7.1 Antihypertensive drugs
5 min read•august 16, 2024
Antihypertensive drugs are crucial in managing high blood pressure, a major risk factor for cardiovascular disease. These medications work through various mechanisms to lower blood pressure, including reducing blood volume, relaxing blood vessels, and decreasing heart rate.
The five main categories of antihypertensives are , , , , and . Each class has unique benefits and side effects, often used in combination for better blood pressure control and reduced risk of complications.
Antihypertensive Drug Categories
Primary Antihypertensive Classes
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- Five main categories of antihypertensive drugs exist based on distinct mechanisms of action
- Diuretics increase sodium and water excretion reducing blood volume and cardiac output
- ACE inhibitors and ARBs target the renin-angiotensin-aldosterone system (RAAS) inhibiting angiotensin II production or action
- Calcium channel blockers (CCBs) block calcium influx into vascular smooth muscle and cardiac cells causing and decreased cardiac contractility
- Beta-blockers block beta-adrenergic receptors reducing heart rate and cardiac output
- Other antihypertensive classes include alpha-blockers, direct vasodilators, and centrally acting agents
- Alpha-blockers relax smooth muscle in blood vessels and prostate (useful for benign prostatic hyperplasia)
- Direct vasodilators () relax arteriolar smooth muscle
- Centrally acting agents () reduce sympathetic outflow from the brain
Mechanism of Action Details
- Diuretics lower blood pressure through multiple mechanisms
- Increase sodium and water excretion in kidneys
- Reduce blood volume and extracellular fluid volume
- Decrease cardiac output initially
- Long-term reduction in peripheral vascular resistance
- ACE inhibitors and ARBs affect the RAAS differently
- ACE inhibitors block conversion of angiotensin I to angiotensin II
- ARBs block angiotensin II receptors directly
- Both reduce vasoconstriction, aldosterone secretion, and sympathetic activity
- Calcium channel blockers have subtypes with varying effects
- () primarily affect vascular smooth muscle
- Non-dihydropyridines (, ) affect both vascular and cardiac tissue
Pharmacological Effects of Antihypertensives
First-line Treatments and Their Effects
- Diuretics serve as effective first-line treatments for uncomplicated
- Reduce blood volume and vascular resistance
- Thiazide diuretics () work in distal convoluted tubule
- Loop diuretics (furosemide) act in the loop of Henle
- ACE inhibitors and ARBs provide multiple benefits beyond blood pressure reduction
- Renoprotective effects slow progression of diabetic nephropathy
- Cardioprotective effects reduce risk of and improve outcomes post-myocardial infarction
- Particularly useful in patients with diabetes, chronic kidney disease, or heart failure
- Calcium channel blockers effectively reduce blood pressure across diverse patient groups
- Especially beneficial in elderly patients and those with isolated systolic hypertension
- Dihydropyridines (amlodipine) preferred due to less effect on heart rate
Specialized Uses and Combinations
- Beta-blockers offer additional benefits in specific patient populations
- Reduce heart rate and cardiac workload beneficial in angina and heart failure
- Improve outcomes in patients post-myocardial infarction
- and commonly used in these scenarios
- Alpha-blockers provide dual benefits in certain patient groups
- Lower blood pressure through peripheral vasodilation
- Relax prostatic smooth muscle helping with benign prostatic hyperplasia (BPH) symptoms
- and examples of drugs with this dual action
- Direct vasodilators and centrally acting agents reserved for specific scenarios
- Used in resistant hypertension when other medications inadequate
- Often added as part of combination therapy
- Hydralazine (direct vasodilator) and clonidine (centrally acting) examples of these agents
Side Effects of Antihypertensives
Common Side Effects by Drug Class
- Diuretics can cause electrolyte imbalances and metabolic changes
- most common especially with thiazides and loop diuretics
- may exacerbate gout (allopurinol sometimes needed)
- Glucose intolerance and dyslipidemia possible with long-term use
- ACE inhibitors and ARBs share some side effects but differ in others
- Dry more common with ACE inhibitors (10-20% of patients)
- Both can cause especially in patients with kidney disease
- First-dose hypotension possible particularly in volume-depleted patients
- Calcium channel blockers have class-specific and subtype-specific side effects
- Peripheral edema common especially with dihydropyridines (amlodipine)
- Headaches and flushing due to vasodilation
- Constipation more common with verapamil
- Non-dihydropyridines can cause heart block and worsen heart failure
Contraindications and Special Considerations
- ACE inhibitors and ARBs contraindicated in pregnancy
- Risk of fetal renal damage and other congenital abnormalities
- Should be discontinued as soon as pregnancy detected
- Beta-blockers have several important contraindications
- Severe asthma due to risk of bronchospasm
- Bradycardia or heart block can be exacerbated
- Can mask symptoms of hypoglycemia in diabetic patients
- Alpha-blockers require caution in certain patient groups
- Contraindicated in patients with history of
- First-dose effect can cause severe orthostatic hypotension
- Caution in elderly patients more prone to falls
- All antihypertensives carry hypotension risk
- Elderly patients more susceptible due to altered baroreceptor function
- Volume-depleted patients (dehydration, diuretic use) at higher risk
- Dose adjustments often needed in patients with liver or kidney disease
Rationale for Combination Therapy
Multifactorial Approach to Blood Pressure Control
- Combination therapy targets multiple pathways in blood pressure regulation
- Hypertension often results from multiple physiological disturbances
- Combining drugs with different mechanisms provides more comprehensive control
- Example: ACE inhibitor (blocks RAAS) + calcium channel blocker (vasodilation)
- Synergistic effects observed with certain drug combinations
- ACE inhibitors or ARBs combined with calcium channel blockers or diuretics
- These combinations show greater blood pressure reduction than expected from individual effects
- ACCOMPLISH trial demonstrated superiority of ACE inhibitor + CCB over ACE inhibitor + diuretic
Benefits of Combination Therapy
- Lower doses of individual drugs often possible in combination therapy
- Reduces risk of dose-dependent side effects
- Maintains or improves efficacy through complementary actions
- Example: Lower dose of diuretic when combined with ACE inhibitor
- Combination therapy overcomes compensatory mechanisms
- Diuretic use can trigger renin surge limiting effectiveness
- Adding ACE inhibitor or ARB blocks this compensatory mechanism
- Results in more effective and sustained blood pressure control
- Fixed-dose combination pills improve patient adherence
- Reduces pill burden simplifying dosing regimens
- Single pill combinations (SPC) like /hydrochlorothiazide
- Improved adherence leads to better blood pressure control and outcomes
Guidelines and Clinical Practice
- Guidelines often recommend initiating combination therapy in specific scenarios
- Stage 2 hypertension (BP ≥ 160/100 mmHg) often requires multiple agents
- High cardiovascular risk patients benefit from more aggressive initial therapy
- African American patients often respond better to combination including CCB or diuretic
- Stepped care approach incorporates combination therapy
- Start with monotherapy, add second agent if target not reached
- Alternatively, begin with low-dose combination and titrate up
- Allows for personalized approach based on patient characteristics and response
Key Terms to Review (34)
Ace inhibitors: ACE inhibitors are a class of medications that inhibit the angiotensin-converting enzyme, which plays a crucial role in the body's renin-angiotensin-aldosterone system (RAAS). By blocking this enzyme, these drugs lower blood pressure and reduce strain on the heart, making them essential in treating conditions like hypertension and heart failure. Their ability to relax blood vessels and decrease fluid retention makes them effective in managing cardiovascular health.
Aha/acc recommendations: The AHA/ACC recommendations refer to guidelines provided by the American Heart Association and the American College of Cardiology for the management and treatment of various cardiovascular conditions, including hypertension. These recommendations are based on extensive research and aim to standardize care practices to improve patient outcomes in cardiovascular health, particularly focusing on lifestyle modifications and pharmacological interventions.
Amlodipine: Amlodipine is a calcium channel blocker that is primarily used to treat high blood pressure and angina. It works by relaxing the blood vessels, allowing blood to flow more easily, which helps to lower blood pressure and reduce the workload on the heart. This makes it a vital medication in managing cardiovascular conditions.
Antagonism: Antagonism refers to the interaction between two substances where one substance blocks or reduces the effect of another. In pharmacology, this term is crucial for understanding how certain drugs can negate the effects of others, particularly in the management of conditions like hypertension. This dynamic can influence drug efficacy and patient outcomes significantly, making it vital in therapeutic decision-making.
ARBs: ARBs, or Angiotensin II Receptor Blockers, are a class of medications used primarily to treat high blood pressure by blocking the action of angiotensin II, a hormone that causes blood vessels to constrict. By inhibiting this hormone, ARBs help relax blood vessels, which reduces blood pressure and improves blood flow. They are often prescribed for patients with hypertension or heart failure, making them important players in the management of cardiovascular health.
Beta-blockers: Beta-blockers are a class of medications that block the effects of adrenaline on beta-adrenergic receptors, which are found in various tissues including the heart, lungs, and blood vessels. By inhibiting these receptors, beta-blockers decrease heart rate, reduce blood pressure, and lower the workload on the heart, making them essential in managing conditions such as hypertension and heart failure.
Bioavailability: Bioavailability refers to the proportion of a drug that enters the systemic circulation when introduced into the body and is available for therapeutic effect. It is influenced by factors such as the route of administration, formulation of the drug, and individual patient characteristics, making it a crucial aspect of pharmacology, drug development, and therapeutic effectiveness.
Calcium Channel Blockers: Calcium channel blockers are a class of medications that prevent calcium from entering cells through calcium channels, primarily affecting vascular smooth muscle and cardiac muscle. By inhibiting calcium influx, these drugs help to relax blood vessels, lower blood pressure, and reduce the workload on the heart. They play a significant role in managing conditions such as hypertension and angina, and they also interact with adrenergic systems by affecting heart rate and vascular tone.
Carvedilol: Carvedilol is a non-selective beta-adrenergic blocker with alpha-1 blocking properties, primarily used to treat hypertension and heart failure. It works by blocking beta receptors, which decreases heart rate and contractility, and by blocking alpha-1 receptors, which leads to vasodilation, ultimately lowering blood pressure and improving heart function.
Clonidine: Clonidine is a medication primarily used as an antihypertensive agent, working by stimulating alpha-2 adrenergic receptors in the brain to reduce sympathetic outflow. This leads to decreased heart rate and blood pressure, making it effective in managing hypertension and certain other conditions like ADHD and withdrawal symptoms from opioids. Its role as an adrenergic drug links it to both the central nervous system effects and peripheral actions on blood vessels.
Cough: A cough is a sudden, forceful expulsion of air from the lungs, often resulting from irritation or inflammation in the respiratory tract. Coughing serves as a reflex mechanism to clear mucus, foreign particles, or pathogens from the airway, and can be a symptom of various underlying health issues including respiratory infections, allergies, and chronic diseases.
Diastolic Pressure: Diastolic pressure is the lower number in a blood pressure reading, representing the pressure in the arteries when the heart is at rest between beats. It is an essential component of cardiovascular health, as it reflects how well the heart and blood vessels are functioning together during the relaxation phase of the cardiac cycle.
Dihydropyridines: Dihydropyridines are a class of calcium channel blockers primarily used as antihypertensive agents to treat high blood pressure. They work by selectively blocking L-type calcium channels in vascular smooth muscle, leading to vasodilation and a reduction in blood pressure. These drugs are characterized by their ability to lower peripheral vascular resistance and improve blood flow, making them effective in managing hypertension.
Diltiazem: Diltiazem is a calcium channel blocker that is primarily used to treat hypertension and certain types of angina, as well as managing arrhythmias. It works by relaxing the blood vessels and reducing the workload on the heart, thereby lowering blood pressure and improving blood flow. This medication also affects the heart's rhythm, making it beneficial in treating various cardiac conditions.
Diuretics: Diuretics are medications that promote the excretion of water and electrolytes, primarily sodium, from the body through urine. These drugs are commonly used to manage conditions like hypertension and heart failure by reducing fluid overload and lowering blood pressure. By increasing urine output, diuretics help in decreasing blood volume, which can lead to a reduction in vascular resistance and improved cardiac function.
Doxazosin: Doxazosin is an alpha-1 adrenergic blocker that is primarily used to treat hypertension and symptoms of benign prostatic hyperplasia (BPH). By inhibiting alpha-1 adrenergic receptors, it relaxes smooth muscle in blood vessels and the prostate, which leads to a decrease in blood pressure and relief from urinary obstruction.
Half-life: Half-life is the time it takes for the concentration of a drug in the bloodstream to reduce to half of its initial value. This concept is essential for understanding how drugs are metabolized and eliminated from the body, influencing dosing regimens and therapeutic outcomes.
Heart failure: Heart failure is a chronic condition where the heart is unable to pump blood effectively, leading to inadequate blood flow to meet the body's needs. This condition can result from various factors, including hypertension, coronary artery disease, and prior heart attacks. Heart failure can lead to fluid buildup in the lungs and other body parts, making it a serious health concern that often requires ongoing management and treatment.
Hydralazine: Hydralazine is a vasodilator medication primarily used to treat hypertension and heart failure by relaxing blood vessels, which reduces blood pressure and improves blood flow. It works mainly by directly affecting the smooth muscles in arterial walls, leading to vasodilation, and is often used in conjunction with other antihypertensive drugs for optimal management of cardiovascular conditions.
Hydrochlorothiazide: Hydrochlorothiazide is a thiazide diuretic primarily used to treat high blood pressure and edema associated with heart failure, liver cirrhosis, or renal disorders. It works by inhibiting sodium reabsorption in the distal convoluted tubule of the nephron, promoting increased excretion of sodium and water, thus lowering blood volume and blood pressure.
Hyperkalemia: Hyperkalemia is a medical condition characterized by an elevated level of potassium in the blood, typically defined as a serum potassium level greater than 5.0 mEq/L. This condition can have serious consequences, particularly affecting cardiac function and muscle contractions, and it can be influenced by various medications and health conditions.
Hypertension: Hypertension, commonly known as high blood pressure, is a chronic medical condition where the force of the blood against the artery walls is consistently too high. It is often asymptomatic, making it a silent risk factor for serious health issues like heart disease, stroke, and kidney failure. Understanding hypertension is crucial for implementing effective treatments and preventive measures involving various drug classes that target different physiological pathways.
Hyperuricemia: Hyperuricemia is a condition characterized by an elevated level of uric acid in the blood, which can lead to the formation of crystals that cause inflammation and pain, particularly in the joints. It is commonly associated with gout and can be influenced by factors such as diet, kidney function, and certain medications. Understanding hyperuricemia is essential, especially since it can interact with various pharmacological treatments affecting blood pressure and renal function.
Hypokalemia: Hypokalemia refers to a condition characterized by low levels of potassium in the bloodstream, typically defined as a serum potassium concentration below 3.5 mEq/L. Potassium is crucial for many bodily functions, especially in maintaining proper heart and muscle function. Imbalances in potassium levels can lead to various complications and may be particularly significant in the context of certain medications and health conditions, affecting how different treatments are managed.
JNC 8 Guidelines: The JNC 8 Guidelines are a set of evidence-based recommendations for the treatment of high blood pressure (hypertension) published by the Eighth Joint National Committee in 2014. These guidelines aim to provide clinicians with a clear framework for managing hypertension in adults to improve patient outcomes and reduce cardiovascular risks.
Lisinopril: Lisinopril is an oral medication classified as an angiotensin-converting enzyme (ACE) inhibitor, primarily used to treat high blood pressure and heart failure. It works by relaxing blood vessels, which lowers blood pressure and improves blood flow, thereby reducing the workload on the heart. This medication is essential in managing hypertension and preventing cardiovascular complications.
Metoprolol: Metoprolol is a selective beta-1 adrenergic blocker commonly used to treat high blood pressure and other cardiovascular conditions. By blocking the beta-1 receptors in the heart, it reduces heart rate and the force of contraction, leading to lowered blood pressure. This medication is an important tool in managing hypertension and provides relief from symptoms associated with heart failure and angina.
Orthostatic Hypotension: Orthostatic hypotension is a form of low blood pressure that occurs when a person stands up from sitting or lying down, leading to dizziness, lightheadedness, or even fainting. This condition is particularly significant as it can impact individuals taking antihypertensive drugs, which are designed to lower blood pressure, sometimes causing a drop that leads to these symptoms when posture changes.
Potentiation: Potentiation refers to the process where one drug enhances the effect of another drug, resulting in a greater therapeutic effect than either drug could achieve alone. This phenomenon is significant in pharmacology, especially with antihypertensive drugs, as it can lead to improved blood pressure control when different classes of medications are combined, maximizing their effectiveness while minimizing side effects.
Renin-Angiotensin System: The renin-angiotensin system (RAS) is a hormonal system that regulates blood pressure and fluid balance in the body. It involves the conversion of angiotensinogen, a protein produced by the liver, into angiotensin I by the enzyme renin, which is released from the kidneys. Angiotensin I is then converted into angiotensin II, a potent vasoconstrictor, by the action of the angiotensin-converting enzyme (ACE), ultimately leading to increased blood pressure and fluid retention, making it a critical target for antihypertensive drugs.
Systolic Pressure: Systolic pressure is the highest pressure in the arteries when the heart beats and pumps blood into the circulation. It is an essential measurement in assessing cardiovascular health and is typically represented as the top number in a blood pressure reading. Understanding systolic pressure helps in evaluating how well the heart is functioning and how much strain is placed on the arteries.
Terazosin: Terazosin is an alpha-1 adrenergic blocker used primarily for treating hypertension and benign prostatic hyperplasia. By blocking alpha-1 receptors in the vascular smooth muscle, terazosin leads to vasodilation, which helps lower blood pressure. Its role in managing both blood pressure and urinary symptoms makes it a versatile medication in clinical practice.
Vasodilation: Vasodilation is the process by which blood vessels widen due to the relaxation of the smooth muscle in their walls. This widening decreases vascular resistance and allows for an increased flow of blood, which can lead to lower blood pressure and improved oxygen delivery to tissues. It's a key mechanism utilized by various antihypertensive drugs to manage hypertension effectively.
Verapamil: Verapamil is a calcium channel blocker primarily used to treat high blood pressure and certain types of heart arrhythmias. It works by inhibiting calcium ions from entering cells of the heart and blood vessel walls, leading to relaxation of the blood vessels and a decrease in heart rate. This medication plays a crucial role in managing cardiovascular conditions, making it significant for treating both hypertension and heart failure.