Intro to Pharmacology Unit 7 ReviewCardiovascular and Renal Pharmacotherapy

Key Concepts and Terminology

• Pharmacodynamics studies how drugs interact with target sites in the body and produce pharmacological effects
• Pharmacokinetics examines the absorption, distribution, metabolism, and excretion of drugs in the body
• Bioavailability represents the fraction of an administered drug that reaches systemic circulation unchanged
• Half-life $(t_{1/2})$ time required for the concentration of a drug in the body to decrease by half
• Steady-state concentration achieved when the rate of drug administration equals the rate of drug elimination
• Therapeutic index $(TI)$ measures the safety of a drug by comparing the dose that produces the desired effect to the dose that causes toxicity
• Adverse drug reactions (ADRs) unintended and harmful responses to medications at normal doses
  • Type A reactions dose-dependent and predictable based on the drug's pharmacology
  • Type B reactions idiosyncratic, unpredictable, and not related to the drug's pharmacology

Cardiovascular System Basics

• Heart serves as a pump to circulate blood throughout the body via a network of blood vessels
• Cardiac cycle consists of systole (contraction) and diastole (relaxation) of the heart chambers
• Coronary arteries supply oxygenated blood to the heart muscle (myocardium)
• Atherosclerosis progressive narrowing and hardening of arteries due to plaque buildup
  • Increases the risk of myocardial infarction (heart attack) and stroke
• Blood pressure product of cardiac output and peripheral vascular resistance
  • Systolic pressure maximum pressure during heart contraction
  • Diastolic pressure minimum pressure during heart relaxation
• Baroreceptors detect changes in blood pressure and initiate compensatory mechanisms via the autonomic nervous system
• Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and fluid balance by controlling vasoconstriction and sodium retention

Renal System Overview

• Kidneys filter blood, remove waste products, and maintain fluid and electrolyte balance
• Nephrons functional units of the kidney, consisting of the glomerulus and tubular system
  • Glomerulus cluster of capillaries where blood filtration occurs
  • Tubular system site of selective reabsorption and secretion of substances
• Glomerular filtration rate (GFR) volume of fluid filtered by the glomeruli per unit time, a measure of kidney function
• Renin enzyme released by the juxtaglomerular cells in response to decreased renal perfusion pressure or sympathetic stimulation
  • Initiates the RAAS cascade, leading to vasoconstriction and sodium retention
• Antidiuretic hormone (ADH) regulates water reabsorption in the collecting ducts to maintain fluid balance
• Aldosterone mineralocorticoid hormone that promotes sodium reabsorption and potassium excretion in the distal tubules and collecting ducts
• Renal clearance rate at which a substance is removed from the plasma by the kidneys, a measure of drug elimination

Drug Classes and Mechanisms

• Diuretics increase urine production and promote the excretion of sodium and water
  • Loop diuretics (furosemide) inhibit the Na+-K+-2Cl- cotransporter in the thick ascending limb of the loop of Henle
  • Thiazide diuretics (hydrochlorothiazide) inhibit the Na+-Cl- cotransporter in the distal convoluted tubule
• ACE inhibitors (lisinopril) block the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion
• Angiotensin receptor blockers (ARBs) (losartan) prevent angiotensin II from binding to its receptor, producing effects similar to ACE inhibitors
• Beta-blockers (metoprolol) block the effects of catecholamines on beta-adrenergic receptors, reducing heart rate and contractility
• Calcium channel blockers (amlodipine) inhibit calcium influx into vascular smooth muscle cells and cardiomyocytes, causing vasodilation and reduced contractility
• Statins (atorvastatin) inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, lowering LDL cholesterol levels
• Antiplatelet agents (aspirin, clopidogrel) inhibit platelet aggregation and reduce the risk of thrombosis

Common Medications and Their Uses

• Furosemide (Lasix) loop diuretic used to treat edema and hypertension
• Hydrochlorothiazide thiazide diuretic used to treat hypertension and heart failure
• Lisinopril ACE inhibitor used to treat hypertension, heart failure, and post-myocardial infarction
• Losartan ARB used to treat hypertension and diabetic nephropathy
• Metoprolol beta-blocker used to treat hypertension, angina, and post-myocardial infarction
  • Selective for beta-1 receptors, reducing cardiac effects compared to non-selective beta-blockers
• Amlodipine calcium channel blocker used to treat hypertension and angina
• Atorvastatin (Lipitor) statin used to lower LDL cholesterol and reduce the risk of cardiovascular events
• Aspirin antiplatelet agent used to prevent thrombotic events in patients with cardiovascular disease
• Clopidogrel (Plavix) antiplatelet agent used to prevent thrombotic events in patients with acute coronary syndrome or after stent placement

Side Effects and Interactions

• Diuretics may cause electrolyte imbalances (hypokalemia, hyponatremia), dehydration, and orthostatic hypotension
  • Thiazide diuretics can cause hyperglycemia and worsen diabetes control
• ACE inhibitors and ARBs may cause hypotension, hyperkalemia, and renal dysfunction, especially in patients with pre-existing renal impairment
  • Can cause dry cough (ACE inhibitors) or angioedema (rare)
• Beta-blockers may cause bradycardia, fatigue, and bronchospasm in patients with asthma or COPD
  • Can mask symptoms of hypoglycemia in diabetic patients
• Calcium channel blockers may cause peripheral edema, headache, and gingival hyperplasia
  • Can cause reflex tachycardia, especially with dihydropyridines (amlodipine)
• Statins may cause myopathy, rhabdomyolysis (rare), and elevated liver enzymes
  • Can interact with other medications metabolized by CYP3A4 (simvastatin, atorvastatin)
• Antiplatelet agents may cause bleeding, especially when combined with other anticoagulants or NSAIDs
  • Aspirin can cause gastrointestinal irritation and ulceration

Patient Assessment and Monitoring

• Assess blood pressure, heart rate, and renal function before initiating therapy and periodically during treatment
• Monitor electrolytes (potassium, sodium) and renal function in patients taking diuretics, ACE inhibitors, or ARBs
• Evaluate for signs and symptoms of fluid overload (edema, dyspnea) or dehydration (orthostatic hypotension, decreased urine output)
• Assess for adverse drug reactions and adjust therapy as needed
  • Consider dose reduction or alternative therapy in patients with intolerable side effects
• Monitor LDL cholesterol levels in patients taking statins and adjust dose to achieve target goals
• Assess for bleeding risk and monitor for signs of bleeding in patients taking antiplatelet agents
  • Educate patients on the importance of reporting any unusual bleeding or bruising
• Regularly review medication adherence and address any barriers to compliance
  • Provide patient education on the proper use, storage, and potential side effects of medications

Clinical Applications and Case Studies

• Case 1 62-year-old male with a history of hypertension and heart failure presents with shortness of breath and peripheral edema
  • Initiate furosemide to reduce fluid overload and improve symptoms
  • Add lisinopril to optimize heart failure management and reduce mortality risk
  • Monitor renal function, electrolytes, and blood pressure closely during titration
• Case 2 55-year-old female with uncontrolled hypertension despite lifestyle modifications
  • Start amlodipine as initial therapy to lower blood pressure
  • If blood pressure remains uncontrolled, consider adding hydrochlorothiazide or switching to a combination product (amlodipine/benazepril)
  • Assess for adverse effects (edema, headache) and adjust therapy as needed
• Case 3 68-year-old male with a history of myocardial infarction and hyperlipidemia
  • Initiate atorvastatin to lower LDL cholesterol and reduce the risk of recurrent cardiovascular events
  • Add aspirin for secondary prevention of thrombotic events
  • Monitor liver function tests and assess for muscle symptoms (myalgia, weakness) during statin therapy
• Case 4 75-year-old female with atrial fibrillation and a history of transient ischemic attack
  • Start metoprolol to control heart rate and reduce the risk of thromboembolism
  • Consider adding clopidogrel for additional stroke prevention, weighing the benefits against the increased bleeding risk
  • Monitor heart rate, blood pressure, and signs of bleeding during therapy