Clinical ph

• Hypertension is defined as persistently elevated arterial blood pressure (BP)

  
• Classification of Blood Pressure in Adults

  • Isolated systolic hypertension
  • Hypertensive crisis

  
• Isolated systolic hypertension


  Diastolic blood pressure (DBP) <80 mm Hg and systolic blood pressure (SBP) ≥130 mm Hg

  
• Hypertensive crisis


  BP >180/120 mm Hg, categorized as hypertensive emergency (extreme BP elevation with acute or progressing end-organ damage) or hypertensive urgency (extreme BP elevation without acute or progressing end-organ injury)
• Causes of hypertension

  • Primary or essential hypertension
  • Secondary hypertension
• Secondary hypertension

  Usually caused by chronic kidney disease (CKD) or renovascular disease
• Drugs that may increase BP

  • Corticosteroids
  • Estrogens
  • NSAIDs
  • Cyclosporine
  • Erythropoietin
  • Venlafaxine
• Major causes of death include cerebrovascular events, cardiovascular (CV) events, and renal failure
• Patients with uncomplicated primary hypertension

  Usually asymptomatic initially
• Patients with secondary hypertension

  May have symptoms of the underlying disorder
• Elevated BP

  May be the only sign of primary hypertension on physical examination
• Diagnosis


  Based on the average of two or more readings taken at each of two or more clinical encounters
• Signs of end-organ damage

  • Eyes
  • Brain
  • Heart
  • Kidneys
  • Peripheral vasculature
• Goals of Treatment

  Reduce morbidity and mortality from CV events, with a goal BP of <130/80 mm Hg for most patients
• Goal for institutionalized older patients and those with a high disease burden or limited life expectancy

  Relaxed SBP goal of <150 mm Hg (or <140 mm Hg if tolerated)
• Lifestyle modifications that lower BP

  • Weight loss if overweight or obese
  • Dietary Approaches to Stop Hypertension (DASH) eating plan
  • Reduced salt intake, ideally to 1.5 g/day sodium (3.8 g/day sodium chloride)
  • Physical activity (90–150 min/week of aerobic or dynamic resistance training)
  • Moderation of alcohol intake
• Smoking cessation does not control BP, but it reduces CV disease risk and should be encouraged
• Initial drug selection

  Depends on the degree of BP elevation and presence of compelling indications for certain drugs
• Initial therapy for stage 1 hypertension

  Use a single first-line drug
• Initial therapy for stage 2 hypertension

  Start combination drug therapy (preferably with two first-line drugs)
• First-line options

  • Angiotensin-converting enzyme (ACE) inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Calcium channel blockers (CCBs)
  • Thiazide diuretics
• β-Blockers

  Should be reserved to treat a specific compelling indication or in combination with a first-line antihypertensive agent for patients without a compelling indication
• Other antihypertensive drug classes

  • α1-blockers
  • Direct renin inhibitors
  • Central α2-agonists
  • Direct arterial vasodilators
• Compelling indications


  Specific comorbid conditions for which clinical trial data support using specific antihypertensive drug classes to treat both hypertension and the compelling indication
• Compelling indications for specific antihypertensive drug classes

  • β-Blockers (without ISA) are first-line therapy in Stable Ischemic Heart Disease (SIHD)
  • For acute coronary syndromes, first-line therapy includes a β-blocker and ACE inhibitor (or ARB)
  • Any first-line agent can be used to control hypertension in patients with diabetes in the absence of albuminuria
  • ACE inhibitors and ARBs reduce intraglomerular pressure, which may further slow chronic kidney disease progression
  • The threshold for starting antihypertensive drug therapy in patients with a history of stroke is when BP is >140/90 mm Hg (goal of <130/80 mm Hg)
• ACE inhibitors

  Block conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion
• ACE inhibitors

  • Starting doses should be low with slow dose titration, acute hypotension may occur at the onset of therapy
  • Decrease aldosterone and can increase serum potassium concentrations, hyperkalemia occurs primarily in patients with CKD or those also taking potassium supplements, potassium-sparing diuretics, mineralocorticoid receptor antagonists, ARBs, or direct renin inhibitors
  • AKI is an uncommon but serious side effect, preexisting kidney disease increases risk, bilateral renal artery stenosis or unilateral stenosis are particularly susceptible to AKI
  • Serum creatinine concentrations often increase, but modest elevations (eg, absolute increases <1 mg/dL) do not warrant treatment changes, discontinue therapy or reduce dose if larger increases occur
  • Angioedema occurs in <1% of patients, drug withdrawal is necessary, and some patients may require drug treatment and/or emergent intubation to support respiration
  • A persistent dry cough occurs in up to 20% of patients and is thought to be due to inhibition of bradykinin breakdown
  • Contraindicated in pregnancy
• ARBs


  Directly block the angiotensin II type 1 receptor that mediates the effects of angiotensin II, unlike ACE inhibitors they do not block bradykinin breakdown and this accounts for the lack of cough as a side effect
• ARBs

  • Have a low incidence of side effects, may cause renal insufficiency, hyperkalemia, and orthostatic hypotension
• Calcium Channel Blockers


  Dihydropyridine and nondihydropyridine CCBs are first-line antihypertensive therapies and are also used in addition to or instead of other first-line agents for the compelling indication of ischemic heart disease
• Dihydropyridine CCBs


  • May cause reflex sympathetic activation, and all agents (except amlodipine and felodipine) may have negative inotropic effects
• Verapamil


  • Produces a negative inotropic effect that may precipitate HF in patients with borderline cardiac reserve
• Diltiazem and verapamil


  • Can cause peripheral edema and hypotension, verapamil causes constipation in about 7% of patients
• Dihydropyridines

  • Cause a baroreceptor-mediated reflex increase in heart rate because of potent peripheral vasodilating effects, other side effects include dizziness, flushing, headache, gingival hyperplasia, and peripheral edema
• Diuretics

  Thiazides are the preferred type and are a first-line option for most patients with hypertension, chlorthalidone (thiazide-like) is preferred over hydrochlorothiazide, especially in resistant hypertension, because it is more potent on a milligram-per-milligram basis
• Loop diuretics

  More potent for inducing diuresis but are not ideal antihypertensives unless edema treatment is also needed, sometimes required over thiazides in patients with severe CKD when eGFR is <30 mL/min/1.73 m2, especially when edema is present
• Potassium-sparing diuretics

  Weak antihypertensives when used alone, primary use is in combination with another diuretic to counteract potassium-wasting properties
• Mineralocorticoid receptor antagonists

  Also potassium-sparing diuretics, usually used to treat resistant hypertension because elevated aldosterone concentrations are prevalent in this setting, also used as add-on agents in patients with HFrEF with or without concomitant hypertension
• Diuretics

  • Acutely lower BP by causing diuresis, with chronic therapy reduced peripheral vascular resistance is responsible for persistent hypotensive effects
  • Side effects include hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperglycemia, dyslipidemia, and sexual dysfunction
  • Loop diuretics have less effect on serum lipids and glucose, but hypokalemia is more pronounced, and hypocalcemia may occur
  • Hypokalemia and hypomagnesemia may cause muscle fatigue or cramps, and severe electrolyte abnormalities may result in serious cardiac arrhythmias
  • Potassium-sparing diuretics may cause hyperkalemia, especially in patients with CKD or diabetes and in patients receiving concurrent treatment with a mineralocorticoid receptor antagonist, ACE inhibitor, ARB, direct renin inhibitor, or potassium supplement
  • Spironolactone may cause gynecomastia in up to 10% of patients, this effect occurs rarely with eplerenone
• β-Blockers

  Evidence suggests they may not reduce CV events as well as ACE inhibitors, ARBs, CCBs, or thiazides when used as the initial drug in patients who do not have a compelling indication for a β-blocker, appropriate first-line agents when used to treat specific compelling indications or when an ACE inhibitor, ARB, CCB, or thiazide cannot be used