Cardiovascular Diseases Quiz

Pharmacological Treatments for Cardiovascular Diseases

• The vascular endothelium plays a key role in regulating blood flow, inflammation, and blood fluidity. It is a target for treating coagulation disorders.
• The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure. Drugs are used to control hypertension by acting on this system.
• Key learning objectives include describing the role of vascular endothelium, revising the RAAS, explaining how drugs control hypertension through their action on RAAS, and describing how drugs treat cardiovascular diseases like stable angina, acute coronary syndrome, heart failure, and arrhythmia.
• Cardiovascular diseases include cardiac problems like ischemic heart disease, myocardial infarction, heart failure, valvular problems (aortic, rheumatic heart disease), myocardial and pericardial issues, congenital defects, and arrhythmias. Vascular problems include peripheral arterial disease, cerebrovascular disease, hypertension, and kidney disease.
• Cardiovascular diseases are a significant global health concern, causing 32% of deaths in 2019. In England and Wales, they were the second leading cause of death in 2019.
• Myocardial infarction and stroke accounted for 85% of CVD deaths globally.
• Cardiovascular disease (CVD) accounted for one million hospital admissions in England, leading to 5.5 million bed days and costing £7.4 billion.
• Major classes of drugs and their mechanisms of action are crucial for treating CVD.

Vascular Endothelium

• Vascular endothelium has a pivotal role in regulating vascular tone.
• It controls blood flow and inflammatory responses and maintains blood fluidity.
• Factors like inflammation, high blood pressure, and high cholesterol levels can damage the endothelium

Rupture and Thrombosis

• Rupture of fibrous cap (protective layer over plaque) leads to blood clot formation.
• This disruption causes platelet aggregation and thrombus formation.
• Loss of endothelial layer integrity contributes

Lipid-Lowering Therapy (Statins)

• Statins, such as atorvastatin, inhibit HMG-CoA reductase.
• This enzyme is a rate-limiting step in cholesterol synthesis.
• Statins reduce hepatic cholesterol synthesis, upregulating LDL receptors.
• This increases LDL clearance from the blood and decreases plasma triglycerides and increases HDL.

Anti-platelet therapy

• Aspirin is an irreversible inhibitor of cyclooxygenase (COX) in platelets.
• It covalently binds to the enzyme, preventing platelets from making new COX, and impeding platelet aggregation.
• Low dose inhibits COX-1 and high dose inhibits COX-2.
• COX-1 converts arachidonic acid to prostaglandin H₂, a precursor for other prostaglandins.
• This also creates thromboxane A₂, which is a potent platelet aggregator.
• Clopidogrel and Ticagrelor are P2Y12 antagonists that prevent platelet aggregation by inhibiting the P2Y12 receptor.
• Inhibition of P2Y₁₂ has anti-platelet aggregation properties and prevents thrombus formation.

Thrombolytic Therapy

• Plasminogen activators (e.g., streptokinase, tissue plasminogen activator (tPA)) are used to activate plasminogen.
• This leads to fibrin degradation.
• Thrombolytic therapy dissolves blood clots and restores blood flow.
• A complication of this treatment is bleeding.

Anticoagulants

• Anticoagulants, sometimes called blood thinners, target different parts of the coagulation pathway.
• Vitamin K antagonists (e.g., warfarin) work indirectly by affecting factors in the coagulation cascade.
• Direct thrombin inhibitors directly inhibit thrombin.
• Direct factor Xa inhibitors target another crucial enzyme in the clotting cascade.
• Indirect thrombin inhibitors (e.g., heparin) also influence thrombin signaling through other pathways.

Renin-Angiotensin-Aldosterone System (RAAS)

• The Renin-Angiotensin-Aldosterone System (RAAS) is a crucial hormonal cascade involved in regulating blood pressure and fluid balance.
• RAAS activation is triggered by various factors, including sympathetic nerve activation, low blood pressure in the renal arteries, and reduced sodium delivery to distal tubules of the kidney.
• Angiotensin-converting enzyme (ACE) inhibitors reduce vascular resistance, lowering blood pressure by interfering with the formation of angiotensin II (a potent vasoconstrictor).
• Angiotensin II receptor blockers (ARBs) directly block angiotensin II receptors.
• This prevents increased vascular tone and blood pressure effects.
• Renin inhibitors block the initial step of the RAAS.
• Aldosterone antagonists interfere with the hormone aldosterone that regulates salt and water reabsorption.
• This helps reduce blood pressure and fluid retention.
• Thiazide diuretics and loop diuretics increase salt loss in the urine to reduce blood pressure and volume.

Therapeutic targets in RAAS

• Angiotensin II receptor blockers (ARBs) block the action of angiotensin II.
• ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II.
• Renin inhibitors limit the formation of angiotensin I.
• Mineralocorticoid receptor antagonists target aldosterone, reducing Na+ reabsorption.
• Thiazide and loop diuretics are used to reduce blood volume by increasing urine excretion.

Hypertension Management

• Hypertension is the leading cause of cardiovascular disease.
• Lifestyle modifications (diet, exercise, stress management) and drug therapy (diuretics, ACE inhibitors, ARBs) help manage hypertension.
• Treatment differs based on severity, the presence of other risk factors like diabetes or other comorbidities, and potential complications.
• The goal of treatment is blood pressure control (within a specific timeframe).

Coronary Artery Disease (CAD)

• CAD involves narrowing of coronary arteries.
• Stable angina is predictable chest pain due to reduced blood supply to the heart.
• Acute coronary syndrome (ACS) occurs when blood flow to the heart is severely reduced or blocked (e.g., heart attack).
• Treatment involves administering vasodilators (like nitrates), calcium channel blockers, and beta-blockers.

Nitrates

• Nitrates increase nitric oxide (NO) production, leading to smooth muscle relaxation, thereby dilating vessels.
• This improves blood flow to the heart, reducing angina pain.

Beta-blockers

• Beta-blockers reduce heart rate and contractility, lowering myocardial oxygen demand.
• They also lower blood pressure through reduced peripheral vascular resistance and decreased sympathetic stimulation.

Heart Failure

• Heart failure occurs when the heart cannot pump enough blood to meet the body's needs.
• It can result from structural or functional abnormalities.
• Treatments aim to improve cardiac function, reduce symptoms, and prevent hospitalizations.
• Heart failure classification is based on the ejection fraction (EF), which measures how much blood is pumped out with each contraction.
• Reduced EF (≤40%) implies systolic heart failure. Preserved EF (≥50%) indicates diastolic heart failure.

Antiarrhythmic Drugs

• Antiarrhythmic drugs correct abnormalities in the cardiac conduction system.
• Different classes target various phases of the cardiac action potential (e.g., sodium, potassium, calcium channels).
• They work differently across different heart cells (pacemaker cells vs cardiac muscle cells) that exhibit varied sensitivity.

SGLT2 Inhibitors

• SGLT2 inhibitors decrease glucose reabsorption in the kidneys.
• They also reduce the risk of composite cardiovascular death or hospitalization in patients with heart failure (HF).

Cardiac Glycosides

• Cardiac glycosides, like Digoxin, increase the force of cardiac contractions (positive inotropy), slow the heart rate, and regulate AV conduction.

General notes

• Each page describes a specific topic/section within the presented cardiac/cardiovascular material
• The presentation, or course material, is organized logically and methodically, presenting details about the effects of drugs on heart function and blood pressure regulation.