L18. Pharmacology -- Pharmacological Regulation of Cardiac Function
40 Questions
1 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of the sarco-endoplasmic reticulum calcium ATPase (SERCA) in cardiac cells?

  • To facilitate troponin activation for muscle contraction
  • To promote calcium release from the sarcoplasmic reticulum
  • To sequester calcium back into the sarcoplasmic reticulum (correct)
  • To increase calcium influx from extracellular space

    • How does sympathetic stimulation affect the L type calcium channels?

  • It inhibits their function, decreasing calcium influx
  • It phosphorylates other proteins to decrease channel activity
  • It phosphorylates them, increasing calcium current (correct)
  • It has no effect on their activation

    • What role does Protein Kinase A (PKA) play in cardiac muscle contraction?

  • It directly induces muscle contraction by activating Troponin C
  • It promotes the opening of potassium channels
  • It reduces intracellular cAMP levels
  • It phosphorylates phospholamban, enhancing calcium reuptake (correct)

    • What effect does calcium-induced calcium release (CICR) have on muscle contraction?

    <p>It increases the strength of the muscle contraction</p> Signup and view all the answers

    What is the effect of phosphorylation of Troponin I in cardiac muscle?

    <p>It increases calcium sensitivity of Troponin C</p> Signup and view all the answers

    What influences the conduction velocity of action potentials in the heart?

    <p>Increased intracellular cAMP levels</p> Signup and view all the answers

    What physiological effect is primarily achieved through sympathetic stimulation in the heart?

    <p>Increased force of contraction and heart rate</p> Signup and view all the answers

    Which mechanism is responsible for the extruding calcium from the cardiac cell?

    <p>Sodium-calcium exchange pump</p> Signup and view all the answers

    What effect does the phosphorylation of Troponin I have on myocyte relaxation?

    <p>It impairs the interaction with Troponin C.</p> Signup and view all the answers

    Which of the following β-adrenergic agonists is selective for the β1 subtype?

    <p>Dobutamine</p> Signup and view all the answers

    What is the primary function of phosphodiesterases (PDEs) in cardiac myocytes?

    <p>To hydrolyze cAMP and cGMP.</p> Signup and view all the answers

    What is a negative effect of non-selective β-adrenergic blockers such as propranolol?

    <p>Negative inotropic and chronotropic effects.</p> Signup and view all the answers

    Which drug is used to inhibit PDE3 and enhance cardiac contractility?

    <p>Milrinone</p> Signup and view all the answers

    What is the primary effect of calcium channel blockers like Verapamil and Diltiazem on cardiac myocytes?

    <p>Reduce action potential duration.</p> Signup and view all the answers

    Which of the following statements about PDE3 is correct?

    <p>PDE3 regulates intracellular cAMP in the heart.</p> Signup and view all the answers

    What is the mechanism by which adrenergic agonists affect heart function?

    <p>Stimulation of Gs proteins to increase cAMP.</p> Signup and view all the answers

    What is the primary reason Digoxin can lead to toxicity at low serum concentrations?

    <p>It has a narrow therapeutic index.</p> Signup and view all the answers

    What effect does hypokalemia have on Digoxin's potency and toxicity?

    <p>It magnifies Digoxin's potency and toxicity.</p> Signup and view all the answers

    Which of the following best describes the role of NCX in the context of delayed afterdepolarizations?

    <p>It translocates calcium ions out of the cell.</p> Signup and view all the answers

    What limitation is commonly associated with drugs that mobilize intracellular calcium?

    <p>They can facilitate cardiac remodeling.</p> Signup and view all the answers

    What mechanism does Pimovendan utilize to affect cardiac myofilaments?

    <p>Sensitization to intracellular calcium.</p> Signup and view all the answers

    Why was the development of Pimovendan in the US discontinued?

    <p>It increased mortality in clinical trials.</p> Signup and view all the answers

    Which drug increases cardiac contractility by binding to troponin C?

    <p>Levosimendan</p> Signup and view all the answers

    What is a common consequence of calcium release from the sarcoplasmic reticulum when Digoxin is present?

    <p>Arrhythmias due to delayed afterdepolarizations.</p> Signup and view all the answers

    What is the primary aim of heart failure therapy in relation to pathological remodeling?

    <p>To block the remodeling process.</p> Signup and view all the answers

    Which of the following drug classes is NOT indicated for the treatment of heart failure with reduced ejection fraction (HFrEF)?

    <p>Calcium Channel Blockers</p> Signup and view all the answers

    What mechanism is primarily targeted by Angiotensin Receptor Blockers (ARBs) in heart failure treatment?

    <p>Regulating blood pressure through hormonal pathways.</p> Signup and view all the answers

    SGLT2 inhibitors have shown effectiveness in treating heart failure independent of what specific condition?

    <p>Diabetes or sugar level control.</p> Signup and view all the answers

    Which combination of treatments is highlighted for its potential effectiveness in heart failure therapy?

    <p>ARB and neprilysin inhibitor combination.</p> Signup and view all the answers

    What role do Mineralocorticoid Receptor Antagonists (MRAs) play in heart failure management?

    <p>They prevent pathological changes in vascular remodeling.</p> Signup and view all the answers

    Which aspect of heart failure does ongoing activation of historical compensatory mechanisms lead to?

    <p>Maladaptive responses and complications.</p> Signup and view all the answers

    Which drug class is specifically recommended for the treatment of heart failure with preserved ejection fraction (HFpEF)?

    <p>Sodium-glucose cotransporter 2 inhibitors.</p> Signup and view all the answers

    What role does calcium play beyond being a charge carrying ion in the heart?

    <p>Calcium serves as a second messenger linking membrane events to intracellular processes.</p> Signup and view all the answers

    What is the primary mechanism by which sympathetic stimulation affects cardiac function?

    <p>It enhances calcium influx through L-type calcium channels.</p> Signup and view all the answers

    Which class of drugs is primarily used to block calcium channels in the heart?

    <p>Calcium channel blockers</p> Signup and view all the answers

    What is the significance of the T tubules in cardiac contractions?

    <p>They propagate the cardiac action potential and facilitate calcium channel activation.</p> Signup and view all the answers

    How do cardiac glycosides function in the regulation of heart function?

    <p>They increase intracellular calcium concentrations by inhibiting sodium-potassium ATPase.</p> Signup and view all the answers

    What is the primary mechanism through which calcium sensitizers affect cardiac contractility?

    <p>They enhance the interaction between calcium and contractile proteins.</p> Signup and view all the answers

    Which phase of the cardiac action potential is primarily responsible for calcium influx?

    <p>Phase 2</p> Signup and view all the answers

    In the context of heart failure, what is a critical pharmacological goal?

    <p>To improve the contractility of the heart.</p> Signup and view all the answers

    Study Notes

    Introduction

    • Cardiac action potential and contractility are important for treating heart failure.

    Excitation-Contraction Coupling in the Heart

    • Calcium influx during phases 2 and 3 of the cardiac action potential is crucial.
    • Calcium acts as a second messenger linking membrane depolarization to contraction.
    • L-type calcium channels are activated by action potentials, triggering calcium release from the sarcoplasmic reticulum (SR).
    • Calcium-induced calcium release (CICR) leads to a transient increase in intracellular calcium, activating troponin C and initiating muscle contraction.
    • Calcium is returned to the SR by SERCA (sarco-endoplasmic reticulum calcium ATPase) and extruded from the cell by NCX (sodium-calcium exchange pump).

    Sympathetic Regulation of Cardiac Calcium Channels

    • Sympathetic stimulation increases heart contractility (inotropic effect) and heart rate (chronotropic effect).
    • Sympathetic stimulation activates β-adrenergic receptors.
    • β-adrenergic receptors act via Gs and adenylate cyclase to increase intracellular cAMP.
    • cAMP activates Protein Kinase A (PKA) which phosphorylates L-type calcium channels leading to:
      • Increased calcium current.
      • Increased rate of rise of the action potential.
      • Increased conduction velocity of the action potential.
    • PKA also phosphorylates phospholamban and troponin I, increasing the rate of relaxation of the myocytes, further supporting the increased heart rate.

    Pharmacological Regulation of Heart Function

    • Adrenergic Mechanisms:
      • Beta-adrenergic agonists (e.g., isoproterenol, dobutamine) increase both heart rate and contractility.
      • Beta-adrenergic blockers (e.g., propranolol, atenolol, metoprolol) decrease both heart rate and contractility.
      • PDE3 inhibitors (e.g., milrinone) potentiate downstream beta receptor stimulation, regulating heart rate and contractility.

    Calcium Channel Blockers

    • Calcium channel blockers target L-type calcium channels on the plasma membrane.
    • Examples include: Verapamil, Diltiazem, and dihydropyridines (e.g. Nifedipine, Amlodipine)
    • Effects:
      • Reduce calcium influx, thus limiting the force of contraction.
      • Reduce the duration of the action potential.

    Cardiac Glycosides

    • Cardiac glycosides (e.g., digoxin) inhibit the Na+/K+ ATPase.
    • Digoxin binds to the potassium binding site, increasing its potency in cases of hypokalemia.
    • Cardiac glycosides can cause delayed afterdepolarizations (DADs) and triggered arrhythmias by overfilling the SR with calcium and activating NCX.

    Beyond Calcium

    • Calcium sensitizers potentiate the effect of calcium on the contractile apparatus.
    • Examples include:
      • Pimobendan: inhibits PDE3 and sensitizes cardiac myofilaments to intracellular calcium, but is associated with increased mortality.
      • Levosimendan: increases cardiac contractility by binding troponin C and activating KATP channels.

    Treatment of Heart Failure

    • Heart failure treatment primarily focuses on:
      • Blocking pathological remodeling.
      • Targeting the vasculature and kidneys.
    • Major drug classes:
      • ACE inhibitors
      • ARBs
      • ARNi (ARB + neprilysin inhibitor)
      • Beta Blockers
      • MRAs
      • SGLT2 inhibitors
    • SGLT2 inhibitors are effective for both HFrEF and HFpEF and are recommended in AHA guidelines.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    Pharmacological Regulation of Cardiac Function PDF - 2022

    Description

    Test your knowledge on cardiac action potential and its role in contractility. This quiz covers topics such as excitation-contraction coupling, calcium's function in heart muscle contraction, and the impact of sympathetic stimulation on heart function. Prepare to explore key physiological concepts critical for understanding heart mechanics.

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser