Chapter 2 Class Antihypertensive Therapies Notes

Blood Pressure

• Blood pressure (BP) is the force of blood on the arteries.

• It is the product of Cardiac Output (CO) and Peripheral Vascular Resistance (PVR): BP = CO
  eq PVR

• Cardiac Output (CO) is the product of Stroke Volume and Heart Rate (HR): CO = Stroke Volume
  eq HR

Blood Pressure Ranges

• Normal: Systolic < 120 and Diastolic < 80

• Elevated: Systolic 120-129 and Diastolic < 80

• High BP Stage 1: Systolic 130-139 or Diastolic 80-89

• High BP Stage 2: Systolic >= 140 or Diastolic >= 90

• Hypertensive Crisis: Systolic > 180 and/or Diastolic > 120

Factors Contributing to Blood Pressure

• Heart

• Arteries

• Kidneys

• Risks

Causes of High Blood Pressure

• Idiopathic/Genetic factors

• Nervous System

• Renin-Angiotensin System

Treatment Strategies

• Lifestyle changes

• Pharmacological therapies

Lifestyle Modifications

• Lowering sodium intake

• Weight loss/control

• Aerobic/cardio exercise

• Smoking cessation

Medication Classes for Hypertension

• Diuretics

• ACE Inhibitors

• Angiotensin II Receptor Blockers (ARBs)

• Renin Inhibitors

• Calcium Channel Blockers (CCBs)

• Adrenergic Blockers

• Vasodilators

Diuretics

• Mechanism: Increase urine output, reducing blood volume.

• Effect: Reduces Cardiac Output, leading to reduced blood pressure.

Loop Diuretics

• Maximum effect diuretics.

• Act on the Loop of Henle.

• Inhibit co-transport of sodium, potassium, and chloride.

• Examples: Lasix (furosemide) and Bumex (bumetanide).

• Indications:

  • Edema due to renal, hepatic, or cardiac failure.

  • Heart failure management.

  • Acute Pulmonary Edema.

  • Hypercalcemia and hyperkalemia. (Note: This is likely a typo in the original transcript and should read "treatment of hypercalcemia")

Thiazide and Thiazide-like Diuretics

• Examples: Chlorothiazide and Hydrochlorothiazide.

• Act on the Loop of Henle and Distal Convoluted Tubule.

• Inhibit sodium and chloride co-transporter.

• Inhibit sodium reabsorption.

• Increase sodium and chloride excretion.

• Allow calcium reabsorption.

• Prolonged use may result in an exchange of potassium ions for sodium, leading to potassium loss.

• Medium efficacy.

• Increased urine output lowers blood volume; volume will recover over time.

• Arteriolar smooth muscle relaxation will lower vascular resistance.

• Indications:

  • Mild to moderate hypertension.

  • Combined therapy with loop diuretics for heart failure.

  • Prevent excess calcium secretion in urine.

• Adverse Effects:

  • Potassium depletion.

  • Hyponatremia.

  • Volume depletion.

  • Hyperuricemia.

  • Hypercalcemia.

  • Hyperglycemia.

Weaker Diuretics: Potassium Sparing

• Act at the site of collecting ducts.

• Inhibit sodium reabsorption.

• Inhibit potassium excretion.

• Can cause hyperkalemia.

Aldosterone Antagonists

• Antagonist action to aldosterone receptors.

• Prevents binding of aldosterone to receptors.

• Indications:

  • Combined therapy with thiazide and/or loop diuretics.

  • Secondary hyperaldosteronism (spironolactone).

  • Resistant hypertension.

  • Heart failure (prevents remodeling of the heart).

• Adverse Effects:

  • Spironolactone – gynecomastia, menstrual irregularities.

  • Hyperkalemia.

ACE Inhibitors (Angiotensin Converting Enzyme Inhibitors)

• Kidneys release renin due to lowered blood pressure.

• Renin converts angiotensinogen (from the liver) to Angiotensin I.

• Angiotensin I is converted to Angiotensin II in the presence of ACE (in the lungs).

• Angiotensin II is a potent vasoconstrictor.

• ACE Inhibitors prevent the conversion of angiotensin I to angiotensin II.

• Effects of ACE Inhibition:

  • Reduced vascular resistance.

  • Reduced sodium and water retention.

  • Decreased preload and afterload on the heart.

• Indications:

  • Hypertension.

  • Congestive Heart Failure.

  • Myocardial Infarction.

  • Diabetic Nephropathy.

• Adverse Effects:

  • Dry cough, fever, altered taste.

  • Headache, nausea.

  • Rash, urticaria, angioedema.

  • Hyperkalemia (do not combine with potassium-sparing diuretics).

Angiotensin II Receptor Blockers (ARBs)

• Block Angiotensin II from binding to its receptors.

• Results:

  • Reduction in blood volume.

  • Prevention of sodium and water reabsorption.

  • Lowered peripheral vascular resistance.

Renin Inhibitors

• Aliskiren inhibits renin.

• Should not be combined with ACE Inhibitors.

Calcium Channel Blockers (CCBs)

• Prevents intracellular influx of calcium.

• Calcium mediates cation potential and muscle contraction in smooth and cardiac muscle.

• Decreases intracellular calcium and prevents action potential.

• Actions:

  • Smooth Muscle relaxation

  • Negative inotrope (lowers contractility)

  • Negative chronotrope (lowers rate)

  • Negative dromotrope (lowers conduction)

• Categories:

  • Diphenylalkylamines: Verapamil

  • Benzothiazepines: Diltiazem

  • Dihydropyridines: amlodipine, nifedipine

• Indications:

  • Hypertension

  • Angina

• Adverse Effects:

  • Constipation

  • Aggravate 1st Degree heart block

  • Headache

  • Fatigue

  • Peripheral Edema

Beta Adrenergic Blockers

• Act on beta receptors in the heart to reduce cardiac output.

• Reduce sympathetic stimulation of kidneys (inhibits renin).

• Selective beta blockers work on the heart only.

• Non-selective beta blockers can affect bronchials.

Alpha Adrenergic Blockers

• Reduce blood pressure by relaxing vascular smooth muscle.

• Examples: Prazosin, terazosin, doxazosin.

Combined Alpha/Beta Blockers

• Example: Carvedilol

• Drastic effects on blood pressure.

Centrally Acting A2 Antagonists

• Decrease sympathetic Outflow

• Relaxes blood vessels.

Vasodilators

• Relaxes smooth muscle in arteries and arterioles.

• Can lead to tachycardia.

• Can lead to reflex stimulation of the heart.

Hypertensive Emergencies

• Defined as a blood pressure of > 180/120 mmHg.

• Causes include:

  • Sudden medication changes (e.g., abrupt cessation of beta blockers).

  • Medication interactions.

  • Adrenal gland tumors.

• Symptoms:

  • Anxiety

  • Blurred vision

  • Chest pain

  • Severe headache

  • Seizures