Heart Failure Pharmacology and Pathophysiology

Heart's inability to pump enough blood due to problems filling or ejecting blood.

Conditions like coronary artery disease, high blood pressure, valve problems, irregular heartbeats, and heart muscle diseases.

The body's response to low blood pressure, involving the sympathetic nervous system releasing hormones to increase heart rate and strength.

The body's response to poor blood flow to the kidneys, involving the renin-angiotensin-aldosterone system (RAAS) to increase blood pressure and volume.

Hormones that help manage fluid overload by relaxing blood vessels and increasing urine output, counteracting the effects of RAAS.

Weakening of the heart's contraction due to stretching, affecting the ability to pump blood effectively.

Difficulty in filling the heart with blood due to thickening of the heart walls, impacting its pumping ability.

Medications that help manage heart failure by affecting preload, afterload, and heart muscle contraction.

Medications that block the enzyme that converts angiotensin I to angiotensin II, leading to reduced vasoconstriction and aldosterone release. This lowers blood pressure and improves heart function.

Side effects of ACE inhibitors, including low blood pressure upon standing, kidney issues, high potassium levels, cough due to bradykinin buildup, and swelling.

Drugs that block angiotensin II receptors, mimicking the effects of ACE inhibitors but without increasing bradykinin, leading to less cough and swelling.

A medication that blocks the effects of aldosterone, reducing sodium retention and cardiac remodeling. This improves heart function and survival.

A combination drug that combines an ARB (valsartan) with a neprilysin inhibitor (sacubitril). It reduces angiotensin II's harmful effects while increasing beneficial natriuretic peptides.

Drugs that block the effects of the sympathetic nervous system, reducing heart rate and preventing heart damage. They improve heart function in heart failure.

A specific type of beta-blocker that also has alpha-blocking and antioxidant properties, providing additional benefits for heart failure.

A key side effect of beta-blockers, especially at the start of treatment. It can cause worsening of heart failure symptoms.

Digoxin is a cardiac glycoside that inhibits the sodium-potassium ATPase pump, leading to increased intracellular calcium and improved contractility. This results in a stronger heartbeat.

Digoxin slows down the electrical conduction through the AV node, which is helpful in managing irregular atrial rhythms like atrial fibrillation.

Reduced levels of potassium in the blood (hypokalemia) can increase the risk of digoxin toxicity. This is because digoxin competes with potassium for the same binding site on the sodium-potassium pump.

Milrinone is a medication that increases the levels of a substance called cAMP in the heart cells. This leads to increased calcium levels and stronger heart contractions.

Dobutamine and dopamine are medications that stimulate the beta-adrenergic receptors in the heart, leading to increased calcium entry and stronger contractions.

Vericiguat is a drug that directly stimulates soluble guanylate cyclase (sGC), increasing the production of cGMP. cGMP improves heart function, relaxes blood vessels, and reduces inflammation in the heart.

Digitalis toxicity can occur due to high doses of digoxin, low potassium levels, or interactions with other medications. Symptoms can include nausea, vomiting, blurred vision, and irregular heartbeat.

Treatment for digoxin toxicity includes increasing potassium levels, using atropine for slow heart rate, and using digibind, an antibody that binds to and removes digoxin from the body.

Diuretics, particularly loop diuretics like furosemide, lessen fluid buildup in the body by decreasing plasma volume, thereby reducing preload. These medications primarily assist in managing the symptoms of fluid overload in patients with heart failure.

Ivabradine specifically targets and slows down the If current in the sinoatrial (SA) node, resulting in a lower heart rate without affecting the heart's ability to contract, the electrical signal's path to the ventricles, or blood pressure.

Venous dilators, such as nitrates and nitroprusside, reduce preload by widening veins. Conversely, arterial dilators, like hydralazine, decrease afterload by expanding arteries.

SGLT2 inhibitors, such as dapagliflozin and empagliflozin, reduce plasma volume by promoting glucose and sodium excretion through urine (glucosuria and natriuresis), thereby lowering both preload and afterload. These medications also have the potential to prevent cardiac fibrosis (scarring). SGLT2 inhibitors like dapagliflozin have been proven to decrease hospitalizations and mortality in patients with heart failure with reduced ejection fraction (HFrEF).

Inotropic drugs enhance the heart's contractility by increasing intracellular calcium levels. However, due to concerns about increased mortality with long-term use, these drugs are usually reserved for acute, severe heart failure situations.

Cardiac glycosides, such as digoxin, derive from the foxglove plant. They inhibit the Na+/K+ ATPase pump, leading to increased intracellular calcium and stronger heart contractions. Primarily, they are used for symptomatic heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation.

Common side effects of diuretics in heart failure include dehydration (loss of body water), low sodium levels in the blood (hyponatremia), and low potassium levels in the blood (hypokalemia). Therefore, regular monitoring of electrolytes is critical to ensure patient safety.

The common side effects of ivabradine include bradycardia (slow heart rate) and visual disturbances such as luminous phenomena (e.g., halos). Ivabradine's selectivity for the sinoatrial node limits its efficacy in controlling heart rate in atrial fibrillation and might even heighten the risk of this heart rhythm irregularity.