SA

Hypertension Lecture Notes

Introduction to Systemic Hypertension and Blood Pressure # Hypertension Facts - Prevalence and Impact

  • Prevalence: >100,000,000 Americans have hypertension, representing 1 in 3 adults.

  • It is the most common chronic medical problem in the industrialized world.

  • Hypertension is the most frequent reason for visits to physicians.

  • It is one of the leading indications for prescription drug therapy.

  • Risk of Mortality: Every increase of 20/10 mmHg in blood pressure significantly doubles the risk of dying from stroke, heart disease, or other vascular diseases.

  • Cardiovascular Disease (CVD) Deaths: Hypertension accounts for more CVD deaths than any other modifiable cause. It is second only to smoking as a preventable cause of death.

  • Cardiovascular Events: Approximately 25\% of all cardiovascular events, including coronary heart disease (CHD), revascularization procedures, stroke, and heart failure, are attributable to hypertension.

  • Systolic Blood Pressure (SBP) Importance: For individuals over age 50, SBP is a more critical CVD risk factor than Diastolic Blood Pressure (DBP).

  • Lifetime Risk: Persons who are normotensive at age 55 have a 90\% lifetime risk for developing hypertension.

Hypertension Co-Morbidities (Percentage of HTN Patients)

  • Current Smoking

  • Obesity

  • Hypercholesterolemia

  • Diabetes

  • Chronic Kidney Disease (CKD)

Natural Course and Complications of Hypertension

  • Stroke: Can manifest as both hemorrhagic and ischemic stroke.

  • Coronary Heart Disease: Leads to angina, myocardial infarction (heart attack), and congestive heart failure.

  • Retinopathy: Involves retinal infarcts and hemorrhages in the eyes.

  • Nephropathy: Progresses to chronic kidney disease.

Classification of Blood Pressure (ACC/AHA 2017)

Category

Systolic (mm Hg)

Diastolic (mm Hg)

Normal

<120

and

<80

Elevated

120-129

and

<80

Hypertension

Stage 1

130-139

or

80-89

Stage 2

{\ge}140

or

{\ge}90

Lifestyle Modifications

  • Weight Reduction:

    • 70.2\% of American adults are overweight or obese, with 39.6\% specifically classified as obese.

    • Reducing weight effectively lowers blood pressure and decreases the total risk of coronary heart disease (CHD).

    • Should be pursued in combination with drug therapy for optimal results.

  • Alcohol Intake:

    • Excessive chronic alcohol intake can cause resistance to antihypertensive drug therapy.

    • Limit intake to 1 oz ethanol per day (approximately 2 drinks) for men.

    • Limit intake to 0.5 oz ethanol per day (approximately 1 drink) for women.

  • Physical Activity:

    • Regular aerobic exercise is effective in lowering blood pressure.

    • It also enhances weight loss and improves overall health.

    • Recommended Regimen:

      • 90-150 minutes per week of aerobic exercise.

      • 90-150 minutes per week of dynamic resistance exercise.

      • 3 sessions per week of isometric resistance (e.g., hand grip exercises).

  • Limit Dietary Sodium:

    • The optimal goal for sodium intake is less than 1500 mg per day.

    • Aim for at least a 1000 mg per day reduction from current intake.

Antihypertensive Agents

First-Line Agents

Thiazide Diuretics

  • Agents: Hydrochlorothiazide (Hydrodiuril®), Chlorthalidone (Hygroton®), Metolazone (Zaroxolyn®).

  • Mechanism of Action (MOA):

    • Initially lower blood pressure through diuresis (increased urine excretion).

    • Chronically, they decrease peripheral vascular resistance.

  • Combination Therapy: Often used in combination with other anti-hypertensive drugs to:

    • Add a second mechanism of action.

    • Offset compensatory sodium retention caused by other antihypertensive drugs.

  • Adverse Drug Reactions (ADRs):

    • Gastrointestinal: Nausea, Diarrhea.

    • Sexual Dysfunction: Erectile dysfunction.

    • Dermatologic: Sun sensitivity.

    • Metabolic: Hypokalemia (low potassium), Hyperglycemia (high blood sugar), Hyperlipidemia (high lipids).

    • Most ADRs are dose related; limiting the dose to 25 mg/day can help mitigate them.

  • Precautions: Pregnant women (risk of fetal hypoperfusion), Diabetes, Gout, Renal failure.

  • Contraindications: Anuria (absence of urine production).

Angiotensin Converting Enzyme (ACE) Inhibitors

  • Agents: Benazepril (Lotensin®), Captopril (Capoten®), Enalapril (Vasotec®), Fosinopril (Monopril®), Lisinopril (Prinivil®), Moexipril (Univasc®), Perindopril (Aceon®), Quinapril (Accupril®), Ramapril (Altace®), Trandolapril (Mavik®).

  • Mechanism of Action (MOA):

    • Blocks the conversion of Angiotensin I (ANG I) to Angiotensin II (ANG II). Angiotensin II is a potent vasoconstrictor.

    • Leads to decreased aldosterone secretion, which reduces sodium and water retention.

    • Blocks the degradation of bradykinin, a natural vasodilator, thereby enhancing vasodilation.

  • RAAS Illustration: When the kidney detects hypo-perfusion, Renin is released, converting Angiotensinogen to Angiotensin I. ACE Inhibitors block the action of ACE, preventing Angiotensin I from converting to Angiotensin II, thus stopping Angiotensin II's effects of vasoconstriction, aldosterone release, activation of the sympathetic nervous system, and sodium and water retention.

  • Clinical Considerations: Particularly beneficial in patients with heart failure and chronic kidney disease.

  • Adverse Drug Reactions (ADRs):

    • Hyperkalemia (high potassium levels).

    • Acute kidney failure: Occurs in less than 1\% of users. Stop or decrease dose if serum creatinine (Scr) rises more than 35\% above baseline.

    • Angioedema: Rare but potentially life-threatening swelling, more likely in Black patients and smokers.

    • Persistent, dry cough: Occurs in approximately 20\% of patients due to bradykinin accumulation.

    • Orthostatic hypotension: Especially in volume-depleted, elderly patients, or those taking other vasodilator drugs.

  • Contraindications: Pregnancy due to risk of fetal harm.

Angiotensin II Receptor Blockers (ARBs)

  • Agents: Candesartan (Atacand®), Eprosartan (Teveten®), Irbesartan (Avapro®), Losartan (Cozaar®), Olmesartan (Benicar®), Telmisartan (Micardio®), Valsartan (Diovan®).

  • Mechanism of Action (MOA):

    • Act as Angiotensin II receptor antagonists, blocking the effects of Angiotensin II from both the Renin-Angiotensin-Aldosterone System (RAAS) and tissue sources.

    • Crucially, they do not affect bradykinin levels, hence no cough side effect.

  • RAAS Illustration: ARBs directly block the binding of Angiotensin II to its receptors, thus preventing Angiotensin II's downstream effects of vasoconstriction, aldosterone release, sympathetic nervous system activation, and sodium and water retention, similar to ACE inhibitors but at a different point.

  • Contraindications: Share a pregnancy warning (contraindicated).

  • Adverse Drug Reactions (ADRs):

    • Orthostatic hypotension.

    • Much less angioedema compared to ACE Inhibitors (potentially none).

Calcium Channel Blockers (CCBs)

  • Dihydropyridine (DHP) Agents: Amlodipine (Norvasc®), Felodipine (Plendil®), Isradipine (Dynacirc®), Nicardipine (Cardene®), Nifedipine (Adalat®, Procardia®), Nisoldipine (Sular®).

  • Non-Dihydropyridine (Non-DHP) Agents: Diltiazem (Cardizem®), Verapamil (Calan®).

  • Mechanism of Action (MOA):

    • Block the influx of calcium across cell membranes, primarily in vascular smooth muscle and the heart.

    • This leads to coronary and peripheral vasodilation, resulting in lower blood pressure.

    • Both types of CCBs are equally effective for hypertension.

    • Have negative inotropic effects (reduce the force of myocardial contraction).

  • ADRs (DHP CCBs): Dizziness, Flushing, Headache, Peripheral edema.

  • ADRs (Non-DHP CCBs): GI effects (Anorexia and Nausea), Peripheral edema (less common than with DHP CCBs), Constipation (especially with verapamil).

Alternative Agents

Direct Renin Inhibitors (DRIs)

  • Agents: Aliskiren (Tekturna®).

  • Mechanism of Action (MOA):

    • Directly blocks renin's activity, preventing the conversion of angiotensinogen to Angiotensin I. This effectively stops the initial step of the RAAS cascade.

  • RAAS Illustration: DRIs stop the RAAS at its origin by preventing Renin from initiating the conversion of angiotensinogen to Angiotensin I.

  • Contraindications: Share a pregnancy warning (contraindicated).

  • Adverse Drug Reactions (ADRs): Orthostatic hypotension, Angioedema.

Beta-Blockers

  • Cardioselective (\beta_1 selective) Agents: Atenolol (Tenormin®), Betaxolol (Kerlone®), Bisoprolol (Zebeta®), Metoprolol (Lopressor®, Toprol XL®), Nebivolol (Bystolic®).

  • Non-selective Agents: Carvedilol (Coreg®) (also has alpha-blocking activity), Nadolol (Corgard®), Propranolol (Inderal®), Timolol (Blocadren®).

  • Agents with Intrinsic Sympathomimetic Activity (ISA): Acebutolol (Sectral®), Penbutolol (Levatol®), Pindolol (Visken®).

  • These agents are generally not preferred for primary hypertension treatment as they do not reduce cardiovascular events as well as other beta-blockers.

  • Mechanism of Action (MOA):

    • While many physiological effects are documented, the precise mechanism causing blood pressure lowering is uncertain. It likely involves reduced cardiac output, decreased renin release, and central nervous system effects.

  • Cardioselectivity: Possess a greater affinity for \beta1 receptors (concentrated in the heart and kidney) than for \beta2 receptors (found in lungs, liver, pancreas, and arteriolar smooth muscle). In general, they are preferred for hypertension treatment.

  • Adverse Drug Reactions (ADRs):

    • Bradycardia (slow heart rate).

    • CNS Effects: Dizziness/Drowsiness.

    • Respiratory: Bronchoconstriction, particularly in patients with COPD or asthma.

  • Abrupt Discontinuation Warning: Abrupt cessation can result in rebound hypertension or an increased heart rate. Doses should be tapered over 1-2 weeks.

Alpha Blockers

  • Agents: Prazosin (Minipress®), Terazosin (Hytrin®), Doxazosin (Cardura®).

  • Mechanism of Action (MOA):

    • Act as selective alpha-1 receptor antagonists in the peripheral vasculature.

    • This results in vasodilation and subsequent blood pressure lowering.

  • Role in Hypertension: Reserved for patients with treatment-resistant hypertension.

  • Adverse Drug Reactions (ADRs):

    • First-dose effect: Characterized by dizziness, faintness, or syncope (sudden loss of consciousness) within 1-3 hours of the first dose. To mitigate this, patients should take the first few doses before bedtime. This effect can also occur with changes in dose or non-adherence.

    • Sustained orthostatic hypotension, especially in the elderly.

    • CNS Effects: Lassitude (lack of energy), Vivid dreams, Depression.

    • Sexual Dysfunction: Priapism (prolonged erection).

Central Alpha Agonists

  • Agents: Clonidine (Catapres®), Methyldopa (Aldomet®).

  • Mechanism of Action (MOA):

    • Reduce sympathetic outflow from the vasomotor center in the brain.

    • This leads to a decrease in heart rate, cardiac output, and ultimately, blood pressure.

  • Role in Hypertension: Reserved for patients with treatment-resistant hypertension.

  • Adverse Drug Reactions (ADRs):

    • Sodium and water retention, often necessitating concurrent use with a diuretic.

    • Depression.

    • High incidence of orthostatic hypotension (caution in the elderly).

    • Anticholinergic Effects: Sedation, dry mouth, urinary retention.

    • Abrupt Cessation Warning: Abrupt discontinuation can result in severe rebound hypertension.

Special Considerations

Pregnant Women

  • Types of Hypertension in Pregnancy: Chronic hypertension, Preeclampsia/Eclampsia, Gestational hypertension.

  • Preferred Drugs for Chronic and Gestational HTN: Labetalol, long-acting nifedipine, methyldopa.

  • Alternative Drugs: Other beta-blockers and calcium channel blockers.

  • Contraindicated Drugs: ACE inhibitors, Angiotensin II Receptor Blockers (ARBs), and Direct Renin Inhibitors due to fetal harm.

Elderly ({\ge}65 years) Patients

  • Often present with isolated systolic hypertension.

  • No single agent is more effective; follow general drug selection guidelines.

  • Drugs to Generally Avoid: Central alpha agonists and peripheral alpha-blockers, primarily due to the increased risk of orthostatic hypotension.

  • Start other drugs at lower doses due to potential increased sensitivity and reduced drug clearance.

Children and Adolescents

  • Hypertension is more common in obese children, emphasizing the importance of lifestyle modifications.

  • Secondary hypertension (due to an underlying cause) is more common in this age group, necessitating a thorough work-up for conditions like kidney disease.

  • Evidence Supports Use of: ACE inhibitors, ARBs, Beta-blockers, Calcium channel blockers, and Thiazide diuretics.