! PHYSIOLOGY OF MUSCLE CONTRACTION " $ ( the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Action potential the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized "pace- maker" cells located in the sinoatrial (SA), and atrioventricular (AV) nodes.
The cardiac cells also have an unusually long action potential, which can be divided into five phases , }
u Cardiac contraction } The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. j % Sources of free intracellular calcium & & ( " The first is from outside the cell, where opening of voltage-sensitive calcium channels causes an immediate rise in free cytosolic calcium.
The second source is the release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium > y @ 9
! Removal of free cytosolic calcium " " ( If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. ! Removal of free cytosolic calcium " " ( \ Sodium-calcium exchange:
Uptake of calcium by the sarcoplasmic reticulum and mitochondria: 3 , Compensatory physiological responses in CHF - - ( K Increased sympathetic activity:
Fluid retention:
Myocardial hypertrophy:
Decompensated heart failure
g If the adaptive mechanisms fail to maintain cardiac output, the heart failure is termed decompensated. X
Therapeutic strategies in CHF reduction in physical activity,
low dietary intake of sodium
and treatment with vasodilators, diuretics and inotropic agents. n
VASODILATORS Preload is the volume of blood that fills the ventricle during diastole.
Afterload is the pressure that must be overcome for the heart to pump blood into the arterial system.
Vasodilators are useful in reducing excessive preload and afterload. , J
/ Angiotensin converting enzyme (ACE) inhibitors 0 0 ( % drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II .
These agents also diminish the rate of bradykinin inactivation.
ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. P $ ' -
> 6 Actions on heart y ACE inhibitors decrease vascular resistance, venous tone, and blood pressure, resulting in an increased car- diac output m
ACE inhibitors may be considered for single-agent therapy in patients who present with mild dyspnea on exertion and who do not show signs or symptoms of volume overload.
ACE inhibitors are useful in decreasing CHF in asymptomatic patients with ejection fraction less than 35% \ Adverse effects These include postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough. The potential of symptomatic hypotension with ACE inhibitor therapy requires careful monitoring. 9
DIURETICS 3 Diuretics relieve pulmonary congestion and peripheral edema.
Diuretics decrease plasma volume and subsequently decrease venous return to the heart (preload). This decreases the cardiac workload and oxygen demand. Diuretics also decrease afterload by reducing plasma volume, thus decreasing blood pressure. 4 Z 4 = INOTROPIC DRUGS Digitalis : most of the drugs come from the digitalis (foxglove) plant. They are a group of chemically similar compounds that can increase the contractility of the heart muscle and are therefore widely used in treating heart failure. h Mode of action Regulation of cytosolic calcium concentration: Cardiac glycosides combine reversibly with the sodium-potassium ATPase of the cardiac cell membrane resulting in an inhibition of pump activity. , X L Mode of action { Increased contractility of the cardiac: Administration of digitalis glycosides increases the force of cardiac contractility Therapeutic uses Digoxin therapy is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy.
Digoxin is not indicated in patients with diastolic or right-sided heart failure. 6 u L Pharmacokinetics These drugs are absorbed after oral administration.
a large volume of distribution.
Digoxin has the advantage of a relatively short half-life,
Digoxin also has a more rapid onset of action, B V 5 ( Adverse effects can often be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels, and if indicated, by giving potassium supplements.
In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.
Digoxin levels must be monitored in the presence of renal insufficiency and dosage adjustment may be necessary.
Severe toxicity resulting in ventricular tachycardia . Z 6 Adverse effects 9 Cardiac effects: more severe dysrhythmia, moving from decreased or blocked atrioventricular nodal conduction, paroxysmal supraventricular tachycardia, to the conversion of atrial flutter to atrial fibrillation, premature ventricular depolarization, ventricular fibrillation, and finally, to complete heart block. : Z : l # # u Gastrointestinal effects Anorexia, nausea, and vomiting ! CNS effects < These include headache, fatigue, confusion, blurred vision, < " * Factors predisposing to digitalis toxicity * Electrolytic disturbances: Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics,
Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. Z {
( # * Factors predisposing to digitalis toxicity * Drugs: Quinidine can cause digitalis intoxication
Verapamil also displaces digitalis from plasma protein binding sites and can increase digoxin levels by 50 to 75%; d # D $ Beta-Adrenergic agonists beta-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digitalis. Z E
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p p ) & Treatment of Congestive Heart Failure
% OVERVIEW OF CONGESTIVE HEART FAILURE & $ ( Congestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of the body. CHF can be caused by an impaired ability of the cardiac muscle to contract or by an increased workload imposed on the heart. Three classes of drugs 1) vasodilators that reduce the load on the myocardium;
2) diuretic agents that decrease extracellular fluid volume;
3) inotropic agents that increase the strength of contraction of cardiac , Z
> ! PHYSIOLOGY OF MUSCLE CONTRACTION " $ ( the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Action potential the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized "pace- maker" cells located in the sinoatrial (SA), and atrioventricular (AV) nodes.
The cardiac cells also have an unusually long action potential, which can be divided into five phases , }
u Cardiac contraction } The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. j % Sources of free intracellular calcium & & ( " The first is from outside the cell, where opening of voltage-sensitive calcium channels causes an immediate rise in free cytosolic calcium.
The second source is the release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium > y @ 9
! Removal of free cytosolic calcium " " ( If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. ! Removal of free cytosolic calcium " " ( \ Sodium-calcium exchange:
Uptake of calcium by the sarcoplasmic reticulum and mitochondria: 3 , Compensatory physiological responses in CHF - - ( K Increased sympathetic activity:
Fluid retention:
Myocardial hypertrophy:
Decompensated heart failure
g If the adaptive mechanisms fail to maintain cardiac output, the heart failure is termed decompensated. X
Therapeutic strategies in CHF reduction in physical activity,
low dietary intake of sodium
and treatment with vasodilators, diuretics and inotropic agents. n
VASODILATORS Preload is the volume of blood that fills the ventricle during diastole.
Afterload is the pressure that must be overcome for the heart to pump blood into the arterial system.
Vasodilators are useful in reducing excessive preload and afterload. , J
/ Angiotensin converting enzyme (ACE) inhibitors 0 0 ( % drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II .
These agents also diminish the rate of bradykinin inactivation.
ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. P $ ' -
> 6 Actions on heart y ACE inhibitors decrease vascular resistance, venous tone, and blood pressure, resulting in an increased car- diac output m
ACE inhibitors may be considered for single-agent therapy in patients who present with mild dyspnea on exertion and who do not show signs or symptoms of volume overload.
ACE inhibitors are useful in decreasing CHF in asymptomatic patients with ejection fraction less than 35% \ Adverse effects These include postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough. The potential of symptomatic hypotension with ACE inhibitor therapy requires careful monitoring. 9
DIURETICS 3 Diuretics relieve pulmonary congestion and peripheral edema.
Diuretics decrease plasma volume and subsequently decrease venous return to the heart (preload). This decreases the cardiac workload and oxygen demand. Diuretics also decrease afterload by reducing plasma volume, thus decreasing blood pressure. 4 Z 4 = INOTROPIC DRUGS Digitalis : most of the drugs come from the digitalis (foxglove) plant. They are a group of chemically similar compounds that can increase the contractility of the heart muscle and are therefore widely used in treating heart failure. h Mode of action Regulation of cytosolic calcium concentration: Cardiac glycosides combine reversibly with the sodium-potassium ATPase of the cardiac cell membrane resulting in an inhibition of pump activity. , X L Mode of action { Increased contractility of the cardiac: Administration of digitalis glycosides increases the force of cardiac contractility Therapeutic uses Digoxin therapy is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy.
Digoxin is not indicated in patients with diastolic or right-sided heart failure. 6 u L Pharmacokinetics These drugs are absorbed after oral administration.
a large volume of distribution.
Digoxin has the advantage of a relatively short half-life,
Digoxin also has a more rapid onset of action, B V 5 ( Adverse effects can often be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels, and if indicated, by giving potassium supplements.
In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.
Digoxin levels must be monitored in the presence of renal insufficiency and dosage adjustment may be necessary.
Severe toxicity resulting in ventricular tachycardia . Z 6 Adverse effects 9 Cardiac effects: more severe dysrhythmia, moving from decreased or blocked atrioventricular nodal conduction, paroxysmal supraventricular tachycardia, to the conversion of atrial flutter to atrial fibrillation, premature ventricular depolarization, ventricular fibrillation, and finally, to complete heart block. : Z : l # # u Gastrointestinal effects Anorexia, nausea, and vomiting ! CNS effects < These include headache, fatigue, confusion, blurred vision, < " * Factors predisposing to digitalis toxicity * Electrolytic disturbances: Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics,
Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. Z {
( # * Factors predisposing to digitalis toxicity * Drugs: Quinidine can cause digitalis intoxication
Verapamil also displaces digitalis from plasma protein binding sites and can increase digoxin levels by 50 to 75%; d # D $ Beta-Adrenergic agonists beta-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digitalis. Z E
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p p ) & Treatment of Congestive Heart Failure
% OVERVIEW OF CONGESTIVE HEART FAILURE & $ ( Congestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of the body. CHF can be caused by an impaired ability of the cardiac muscle to contract or by an increased workload imposed on the heart. Three classes of drugs 1) vasodilators that reduce the load on the myocardium;
2) diuretic agents that decrease extracellular fluid volume;
3) inotropic agents that increase the strength of contraction of cardiac , Z
> ! PHYSIOLOGY OF MUSCLE CONTRACTION " $ ( the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Action potential the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized "pace- maker" cells located in the sinoatrial (SA), and atrioventricular (AV) nodes.
The cardiac cells also have an unusually long action potential, which can be divided into five phases , }
u Cardiac contraction } The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. j % Sources of free intracellular calcium & & ( " The first is from outside the cell, where opening of voltage-sensitive calcium channels causes an immediate rise in free cytosolic calcium.
The second source is the release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium > y @ 9
! Removal of free cytosolic calcium " " ( If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. ! Removal of free cytosolic calcium " " ( \ Sodium-calcium exchange:
Uptake of calcium by the sarcoplasmic reticulum and mitochondria: 3 , Compensatory physiological responses in CHF - - ( K Increased sympathetic activity:
Fluid retention:
Myocardial hypertrophy:
Decompensated heart failure
g If the adaptive mechanisms fail to maintain cardiac output, the heart failure is termed decompensated. X
Therapeutic strategies in CHF reduction in physical activity,
low dietary intake of sodium
and treatment with vasodilators, diuretics and inotropic agents. n
VASODILATORS Preload is the volume of blood that fills the ventricle during diastole.
Afterload is the pressure that must be overcome for the heart to pump blood into the arterial system.
Vasodilators are useful in reducing excessive preload and afterload. , J
/ Angiotensin converting enzyme (ACE) inhibitors 0 0 ( % drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II .
These agents also diminish the rate of bradykinin inactivation.
ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. P $ ' -
> 6 Actions on heart y ACE inhibitors decrease vascular resistance, venous tone, and blood pressure, resulting in an increased car- diac output m
ACE inhibitors may be considered for single-agent therapy in patients who present with mild dyspnea on exertion and who do not show signs or symptoms of volume overload.
ACE inhibitors are useful in decreasing CHF in asymptomatic patients with ejection fraction less than 35% \ Adverse effects These include postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough. The potential of symptomatic hypotension with ACE inhibitor therapy requires careful monitoring. 9
DIURETICS 3 Diuretics relieve pulmonary congestion and peripheral edema.
Diuretics decrease plasma volume and subsequently decrease venous return to the heart (preload). This decreases the cardiac workload and oxygen demand. Diuretics also decrease afterload by reducing plasma volume, thus decreasing blood pressure. 4 Z 4 = INOTROPIC DRUGS Digitalis : most of the drugs come from the digitalis (foxglove) plant. They are a group of chemically similar compounds that can increase the contractility of the heart muscle and are therefore widely used in treating heart failure. h Mode of action Regulation of cytosolic calcium concentration: Cardiac glycosides combine reversibly with the sodium-potassium ATPase of the cardiac cell membrane resulting in an inhibition of pump activity. , X L Mode of action { Increased contractility of the cardiac: Administration of digitalis glycosides increases the force of cardiac contractility Therapeutic uses Digoxin therapy is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy.
Digoxin is not indicated in patients with diastolic or right-sided heart failure. 6 u L Pharmacokinetics These drugs are absorbed after oral administration.
a large volume of distribution.
Digoxin has the advantage of a relatively short half-life,
Digoxin also has a more rapid onset of action, B V 5 ( Adverse effects can often be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels, and if indicated, by giving potassium supplements.
In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.
Digoxin levels must be monitored in the presence of renal insufficiency and dosage adjustment may be necessary.
Severe toxicity resulting in ventricular tachycardia . Z 6 Adverse effects 9 Cardiac effects: more severe dysrhythmia, moving from decreased or blocked atrioventricular nodal conduction, paroxysmal supraventricular tachycardia, to the conversion of atrial flutter to atrial fibrillation, premature ventricular depolarization, ventricular fibrillation, and finally, to complete heart block. : Z : l # # u Gastrointestinal effects Anorexia, nausea, and vomiting ! CNS effects < These include headache, fatigue, confusion, blurred vision, < " * Factors predisposing to digitalis toxicity * Electrolytic disturbances: Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics,
Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. Z {
( # * Factors predisposing to digitalis toxicity * Drugs: Quinidine can cause digitalis intoxication
Verapamil also displaces digitalis from plasma protein binding sites and can increase digoxin levels by 50 to 75%; d # D $ Beta-Adrenergic agonists beta-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digitalis. Z E
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p p ) & Treatment of Congestive Heart Failure
% OVERVIEW OF CONGESTIVE HEART FAILURE & $ ( Congestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of the body. CHF can be caused by an impaired ability of the cardiac muscle to contract or by an increased workload imposed on the heart. Three classes of drugs 1) vasodilators that reduce the load on the myocardium;
2) diuretic agents that decrease extracellular fluid volume;
3) inotropic agents that increase the strength of contraction of cardiac , Z
> ! PHYSIOLOGY OF MUSCLE CONTRACTION " $ ( the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Action potential the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized "pace- maker" cells located in the sinoatrial (SA), and atrioventricular (AV) nodes.
The cardiac cells also have an unusually long action potential, which can be divided into five phases , }
u Cardiac contraction } The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. j % Sources of free intracellular calcium & & ( " The first is from outside the cell, where opening of voltage-sensitive calcium channels causes an immediate rise in free cytosolic calcium.
The second source is the release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium > y @ 9
! Removal of free cytosolic calcium " " ( If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. ! Removal of free cytosolic calcium " " ( \ Sodium-calcium exchange:
Uptake of calcium by the sarcoplasmic reticulum and mitochondria: 3 , Compensatory physiological responses in CHF - - ( K Increased sympathetic activity:
Fluid retention:
Myocardial hypertrophy:
Decompensated heart failure
g If the adaptive mechanisms fail to maintain cardiac output, the heart failure is termed decompensated. X
Therapeutic strategies in CHF reduction in physical activity,
low dietary intake of sodium
and treatment with vasodilators, diuretics and inotropic agents. n
VASODILATORS Preload is the volume of blood that fills the ventricle during diastole.
Afterload is the pressure that must be overcome for the heart to pump blood into the arterial system.
Vasodilators are useful in reducing excessive preload and afterload. , J
/ Angiotensin converting enzyme (ACE) inhibitors 0 0 ( % drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II .
These agents also diminish the rate of bradykinin inactivation.
ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. P $ ' -
> 6 Actions on heart y ACE inhibitors decrease vascular resistance, venous tone, and blood pressure, resulting in an increased car- diac output m
ACE inhibitors may be considered for single-agent therapy in patients who present with mild dyspnea on exertion and who do not show signs or symptoms of volume overload.
ACE inhibitors are useful in decreasing CHF in asymptomatic patients with ejection fraction less than 35% \ Adverse effects These include postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough. The potential of symptomatic hypotension with ACE inhibitor therapy requires careful monitoring. 9
DIURETICS 3 Diuretics relieve pulmonary congestion and peripheral edema.
Diuretics decrease plasma volume and subsequently decrease venous return to the heart (preload). This decreases the cardiac workload and oxygen demand. Diuretics also decrease afterload by reducing plasma volume, thus decreasing blood pressure. 4 Z 4 = INOTROPIC DRUGS Digitalis : most of the drugs come from the digitalis (foxglove) plant. They are a group of chemically similar compounds that can increase the contractility of the heart muscle and are therefore widely used in treating heart failure. h Mode of action Regulation of cytosolic calcium concentration: Cardiac glycosides combine reversibly with the sodium-potassium ATPase of the cardiac cell membrane resulting in an inhibition of pump activity. , X L Mode of action { Increased contractility of the cardiac: Administration of digitalis glycosides increases the force of cardiac contractility Therapeutic uses Digoxin therapy is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy.
Digoxin is not indicated in patients with diastolic or right-sided heart failure. 6 u L Pharmacokinetics These drugs are absorbed after oral administration.
a large volume of distribution.
Digoxin has the advantage of a relatively short half-life,
Digoxin also has a more rapid onset of action, B V 5 ( Adverse effects can often be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels, and if indicated, by giving potassium supplements.
In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.
Digoxin levels must be monitored in the presence of renal insufficiency and dosage adjustment may be necessary.
Severe toxicity resulting in ventricular tachycardia . Z 6 Adverse effects 9 Cardiac effects: more severe dysrhythmia, moving from decreased or blocked atrioventricular nodal conduction, paroxysmal supraventricular tachycardia, to the conversion of atrial flutter to atrial fibrillation, premature ventricular depolarization, ventricular fibrillation, and finally, to complete heart block. : Z : l # # u Gastrointestinal effects Anorexia, nausea, and vomiting ! CNS effects < These include headache, fatigue, confusion, blurred vision, < " * Factors predisposing to digitalis toxicity * Electrolytic disturbances: Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics,
Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. Z {
( # * Factors predisposing to digitalis toxicity * Drugs: Quinidine can cause digitalis intoxication
Verapamil also displaces digitalis from plasma protein binding sites and can increase digoxin levels by 50 to 75%; d # D $ Beta-Adrenergic agonists beta-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digitalis. Z E
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p p ) & Treatment of Congestive Heart Failure
% OVERVIEW OF CONGESTIVE HEART FAILURE & $ ( Congestive heart failure (CHF) is a condition in which the heart is unable to pump sufficient blood to meet the needs of the body. CHF can be caused by an impaired ability of the cardiac muscle to contract or by an increased workload imposed on the heart. Three classes of drugs 1) vasodilators that reduce the load on the myocardium;
2) diuretic agents that decrease extracellular fluid volume;
3) inotropic agents that increase the strength of contraction of cardiac , Z
> ! PHYSIOLOGY OF MUSCLE CONTRACTION " $ ( the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Action potential the cells of cardiac muscle show a spontaneous, intrinsic rhythm generated by specialized "pace- maker" cells located in the sinoatrial (SA), and atrioventricular (AV) nodes.
The cardiac cells also have an unusually long action potential, which can be divided into five phases , }
u Cardiac contraction } The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. j % Sources of free intracellular calcium & & ( " The first is from outside the cell, where opening of voltage-sensitive calcium channels causes an immediate rise in free cytosolic calcium.
The second source is the release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium > y @ 9
! Removal of free cytosolic calcium " " ( If free cytosolic calcium levels were to remain high, the cardiac muscle would be in a constant state of contraction, rather than showing a periodic contraction. Mechanisms of removal include two alternatives. ! Removal of free cytosolic calcium " " ( \ Sodium-calcium exchange:
Uptake of calcium by the sarcopla
smic reticulum and mitochondria: 3 , Compensatory physiological responses in CHF - - ( K Increased sympathetic activity:
Fluid retention:
Myocardial hypertrophy:
Decompensated heart failure
g If the adaptive mechanisms fail to maintain cardiac output, the heart failure is termed decompensated. X
Therapeutic strategies in CHF reduction in physical activity,
low dietary intake of sodium
and treatment with vasodilators, diuretics and inotropic agents. n
VASODILATORS Preload is the volume of blood that fills the ventricle during diastole.
Afterload is the pressure that must be overcome for the heart to pump blood into the arterial system.
Vasodilators are useful in reducing excessive preload and afterload. , J
/ Angiotensin converting enzyme (ACE) inhibitors 0 0 ( % drugs block the enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II .
These agents also diminish the rate of bradykinin inactivation.
ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. P $ ' -
> 6 Actions on heart y ACE inhibitors decrease vascular resistance, venous tone, and blood pressure, resulting in an increased car- diac output m
ACE inhibitors may be considered for single-agent therapy in patients who present with mild dyspnea on exertion and who do not show signs or symptoms of volume overload.
ACE inhibitors are useful in decreasing CHF in asymptomatic patients with ejection fraction less than 35% \ Adverse effects These include postural hypotension, renal insufficiency, hyperkalemia, and a persistent dry cough. The potential of symptomatic hypotension with ACE inhibitor therapy requires careful monitoring. 9
DIURETICS 3 Diuretics relieve pulmonary congestion and peripheral edema.
Diuretics decrease plasma volume and subsequently decrease venous return to the heart (preload). This decreases the cardiac workload and oxygen demand. Diuretics also decrease afterload by reducing plasma volume, thus decreasing blood pressure. 4 Z 4 = INOTROPIC DRUGS Digitalis : most of the drugs come from the digitalis (foxglove) plant. They are a group of chemically similar compounds that can increase the contractility of the heart muscle and are therefore widely used in treating heart failure. h Mode of action Regulation of cytosolic calcium concentration: Cardiac glycosides combine reversibly with the sodium-potassium ATPase of the cardiac cell membrane resulting in an inhibition of pump activity. , X L Mode of action { Increased contractility of the cardiac: Administration of digitalis glycosides increases the force of cardiac contractility Therapeutic uses Digoxin therapy is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy.
Digoxin is not indicated in patients with diastolic or right-sided heart failure. 6 u L Pharmacokinetics These drugs are absorbed after oral administration.
a large volume of distribution.
Digoxin has the advantage of a relatively short half-life,
Digoxin also has a more rapid onset of action, B V 5 ( Adverse effects can often be managed by discontinuing cardiac glycoside therapy, determining serum potassium levels, and if indicated, by giving potassium supplements.
In general, decreased serum levels of potassium predispose a patient to digoxin toxicity.
Digoxin levels must be monitored in the presence of renal insufficiency and dosage adjustment may be necessary.
Severe toxicity resulting in ventricular tachycardia . Z 6 Adverse effects 9 Cardiac effects: more severe dysrhythmia, moving from decreased or blocked atrioventricular nodal conduction, paroxysmal supraventricular tachycardia, to the conversion of atrial flutter to atrial fibrillation, premature ventricular depolarization, ventricular fibrillation, and finally, to complete heart block. : Z : l # # u Gastrointestinal effects Anorexia, nausea, and vomiting ! CNS effects < These include headache, fatigue, confusion, blurred vision, < " * Factors predisposing to digitalis toxicity * Electrolytic disturbances: Hypokalemia can precipitate serious arrhythmia. Reduction of serum potassium levels is most frequently observed in patients receiving thiazide or loop diuretics,
Hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. Z {
( # * Factors predisposing to digitalis toxicity * Drugs: Quinidine can cause digitalis intoxication
Verapamil also displaces digitalis from plasma protein binding sites and can increase digoxin levels by 50 to 75%; d # D $ Beta-Adrenergic agonists beta-Adrenergic stimulation improves cardiac performance by positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digitalis. Z E
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de of action Therapeutic uses Pharmacokinetics Adverse effects Adverse effects Gastrointestinal effects
CNS effects + Factors predisposing to digitalis toxicity + _缿 d 微软用户 甠o(u7b Factors predisposing to digitalis toxicity Beta-Adrenergic agonists
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