Katzung - Chapter 13

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Questions and Answers

What is the presumptive diagnosis for the case study described?

Ischemic cardiomyopathy

Restrictive cardiomyopathy

Dilated cardiomyopathy (correct)

Hypertrophic cardiomyopathy

What is the normal left ventricular ejection fraction percentage?

40%

60% (correct)

70%

50%

What is the primary goal of treatment in heart failure?

Reduce symptoms and slow progression (correct)

Increase heart rate significantly

Eliminate all underlying causes

Completely restore normal heart function

Which condition is a significant cause of heart failure in the USA?

Coronary artery disease Signup and view all the answers

What symptom is mentioned as occurring when the patient lies down?

Orthopnea Signup and view all the answers

What is a common mortality rate for heart failure over a period of five years?

50% Signup and view all the answers

What is indicated by a dilated, poorly contracting heart found in the echocardiogram?

Systolic dysfunction Signup and view all the answers

What is the effect of a viral infection in relation to the case presented?

Leading to dilated cardiomyopathy Signup and view all the answers

Which of the following is NOT a focus in managing heart failure?

Preventing exercise Signup and view all the answers

What primarily determines the vigor of contraction of heart muscle?

The interaction of actin and myosin filaments Signup and view all the answers

Where is activator calcium primarily released from during cardiac contraction?

Sarcoplasmic reticulum Signup and view all the answers

What influences the amount of calcium released from the sarcoplasmic reticulum?

The amount of trigger calcium entering the cell Signup and view all the answers

The sodium-calcium exchanger operates by moving calcium where?

Against its concentration gradient from the cytoplasm to the extracellular space Signup and view all the answers

What role do sympathomimetics play in cardiac contractility?

Increase calcium influx Signup and view all the answers

What happens to contractility when calcium channel blockers are used?

Reduce contractility Signup and view all the answers

What does calcium sensitivity refer to in cardiac myofibrils?

The relationship between calcium concentration and myofibril shortening Signup and view all the answers

Which ion primarily influences the sodium-calcium exchanger's activity?

Sodium Signup and view all the answers

What does the duration of calcium channel openings affect?

Amount of trigger calcium entering the cell Signup and view all the answers

Which factor does NOT contribute to the amount of calcium release from the sarcoplasmic reticulum?

Presence of potassium in the extracellular fluid Signup and view all the answers

What are bosentan and tezosentan primarily known for?

Being approved for use in pulmonary hypertension Signup and view all the answers

What is a key benefit of using ACE inhibitors in chronic heart failure?

Reduction of peripheral resistance Signup and view all the answers

Which beta-blocker has shown a reduction in mortality in patients with heart failure?

Metoprolol Signup and view all the answers

What adverse effect can occur with beta-blockers in heart failure?

Acute decompensation of cardiac function Signup and view all the answers

What is a possible mechanism through which beta-blockers exert their effects?

Diminished release of norepinephrine Signup and view all the answers

What effect do angiotensin AT1 receptor blockers like losartan have?

Inhibit the mitogenic activity of catecholamines Signup and view all the answers

What is the function of Na+/K+-ATPase in cardiac physiology?

Maintains sodium and potassium gradients Signup and view all the answers

Which protein serves as a calcium binding agent in the sarcoplasmic reticulum?

CalS Signup and view all the answers

How does diastolic dysfunction typically affect cardiac output and ejection fraction?

Only cardiac output is reduced Signup and view all the answers

What role do calcium sensitizers play in cardiac function?

Enhance the interaction between actin and myosin Signup and view all the answers

Which channel is known as the voltage-gated, L-type calcium channel?

Cav-L Signup and view all the answers

What characterizes high-output heart failure?

It is a rare form of heart failure Signup and view all the answers

What effect does the Ryanodine RyR2 receptor have in cardiac muscle?

Triggers release of stored calcium Signup and view all the answers

What is the renal clearance of digoxin proportional to?

Creatinine clearance Signup and view all the answers

Which of the following conditions is NOT typically associated with diastolic dysfunction?

Increased contractility Signup and view all the answers

What might cause a decrease in action potential duration?

Increased potassium conductance Signup and view all the answers

What type of exchange does the NCX perform in cardiac cells?

Sodium-calcium exchange Signup and view all the answers

What is the half-life of digoxin in patients with normal renal function?

36–40 hours Signup and view all the answers

Which physiological process is represented by green arrows in the context of cardiac function?

Promotion of relaxation Signup and view all the answers

What is associated with overloading of intracellular calcium stores?

Delayed after-depolarizations (DADs) Signup and view all the answers

Which membrane-bound transporter is inhibited by cardiac glycosides?

Na+/K+-ATPase Signup and view all the answers

What occurs when afterpotentials reach threshold in the Purkinje conducting system?

Elicitation of ectopic beats Signup and view all the answers

What effect can digoxin have on the central nervous system?

Undesirable effects Signup and view all the answers

At higher concentrations, what happens to resting membrane potential?

It is reduced and made less negative Signup and view all the answers

Inhibition of Na+/K+-ATPase can lead to what electrical phenomena in cardiac myocytes?

Oscillatory depolarizing afterpotentials Signup and view all the answers

What effect does digoxin toxicity have on action potentials?

Causes oscillatory depolarizing afterpotentials Signup and view all the answers

Study Notes

Heart Failure Overview

Heart failure occurs when cardiac output is insufficient to meet the body's oxygen needs, leading to significant morbidity and a 5-year mortality rate of approximately 50%.
Common causes in the USA include coronary artery disease and hypertension, with systolic failure being common among younger patients, characterized by reduced contractility and ejection fraction (normal: > 60%, heart failure: < 45%).

Symptoms and Diagnosis

Typical symptoms include shortness of breath, swelling in extremities (3+ edema), crackles in the lungs, elevated jugular venous pressure, and fatigue.
A left ventricular ejection fraction of around 20% indicates severe dysfunction, often linked to conditions such as dilated cardiomyopathy due to previous viral infections.

Mechanisms of Cardiac Function

Cardiac contractility is influenced by calcium dynamics, including calcium influx through L-type calcium channels and release from the sarcoplasmic reticulum (SR).
The sodium-calcium exchanger (NCX) regulates intracellular calcium levels, while sympathomimetics enhance calcium influx, and calcium channel blockers reduce it.

Types of Heart Failure

Systolic dysfunction presents with reduced ejection fraction, while diastolic dysfunction may maintain a normal ejection fraction despite reduced cardiac output due to stiffening of the myocardium.
"High-output" failure is rare and characterized by normal or high cardiac outputs but inadequate perfusion.

Treatment Goals

Treatment aims to alleviate symptoms and slow disease progression during stable periods, and to manage acute episodes of decompensated heart failure.

Pharmacology Key Points

Digoxin, a cardiac glycoside, enhances contractility by inhibiting Na+/K+-ATPase, leading to increased intracellular calcium concentrations and improved cardiac output.
Multiple mechanisms such as impaired excitability and association with delayed after-depolarizations (DADs) are critical in understanding digoxin's therapeutic and toxic effects.

ACE Inhibitors and Beta-Blockers

Angiotensin-converting enzyme (ACE) inhibitors like captopril reduce afterload and preload, decreasing heart stress and improving outcomes. They also mitigate long-term cardiac remodeling.
Beta-blockers, including bisoprolol and carvedilol, have been shown to decrease mortality and are associated with reduced heart rate, improved ventricular function, and remodeling inhibition despite their potential to precipitate acute heart failure in some cases.

Emerging Treatments

Competitive endothelin inhibitors like bosentan have shown promise in experimental models for heart failure but have variable efficacy in human trials and significant side effects, such as hepatotoxicity.

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Description

This quiz covers key concepts related to drugs used in the treatment of heart failure, as discussed in Katzung's pharmacology textbook. It includes case studies and clinical scenarios that enhance understanding of pharmacotherapeutics in cardiovascular medicine.