Heart Failure.pdf

Heart Failure Certainly! Here's the summary with the same headings: ### **I. Heart Failure (HF) Overview** **De nition:** - Heart failure (HF) is a condition where the heart cannot pump enough blood to meet the body’s needs. - **Cardinal Symptoms:** Dyspnea (shor...

Heart Failure Certainly! Here's the summary with the same headings: ### **I. Heart Failure (HF) Overview** **De nition:** - Heart failure (HF) is a condition where the heart cannot pump enough blood to meet the body’s needs. - **Cardinal Symptoms:** Dyspnea (shortness of breath), fatigue, and uid retention. **Causes:** - **Arteriosclerotic Heart Disease:** Hardening of the arteries. - **Myocardial Infarction (MI):** Heart attack. - **Hypertensive Heart Disease:** Damage from high blood pressure. - **Valvular Heart Disease:** Issues with heart valves. - **Dilated Cardiomyopathy:** Enlarged and weakened heart muscle. - **Congenital Heart Disease:** Heart defects present at birth. ### **II. Role of Physiologic Compensatory Mechanisms in the Progression of HF** **1. Increased Sympathetic Activity:** - **Trigger:** Decreased blood pressure. - **Response:** Increased heart rate, force of contraction, and vasoconstriction. - **Outcome:** Initially helps but increases heart workload, worsening HF over time. **2. Activation of the Renin-Angiotensin-Aldosterone System (RAAS):** - **Trigger:** Reduced blood ow to kidneys. - **Response:** Increased angiotensin II and aldosterone leading to vasoconstriction and uid retention. - **Outcome:** Increased blood volume and pressure, worsening HF symptoms. **3. Myocardial Hypertrophy:** - **Response:** Heart muscle thickens and chambers dilate. - **Types of HF:** - **Systolic HF (HFrEF):** Reduced ejection fraction due to weakened heart contraction. - **Diastolic HF (HFpEF):** Impaired relaxation and lling of the heart. ### **III. Goals of Pharmacologic Intervention in HF** **Objectives:** - **Alleviate Symptoms:** Reduce discomfort and improve quality of life. - **Slow Disease Progression:** Delay worsening of HF. - **Improve Survival:** Enhance long-term outcomes. **Drug Classes Used:** 1. **Angiotensin-Converting Enzyme (ACE) Inhibitors:** - **Examples:** Enalapril, Lisinopril. fi fl fi fl fl  - **Action:** Block conversion of angiotensin I to angiotensin II, reducing blood pressure and uid overload. 2. **Angiotensin-Receptor Blockers (ARBs):** - **Examples:** Losartan, Valsartan. - **Action:** Block the e ects of angiotensin II on its receptors, similar to ACE inhibitors but without a ecting bradykinin levels. 3. **Aldosterone Antagonists:** - **Examples:** Spironolactone, Eplerenone. - **Action:** Block aldosterone receptors, reducing sodium and water retention, and mitigating myocardial brosis. 4. **β-Blockers:** - **Examples:** Metoprolol, Carvedilol, Bisoprolol. - **Action:** Decrease heart rate and contractility, reducing workload and protecting against adverse cardiac remodeling. 5. **Diuretics:** - **Examples:** Furosemide, Hydrochlorothiazide. - **Action:** Reduce uid overload by increasing urine production. 6. **Direct Vaso- and Venodilators:** - **Examples:** Hydralazine, Nitrates (e.g., Nitroglycerin). - **Action:** Directly dilate blood vessels to reduce blood pressure and preload. 7. **Inotropic Agents:** - **Examples:** Digoxin, Dobutamine. - **Action:** Increase the force of heart contraction; used for acute HF or in cases where other treatments are insu cient. ### **IV. Acute (Decompensated) HF** **De nition:** - **Compensated HF:** When adaptive mechanisms restore cardiac output. - **Decompensated HF:** Worsening symptoms due to failure of adaptive mechanisms. **Typical Symptoms:** - Dyspnea on exertion. - Orthopnea (di culty breathing while lying at). - Paroxysmal nocturnal dyspnea. - Fatigue. - Peripheral edema. ### **V. Therapeutic Strategies in HF** **Management:** - **Fluid Limitation:** Restrict intake to less than 1.5-2 liters daily. - **Sodium Restriction:** Limit to less than 2000 mg per day. - **Comorbid Conditions:** Treat associated health issues. - **Medications:** Use diuretics, ACE inhibitors, ARBs, β-blockers, and aldosterone antagonists. **Drugs to Avoid:** - **NSAIDs:** Can worsen uid retention and hypertension. - **Alcohol:** Can exacerbate HF symptoms. - **Nondihydropyridine Calcium Channel Blockers:** (e.g., Verapamil, Diltiazem) Can negatively impact heart function. - **Certain Antiarrhythmics:** May worsen HF. fl fi ff fi ffi ffi fl ff fl fl  Certainly! Here’s the summary and explanation of the information on the **Renin-Angiotensin- Aldosterone System (RAAS) inhibitors** and **β-Blockers**, with a focus on the drugs mentioned: --- ### **III. INHIBITORS OF THE RENIN–ANGIOTENSIN– ALDOSTERONE SYSTEM** **Overview:** HF triggers activation of the RAAS through two main mechanisms: 1. **Reduced Renal Perfusion Pressure:** Caused by the failing heart. 2. **Sympathetic Stimulation:** Activates β receptors on juxtaglomerular cells. **E ects of RAAS Activation:** - **Angiotensin II:** A strong vasoconstrictor that increases blood pressure and stimulates aldosterone release. - **Aldosterone:** Causes salt and water retention, increasing preload (volume of blood returning to the heart) and afterload (resistance the heart has to pump against). - **Direct E ects:** Angiotensin II and aldosterone promote cardiac remodeling, brosis, and in ammation. #### **A. Angiotensin-Converting Enzyme (ACE) Inhibitors** **Mechanism of Action:** - **Function:** Block the enzyme that converts angiotensin I to angiotensin II, reducing its levels. They also increase bradykinin, a vasodilator. - **E ects:** Decreased vasoconstriction, reduced aldosterone secretion, and improved blood ow. They help reduce symptoms and improve survival in HF. **Drugs:** 1. **Captopril** - **Note:** Should be taken on an empty stomach as food can decrease absorption. 2. **Enalapril, Lisinopril** - **Note:** Prodrugs that require hepatic activation, except for captopril. 3. **Fosinopril** - **Note:** Does not require hepatic activation. **Pharmacokinetics:** - Absorbed orally; vary in half-life from 2 to 12 hours. Most are eliminated through the kidneys. **Adverse E ects:** - **Common Issues:** Postural hypotension, renal insu ciency, hyperkalemia (high potassium levels), dry cough, angioedema (rare). - **Monitoring:** Potassium and creatinine levels need regular checks, especially if used with potassium-sparing diuretics or other drugs a ecting renal function. - **Contraindication:** Teratogenic (can cause harm to a fetus) and should not be used during pregnancy. #### **B. Angiotensin Receptor Blockers (ARBs)** **Mechanism of Action:** - **Function:** Block the angiotensin II type 1 receptor, preventing angiotensin II e ects without a ecting bradykinin levels. fl ff fl ff ff ff ff ff ffi fi ff  - **E ects:** Similar to ACE inhibitors but are a good alternative for patients who experience cough or angioedema with ACE inhibitors. **Drugs:** 1. **Losartan** - **Note:** Undergoes extensive rst-pass metabolism to its active metabolite. 2. **Valsartan** - **Note:** Dosed twice a day. 3. **Candesartan** - **Note:** Has a large volume of distribution. **Pharmacokinetics:** - Generally dosed once daily (except valsartan). Eliminated through urine and feces. **Adverse E ects:** - Similar to ACE inhibitors but with a lower incidence of cough and angioedema. Contraindicated in pregnancy. #### **C. Aldosterone Antagonists** **Mechanism of Action:** - **Function:** Block the e ects of aldosterone, reducing sodium and water retention, myocardial hypertrophy, and preventing hypokalemia (low potassium levels). **Drugs:** 1. **Spironolactone** - **Action:** Directly antagonizes aldosterone. 2. **Eplerenone** - **Action:** Selectively antagonizes aldosterone with fewer endocrine-related side e ects due to lower a nity for other hormone receptors. **Indications:** - Used in advanced stages of HFrEF or in patients with recent myocardial infarction. --- ### **IV. β-Blockers** **Overview:** - **Bene t:** Despite their negative inotropic e ect (decreasing force of contraction), β-blockers improve heart function and reverse cardiac remodeling by counteracting chronic sympathetic nervous system activation. **Drugs:** 1. **Bisoprolol** - **Action:** β1-selective antagonist, reducing heart rate and myocardial workload. 2. **Carvedilol** - **Action:** Nonselective β-blocker with additional α1-blocking activity, bene cial for reducing vascular resistance. 3. **Metoprolol Succinate** - **Action:** Long-acting β1-selective blocker. **Administration and Monitoring:** - **Starting Dose:** Begin with low doses and gradually increase based on tolerance. ff fi ffi ff ff fi ff fi ff  - **Interactions:** Metabolized by CYP2D6; caution with CYP2D6 inhibitors and P-glycoprotein (P- gp) inhibitors. Monitor for interactions with other drugs a ecting heart conduction (e.g., amiodarone, verapamil, diltiazem). **E ects:** - **Positive Outcomes:** Reduced morbidity and mortality in HFrEF. **Note:** β-blockers should be used with caution in combination with other drugs that slow AV conduction or have similar metabolic pathways. Certainly! Here’s a detailed summary of each section: --- ### **V. DIURETICS** **Purpose:** - **Relieve Symptoms:** Diuretics are primarily used to alleviate symptoms of uid overload in heart failure (HF), such as pulmonary congestion ( uid in the lungs) and peripheral edema (swelling in the legs and arms). - **Mechanism:** They reduce the volume of plasma in the blood (plasma volume), which lowers the amount of blood returning to the heart (venous return or preload). This helps to decrease the workload on the heart and reduce oxygen demand. By decreasing plasma volume, they can also lower blood pressure, which can reduce resistance (afterload) on the heart. **Types of Diuretics:** 1. **Loop Diuretics:** - **Commonly Used:** These are the most e ective diuretics for HF, particularly when patients require signi cant diuresis or have renal insu ciency. - **Examples:** - **Furosemide [FU-roe-se-mide]:** Often used for its strong diuretic e ect. - **Bumetanide [bue-MET-a-nide]:** Similar to furosemide but more potent. - **Torsemide [TOR-se-mide]:** Another option with a longer duration of action. - **Note:** Overdosing can lead to hypovolemia (severely low blood volume), which can be dangerous. **E ectiveness:** - **No Impact on Survival:** While diuretics are e ective in managing symptoms related to uid overload, they do not improve overall survival in HF. They are used to treat signs and symptoms rather than to modify the underlying disease course. --- ### **VI. VASO- AND VENODILATORS** **Purpose:** - **Decrease Preload:** By dilating venous blood vessels, these agents increase the capacity of the veins to hold blood, thus reducing the volume of blood returning to the heart (preload). This reduces the heart's workload. - **Decrease Afterload:** Arterial dilators reduce the resistance that the heart has to pump against (afterload), which can lower blood pressure and make it easier for the heart to pump blood. **Types of Vasodilators:** 1. **Nitrates:** - **Function:** Act primarily as venous dilators, reducing preload. - **Examples:** - **Isosorbide Dinitrate [eye-soe-SOR-bide dye-NYE-trate]:** Often used in combination with other agents. ff ff fi ffi ff ff fl ff ff fl fl  - **Nitroglycerin:** Commonly used for its rapid action. - **Adverse E ects:** Headaches, hypotension (low blood pressure), and tachycardia (rapid heart rate) are common. Rarely, hydralazine (a type of nitrate) can cause drug-induced lupus. 2. **Arterial Dilators:** - **Function:** Reduce systemic arteriolar resistance, thus decreasing afterload. - **Example:** - **Hydralazine [hye-DRAL-a-zeen]:** E ective in lowering systemic vascular resistance. 3. **Combination Therapy:** - **Example:** A xed-dose combination of hydralazine and isosorbide dinitrate. - **Bene t:** Shown to improve symptoms and survival in black patients with HFrEF (Heart Failure with reduced Ejection Fraction) when used alongside standard treatments (such as β- blockers and ACE inhibitors). --- ### **VII. INOTROPIC DRUGS** **Purpose:** - **Enhance Cardiac Contractility:** These drugs increase the force of heart muscle contractions, which improves cardiac output (the amount of blood the heart pumps). They are used to improve heart function in HF. **Types of Inotropic Drugs:** **A. Digitalis Glycosides** ### **Digoxin [di-JOX-in]** **Overview:** Digoxin is a cardiac glycoside used primarily for its positive inotropic e ects, which enhance cardiac contractility. It is derived from the foxglove plant and has been a staple in heart failure management for decades. Despite its bene ts, digoxin has a narrow therapeutic index, making careful monitoring essential. **1. Mechanism of Action:** - **Calcium Regulation:** - **Inhibition of Na+/K+-ATPase:** Digoxin inhibits the Na+/K+-ATPase enzyme on the cell membrane of cardiac myocytes (heart muscle cells). This enzyme normally pumps sodium (Na+) out of the cell and potassium (K+) into the cell. - **Increased Intracellular Sodium:** By inhibiting this pump, digoxin decreases the concentration of sodium inside the cell. - **Reduced Na+/Ca2+ Exchanger Activity:** The decrease in intracellular sodium reduces the activity of the Na+/Ca2+ exchanger, which normally pumps calcium (Ca2+) out of the cell in exchange for sodium. - **Increased Intracellular Calcium:** As a result, calcium accumulates inside the cell, increasing the availability of calcium for cardiac muscle contraction. - **Enhanced Contractility:** - **Improved Cardiac Output:** The increased intracellular calcium enhances the contractility of cardiac muscle cells, leading to stronger heart contractions and improved cardiac output. - **Increased Vagal Tone:** Digoxin enhances vagal (parasympathetic) tone, slowing down the heart rate and reducing myocardial oxygen demand. This e ect helps in controlling atrial brillation and utter. - **Slowed Conduction Through AV Node:** - **Use in Atrial Fibrillation:** By slowing conduction through the atrioventricular (AV) node, digoxin can help control ventricular rates in atrial brillation and atrial utter. fi fi fl ff fi ff fi fi ff fl ff  **2. Therapeutic Uses:** - **Heart Failure:** - **Indication:** Used in patients with severe Heart Failure with reduced Ejection Fraction (HFrEF) after initiating therapy with ACE inhibitors, β-blockers, and diuretics. It is not typically used as a rst-line treatment but is considered when symptoms persist despite other therapies. - **Serum Concentration:** E ective at low serum concentrations (0.5 to 0.8 ng/mL). At this level, it can help reduce HF hospitalizations and improve symptoms. - **Atrial Fibrillation:** - **Rate Control:** Bene cial for controlling ventricular rates in patients with atrial brillation or atrial utter. **3. Pharmacokinetics:** - **Absorption:** - **Forms:** Available in oral (tablet, capsule) and injectable (intravenous) forms. - **Volume of Distribution:** Large volume of distribution; digoxin accumulates in muscle tissue. - **Dosage:** Dosed based on lean body weight. - **Half-Life:** - **Duration:** Long half-life of 30 to 40 hours, allowing for once-daily dosing or less frequent administration in stable patients. - **Elimination:** - **Excretion:** Primarily excreted by the kidneys. Dosage adjustments are necessary in patients with renal impairment to avoid toxicity. **4. Adverse E ects:** - **Common Adverse E ects:** - **Gastrointestinal Symptoms:** Anorexia, nausea, vomiting. - **Visual Changes:** Blurred vision, yellow vision (xanthopsia). - **Cardiac Arrhythmias:** Due to its e ect on the Na+/K+-ATPase pump, digoxin can cause various arrhythmias, including premature ventricular contractions and, rarely, ventricular tachycardia. - **Toxicity:** - **Symptoms:** Symptoms of digoxin toxicity can include severe nausea, vomiting, confusion, visual disturbances, and arrhythmias. - **Management:** Manage toxicity by discontinuing the drug, monitoring and correcting electrolyte imbalances (particularly potassium), and using digoxin-speci c antibodies (digoxin immune Fab) if necessary. - **Drug Interactions:** - **P-glycoprotein (P-gp) Inhibitors:** Drugs like clarithromycin, verapamil, and amiodarone can increase digoxin levels by inhibiting P-gp, leading to higher risk of toxicity. - **Diuretics:** Use of diuretics (especially thiazide or loop diuretics) can cause hypokalemia, which can increase the risk of digoxin toxicity, as digoxin competes with potassium for binding to the Na+/K+-ATPase pump. **5. Special Considerations:** - **Therapeutic Monitoring:** - **Regular Monitoring:** Regular monitoring of serum digoxin levels is necessary to ensure they remain within the therapeutic range and to adjust dosage as needed. - **Electrolyte Levels:** Monitoring and managing electrolyte levels (especially potassium) is critical due to the risk of toxicity. fi fl ff ff fi ff ff fi fi  - **Cautions:** - **Renal Function:** Dose adjustments are crucial for patients with impaired renal function to avoid accumulation and toxicity. **Conclusion:** Digoxin is a valuable drug for certain patients with heart failure and atrial brillation due to its e ects on cardiac contractility and rate control. However, its narrow therapeutic index requires careful monitoring to avoid toxicity. Digitoxin [dij-i-TOK-sin] Overview: Digitoxin is another cardiac glycoside similar to digoxin, derived from the foxglove plant. It is used to enhance cardiac contractility and manage heart failure, but it is less commonly used today due to its prolonged duration of action and potential for toxicity. 1. Mechanism of Action: Similar to Digoxin: ◦ Inhibition of Na+/K+-ATPase: Like digoxin, digitoxin inhibits the Na+/K+-ATPase enzyme on the cell membranes of cardiac myocytes. This inhibition decreases the intracellular concentration of potassium and increases the concentration of sodium inside the cell. ◦ Increased Intracellular Calcium: The increased intracellular sodium reduces the activity of the Na+/Ca2+ exchanger, leading to an accumulation of calcium inside the cell. This elevated calcium enhances the contractility of cardiac muscle cells. Increased Contractility: ◦ Enhanced Cardiac Output: Digitoxin increases the force of cardiac muscle contraction, improving cardiac output and e cacy. ◦ Decreased Heart Rate: Similar to digoxin, digitoxin can enhance vagal tone, slowing the heart rate and reducing myocardial oxygen demand. Neurohormonal E ects: ◦ Sympathetic Activation: Digitoxin also impacts neurohormonal regulation, but its speci c e ects are less well understood compared to digoxin. 2. Therapeutic Uses: Heart Failure: ◦ Indication: Digitoxin was used in the treatment of heart failure, particularly when digoxin was not available or suitable. It is less frequently used today due to the preference for digoxin and other modern treatments. ◦ Usage: Like digoxin, it was used to improve symptoms of heart failure and enhance cardiac output. Atrial Fibrillation: ◦ Rate Control: Similar to digoxin, digitoxin may have been used to control the ventricular rate in patients with atrial brillation, though this use has declined. 3. Pharmacokinetics: Absorption: ◦ Forms: Available in oral form. It is well-absorbed from the gastrointestinal tract. ◦ Volume of Distribution: Digitoxin has a large volume of distribution, and it accumulates in tissues, including the heart. Half-Life: ◦ Duration: Digitoxin has a long half-life, generally longer than digoxin, ranging from several days to weeks. This long half-life necessitates careful dosing and monitoring. Elimination: ◦ Metabolism: Primarily metabolized in the liver. It is excreted slowly, mainly through bile and feces, which contributes to its prolonged duration of action. 4. Adverse E ects: Common Adverse E ects: ◦ Similar to Digoxin: Includes gastrointestinal symptoms like nausea, vomiting, and loss of appetite. ◦ Visual Disturbances: Can cause blurred vision and yellow vision. Toxicity: ff ff ff ff ff fi ffi fi fi  ◦ Symptoms: Toxicity can present with severe gastrointestinal symptoms, confusion, and arrhythmias. ◦ Management: Toxicity management involves discontinuation of the drug and supportive care, including correction of electrolyte imbalances and, if necessary, the use of digoxin immune Fab (though this is more commonly used for digoxin). Drug Interactions: ◦ Similar Considerations: Like digoxin, digitoxin interacts with other drugs that a ect P- glycoprotein and renal function. 5. Special Considerations: Therapeutic Monitoring: ◦ Regular Monitoring: Due to its long half-life and narrow therapeutic index, regular monitoring of serum levels is crucial. ◦ Electrolyte Levels: Monitoring electrolytes, especially potassium, is important to prevent toxicity. Historical Context: ◦ Current Use: Digitoxin is less commonly used today due to the availability of newer therapies and the potential for more severe and prolonged side e ects compared to digoxin. Digitoxin [dij-i-TOK-sin] Overview: Digitoxin is another cardiac glycoside similar to digoxin, derived from the foxglove plant. It is used to enhance cardiac contractility and manage heart failure, but it is less commonly used today due to its prolonged duration of action and potential for toxicity. 1. Mechanism of Action: Similar to Digoxin: ◦ Inhibition of Na+/K+-ATPase: Like digoxin, digitoxin inhibits the Na+/K+-ATPase enzyme on the cell membranes of cardiac myocytes. This inhibition decreases the intracellular concentration of potassium and increases the concentration of sodium inside the cell. ◦ Increased Intracellular Calcium: The increased intracellular sodium reduces the activity of the Na+/Ca2+ exchanger, leading to an accumulation of calcium inside the cell. This elevated calcium enhances the contractility of cardiac muscle cells. Increased Contractility: ◦ Enhanced Cardiac Output: Digitoxin increases the force of cardiac muscle contraction, improving cardiac output and e cacy. ◦ Decreased Heart Rate: Similar to digoxin, digitoxin can enhance vagal tone, slowing the heart rate and reducing myocardial oxygen demand. Neurohormonal E ects: ◦ Sympathetic Activation: Digitoxin also impacts neurohormonal regulation, but its speci c e ects are less well understood compared to digoxin. 2. Therapeutic Uses: Heart Failure: ◦ Indication: Digitoxin was used in the treatment of heart failure, particularly when digoxin was not available or suitable. It is less frequently used today due to the preference for digoxin and other modern treatments. ◦ Usage: Like digoxin, it was used to improve symptoms of heart failure and enhance cardiac output. Atrial Fibrillation: ◦ Rate Control: Similar to digoxin, digitoxin may have been used to control the ventricular rate in patients with atrial brillation, though this use has declined. 3. Pharmacokinetics: Absorption: ◦ Forms: Available in oral form. It is well-absorbed from the gastrointestinal tract. ◦ Volume of Distribution: Digitoxin has a large volume of distribution, and it accumulates in tissues, including the heart. Half-Life: ◦ Duration: Digitoxin has a long half-life, generally longer than digoxin, ranging from several days to weeks. This long half-life necessitates careful dosing and monitoring. Elimination: ff ff fi ffi ff ff fi  ◦ Metabolism: Primarily metabolized in the liver. It is excreted slowly, mainly through bile and feces, which contributes to its prolonged duration of action. 4. Adverse E ects: Common Adverse E ects: ◦ Similar to Digoxin: Includes gastrointestinal symptoms like nausea, vomiting, and loss of appetite. ◦ Visual Disturbances: Can cause blurred vision and yellow vision. Toxicity: ◦ Symptoms: Toxicity can present with severe gastrointestinal symptoms, confusion, and arrhythmias. ◦ Management: Toxicity management involves discontinuation of the drug and supportive care, including correction of electrolyte imbalances and, if necessary, the use of digoxin immune Fab (though this is more commonly used for digoxin). Drug Interactions: ◦ Similar Considerations: Like digoxin, digitoxin interacts with other drugs that a ect P- glycoprotein and renal function. 5. Special Considerations: Therapeutic Monitoring: ◦ Regular Monitoring: Due to its long half-life and narrow therapeutic index, regular monitoring of serum levels is crucial. ◦ Electrolyte Levels: Monitoring electrolytes, especially potassium, is important to prevent toxicity. Historical Context: ◦ Current Use: Digitoxin is less commonly used today due to the availability of newer therapies and the potential for more severe and prolonged side e ects compared to digoxin. **B. β-Adrenergic Agonists** 1. **Dobutamine [doe-BYOO-ta-meen]:** - **Action:** Increases cardiac contractility and causes vasodilation through enhanced cAMP levels and calcium entry into heart cells. - **Use:** Primarily for short-term treatment of acute HF in a hospital setting. 2. **Dopamine [DOH-puh-meen]:** - **Action:** Similar to dobutamine, it increases intracellular cAMP and calcium, improving cardiac contractility. - **Use:** Used in acute HF, administered via intravenous infusion. **C. Phosphodiesterase Inhibitors** 1. **Milrinone [MIL-rih-nohn]:** - **Action:** Inhibits phosphodiesterase, increasing intracellular cAMP and calcium levels, thereby enhancing cardiac contractility. - **Use:** Short-term treatment for acute HF. Long-term use may increase mortality risk, particularly in patients with coronary artery disease. Short-term use is generally considered safe and bene cial. --- This detailed explanation covers each drug class, their speci c actions, therapeutic uses, pharmacokinetics, and potential adverse e ects. fi ff ff ff ff fi ff