Pharmacology of SGLT2 Inhibitors and sGC Stimulators

Vocabulary flashcards covering the pharmacological mechanisms, indications, and adverse effects of SGLT2 inhibitors and sGC stimulators in heart failure management.

Sodium Glucose Co-Transporter Type 2 (SGLT2) Inhibitors

A class of medications, originally developed for Type 2 Diabetes, that promotes the excretion of glucose and sodium to manage heart failure.

Dapagliflozin

The first SGLT2 inhibitor indicated for heart failure and the primary drug focus within its class for heart failure management.

Thiazolidinediones

A class of diabetes medications, specifically rosiglitazone, that was found to cause heart failure, leading to safety studies for SGLT2 inhibitors.

Proximal tubules

The specific anatomical part of the kidney where the SGLT2 transporter protein is expressed and targeted by inhibitors.

Osmotic Diuresis

A process where water follows the concentration gradient of excreted sodium ($Na^+$) and glucose ($C_6H_{12}O_6$) through osmosis, leading to increased water excretion.

Cardiac Preload Reduction

The reduction of total plasma volume through increased water excretion, decreasing the initial stretching of the heart muscles.

Cardiac Afterload Reduction

The result of decreased vascular tone occurring when the loss of sodium ($Na^+$) prevents calcium ($Ca^{2+}$) channels from stimulating vascular smooth muscle contraction.

Sympathetic Nervous System Downregulation

Considered the most important mechanism of dapagliflozin in heart failure, it counteracts disease progression driven by overactivation of the sympathetic system.

Glycosuria

The excretion of multiple sugars into the urine, including glucose, fructose, galactose, and lactose, due to SGLT2 inhibition.

Euglycemic Diabetic Ketoacidosis (UDKA)

A rare complication characterized by the buildup of acidic ketone bodies in the system while blood glucose levels remain relatively normal.

Acetone

A component of ketone bodies that produces a distinct "fruity smell" on the breath of patients experiencing ketoacidosis.

Vericiguat

A soluble guanylate cyclase (sGC) stimulator introduced in late 2023 for the treatment of heart failure with reduced ejection fraction (HFrEF).

Soluble Guanylate Cyclase (sGC)

An enzyme comprised of alpha ($\alpha$) and beta ($\beta$) subunits that regulates the biological actions of Nitric Oxide (NO).

cyclic Guanosine Monophosphate (cGMP)

A second messenger molecule converted from GTP that binds to Protein Kinase G (PKG) to facilitate relaxation and vasodilation.

Protein Kinase G (PKG)

An enzyme that, when activated by cGMP, promotes ventricular relaxation, increases coronary blood flow, and inhibits cardiac hypertrophy.

Megakaryocyte Erythroid Progenitor Cells

Bone marrow cells whose production is decreased by high levels of cyclic GMP during vericiguat therapy, potentially leading to anemia.

Iron Polymaltose

A supplement co-administered with vericiguat in iron-deficient patients to support the sGC enzyme which relies on iron for stimulation.

HFrEF

Heart failure with reduced ejection fraction, a specific classification of heart failure addressed by both SGLT2 inhibitors and vericiguat.