Hypertension and Blood Pressure Control

Hypertension

• Occurs when systolic blood pressure is above 130 mm Hg or diastolic blood pressure exceeds 80 mm Hg, confirmed on at least two separate occasions
• Results from increased peripheral vascular arteriolar smooth muscle tone
• Leads to increased arteriolar resistance accompanied by reduced capacitance in the venous system
• Diagnosed through repeated and reproducible elevated blood pressure readings
• Chronic hypertension can lead to heart disease, stroke, chronic kidney disease and heart failure
• Lowering blood pressure pharmacologically can prevent vessel damage while substantially reducing morbidity and mortality rates

Physiologic Control of Blood Pressure

• Blood Pressure (BP) is the product of Cardiac Output (CO) and Systemic Vascular Resistance (SVR)
• CO is the product of Heart Rate (HR) and Stroke Volume (SV)
• Factors which must be considered include:
  • Heart Rate
  • Blood Volume
  • Contractility
  • Arteriolar Constriction

Mechanisms Regulating Blood Pressure

• Sympathetic Nervous System: Baroreceptors are involved
• Renin-Angiotensin-Aldosterone System:
  • Angiotensinogen is activated by renin
  • Renin is produced by JG cells in the kidney
  • Renin is increased by decreased renal blood flow and B₁ stimulation

Lifestyle Changes for Hypertension Management

• Inadequate response to lifestyle changes warrants initiating drug therapy
• Adjustments to drug therapy include:
  • Increasing drug dose
  • Substituting another drug
  • Adding a second drug from a different class

Antihypertensive Drug Classes

• Diuretic agents
• Beta Receptor Blockers
• Calcium channel blockers
• Angiotensin-Converting Enzyme Inhibitors
• Angiotensin II Receptor Blockers
• Renin inhibitors
• Alpha₁ Receptors Blockers
• Others

Diuretics

• Increase urine flow
• Initial mechanism reduces blood volume through electrolyte excretion, leading to osmotic water excretion, which in turn increases 24-hr urine volume
• Can change urine pH and ionic composition
• Used to treat edema, heart failure, and hypertension
• Lower blood pressure by:
  • Increasing Na+ and water secretion in the kidney reducing blood volume and cardiac output
  • Increasing synthesis of prostaglandins (PGs), causing vasodilation and reducing peripheral vascular resistance (PVR)

Diuretic Drug Types

• Thiazides and thiazide-like diuretics
• Loop diuretics
• Potassium-sparing diuretics
• Carbonic anhydrase inhibitors
• Osmotic diuretics

Thiazides Diuretics

• Related to organic acids such as Hydrochlorothiazide and Chlorthalidone

• Inhibit Na+/Cl- transport in the distal convoluted tubule

• Natriuresis may cause loss of potassium and H+

• Increase Ca2+ reabsorption in the distal convoluted tubule by increasing Na+/Ca2+ exchange; reduces urinary excretion of Ca2+

Loop Diuretics

• Inhibit the NKCC2 (luminal Na/K/2Cl co-transporter) in the thick ascending limb of the loop of Henle

• Useful in individuals with poor renal function or resistant to thiazide diuretics

• Decrease renal vascular resistance and increase renal blood flow

• Commonly used examples include Furosemide (Lasix), Bumetanide, Ethacrynic acid, and Torsemide

Potassium-Sparing Diuretics

• Inhibit Na+ reabsorption and potassium excretion in the collecting tubule
• Potassium levels should be monitored due to risk of hyperkalemia
• Should be avoided in patients in severe renal dysfunction
• Include:
  • Aldosterone antagonists: spironolactone and eplerenone
  • Epithelial sodium channel blockers: Triamterene and amiloride

Beta-Adrenergic Blocking Agents

• Reduce blood pressure, primarily by decreasing cardiac output
• May also decrease sympathetic outflow from the central nervous system (CNS)
• Inhibit renin release from the kidneys, decreasing angiotensin II formation and aldosterone secretion

Selective and Nonselective Beta-Adrenergic Blocking Agents

• Nonselective β- antagonists: propranolol
• Selective β1- antagonists: Atenolol, metoprolol, and Nebivolol
  • Nebivolol selectively blocks β1- receptors and increases nitric oxide production, promoting vasodilation.
• Partial β- agonists: Pindolol
• Antagonists of both α and β-adrenoreceptors: Carvedilol

Beta-Adrenergic Blocking Agents Side Effects

• Noncardioselective beta-blockers can disturb lipid metabolism, decreasing HDL and increasing triglycerides
• Drug withdrawal must be tapered to avoid severe hypertension, angina, myocardial infarction, and sudden death

ACE Inhibitors

• Examples include: captopril, enalapril, and lisinopril
• Lower blood pressure by reducing peripheral vascular resistance without increasing cardiac output, heart rate, or contractility
• Block the ACE enzyme, preventing the conversion of angiotensin I to angiotensin II
• Prevent the cleavage of angiotensin I into the potent vasoconstrictor angiotensin II
• Prevent the breakdown of bradykinin
• Decrease secretion of aldosterone
• Induce vasodilation in both arterioles and veins due to decreased vasoconstriction and enhanced bradykinin vasodilation
• Decrease aldosterone secretion, reducing sodium and water retention
• Decrease both cardiac preload and afterload, thereby decreasing workload on the heart
• Recommended as first-line treatment for hypertension in patients with high coronary disease risk, diabetes, history of stroke, heart failure, myocardial infarction, or chronic kidney disease

ACE Inhibitors: Adverse Effects

• Dry cough: Caused by increased bradykinin and substance P levels in the pulmonary tree, more frequent in women and resolves after discontinuation
• Angioedema: Rare but life-threatening reaction
• Hyperkalemia: Potassium levels must be monitored
• Contraindicated in pregnant women due to risk of fetal malformations

Angiotensin II Receptor Blockers (ARBs)

• Examples include: Losartan and Irbesartan

• Block AT1 receptors, reducing the activation of angiotensin II

• Similar pharmacologic effects to ACE inhibitors: causing arteriolar and venous dilation and blocking aldosterone secretion, lowering blood pressure, and decreasing salt and water retention

• Do not increase bradykinin levels

• Used as first-line agents to treat hypertension, especially in patients with diabetes, heart failure, or chronic kidney disease

• Reduced risks of cough and angioedema compared to ACE inhibitors

• Contraindicated with ACE inhibitors for treating hypertension due to similar mechanisms and adverse effects

• Teratogenic and should not be used by pregnant women

Calcium Channel Blockers

• Intracellular calcium concentration plays an important role in smooth muscle tone and myocardial contraction
• Calcium channel antagonists block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature
• Relaxes vascular smooth muscle, dilating arterioles
• Do not dilate veins
• Non-Dihydropyridines: Verapamil, Diltiazem
• Dihydropyridines: Nifedipine, amlodipine
• Recommended as a first-line treatment option in black patients
• Can be used as an initial or add-on therapy for hypertension management

Alpha Blocking Agents

• Used in hypertension treatment: prazosin, doxazosin and terazosin
• Produce a competitive block of α1-adrenoceptors
• Decrease peripheral vascular resistance and lower arterial blood pressure by relaxing arterial and venous smooth muscle
• Not recommended as initial treatment for hypertension, reserved for refractory cases