Cardiovascular Medications and Blood Pressure Regulation

Introduction to Blood Pressure Medications

  • Focus for today's lecture is on blood pressure medications and is not covering the entirety of cardiovascular medications.

  • Two informative videos on cardiac pathophysiology recommended, each under six minutes.

  • Emphasis on understanding heart function is crucial for comprehending how medications work.

Key Concept: Cardiac Output

  • Cardiac Output (CO): The amount of blood pumped by the heart per minute.

    • Equation: Cardiac Output=Heart Rate×Stroke Volume\text{Cardiac Output} = \text{Heart Rate} \times \text{Stroke Volume}

    • Heart Rate: Speed of heartbeat.

    • Stroke Volume: Volume of blood pumped with each heartbeat.

    • Cardiac output is influenced by both heart rate and stroke volume.

  • Preload and Afterload:

    • Preload: Amount of blood in the heart prior to contraction.

    • Afterload: Pressure the heart contracts against to push blood through the circulatory system.

Antihypertensive Therapy Goals

  • Target systolic blood pressure: below 130 mmHg.

  • Target diastolic blood pressure: below 80 mmHg.

  • Individualized blood pressure goals may be necessary, especially for long-term hypertensive patients, who might feel hypotensive if brought to "normal" values.

Renin-Angiotensin-Aldosterone System (RAS)

  • RAS system: A key regulator of blood pressure in response to low blood pressure.

    • Renin release in response to decreased blood pressure.

    • Renin conversion of angiotensinogen (from the liver) to angiotensin I, which is an inactive form.

    • Angiotensin-converting enzyme (ACE): Converts angiotensin I to active angiotensin II.

    • Angiotensin II: Leads to vasoconstriction and stimulates aldosterone release from kidneys.

    • Aldosterone causes potassium excretion and sodium retention, influencing fluid balance and blood pressure.

Medication Classes for Hypertension

1. ACE Inhibitors

  • Example: Captopril.

  • Mechanism: Block conversion of angiotensin I to angiotensin II, reducing blood pressure.

  • Common side effects:

    • Possible initial severe hypotension; monitor closely during first dose.

    • Dry, nonproductive cough.

    • Metallic taste.

    • Mouth and throat swelling; may require emergency intervention.

    • Risk of hyperkalemia; monitor potassium levels (normal range: 3.5-5.0 mmol/L).

    • Potential for neutropenia; monitor white blood cell count.

  • Contraindications:

    • Pregnant or lactating individuals.

    • Renal dysfunction.

    • Certain demographics (e.g., less effective in African Americans).

  • Interactions with potassium supplements, NSAIDs, and lithium (may lead to toxicity).

2. Angiotensin II Receptor Blockers (ARBs)

  • Example: Losartan.

  • Mechanism: Block angiotensin II effect at its receptor, promoting vasodilation.

  • Side effects: Similar risks for angioedema and dizziness as ACE inhibitors.

  • Contraindications:

    • Pregnant or lactating individuals.

    • Kidney dysfunction in children.

3. Beta Blockers

  • Examples: Atenolol, Metoprolol.

  • Mechanism: Decrease heart rate and myocardial contractility; suppress reflex tachycardia.

  • Side effects: Bradycardia, potential heart failure symptoms (SOB during activities, edema).

  • Administration precautions: Monitor heart rate before dosing; patients should report heart rates <60 bpm at home but notify providers for <50 bpm in a hospital.

  • Contraindications: Heart block disorders, severe heart failure, asthma/COPD significance.

4. Calcium Channel Blockers (CCBs)

  • Example: Nifedipine.

  • Mechanism: Affect smooth muscle contraction; prevent artery constriction.

  • Side effects: Similar to beta blockers; monitor heart rate and possibly prevent reflex tachycardia.

  • C

Antihypertensive Drug Classes
1. ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors)

  • Mechanism of Action: Block the enzyme ACE, which converts angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release. By inhibiting its formation, ACE inhibitors lead to:

    • Vasodilation (decreased peripheral vascular resistance).

    • Reduced aldosterone secretion (decreased sodium and water retention).

    • Reduced bradykinin breakdown (may contribute to vasodilation, but also to cough).

  • Examples: Lisinopril, Enalapril, Ramipril, Captopril.

  • Key Considerations: Can cause dry cough, angioedema, hyperkalemia, and are not recommended in pregnancy.

2. ARBs (Angiotensin Receptor Blockers)

  • Mechanism of Action: Directly block angiotensin II from binding to its AT1 receptors on target tissues (blood vessels, heart, kidneys, adrenal glands). This prevents angiotensin II's vasoconstrictive and aldosterone-secreting effects.

  • Examples: Valsartan, Losartan, Irbesartan, Candesartan.

  • Key Considerations: Similar effects to ACE inhibitors but generally do not cause cough. Can cause hyperkalemia and are not recommended in pregnancy.

3. Beta Blockers (Beta-Adrenergic Blockers)

  • Mechanism of Action: Block beta-adrenergic receptors, leading to:

    • Beta-1 selective (e.g., in heart): Decreased heart rate, decreased myocardial contractility, and reduced renin release from kidneys.

    • Non-selective (Beta-1 and Beta-2, e.g., in bronchi): In addition to cardiac effects, can cause bronchoconstriction (Beta-2 blockade).

  • Examples: Metoprolol (Beta-1 selective), Atenolol (Beta-1 selective), Propranolol (non-selective), Carvedilol (Alpha and Beta blocker).

  • Key Considerations: Can cause bradycardia, fatigue, bronchospasm (especially non-selective in asthma/COPD), and mask hypoglycemia symptoms in diabetics. Should not be abruptly discontinued.

4. CCBs (Calcium Channel Blockers)

  • Mechanism of Action: Block the influx of calcium ions into vascular smooth muscle cells and/or cardiac muscle cells, leading to:

    • Dihydropyridines (vascular selective): Primarily cause peripheral and coronary vasodilation, reducing peripheral vascular resistance. Often less effect on heart rate.

    • Non-dihydropyridines (cardiac and vascular effects): Reduce heart rate, slow AV nodal conduction, and decrease myocardial contractility, in addition to vasodilation.

  • Examples:

    • Dihydropyridines: Amlodipine, Nifedipine, Felodipine.

    • Non-dihydropyridines: Verapamil, Diltiazem.

  • Key Considerations: Dihydropyridines can cause peripheral edema and reflex tachycardia. Non-dihydropyridines can cause bradycardia, AV block, and constipation (especially Verapamil).

5. Direct Acting Vasodilators

  • Mechanism of Action: Directly relax vascular smooth muscle, leading to vasodilation and decreased peripheral vascular resistance. The precise mechanism varies but often involves activation of guanylyl cyclase or opening potassium channels.

  • Examples: Hydralazine, Minoxidil, Nitroprusside.

  • Key Considerations: Often cause reflex tachycardia and fluid retention due to sympathetic activation and activation of the renin-angiotensin-aldosterone system. Usually used in combination with beta-blockers and diuretics.

6. Central Acting Vasodilators (Alpha-2 Agonists)

  • Mechanism of Action: Stimulate alpha-2 adrenergic receptors in the brainstem, which reduces sympathetic outflow from the central nervous system. This leads to decreased heart rate, vasodilation, and reduced peripheral vascular resistance.

  • Examples: Clonidine, Methyldopa.

  • Key Considerations: Can cause sedation, dry mouth, and rebound hypertension if abruptly discontinued. Methyldopa is often used in pregnancy-induced hypertension due to its safety profile. Can cause orthostatic hypotension.