dose in each patient.
In one normal dog study, a fivefold difference between dogs administered the same dose of oral carvedilol was reported.[13] As a result of this, BB dosage may need to be titrated to an effective endpoint or maximum tolerated target dose in each patient.
Clinical side effects can be divided into two primary groups; those affecting the cardiovascular system and those affecting other systems.
Cardiovascular adverse effects?
BB are dose-dependant negative …………….. and ……………….and can cause ……………….. and myocardial ………………..
BB are dose-dependant negative chronotropes and inotropes and can cause bradycardia and myocardial depression.
These effects may result in systemic hypotension and congestive heart failure with commensurate clinical signs: weakness, exercise intolerance, collapse, syncope, cough, orthopnea, tachypnea, dyspnea and even death. Development of these adverse effects is influenced by the underlying disease and is typically dose dependant. Patients with active heart failure and diseases characterized by ventricular systolic dysfunction (e.g., DCM, advanced CVD) are at increased risk. These effects are typically encountered during up-titration of β-blockade and can be minimized by gradual up-titration, dosage adjustments, and the passage of time. Patients receiving chronic β-blockade may have the risk of hypotension and bradycardia increased by anesthesia and may be partially refractory to atropine and dobutamine as well as other sympathomimetics. Thus chronic β-blockade should be considered when designing anesthetic protocols and when troubleshooting anesthetic complications in these patients. In general, patients receiving BB who require inotropic support may respond better to phosphodiesterase III inhibitors (e.g., milrinone, pimobendan) and calcium sensitizers (pimobendan) or glucagon. A final potential adverse cardiovascular effect, tachyarrhythmia and sudden death, may be encountered following abrupt cessation of chronic β-blockade and involves the potentially deleterious effects of an acute increase in β-receptor binding.
Patients receiving chronic β-blockade may have the risk of …………………..and ………………increased by anesthesia and may be partially refractory to ……………and dobutamine as well as other sympathomimetics.
Thus chronic β-blockade should be considered when designing anesthetic protocols and when troubleshooting anesthetic complications in these patients. In general, patients receiving BB who require inotropic support may respond better to ………………………. inhibitors (e.g., milrinone, pimobendan) and calcium sensitizers (…………..) or …………….
A final potential adverse cardiovascular effect, …………………. and sudden death, may be encountered following ……………………………………of chronic β-blockade and involves the potentially deleterious effects of an acute increase in ……………………….. binding.
Patients receiving chronic β-blockade may have the risk of hypotension and bradycardia increased by anesthesia and may be partially refractory to atropine and dobutamine as well as other sympathomimetics. Thus chronic β-blockade should be considered when designing anesthetic protocols and when troubleshooting anesthetic complications in these patients. In general, patients receiving BB who require inotropic support may respond better to phosphodiesterase III inhibitors (e.g., milrinone, pimobendan) and calcium sensitizers (pimobendan) or glucagon.
A final potential adverse cardiovascular effect, tachyarrhythmia and sudden death, may be encountered following abrupt cessation of chronic β-blockade and involves the potentially deleterious effects of an acute increase in β-receptor binding.
Clinically significant adverse effects that may affect other systems most commonly involve ………..-receptor antagonism in the …………….. smooth muscle leading to ……………….. The potential for this adverse effect is heightened in patients with preexisting reactive airway disease (e.g., feline asthma) receiving …………. BB or high dose …………… BB. This is not typically a problem in the majority of canine and feline patients.
Clinically significant adverse effects that may affect other systems most commonly involve β2-receptor antagonism in the bronchial smooth muscle leading to bronchoconstriction. The potential for this adverse effect is heightened in patients with preexisting reactive airway disease (e.g., feline asthma) receiving nonselective BB or high dose selective BB. This is not typically a problem in the majority of canine and feline patients.
Drugs that block β2 receptors should be avoided in diabetic patients. Why?
Drugs that block β2 receptors also limit the ability of patients with diabetes mellitus to respond to …………………………. with ……………………… and may limit …………………….blood flow.
Drugs that block β2 receptors also limit the ability of patients with diabetes mellitus to respond to hypoglycemia with glycogenolysis and may limit hepatic blood flow.
