What is the mechanism of action of Enstro and what can be substituted for it that can be crushed and administered via a Percutaneous Endoscopic Gastrostomy (PEG) tube?

Mechanism of Action of Entresto and PEG Tube Administration Alternatives

Entresto (sacubitril/valsartan) can be substituted with individual components of valsartan and a neprilysin inhibitor that can be crushed, as Entresto itself cannot be administered through a PEG tube due to its formulation.

Mechanism of Action of Entresto

Entresto (sacubitril/valsartan) works through a dual mechanism of action:

1. Neprilysin Inhibition (Sacubitril):

   • Sacubitril is a prodrug that is metabolized to its active form LBQ657
   • Inhibits neprilysin, an enzyme that degrades natriuretic peptides
   • This increases levels of natriuretic peptides, which promote vasodilation, natriuresis, and diuresis
   • Results in reduced cardiac preload and afterload 1, 2

2. Angiotensin Receptor Blockade (Valsartan):

   • Blocks the angiotensin II type 1 (AT1) receptor
   • Inhibits the renin-angiotensin-aldosterone system (RAAS)
   • Prevents vasoconstriction, sodium retention, and cardiac remodeling 3, 4

This combined action provides superior cardiovascular benefits compared to ACE inhibitors alone in heart failure with reduced ejection fraction (HFrEF) 5.

PEG Tube Administration Alternatives

Since Entresto cannot be crushed for PEG tube administration, the following alternatives can be considered:

Recommended Alternatives:

1. Valsartan tablets (crushed):

   • Can be crushed and administered through PEG tube
   • Mix with 15-30mL of water after crushing
   • Flush tube with 30mL water before and after administration 6

2. ACE inhibitor alternatives that can be crushed:

   • Lisinopril tablets can be crushed and mixed with water
   • Enalapril tablets can be crushed and administered via PEG tube
   • These provide RAAS blockade but lack neprilysin inhibition

Administration Guidelines for PEG Tube Medication:

1. Proper preparation:

   • Consult with a pharmacist before crushing any medication
   • Crush tablets to fine powder (only immediate-release formulations)
   • Mix completely with 15-30mL of water 6

2. Administration technique:

   • Flush tube with 30mL water before medication
   • Administer medications individually (not mixed together)
   • Flush with 30mL water between medications
   • Flush with 30mL water after all medications 6

3. Important precautions:

   • Never crush extended-release or enteric-coated formulations
   • Consider pausing enteral feeding 1-2 hours before and after administration for medications that interact with formula components
   • Use appropriate ENFit syringes to avoid misconnection errors 6

Clinical Considerations

• The loss of neprilysin inhibition when substituting with valsartan alone may result in reduced clinical efficacy compared to Entresto
• Monitor patient closely for changes in heart failure symptoms and adjust therapy as needed
• Consider consulting with a cardiologist regarding the clinical implications of switching from Entresto to alternative therapy

Remember that proper administration technique is critical to prevent tube occlusion and ensure medication efficacy when administering medications through PEG tubes 7, 6.