Pharmacology of Digoxin and Heart Conditions

Heart Failure

• Heart failure is a condition, once called "dropsy" or decompensation, involving dysfunction of the cardiac muscle.
• The sarcomere is the basic unit of the cardiac muscle.
• A sarcomere contains contractile proteins, actin and myosin, that interact but are kept apart at rest by troponin.
• Heart failure results from conditions damaging or overworking the heart muscle.
• Coronary artery disease is a cause of heart failure. It reduces blood flow, causing oxygen deficiency and impaired muscle function. Severe heart failure can result in a heart attack (MI), leading to heart muscle death and further impairing the heart's ability to pump blood.

Cardiomyopathy

• Cardiomyopathy is a heart muscle disease that can lead to an enlarged heart and eventual complete heart failure.
• Cardiomyopathy can be caused by viral infections, alcoholism, steroid abuse, or collagen disorders.
• It alters the heart muscle so that contraction and pumping are ineffective.

Hypertension

• Hypertension (high blood pressure) forces the heart to work harder, leading to enlarged heart muscle.
• Increased workload can cause heart failure.

Valvular Heart Disease

• Valvular heart disease leads to an overload of the ventricles.
• This occurs because the heart valves do not close tightly, allowing blood to leak backward into the ventricles.

Cardiotonic Agents

• Cardiotonic drugs increase calcium levels in heart muscle, boosting contraction strength and cardiac output, increasing urine production and decreasing blood volume, resulting in reduced heart workload.
• Cardiac glycosides were originally derived from the foxglove or digitalis plant. Digoxin (Lanoxin) is the most commonly used drug in modern times.

Actions and Indications of Digoxin

• Digoxin increases calcium in heart muscles, leading to stronger contractions (positive inotropic effect) and a slower heart rate (negative chronotropic effect).
• It reduces the heart's workload and increases urine output, lowering blood volume.
• It is used to treat heart failure, atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia.
• A narrow therapeutic margin exists, requiring careful monitoring between the therapeutic dose and toxic dose.

Pharmacokinetics of Digoxin

• Digoxin is available in oral and intravenous forms.
• Digoxin has rapid onset of action and absorption, typically within 30-120 minutes after oral dosing and 5-30 minutes after IV administration.
• Digoxin is distributed throughout the body.
• It is primarily excreted unchanged in the urine, so caution is required in patients with renal impairment, where the drug can accumulate and cause toxicity.

Contraindications and Cautions of Digoxin

• Digoxin use is contraindicated in patients with allergies to its components and with ventricular tachycardia or fibrillation, heart block, sick sinus syndrome, idiopathic hypertrophic subaortic stenosis (IHHS), acute MI, and renal/electrolyte abnormalities (high calcium, low potassium or magnesium).
• Use is also cautious in pregnant or lactating women due to potential effects on the fetus or neonate.
• Pediatric and geriatric patients are at higher risk for adverse effects and require close monitoring.

Adverse Effects of Digoxin

• Common adverse effects with Digoxin include headache, weakness, drowsiness, and vision changes (yellow halo around objects).

Antiarrhythmics

• Arrhythmias are abnormal heart rhythms where the electrical impulses coordinatating heartbeats don't work properly, and the heart beats too fast, too slowly, or irregularly.

Classification of Antiarrhythmics

• Class 1 Antiarrhythmics are sodium channel blockers.
• Class IB: Lidocaine is rapidly absorbed and has a short duration of action, used intravenously.
• Class IC: Flecainide and Propafenone are absorbed orally and have a longer duration of action.
• Class IA: Quinidine and Procainamide are absorbed orally with a long half-life.

Adverse Effects of Class 1 Antiarrhythmics

• CNS: dizziness, drowsiness, fatigue, twitching, numbness, slurred speech, vision changes, including convulsions.
• Gastrointestinal System: nausea, vomiting, changes in taste
• Other systems: Adverse effects with cardiac glycosides include headache, weakness, drowsiness, and vision changes (yellow halo around objects)
• Class I and other antiarrhythmics can induce adverse effects affecting the central nervous system (CNS), gastrointestinal (GI) system, cardiovascular system, and respiratory system.

Class II Antiarrhythmics

• Class II antiarrhythmics work by blocking beta-adrenergic receptors, inhibiting the effects of norepinephrine and epinephrine on the heart.
• This leads to decreased heart rate, reduced cardiac contractility, and prolonged atrioventricular (AV) node conduction time.
• Common uses include management of premature ventricular contractions, intraoperative/postoperative tachycardia, and as an antihypertensive.

Class III Antiarrhythmics

• Class III antiarrhythmics block potassium channels, slowing the outward movement of potassium during phase III of the action potential, prolonging it.
• Includes drugs like amiodarone, dofetilide, ibutilide, sotalol, and sotalol betapace AP.

Class IV Antiarrhythmics

• These drugs block the movement of calcium ions across the cell membrane, depressing the generation of action potentials and delaying repolarization.
• This slows automaticity and conduction.
• Includes diltiazem and verapamil.

Other Antiarrhythmics

• Drugs such as adenosine and Digoxin (discussed above).

Antianginal Agents

• Antianginal agents are used to relieve and prevent angina (chest pain).
• They work by either increasing the heart's oxygen supply or decreasing oxygen demand.

Types of Antianginal Agents

• Nitrates: Examples: Nitroglycerin, Isosorbide Mononitrate, Isosorbide Dinitrate, Mechanism: Dilate blood vessels, increasing blood flow to the heart.
• Beta-Adrenergic Blockers: Examples: Propranolol, Metoprolol, Atenolol, Mechanism: Reduce heart rate and contractility, decreasing oxygen demand
• Calcium Channel Blockers: Examples: Amlodipine, Diltiazem, Verapamil, Mechanism: Inhibit calcium entry into cells, relaxing blood vessels and reducing heart workload
• Ranolazine: Mechanism: Inhibits ion channels during cardiac repolarization, reducing oxygen demand, Uses: Chronic angina management.

Lipid-Lowering Agents

• Lipid-lowering agents are used to lower lipids (fats) in the blood, particularly cholesterol and triglycerides.
• They are crucial in managing and preventing cardiovascular diseases.
• These include statins (HMG-CoA Reductase Inhibitors), fibrates, bile acid sequestrants, cholesterol absorption inhibitors, and PCSK9 inhibitors.
• Common side effects include muscle pain, increased liver enzymes, and (rarely) increased diabetes risk.

Drugs Affecting Coagulation

• Anticoagulants: Prevent clot formation.
• Antiplatelets: Prevent platelets from clumping to form clots.
• Thrombolytics: Dissolve existing clots.

Anemia

• Anemia is a condition characterized by a deficiency in the number or quality of red blood cells or hemoglobin, a protein that carries oxygen.
• This reduced oxygen-carrying capacity in the blood leads to a variety of symptoms and complications.
• Conditions that can cause anemia can be treated with iron, vitamin B12, or folate supplements depending on underlying cause.

Medications for Hemolytic Anemias

• Used to treat anemias caused by the destruction of red blood cells.
• Examples include corticosteroids and immunosuppressants.

Medications for Thalassemia and Sickle Cell Anemia

• Medications help manage symptoms.
• Examples include hydroxyurea and luspatercept.

Medications for Anemia of Chronic Disease

• Medications aim to address the underlying inflammation or infection.
• Examples include erythropoiesis-stimulating agents and iron supplements.

Test your knowledge on the pharmacology of Digoxin, including its onset of action, contraindications, and effects on heart rhythm. This quiz covers critical aspects related to cardiac glycosides and their impact on heart failure and arrhythmias.