9-16 & 9-21 Anti CHF Drugs Flashcards Preview

Cardiovascular II Exam 3 > 9-16 & 9-21 Anti CHF Drugs > Flashcards

Flashcards in 9-16 & 9-21 Anti CHF Drugs Deck (105)
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What are the major types of positive inotropic agents for heart failure?

cardiac glycosides


beta-adrenergic receptor agonists


What are some important classes of drugs in the treatment of HF that have NO positive inotropic effects?


ACE inhibitors

Angiotensin receptor blockers


beta-adrenergic receptor blockers

natriuretic peptide



When does HF occur?

HF occurs when cardiac output is inadequate to provide the oxygen needed by the body, usually due to a decrease in contractility of the myocardium, which can be caused by diminished coronary blood flow (i.e., coronary artery disease)


Reduction in myocardium contractility is a frequent problem associated with HF. What can this reduction in contractility be caused by?

caused by damaged heart valves

external pressure around the heart

vitamin B deficiency

 primary cardiac muscle disease,

or any abnormality that makes the heart an ineffective pump


What is the primary defect in early HF?

deficits in the excitation-contraction coupling machinery of the heart. 

As HF develops, additional organs and systems become involved and pathological events occur within the baroreceptor reflex, sympathetic nervous system, kidneys, angiotensin II, aldosterone, and cardiac cells (apoptosis).


What improves relief of symptoms of HF? (not survival)

diuretics --> address volume overload

positive inportopic agents --> address myocardial dysfxn/contractility


What improves survival in HF?

agents that act directly on organs and systems other than the heart are more valuable in the long-term treatment of heart failure

(e.g., angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-blockers, and aldosterone receptor antagonists have been shown to reduce mortality).


HF results in a decreased CO. What are 2 direct consequence of this?

decreased carotid sinus firing

decreased renal blood flow


HF-associated decrease in CO is associated with a drop in carotid sinus firing, which will increase what type of nerve signalling? How will this lead to compensatory cardiac measures?

drop in carotid sinus firing = increased sympathetic discharge


results in increased force, rate and preload

 - increases CO ultimately. for awhile at least


HF-associated decreased CO will also lead to a decrease in renal blood flow. What are the humoral and cardiac responses to this that?

decreased renal blood flow = increased renin release

increased renin = increased Ang II

increased Ang II = increased preload, afterload, remodeling


Increased Ang II released associated with HF will also increase what step before compensation?

increased renin = increased NE released, sympathetic discharge

increased sympathetic discharge = more renin released


What 2 signs or changes would you associated with systolic failure in HF? What kind of HF are these signs typical for, and what drugs do they respond to?

  1. Reduced cardiac output and contractility
  2. Reduced ejection fraction (≤40%, although definitions vary; normal > 60%)
  3. Typical of acute failure (e.g., resulting from myocardial infarction)
  4. Responds to positive inotropic agents


HF is also associated with diastolic failure. What changes would you expect, and what drugs do they tend NOT to respond to?

  1. Occurs as a result of hypertrophy and stiffening of the myocardium
  2. Although cardiac output is reduced, ejection fraction may be normal
  3. Does not typically respond optimally to positive inotropic agents


What are the signs and Sx's of all forms of HF?

Signs and symptoms of all forms of heart failure include:


decreased exercise tolerance,

shortness of breath,

peripheral and pulmonary edema,



decreased exercise tolerance is the major direct consequence of diminished cardiac output while other manifestations result from compensatory adaptations


What is the prototype for cardiac glycosides?



What is digoxin used for?

HF and A-fib


How is digoxin distributed in tissues? How is it cleared from the body?

Widely distributed to tissues, including the CNS


For patients with normal renal function, the half life is 36-48 hours, permitting once-a-day dosing (66% is eliminated unchanged by the kidney)


Since digoxin is cleared by the kidney, what kinds of changes in clearance should you watch out for?

  1. In patients with renal insufficiency (or elderly patients), the half life increases to 3.5-5 days and requires dosing adjustments


  1. In patients with HF who are taking vasodilators or sympathomimetic agents, cardiac output and renal blood flow are increased, which may increase renal digoxin clearance


What is the MOA for digoxin?

  1. MOA: at the molecular level, digoxin causes inhibition of the membrane-bound (sarcolemma) Na+/K+ ATPase, ultimately causing an increase in the contraction of the cardiac sarcomere


What are the 2 desired effects of digoxin?

(1) to improve contractility of the failing heart and


(2) to prolong the refractory period of the atrioventricular node in patients with supraventricular arrhythmias (no effect on preload or afterload)


Describe the mechanism for the positive inotropic effect. (More of an FYI slide)

  1. nhibition of the Na+/K+ ATPase stops the cellular Na+ pump activity and reduces the rate of active Na+ extrusion out of the cell, which results in a rise in intracellular Na+ concentrations
  2. Rising intracellular Na+ concentrations reduce the transmembrane Na+ gradient that drives the extrusion of intracellular Ca2+ during myocyte repolarization by the Na+/Ca2+ exchanger (NCX)
  3. With reduced Ca2+ efflux and repeated entry of Ca2+ with each action potential, Ca2+ accumulates in the myocyte
  4. Ca2+ uptake into the sarcoplasmic reticulum (SR) is increased and more Ca2+ becomes available for release from the SR during the next action potential, which enhances myocardial contractility
  5. Therefore, cardiac glycosides increase myocardial contractility by ultimately increasing the releasable Ca2+ from the SR (see lecture slides for more information)
  6. The magnitude of the positive inotropic effect correlates with the degree of Na+/K+ ATPase inhibition


Summarize the mechanism of digoxin's positive inotropic effect.

Na/K ATPase pump is inhibited

intracellular Na+ increases

Na+ importer/Ca++ exporter gradient stops

Intracellular Ca++ increased

more Ca++ taken up then released from SR

more Ca++ released from SR = more contractility


The magnitude of digoxin's positive inotropic effect is actually dependent on what?

correllates with degree of Na+/K+ ATPase inhibition


Digoxin causes what electrical changes in the action potential?

early, brief prolongation of the action potential,

followed by action potential shortening (especially the plateau phase)


What causes the decrease in AP duration with digoxin?


The decrease in action potential duration may be the result of increased potassium conductance that is caused by increased intracellular calcium


Digoxin-induced elevated intracellular Ca2+ increases the activity of Ca2+-dependent K+ channels


Increased Ca2+-dependent K+ channel activity promotes K+ efflux and a more rapid repolarization (i.e., shortened cardiac action potential)


Digoxin will also increase PNS tone and reduce SNS tone. How does it accomplish this? What inhibits the PNS effect?

Something something rib raising?


Actually, it's this:

Parasympathomimetic effects predominate on cardiac tissue at therapeutic levels of digoxin 

Parasympathomimetic effects are inhibited by atropine


What are the PSNS effects that digoxin potentiates?

Parasympathomimetic effects involve:


sensitization of the baroreceptors,

central vagal stimulation, and

facilitation of muscarinic transmission at the cardiac muscle cell (unknown mechanism)


Where is cholinergic stimulation at the heart concentrated, and what does that mean for digoxin's effect on the heart?

Cholinergic innervation is more concentrated in the atria, resulting in increased actions of digoxin on atrial and atrioventricular nodes compared to Purkinje or ventricular function


What are the rhythm changes associated with toxic levels of digoxin?

changes to atrioventricular junctional rhythm,

premature ventricular depolarization,

bigeminal rhythm,

and second-degree atrioventricular blockade

(it is claimed that digoxin can cause virtually any arrhythmia)


If digoxin toxicity is persistent, what arrhythmia can develop? What exacerbates digoxin toxicity?

If allowed to progress, the tachycardia may deteriorate into fibrillation that could be fatal unless corrected

At toxic levels, sympathetic outflow is increased by digoxin, which exaggerates toxic effects of the drug