Inotropic Drugs And Other Drugs Used In Heart Failure

Front 1

What are the inotropic drugs?

Back 1

digoxin, dobutamine, dopamine, milrinone

Front 2

What are the drugs affecting the RAA system?

Back 2

captopril, enalaprilat, losartan, spironolactone

Front 3

What are the diuretics used in heart failure?

Back 3

furosemide and thiazides

Front 4

what are the beta blockers used in heart failure?

Back 4

metoprolol and carvedilol

Front 5

what are the vasodilators used in heart failure?

Back 5

nitrates, hydralazine, nesiritide

Front 6

what is the MOA of cardiac glycosides? (digoxin)

Back 6

inhibition of Na/K ATPase, leads to increased intracellular calcium which leads to increased force of contraction, also facilitation of calcium entry through voltage gated Ca channels and effect on SR that results in increased release of calcium from intracellular storage site

Front 7

What are some characteristics of of the inotropic actions of cardiac glycosides?

Back 7

does not occur in skeletal muscle, similar on atria and ventricles, does not depend on sympathetic activation in myocardium, occurs in normal heart and failing heart, increases myocardial oxygen consumption in normal heart but reduces it in failing heart

Front 8

what effect does cardiac glycosides have on action potential?

Back 8

at therapeutic concentrations it decreased AP duration, at higher concentrations it increases the slope of phase 4 depol, increased max diastolic mem potential, appearance of oscillatory depolarizing afterpotentials, appearance of abnormal APs

Front 9

what effect does cardiac glycosides have on ECG?

Back 9

increased PR interval, decreased QRS duration, decreased QT interval, depression of ST segment(hockey stick config), flattened or inverted T wave

Front 10

do cardiac glycosides increase or decrease heart rate? and what are the mechanisms?

Back 10

decrease by vagal activation, direct depressive action upon the SA/AV node, compensation of cardiac insufficiency

Front 11

what effect does digoxin have on vessels in normal subjects and in patients with heart failure?

Back 11

normal:increased vascular tone
patients: decreased vascular tone

Front 12

what effect does digoxin have on the CNS?

Back 12

direct stimulation of chemoreceptor trigger zone(emetic), direct stimulation of vagus nucleus, digitalis delerium

Front 13

what is the half life of digoxin?

Back 13

40 hours

Front 14

what are the general features of cardiac glycoside toxicity?

Back 14

narrow therapeutic index, serious toxic effects can be seen with doses 2-3 times higher than standard therapeutic doses, toxicity is dose dependent and concerns mainly the heart and CNS

Front 15

what are some symptoms of cardiac glycoside toxicity?

Back 15

cardiac arrhythmias, anorexia, vomiting, nausea, confusion, hallucinations, visual disturbances(blurred vision, green yellow halos around bright objects), hyperkalemia

Front 16

what is the therapy for cardiac glycoside toxicity?

Back 16

lidocaine, phenytoin(for vtach), digitalis Ab(FAB fragments, Digibind)

Front 17

what are the top 3 most common arrhythmias seen in cardiac glycoside toxicity?

Back 17

ventricular extrasystoles, 2nd or 3rd degree AV block, nonparoxysmal junctional tachycardia

Front 18

what are some factors affecting sensitivity to cardiac glycosides?

Back 18

type and severity of underlying heart disease, myocardial ischemia, electrolyte disturbances, acidosis, renal impairment, hypoxemia, thyroid disease(sensitivity increased in hypo and decreased in hyper), advanced age, therapy with diuretics, antiarrhythmics, macrolide, catecholamines

Front 19

name three very important drug interactions involving digoxin

Back 19

1)quinidine, amiodarone, verapamil, cyclosporine can increase the serum level of digoxin(Cp can double)
2)macrolides, tetracyclines, aminoglycosides decrease intestinal biotransformation of digoxin by bacteria of intestinal flora(Cp can be doubled) 3)loop and thiazide diuretics lead to hypokalemia and hypomagnesemia

Front 20

what are the C/I of cardiac glycosides?

Back 20

hypertrophic cardiomyopathy, states associated with diastolic dysfunction, chronic cor pulmonale, WPW syndrome, ventricular arrhytmias, AV block

Front 21

what are the therapeutic uses of cardiac glycosides?

Back 21

acute and chronic systolic heart failure and atrial flutter, atrial fib, and atrial and nodal tachycardia

Front 22

what is the mechanism of increased cardiac contractility by beta 1 receptor agonists?

Back 22

activation of b1 receptors, activation of Gs, increased camp, increased contraction

Front 23

what does the activation of camp dependent protein kinase A lead to?

Back 23

increase speed of contraction and speed of relaxation

Front 24

what is the MOA of dopamine?

Back 24

lose doses: activation of D1 receptors, intermediate doses: also activation of beta 1 and beta 2 receptors and release of NEPI from nerve terminals, high doses: also activation of alpha 1 receptors and of D2 receptors

Front 25

what are the pharmacological actions of dopamine?

Back 25

low doses: vasodilation in renal, mesenteric, and coronary beds, intermediate doses: positive inotropic effects, high doses: increase HR, hypertension, nausea, vomiting

Front 26

what are the therapeutic uses of dopamine?

Back 26

acute decompensated heart failure, cardiogenic shock(mainly in pts with marked hypotension and elevated ventricular fillin pressure), distributive shock(neurogenic, septic)
*drug especially useful when thought that poor renal perfusion contributes to clinical picture

Front 27

what is the MOA of dobutamine?

Back 27

selective activation of beta 1 receptors, higher doses my cause activation of b2, a1 receptors

Front 28

what are the pharmacological actions of dobutamine on the heart?

Back 28

marked positive inotropic effect(greater than glycosides, similar to milrinone), positive dromotropic effect(conduction speed through AV node), positive chronotropic(affect HR) and bathmotropic(affect threshold of excitation) effects

Front 29

what are the actions of dobutamine in heart failure?

Back 29

lowering of left ventricular filling pressure(improves coronary perfusion), modest decrease in myocardial O2 consumption

Front 30

what are the actions of dobutamine on vessels?

Back 30

peripheral vasodilation, no major changes in mean BP

Front 31

what are the therapeutic uses of dobutamine?

Back 31

acute decompensated heart failure or cardiogenic shock, when left ventricular function is severely depressed

Front 32

what are the A/E of adrenergic inotropic agents?

Back 32

cardiac arrhythmias, anginal pain

Front 33

what is the MOA of phosphodiesterase inhibitors?

Back 33

inhibition of phosphodiesterase isozyme 3, increase in camp, in myocardium leads to increase calcium, in smooth muscle it decreases the phosphorylation of myosin light chain

Front 34

what are the pharmocological actions of PDE3 inhibitors?

Back 34

marked positive inotropic effect, slight increase in HR, peripheral vasodilation(leads to decrease in pulmonary vascular resistance and left and right ventricular filling pressure)

Front 35

what are the A/E of PDE3 inhibitors?

Back 35

hypotension, syncope, ventricular arrhythmias

Front 36

what are the therapeutic uses of PDE3 inhibitors?

Back 36

acute decompensated heart failure or cardiogenic shock in patients who did not respond to other therapies or are under beta blocker treatment

Front 37

what is the problem associated with giving milrinone chronically?

Back 37

mortality increase

Front 38

what is the therapeutic strategy in chronic heart failure?

Back 38

1)reduction of workload(physical and emotional rest, treatment of obesity, vasodilator therapy, assisted circulation) 2)control of excessive salt and water retention(low sodium diet, diuretics, mechanical removal of fluid)3)improvement of pumping performance(digitalis glycosides, other positive inotropic agents, pacemaker)

Front 39

what are the two main effects of cardiac glycosides in heart failure?

Back 39

positive inotropic effect and negative chronotropic effect

Front 40

what is the benefit of the positive inotropic effect ?

Back 40

increases stroke work and CO which leads to elimination of stimuli evoking increased sympathetic outflow(decreases HR and vasc. tone), lowering of end diastolic fiber tension(decreases heart size and oxygen demand), increased renal blood flow(reduces aldosterone driven Na reabsorption)

Front 41

what subset of heart failure patients don't respond as well to cardiac glycosides?

Back 41

pts with increased filling pressure and ventricular hypertrophy but normal ejection fraction

Front 42

what type of patients respond well to cardiac glycosides?

Back 42

pts with dilated heart, decreased ejection fraction and tachycardia

Front 43

do cardiac glycoside reduce mortality?

Back 43

no

Front 44

what causes vasoconstriction in heart failure?

Back 44

sympathetic tone, concentration of plasma catecholamines, concentration of plasma vasopressin, renin secretion, thickness of arteriolar wall

Front 45

how do vasodilators help in heart failure?

Back 45

offset vasoconstriction so reducing preload and afterload, this reduces cardiac work and oxygen demand

Front 46

when are arteriolar dilators preferred?

Back 46

in patients with primary symptoms of low cardiac output

Front 47

when are venous dilators preferred?

Back 47

in patients with primary symptoms of pulmonary congestion

Front 48

what are the vasodilators used in heart failure?

Back 48

nitrates/nitroprusside(nitrovasodilators), captopril(ACEI), Losartan(ARB), Milrinone(PDEI), hydralazine(direct vasodilator)

Front 49

what is the efficacy of ACEI mainly due to?

Back 49

1)reduction of angiotensin levels(reduces peripheral resistance, afterload reduced),2)reduction of aldosterone secretion(reduced salt and water retention, preload reduced)

Front 50

what are some of the other effects of ACEI?

Back 50

reduction of ATII which lead to reduced myocardial fibrosis and myocyte apoptosis, reduced cardiac hypertrophy and ventricular remodeling, and reduced NEPI release

Front 51

what is the MOA of Nesiritide(recombinant brain natriuretic peptide)

Back 51

activation of guanylyl cyclase and increased synthesis of cGMP

Front 52

what are the pharmocological effects of nesiritide?

Back 52

arteriolar and venous vasodilation, increased diuresis

Front 53

what are the A/E of nesiritide?

Back 53

excessive hypotension, renal failure

Front 54

what is the therapeutic use of nesiritide?

Back 54

IV treatment of patients with acute decompensated heart failure

Front 55

what is the benefit of spironolactone?

Back 55

significantly reduced mortality and hospitalization for heart failure, attenuates pathologic remodeling that occurs in heart failure
-beneficial effects are additive to those of ACEI

Front 56

what condition are beta blockers dangerous in and why?

Back 56

acute heart failure because of their negative inotropic effects

Front 57

how do beta blockers reduce morbidity and mortality in chronic systolic heart failure?

Back 57

1)prevention of chronic overactivity of sympathetic nervous system(decreased HR, reduced myocardial remodeling)2)inhibition of renin secretion 3)up reg of beta 1 receptors

Front 58

which beta blockers are recommended for heart failure?

Back 58

metoprolol, bisoprolol, carvedilol