Hypertension is a common condition that affects one in every three adults in the United
States and is becoming increasingly prevalent among children.
The 2017 American College of Cardiology (ACC)/American Heart Association (AHA)
guidelines define hypertension in adults as a blood pressure of ≥ 130/80 mm Hg and the
Eighth Joint National Committee (JNC 8) criteria specify ≥ 140/90 mm Hg.
Hypertension can be classified as either primary (essential) or secondary.
Primary hypertension accounts for ∼ 90% of cases of hypertension and has no
detectable cause, whereas secondary hypertension is caused by a specific underlying
condition. Typical underlying conditions include renal, endocrine, and vascular diseases
(e.g., renal failure, primary hyperaldosteronism, coarctation of the aorta).
Clinically, hypertension is usually asymptomatic until organ damage occurs, with the
brain, heart, kidneys, and/or eyes (e.g., retinopathy, myocardial infarction, stroke) most
commonly affected. If present, early symptoms of hypertension may
include headache, dizziness, tinnitus, and chest discomfort.
Hypertension is suspected if in-office blood pressure is persistently elevated on two or more
separate measurements and is confirmed with out-of-office measurement. Further diagnostic
measures include assessment of cardiovascular risk, evaluation of possible target organ
damage (e.g., kidney function tests), and additional tests if an underlying disease is suspected.
Treatment of primary hypertension includes lifestyle changes (e.g., diet, weight loss, exercise)
and pharmacotherapy. Commonly prescribed antihypertensive medications include angiotensin-
converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics,
and calcium channel blockers (CCBs); pharmacological management of pediatric and pregnant
patients differs, as some of these drugs are contraindicated in these patient populations. To
treat secondary hypertension, the underlying cause needs to be addressed.
•Hypertension in adults
• 2017 ACC/AHA: persistent systolic blood pressure (SBP) ≥ 130 mm
Hg and/or diastolic blood pressure (DBP) ≥ 80 mm Hg
• 2020 International Society of Hypertension (ISH) and 2014 JNC 8:
persistent SBP ≥ 140 mm Hg and/or DBP≥ 90 mm Hg
•Primary hypertension: hypertension with no identifiable cause
•Secondary hypertension: hypertension caused by an identifiable underlying
•Resistant hypertension: hypertension that remains uncontrolled (≥ 130/80
mm Hg) despite treatment with ≥ 3antihypertensives OR requires ≥ 4
medications to be controlled
The renin-angiotensin-aldosterone system (RAAS)
•Drops in blood pressure reduce renal perfusion.
•If the pressure in the renal artery falls by more than 10–15 mmHg,
proteolytic renin is released from the juxtaglomerular
apparatus → renin converts angiotensinogen to angiotensin
I → ACE cleaves C-terminalpeptides on angiotensin I, converting it
to angiotensin II → increases the blood pressure in two
ways: vasoconstriction and stimulation of the release of aldosterone,
Angiotensin-converting enzyme inhibitors (ACE inhibitors)
•Drug names: enalapril, lisinopril, ramipril, captopril, benazepril
• Arterial hypertension
• Diabetes mellitus (type I and type II) with
• Nephroprotective indications, such as:
• Arterial hypertension
• Microalbuminuria and proteinuria (especially ≥ 300 mg/g)
• Coronary heart disease
• Heart failure with reduced ejection fraction
• Survival benefit (the exact mechanisms are poorly understood)
• Any murmur that decreases with amyl nitrite has an etiology that is
treatable with ACE inhibitors.
• History of myocardial infarction
• Nondiabetic chronic kidney disease with proteinuria
• Scleroderma-associated hypertensive crisis (even if creatinine is elevated)
•Mechanism of action: inhibition of ACE → ↓ conversion of angiotensin I to angiotensin II
• ↓ Angiotensin II
• ↓ Vasoconstriction → ↓ blood pressure
• ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure
• Dilation of efferent arteriole → ↑ renal plasma flow → ↓ GFR → ↓ filtration fraction
• ↑ Renin secretion (due to lack of feedback inhibition) → ↑ angiotensin I
• ↓ Breakdown of bradykinin → ↑ production of arachidonic acid metabolites
→ ↑ vasodilation →↓ blood pressure
• ↓ Proteinuria and ↓ progression of proteinuric chronic kidney disease: ↓
intraglomerular hydrostatic pressure attenuates thickening and sclerosis of the GBM
• ↓ Preload and afterload → ↓ cardiac remodeling after acute myocardial infarction or in
chronic hypertensive disease
•Increase in bradykinin concentration, which can lead to:
• Dry cough (can be treated by discontinuing ACE inhibitor, consider
switching to ARB)
• Bradykinin-mediated angioedema due to increased vascular
permeability and vasodilation
•↓ GFR (with ↑ creatinine): can cause acute kidney injury in patients with
preexisting renal hypoperfusion (e.g., renal artery
stenosis, hypovolemia, heart failure)
•Pemphigus vulgaris (unknown mechanism)
•Teratogenicity: renal malformations
Angiotensin-receptor blocker (ARBs, sartans)
•Drug names: valsartan, candesartan, losartan, irbesartan
•Indications: same as ACE inhibitors, mostly used as second-
line treatment if ACE inhibitors are not tolerated
• Angioedema: can be tried under close surveillance if no
adequate alternative is available
• Non-life-threatening side effects
(e.g., dry cough ): commonly used
•Mechanism of action: inhibition of angiotensin II
receptor type 1 (AT1 receptor)
• ↓ Vasoconstriction → ↓ blood pressure
• ↓ Secretion of aldosterone → ↓ reabsorption of
Na+ and water → ↓ blood pressure
• ↑ Renin secretion (compensatory) → ↑ angiotensin
I → ↑ angiotensin II
• ↓ Proteinuria and ↓
progression of proteinuric kidney disease
• ↓ Cardiac remodeling after acute myocardial infarction or
chronic hypertensive disease
• No bradykinin elevation (opposed to ACE inhibitors)
Contraindications for ACE inhibitors and ARBs
• C1 esterase inhibitor deficiency (due to predisposition
• Pregnancy: risk of harm to the fetus (e.g., renal impairment,
renal malformations, oligohydramnios, placental insufficiency) 
• Aortic stenosis
• Renal dysfunction, consider altering dose if GFR < 60
• Bilateral renal artery stenosis or a solitary kidney: GFR is already
decreased and further reduction may lead to acute kidney injury.
• Drug interactions: See “Interactions” below.
ACE inhibitors and ARBs
•Other antihypertensive drugs → ↑ hypotensive effect
•NSAIDs → ↓ antihypertensive effect
•Potassium-sparing diuretics or other drugs that
increase potassium level: ↑ hyperkalemia
•↑ Level of lithium due to ↓ renal elimination
•Allopurinol: ↑ risk of immunological reactions
or leukopenia 
•Sulfonamides: furosemide, torsemide, bumetanide
•Other: ethacrynic acid
Mechanism of action
•Blockage of Na+-K+-2Cl- cotransporter in the thick ascending loop of
• Diminishing concentration gradient between the (usually
hypertonic) renal medulla and the cortex →concentration of
urine is no longer possible → increased diuresis
• Decreased reabsorption of Ca2+ and Mg2+
•Increased PGE release (can be inhibited by NSAIDs)
• Dilation of renal afferent arterioles → diuresis
• General venodilation (rapid venous pooling) → ↓
• Cardiac (acute and congestive heart failure, peripheral edema, lung edema)
• Renal (nephrotic syndrome)
• Hepatic (liver cirrhosis)
•Renal failure (acute and chronic)
• Definition: massive diuresis for forced renal elimination of (toxic) substances
• Implementation: IV administration of large amounts of fluids in combination with loop diuretics
• Indications: hypercalcemic crisis, severe hyperkalemia, rhabdomyolysis, intoxication (e.g., lithium)
•Sequential nephron blockade
• Used to overcome resistance to diuretic treatment
• Method: combination of loop diuretics and thiazides → restoration of diuretic effects
• Hypokalemia, hypomagnesemia, hypocalcemia, hypochloremia,
, hyponatremia (moderate)
• Metabolic alkalosis
•Ototoxicity (potentially permanent hearing damage): especially high
risk with ethacrynic acid
•Sulfonamide hypersensitivity (except ethacrynic acid, which can be
used for diuresis in patients
with allergies to sulfonamides) → rash, interstitial nephritis
Mechanism of action
Although the molecular pathways differ, both types of potassium-sparing diuretics have very
similar clinical effects.
•Aldosterone receptor antagonists (spironolactone, eplerenone)
• Competitively bind to aldosterone receptors in the late distal convoluted
tubule and the collecting duct → inhibition of the effects
of aldosterone → decreased Na+ reabsorption and K+ excretion → diuresis
• Decreased H+ excretion → acidosis
• Evolving hyperkalemia induces H+/K+-ATPases in all cells to counteract the increase
in serum K+ → K+ enters cells in exchange for H+ → amplifies acidosis
• Spironolactone also acts (nonspecifically) on sex hormone receptors → endocrine side
• Epithelial sodium channel blockers (triamterene, amiloride): direct inhibition of
the epithelial sodium channels(ENaC) in the distal convoluted tubule and the
collecting duct → reduced Na+ reabsorption and reduced K+ secretion → diuresis
Mechanism of action: potassium-
Aldosterone and the cytosolic
mineralocorticoid receptor form an
intracellular complex, acting as a
transcription factor for several
transport proteins that move
potassium, sodium, and water.
Potassium-sparing diuretics (e.g.,
spironolactone, eplerenone) are
aldosterone antagonists that inhibit
the expression of these transport
proteins, as well as basolateral
Na+/K+-ATPases, through competitive
binding of the aldosterone receptor.
This leads to increased retention of
potassium and increased excretion of
sodium and water.
•Hypertension (especially if hypokalemia is also present)
•Ascites/edema due to congestive heart failure, nephrotic
syndrome, or cirrhosis of
the liver (mainly spironolactone)
•Hyperaldosteronism (Conn syndrome)
•Nephrogenic diabetes insipidus (amiloride) 
•Hyperandrogenic states, e.g., polycystic ovary
•Anuria and/or renal insufficiency
•Combination with other potassium-sparing diuretics or potassium supplements
•Spironolactone: Use with caution in patients with CHF with either of the following:
• GFR < 30 mL/min
• Creatinine ≥ 2.5 mg/dL (men) or ≥ 2 mg/dL (women)
• Concomitant use of strong CYP3A4 inhibitors
• Patients with hypertension with concomitant type II diabetes mellitus
and microalbuminuria or with renal insufficiency (serum creatinine > 2.0 mg/dL for men or >
or > 1.8 mg/dL for women; or creatinine clearance< 50 mL/min)
• Creatinine clearance < 30 mL/min
•Amiloride: diabetic nephropathy
Calcium channel blockers (CCBs) are drugs that bind to and block L-type calcium channels, which are
the predominant calcium channels in the myocardium and vascular smooth muscles.
By blocking these channels, CCBs cause peripheral arterial vasodilation (leading to a drop in blood pressure)
and myocardial depression (leading to negative chronotropic, inotropic, and dromotropic effects on
CCBs are classified into two major groups according to the main site of
action: Dihydropyridines (e.g., nifedipine, amlodipine) are potent vasodilators,
and nondihydropyridines (e.g., verapamil) are potent myocardial depressants.
Diltiazem, a common nondihydropyridine, has moderate vasodilatory and myocardial depressant effects.
Nondihydropyridines are also categorized as class IV antiarrhythmic drugs and are used in the treatment
of supraventricular arrhythmias. The most common indications for CCB use are arterial hypertension and stable
angina. The main side effects of dihydropyridines are caused by vasodilation (e.g., headache, peripheral edema);
those of nondihydropyridines are caused by myocardial depression (e.g., bradyarrhythmias, atrioventricular block).
CCBs are contraindicated in patients with preexisting cardiac conduction disorders, symptomatic hypotension,
and/or acute coronary syndrome.
•CCBs bind to and block L-type calcium channels in cardiac and vascular smooth muscle
cells → decreased frequency of Ca2+ channel opening in response to cell
membrane depolarization → decreased transmembrane Ca2+ current
•Effects of decreased Ca2+ influx
• Vascular smooth muscle relaxation → vasodilation → decreased
peripheral vascular resistance → decreased afterload → decreased blood pressure
• Decreased cardiac muscle contractility (negative inotropic action)
→ decreased cardiac output → decreased blood pressure
• Decreased SA node discharge rate (negative chronotropic action) →
decreased heart rate (bradycardia) →decreased cardiac output → decreased
• Decreased AV node conduction (negative dromotropic action) → termination
of supraventricular arrhythmias
CCBs (nifedipine and amlodipine)
primarily act on vascular smooth
CCBs (verapamil > diltiazem)
primarily act on the heart.
•Dihydropyridines act mainly on
vascular smooth muscle. The order
of potency is nifedipine/amlodipine followed by
the nondihydropyridines verapamil and diltiaze
•Nondihydropyridines act mainly on the heart.
of potency is verapamil > diltiazem >amlodipine
•Arterial hypertension (esp. amlodipine )
•Stable angina: for patients with contraindications for
beta blockers or who are not responsive to beta
•Vasospastic angina (Prinzmetal angina)
•Diffuse esophageal spasm
arrhythmias (verapamil and diltiazem )
• Supraventricular tachycardia
• Atrial fibrillation, atrial flutter
•Cardiomyopathy (hypertrophic obstructive
cardiomyopathy, restrictive cardiomyopathy)
•Verapamil: cluster headache
Short-acting CCBs (e.g., nifedipine) are not indicated for
monotherapy of angina because they cause hypotension and
secondary reflex tachycardia, which can worsen
•Effects due to vasodilation
• Peripheral edema (esp. amlodipine)
• Headaches, dizziness
• Facial flushing, feeling of warmth
• Reflex tachycardia: a condition of tachycardia secondary to a decrease
in blood pressure (esp. nifedipine)
• Vasodilation lowers the blood pressure, which
stimulates baroreceptors of the sympathetic nervous system,
resulting in reflex tachycardia.
• May worsen symptoms of angina
•Allergy/hypersensitivity to CCBs
•Acute coronary syndrome
•Hypertrophic obstructive cardiomyopathy (HOCM)
•Severe stenotic heart valve defects
•Preexisting cardiac conduction disorders
• Wolff-Parkinson-White syndrome
• Sick sinus syndrome
• Systolic dysfunction (in congestive heart failure)
• 2° AV block/3° AV block
•Combination with beta blockers: risk of AV block, bradycardia,
and/or decreased cardiac contractility
Patients are usually symptomatic but those who present early or have
only consumed a small quantity of CCBs may be asymptomatic.
• Hypotension: may be profound, including cardiogenic shock
• Cardiac arrhythmias
• Cardiac arrest
•Respiratory: respiratory depression (including apnea), pulmonary
•Gastrointestinal: nausea and vomiting
•Central nervous system: confusion, lethargy, and coma
•Diagnosis is based on clinical observation and a thorough history
• Determine the time of intake, type, amount, and preparation (extended-release vs.
immediate-release) of the drug.
• Assess for risk of self harm.
•Any ingestion exceeding the maximum therapeutic dosage is usually clinically relevant.
•BMP: typically shows mild hyperglycemia and hyperkalemia
•VBG/ABG: metabolic acidosis
May show any of the following associated arrhythmias:
Beta blockers are a group of drugs that inhibit the sympathetic activation of β-
adrenergic receptors. Cardioselective blockers (e.g., atenolol, bisoprolol) primarily
block β1 receptors in the heart, causing decreased heart rate, cardiac contractility, cardiac
workload, and AVN conduction. Nonselective beta blockers (e.g., pindolol, propranolol)
inhibit all β receptors and may cause bronchoconstriction, peripheral vasoconstriction, and
metabolic imbalances (e.g., hypoglycemia and hyperglycemia, hypertriglyceridemia) in
addition to cardiac effects. Cardioselective beta blockers have a lower side-effect profile and
are preferred in the management of coronary heart disease, compensated heart
failure, acute coronary syndrome, and certain types of arrhythmias. Propranolol, a
nonselective beta blocker, is the first-line drug in the management of essential
tremor, portal hypertension, migraine prophylaxis, and thyroid storm. Beta blockers are
contraindicated in patients with symptomatic bradycardia, AV block, decompensated heart
failure, and asthma. Initiation and cessation of beta-blocker therapy should always be
gradual to avoid side effects or symptoms of withdrawal (e.g.,
rebound tachycardia, hypertension, acute cardiac death).
•Hypertension : beta blockers lower BP by ↓ cardiac output and ↓ renin secretion
•Coronary artery disease
• Acute myocardial infarction
• Beta blockers should be initiated early in all patients (without
contraindications) and continued long-term if tolerated. 
• Beta blockers decrease the size of the infarct and also reduce early and
delayed mortality rates in patients with acute MI.
• Angina pectoris: first-line treatment for stable angina pectoris in addition to ACE
Specific indications for propranolol
•Hyperthyroidism and thyroid storm
•Hypertensive crises (e.g., malignant hypertension): IV labetalol (rapid onset of
•Glaucoma: topical beta blockers (timolol, betaxolol)
•Pregnancy-induced hypertension: Labetalol is the first-line drug.
• Cardiogenic shock (hypotension; cold, clammy extremities)
• Wheezing (bronchoconstriction)
• Neurological symptoms (seizure, delirium, coma)
• Secure the airways.
• Correct cardiovascular decompensation (hypotension, bradycardia, and cardiogenic shock) via IV access:
inhibit the activity of the sympathetic nervous system, which is mediated
by epinephrine and norepinephrine. They act primarily by blocking the
postsynaptic adrenergic receptors (alpha and beta receptor antagonism) in target
organs or by inhibiting the synthesis and storage
of endogenous catecholamines (mainly norepinephrine).
A sympatholytic effect can also be achieved via stimulation of the presynaptic alpha-2
receptor with an alpha-2 agonist, which inhibits the release of catecholamines.
Sympatholytic drugs are most commonly used in the treatment of ischemic heart
disease and hypertension but may also be used for urinary retention secondary
to benign prostatic hyperplasia and for psychiatric conditions such as anxiety
disorders and posttraumatic stress disorder.
The thresholds for pharmacological treatment are controversial and vary
depending on age; the following recommendations are based on the 2017
•Adults with SBP ≥ 130 mm Hg or DBP ≥ 80 mm Hg and ≥ 1 of the following:
• Clinical ASCVD (e.g., ischemic heart disease, peripheral artery disease, or
previous stroke) or congestive heart failure (CHF)
• 10-year ASCVD risk ≥ 10% (includes age ≥ 65 years and diabetes mellitus)
•All adults with SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg
Choice of initial medication should be based on the following:
•Patient's initial blood pressure 
• SBP 130–139 mm Hg or DBP 80–89 mm Hg (stage 1 hypertension): Consider
• SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg AND an average blood pressure > 20/10
mm Hg above target
• Initiate combination therapy.
• Commonly used combinations are an ACEI or ARBPLUS either
a dihydropyridine CCB OR a thiazide-type diuretic.
•Additional factors to consider
• Major comorbidities
• Major contraindications
• Adverse effects that may be unacceptable to patients
• Patient race: For Black patients (including individuals with diabetes)
without CHF or CKD, initial antihypertensive therapy should include a thiazide-
typediuretic or CCB.
Long-term management and follow-up
Goals include evaluating medication adherence, monitoring treatment and
relevant laboratory studies, and adjusting medication.
•Patients on nonpharmacological treatment alone: Follow up after 3–6 months.
• If blood pressure is uncontrolled: Initiate pharmacological treatment.
•Most patients initiated on pharmacological treatment: Follow up after ∼ 1 month.
• If blood pressure is uncontrolled: Continue to escalate therapy at one-month
• Once blood pressure is controlled: Reassess after 3–6 months and annually
thereafter if blood pressure remains stable.
Laboratory studies 
• For most patients, check at the one-month follow-up visit.
• Check within 2–4 weeks in patients with CKD who were started on
an ACEI or ARB.