Mechanism of action of Vericiguat

Mechanism of Action of Vericiguat (Verquvo)

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Introduction

Vericiguat is a soluble guanylate cyclase (sGC) stimulator used in patients with chronic heart failure with reduced ejection fraction (HFrEF) following hospitalization or intravenous diuretics. It enhances the nitric oxide (NO)–sGC–cGMP pathway to support cardiovascular function.

Step-by-Step Mechanism of Action

  1. Direct stimulation of sGC
    Vericiguat binds directly to the β-subunit of sGC, increasing enzyme activity even when NO levels are low youtube.com+10pmc.ncbi.nlm.nih.gov+10thecvc.ca+10go.drugbank.com+1en.wikipedia.org+1.
  2. Sensitization to nitric oxide
    It enhances sGC’s responsiveness to any remaining endogenous NO, facilitating more robust cGMP production .
  3. Elevation of cGMP levels
    Increased cGMP leads to smooth muscle relaxation, vasodilation, and lowered vascular resistance youtube.com+10mdpi.com+10thecvc.ca+10go.drugbank.com+1merckconnect.com+1.
  4. Cardioprotective effects
    Enhanced cGMP supports reduced myocardial remodeling, decreased inflammation, and improved endothelial function .
Vericiguat mechanism of action flowchart

Pharmacokinetic Parameters

Clinical Uses

Adverse Effects

Comparative Analysis

FeatureVericiguat (sGC Stimulator)NitratesPDE5 Inhibitors
NO-dependent actionNO-independent + sensitizingNO-dependentRequires NO; blocks breakdown of cGMP
Tolerance developmentNone reported with daily useCommon with nitratesNot significant
TargetcGMP productioncGMP productioncGMP accumulation

MCQs

  1. Vericiguat primarily stimulates which enzyme?
    a) PDE5 b) sGC c) NO synthase d) Guanylate kinase
    Answer: b) sGC
  2. It increases production of which second messenger?
    a) cAMP b) cGMP c) IP3 d) DAG
    Answer: b) cGMP
  3. Vericiguat enhances responsiveness to:
    a) Endothelin b) NO c) Angiotensin II d) Vasopressin
    Answer: b) NO
  4. Main metabolic pathway is:
    a) CYP3A4 b) UGT1A9/1A1 c) CYP2D6 d) Renal filtration
    Answer: b) UGT1A9/1A1
  5. Typical elimination half-life allows:
    a) Once-daily dosing b) Twice-daily dosing c) Weekly dosing d) PRN dosing
    Answer: a) Once-daily dosing
  6. Vericiguat reduces hospitalization in patients with:
    a) Stable HFpEF b) Worsened HFrEF c) Acute MI d) Stable angina
    Answer: b) Worsened HFrEF
  7. Food intake affects bioavailability by:
    a) Decreasing it significantly b) Increasing it to ~93% c) No effect d) Doubling it
    Answer: b) Increasing it to ~93%
  8. Protein binding is approximately:
    a) 50% b) 70% c) 98% d) 10%
    Answer: c) 98%
  9. Adverse effect seen in clinical trials:
    a) Severe hypotension b) Anemia c) Arrhythmias d) Hyperkalemia
    Answer: b) Anemia
  10. Compared to nitrates, vericiguat does NOT cause:
    a) Vasodilation b) Tolerance c) Hypotension d) cGMP increase
    Answer: b) Tolerance

FAQs

1. When should vericiguat be given?
To patients with HFrEF who remain symptomatic after hospitalization or IV diuretics.

2. Can it be taken without food?
No—must be taken with food to ensure proper absorption.

3. Is it safe with nitrates or PDE5 inhibitors?
Avoid concurrent PDE5 inhibitors. Short‑acting nitrates tolerated but avoid combined vasodilation.

4. Does vericiguat cause reflex tachycardia?
No significant reflex tachycardia has been reported.

5. What follow-up is needed?
Monitor blood pressure and hematocrit for anemia, especially after dosage titration.

References

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