Cardiac therapy: Calcium Channel Blockers & diuretics- Ettinger Flashcards
(34 cards)
Calcium ions are involved in electrophysiologic processes, link excitation to contraction in cardiac and skeletal muscles, control energy storage and utilization, and constrict vascular smooth muscles in coronary and systemic arteries.
Calcium ions are involved in electrophysiologic processes, link excitation to contraction in cardiac and skeletal muscles, control energy storage and utilization, and constrict vascular smooth muscles in coronary and systemic arteries.
Reducing the ……….. and ………….. of calcium ………… through the calcium channels constitutes the pharmacologic basis for the therapeutic effects of calcium channel blockers (CCB).
Reducing the rate and quantity of calcium ions through the calcium channels constitutes the pharmacologic basis for the therapeutic effects of calcium channel blockers (CCB).
Calcium channel blockers affect only cardiac and vascular …………………., as significant transmembrane exchange of calcium does not involve these channels in………………………
Calcium channel blockers affect only cardiac and vascular muscle, as significant transmembrane exchange of calcium does not involve these channels in skeletal muscles.
In the Vaughan-Williams classification of antiarrhythmic agents, CCB constitute Class ………. drugs. Their predominant electrophysiologic action is based on their ability to block the slow …………… calcium current via the voltage dependent ……..-type and……..-type channels. The ……….-type CCB drugs are used as antiarrhythmic and antihypertensive drugs, whereas the ………-type drugs are primarily used as antiepileptic drugs. Classification of CCB is commonly based on their chemical structure into ………………… and …………………
In the Vaughan-Williams classification of antiarrhythmic agents, CCB constitute Class IV drugs. Their predominant electrophysiologic action is based on their ability to block the slow inward calcium current via the voltage dependent L-type and T-type channels. The L-type CCB drugs are used as antiarrhythmic and antihypertensive drugs, whereas the T-type drugs are primarily used as antiepileptic drugs. Classification of CCB is commonly based on their chemical structure into dihydropyridines and nondihydropyridines.
The ……………………… (amlodipine, nifedipine, felodipine) do not affect conduction and act principally on the vasculature. The ……………………………….. include phenylalkylamines (verapamil, gallopamil), benzothiazepines (diltiazem) and pipearzines (cinnarizine, flunarizine). Verapamil and diltiazem are mainly used for their cardiac effects.
The dihydropyridines (amlodipine, nifedipine, felodipine) do not affect conduction and act principally on the vasculature. The nondihydropyridines include phenylalkylamines (verapamil, gallopamil), benzothiazepines (diltiazem) and pipearzines (cinnarizine, flunarizine). Verapamil and diltiazem are mainly used for their cardiac effects.
Cardiac effects of CCB include slowing of the……………………… …………… depolarization rate, slowing of …………………………. conduction and depolarization rate, reducing ………………., coronary ………………….., prevention of calcium ……………. after ischemia, and possibly modulation of cardiac …………………..
Cardiac effects of CCB include slowing of the sinoatrial node pacemaker depolarization rate, slowing of atrioventricular (AV) node conduction and depolarization rate, reducing myocardial contractility, coronary vasodilatation, prevention of calcium overload after ischemia, and possibly modulation of cardiac hypertrophy.
Antiarrhythmic effects of CCB (i.e., verapamil and diltiazem) act predominantly through the dose-dependent reduction of ……………………. The effect is more pronounced on “……………………….” myocardial cells and at …………………………rates, which makes verapamil and diltiazem effective in abolishing supraventricular arrhythmias and in slowing ventricular heart rate in atrial fibrillation.
Verapamil has potent ………………………… effects, whereas diltiazem has minimal effect on myocardial contractility.
Coronary vasodilatation is best achieved through the use of …………………….via both adenosine- and nitric oxide-dependent mechanisms
Antiarrhythmic effects of CCB (i.e., verapamil and diltiazem) act predominantly through the dose-dependent reduction of AV conduction. The effect is more pronounced on “damaged” myocardial cells and at higher heart rates, which makes verapamil and diltiazem effective in abolishing supraventricular arrhythmias and in slowing ventricular heart rate in atrial fibrillation.
Verapamil has potent negative inotropic effects, whereas diltiazem has minimal effect on myocardial contractility.
Coronary vasodilatation is best achieved through the use of amlodipine via both adenosine- and nitric oxide-dependent mechanisms
VASCULAR EFFECTS
All CCB agents, however with different potency, reduce the rate of calcium influx into……………………….cells, thereby reducing ………………. calcium concentration and the resultant ………………….. tone.
The …………………………., i.e., nifedipine and amlodipine, have potent inhibitory effects on systemic ……………………vessels at concentrations that have minimal effect on the myocardium. The venous capacitance vessels and the pulmonary vasculature are much ……………………… to the ……………………. effects of CCB.
VASCULAR EFFECTS
All CCB agents, however with different potency, reduce the rate of calcium influx into vascular smooth muscle cells, thereby reducing intracellular calcium concentration and the resultant vascular tone.
The dihydropyridines, i.e., nifedipine and amlodipine, have potent inhibitory effects on systemic resistance vessels at concentrations that have minimal effect on the myocardium.
The venous capacitance vessels and the pulmonary vasculature are much less sensitive to the vasodilatory effects of CCB.
The dihydropyridines are mainly used for the treatment of systemic ………………….. and for their ……………………..properties by dilating preferentially …………………….. (increases glomerular capillary pressure and filtration rate) and to some degree ………………………(decreases glomerular capillary pressure and filtration rate) renal arterioles and preventing progression of …………………
The dihydropyridines are mainly used for the treatment of systemic hypertension and for their renoprotective properties by dilating preferentially afferent (increases glomerular capillary pressure and filtration rate) and to some degree efferent (decreases glomerular capillary pressure and filtration rate) renal arterioles and preventing progression of proteinuria
SPECIFIC AGENTS
Verapamil is the prototype class IV antiarrhythmic agent that slows conduction in the …….node, thereby suppressing ……………… supraventricular tachycardia and slowing the ……………response in atrial fibrillation.
However, verapamil has also been shown to promote atrial fibrillation in normal dogs. In addition, verapamil has been reported to be effective in controlling ventricular arrhythmias. Verapamil in combination with β-blockers appears superior to β-blockers alone for preventing exercise-induced ventricular ectopy.
Due to extensive first-pass metabolism the oral bioavailability is low and verapamil is therefore mainly used …………………………. at a dosage of 0.05 mg/kg increments to a maximum of 0.15 mg/kg. Verapamil has potent negative inotropic effects. Other adverse reactions include sinus bradycardia, AV block, hypotension, and heart failure. Verapamil decreases…………………….. of digoxin, resulting in increased serum digoxin concentrations.
SPECIFIC AGENTS
Verapamil is the prototype class IV antiarrhythmic agent that slows conduction in the AV node, thereby suppressing reentrant supraventricular tachycardia and slowing the ventricular response in atrial fibrillation.
However, verapamil has also been shown to promote atrial fibrillation in normal dogs. In addition, verapamil has been reported to be effective in controlling ventricular arrhythmias.[8-10] Verapamil in combination with β-blockers appears superior to β-blockers alone for preventing exercise-induced ventricular ectopy.
Due to extensive first-pass metabolism the oral bioavailability is low and verapamil is therefore mainly used intravenously at a dosage of 0.05 mg/kg increments to a maximum of 0.15 mg/kg. Verapamil has potent negative inotropic effects. Other adverse reactions include sinus bradycardia, AV block, hypotension, and heart failure. Verapamil decreases renal clearance of digoxin, resulting in increased serum digoxin concentrations.
Diltiazem is an effective antiarrhythmic agent slowing supraventricular arrhythmias including atrial fibrillation with minimal negative inotropic effect. In dogs, diltiazem is administered alone or in combination with digoxin at a dosage of 0.5 to 1.5 mg/kg tid or 3 mg/kg bid. A recent study showed that digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with atrial fibrillation. Diltiazem does ……………….. with the dosing requirements for digoxin.
Diltiazem has been used in cats with hypertrophic cardiomyopathy with reported benefits of heart rate reduction, improved myocardial relaxation and increased myocardial perfusion. Diltiazem has also been reported to resolve myocardial hypertrophy in cats in one study although similar results have not been reported by other investigators. In dogs with induced atrial fibrillation treated with diltiazem, slowing of the heart rate resulted in cardiovascular function not different from that observed during sinus rhythm.
Diltiazem is an effective antiarrhythmic agent slowing supraventricular arrhythmias including atrial fibrillation with minimal negative inotropic effect. In dogs, diltiazem is administered alone or in combination with digoxin at a dosage of 0.5 to 1.5 mg/kg tid or 3 mg/kg bid. A recent study showed that digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with atrial fibrillation.[12] Diltiazem does not interfere with the dosing requirements for digoxin.
Diltiazem has been used in cats with hypertrophic cardiomyopathy with reported benefits of heart rate reduction, improved myocardial relaxation and increased myocardial perfusion. Diltiazem has also been reported to resolve myocardial hypertrophy in cats in one study although similar results have not been reported by other investigators. In dogs with induced atrial fibrillation treated with diltiazem, slowing of the heart rate resulted in cardiovascular function not different from that observed during sinus rhythm.
Overdosing verapamil or diltiazem results in ………………… due to blockade of ……………… ……..-type calcium channels, and serum …………… concentrations correlate directly with severity of CCB intoxication.
Overdosing verapamil or diltiazem results in hyperglycemia due to blockade of pancreatic L-type calcium channels, and serum glucose concentrations correlate directly with severity of CCB intoxication.
Amlodipine and nifedipine are potent ………………. and are mainly used for their antihypertensive and renoprotective properties. Because amlodipine treatment in dogs has been reported to activate………………………………., it may be prudent to concurrently administer agents that block the ………….. in patients with systemic hypertension or heart failure
Amlodipine and nifedipine are potent vasodilators and are mainly used for their antihypertensive and renoprotective properties. Because amlodipine treatment in dogs has been reported to activate the renin-angiotensin-aldosterone system (RAAS), it may be prudent to concurrently administer agents that block the RAAS in patients with systemic hypertension or heart failure
Diuretics:
Overuse and monotherapy with diuretics for CHF may result in chronic activation of the renin-angiotensin-aldosterone system (RAAS) and acceleration of the decline into refractory heart failure and, ultimately, the death of the patient.
As a group, diuretics act on the kidney to increase urine output via one mechanism or another to increase urine flow, reducing total blood volume, ameliorating the signs associated with congestion.
Overuse and monotherapy with diuretics for CHF may result in chronic activation of the renin-angiotensin-aldosterone system (RAAS) and acceleration of the decline into refractory heart failure and, ultimately, the death of the patient.
As a group, diuretics act on the kidney to increase urine output via one mechanism or another to increase urine flow, reducing total blood volume, ameliorating the signs associated with congestion.
Other indications for diuretic administration include?
Cerebral edema,
Hypercalcemia,
Iatrogenic volume overload,
Acute renal failure,
Systemic hypertension,
Noncardiogenic pulmonary edema
Three main classes of diuretic drugs exist for use in the patient suffering from CHF. Which ones?
These include:
Loop diuretics,
Thiazides, and
Potassium-sparing diuretics.
Carbonic anhydrase inhibitors are another class of relatively weak diuretics used mainly for glaucoma. Other drugs commonly administered for CHF may also have diuretic effects.
Loop diuretics comprise the most widely used class of diuretics, and are considered the most potent. These drugs reversibly inhibit the…………………… cotransporter on the ……………………… side of the epithelial cells in the thick …………………limb of the Loop of Henle of the nephron to ……………………the amount of chloride, potassium, sodium, and hydrogen ions transported intraluminally (Figure 241-1).
Loop diuretics comprise the most widely used class of diuretics, and are considered the most potent. These drugs reversibly inhibit the sodium/potassium/2 chloride (Na+/K+/2 Cl-) cotransporter on the luminal side of the epithelial cells in the thick ascending limb of the Loop of Henle of the nephron to increase the amount of chloride, potassium, sodium, and hydrogen ions transported intraluminally (Figure 241-1). ]
The electrolyte loss draws …………………. into the tubules, resulting in ……………….urine volume and subsequent reduced blood volume.
This ………………… diastolic intraventricular pressure and ………… pressure, facilitating the resolution of pulmonary edema, pleural effusion and ascites, and thus the clinical signs associated with CHF.
The electrolyte loss draws free water into the tubules, resulting in increased urine volume and subsequent reduced blood volume.
This reduces diastolic intraventricular pressure and capillary pressure, facilitating the resolution of pulmonary edema, pleural effusion and ascites, and thus the clinical signs associated with CHF.
Loop diuretics also increase the fractional excretion of …………..,……………,………………and…………………
Sodium accumulation in the distal nephron increases ……………. and …………………….. secretion. Hypokalemia appears to be clinically rare; however, …………………….. hypochloremic ……………….. may occur with overzealous administration
Loop diuretics also increase the fractional excretion of sodium, chloride, calcium, and magnesium.
Sodium accumulation in the distal nephron increases potassium and hydrogen ion (H+) secretion.
Hypokalemia appears to be clinically rare; however, hyponatremic hypochloremic alkalosis may occur with overzealous administration
Figure 241-1 The nephron with sites of actions of the diuretic classes. A, Glomerulus. B, Proximal convoluted tubule. C, Loop of Henle.
D, Thick ascending Loop of Henle—site of action of the………….diuretics.
E, Distal convoluted tubule—site of action of the ………………….diuretics and ………………. diuretics.
F, Collecting duct—site of action of the …………………..diuretics.
Figure 241-1 The nephron with sites of actions of the diuretic classes. A, Glomerulus. B, Proximal convoluted tubule. C, Loop of Henle.
D, Thick ascending Loop of Henle—site of action of the loop diuretics.
E, Distal convoluted tubule—site of action of the thiazide diuretics and potassium-sparing diuretics.
F, Collecting duct—site of action of the potassium-sparing diuretics.
Furosemide is a ……………. diuretic that is the first-choice, and most commonly used drug administered to induce diuresis for the patient suffering from acute CHF.
Furosemide is a sulfonamide diuretic that is the first-choice, and most commonly used drug administered to induce diuresis for the patient suffering from acute CHF.
Considered a high-ceiling diuretic, standard doses for acute CHF are 2 to 8 mg/kg intravenously (IV) in dogs, and 1 to 4 mg/kg IV in cats, intramuscularly (IM) or subcutaneously (SQ) every 1 to 8 hours until the respiratory rate falls to within normal limits.[11-13] A constant rate infusion (0.6 to 1 mg/kg/hr IV) may achieve better diuresis.[13],[14] This may be followed up by doses between 1 to 4 mg/kg orally (PO) every-other-day to three times daily as needed to control congestion.[11] Given IV, furosemide acts within 5 minutes, with a peak at 30 minutes and is virtually eliminated within 3 hours.[2] Furosemide has a biexponential terminal half-life after oral administration, with the initial phase having a half-life of 30 minutes, and a second phase half-life of around 7 hours.[2] The onset of action occurs within the first hour, peaking at 1 to 2 hours, with a total duration of action of approximately 6 hours.[2] Generally, reduction to the minimal dose controlling clinical signs of congestion (coughing, shortness of breath, pleural effusion or ascites) is recommended.
Considered a high-ceiling diuretic, standard doses for acute CHF are 2 to 8 mg/kg intravenously (IV) in dogs, and 1 to 4 mg/kg IV in cats, intramuscularly (IM) or subcutaneously (SQ) every 1 to 8 hours until the respiratory rate falls to within normal limits.[11-13] A constant rate infusion (0.6 to 1 mg/kg/hr IV) may achieve better diuresis.[13],[14] This may be followed up by doses between 1 to 4 mg/kg orally (PO) every-other-day to three times daily as needed to control congestion.[11] Given IV, furosemide acts within 5 minutes, with a peak at 30 minutes and is virtually eliminated within 3 hours.[2] Furosemide has a biexponential terminal half-life after oral administration, with the initial phase having a half-life of 30 minutes, and a second phase half-life of around 7 hours.[2] The onset of action occurs within the first hour, peaking at 1 to 2 hours, with a total duration of action of approximately 6 hours.[2] Generally, reduction to the minimal dose controlling clinical signs of congestion (coughing, shortness of breath, pleural effusion or ascites) is recommended.
Furosemide has systemic effects in addition to causing diuresis. Furosemide administration is associated with an initial …………………. effect (following IV administration), probably an indirect effect that requires the kidney to occur. Furosemide has also been shown to increase …………………… through the thoracic duct, and has ………….., ……………………, and anticonvulsant effects.
Furosemide has systemic effects in addition to causing diuresis. Furosemide administration is associated with an initial venodilating effect (following IV administration), probably an indirect effect that requires the kidney to occur. Furosemide has also been shown to increase lymphatic flow through the thoracic duct, and has antioxidant, bronchodilating, and anticonvulsant effects.
A few patients may experience adverse side effects associated with hypersensitivity or allergy to ……………….., necessitating discontinuation or reduction in the dosage and/or frequency of administration of furosemide.
……………… may result after doses over 20 mg/kg IV are given, and furosemide may potentiate the …………………..associated with aminoglycoside antibiotic association.
A few patients may experience adverse side effects associated with hypersensitivity or allergy to sulfonamides, necessitating discontinuation or reduction in the dosage and/or frequency of administration of furosemide.
Ototoxicity may result after doses over 20 mg/kg IV are given, and furosemide may potentiate the nephrotoxicity associated with aminoglycoside antibiotic association.[2]
