Hypertension

• Patient Population
• Target Blood Pressure

• Most patients
• < 140/90 mmHg

• Diabetes mellitus
• < 130/80 mmHg

• Chronic kidney disease
• <130/80 mmHg

• Most patients for general prevention
• <140/90 mmHg

• Patients with diabetes (CAD risk equivalent), significant CKD, known CAD (MI, stable angina, unstable angina), noncoronary atherosclerotic vascular disease (ischemic stroke, TIA, PAD, abdominal aortic aneurism [CAD risk equivalents]), Framingham risk score > 10%
• <130/80 mmHg

• Patients with left ventricular dysfunction (HF)
• <120/80 mmHg

Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Thiazide type diuretics

fatal CHD

nonfatal MI

HF

stroke

Thiazide-like diuretic

based on clinical trials showing morbidity & mortality reductions

Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension

A. benazepril + amlodipine

• Heart Failure
• Post Myocardial Infarction
• High Coronary Disease Risk
• Diabetes Mellitus
• Chronic Kidney Disease
• Recurrent Stroke Prevention

Thiazide-type diuretics

ACE inhibitor, ARB, CCB, or combination

Two-drug combination for most

Usually a thiazide-type diuretic with an ACE inhibitor, or ARB, or CCB

• Standard: Diuretic with ACE inhibitor
• then add Beta-Blocker

Add-on: ARB or aldosterone anatagonist

Standard: Beta-Blocker than add ACE inhibitor or ARB

Add-on: Aldosterone antagonist

Standard: Beta-Blocker then add ACE inhibitor or ARB

Add-on: CCB, diuretic

Stanard: Ace inhibitor or ARB

Add-on: diuretic

2nd add-on: Beta-blocker, CCB

Standard: ACE inhibitor or ARB

Standard: Diuretic with ACE inhibitor or ARB

candesartan - ARB

BP>140/90 mmHg after 20 weeks’ gestation with proteinuria

Methyldopa-(Central Sympatholytics)

While Labetolol -(Alpha/Beta-Blocker) has increasingly been preferred over methyldopa because of fewer side effects

diuresis

• Thiazide - chlorthalidone, hydrochlorothiazide (HCTZ), indapamide, metolazone
• Loop - bumetanide, furosemide, torsemide
• Potassium-sparing - amiloride, triamterene
• Aldosterone antagonists - eplerenone, spironolactone

• Dose in morning to avoid nocturnal diuresis
• —Adverse effects: hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperuricemia, hyperglycemia, hyperlipidemia, sexual dysfunction
• —lithium toxicity with concurrent administration

• Dose in AM or afternoon to avoid nocturnal diuresis
• Higher doses may be needed for patients with severely decreased glomerular filtration rate or heart failure
• Used in patients with kidney dysfunction (SCr > 2.5)
• Adverse effects: hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia, hyperuricemia

• Dose in AM or afternoon to avoid nocturnal diuresis
• Generally reserved for diuretic-induced hypokalemia patients
• Weak diuretics, generally used in combination with thiazide diuretics to minimize hypokalemia
• Adverse effects: may cause hyperkalemia especially in combination with an ACE inhibitor, angiotensin-receptor blocker or potassium supplements
• avoid in patients with CKD or diabetes

Dose in AM or afternoon to avoid nocturnal diuresis

Due to increased risk of hyperkalemia, eplerenone contraindicated in CrCl < 50 mL/min & patients with type 2 diabetes & proteinuria

• Adverse effects:
• may cause hyperkalemia especially in combination with ACE inhibitor, angiotensin-receptor blocker or potassium supplements

avoid in CKD or DM patients

Gynecomastia: up to 10% of patients taking spironolactone

ACE Inhibitors

• Block bradykinin degradation; stimulate synthesis of other vasodilating substances such as prostaglandin E2 & prostacyclin
• Prevent or regress left ventricular hypertrophy by reducing angiotensin II myocardial stimulation

Monitor serum K+ & SCr within 4 weeks of initiation or dose increase

• Adverse effects:
• cough - up to 20% of patients due to increased bradykinin
• angioedema
• hyperkalemia: particularly in patients with CKD or DM
• neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure

• Adverse effects:
• orthostatic hypotension
• renal insufficiency
• hyperkalemia

• True
• Do not block bradykinin breakdown
• less cough than ACE Inhibitors

• NO
• Pregnancy category C in 1st trimester
• Pregnancy category D in 2nd & 3rd trimester

• Inhibits angiotensinogen to angiotensin I conversion
• Does not block bradykinin breakdown
• less cough than ACE Inhibitors
• Adverse effects: orthostatic hypotension, hyperkalemia

• Inhibit renin release
• weak association with antihypertensive effect
• Negative chronotropic & inotropic cardiac effects reduce CO

• do not reduce CO
• lower BP
• decrease peripheral resistance

• bradycardia
• atrioventricular conduction abnormalities
• acute heart failure
• abrupt discontinuation may cause rebound hypertension or unstable angina, myocardial infarction, & death in patients with high coronary disease risk
• bronchospastic pulmonary disease exacerbation
• may aggravate intermittent claudication, Raynaud’s phenomenon

• heart, kidney
• stimulation increases HR, contractility, renin release

• lungs, liver, pancreas, arteriolar smooth muscle
• stimulation causes bronchodilation & vasodilation
• mediate insulin secretion & glycogenolysis

• Cardioselective - atenolol, betaxolol, bisoprolol, metoprolol, nebivolol
• Nonselective - nadolol, propranolol, timolol
• Intrinsic sympathomimetic activity -acebutolol, carteolol, penbutolol, pindolol
• Mixed α- and β-blockers - carvedilol, labetolol

• Cardioselective Beta-Blockers
• (Beta1)

• Cardioselective Beta-Blockers
• (Beta1)
• Safer in patients with bronchospastic disease, peripheral arterial disease, diabetes
• may exacerbate bronchospastic disease when selectivity lost at high doses
• dose where selectivity lost varies from patient to patient

• essential tremor
• migraine headache
• thyrotoxicosis

additional blockade produces more orthostatic hypotension

• Inhibit influx of Ca2+ across cardiac & smooth muscle cell membranes
• muscle contraction requires increased free intracellular Ca2+ concentration
• CCBs block high-voltage (L-type) Ca2+ channels resulting in coronary & peripheral vasodilation

• Dihydropyridines: amlodipine, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, clevidipine
• Non-dihydropyridines: diltiazem, verapamil

• bradycardia
• atrioventricular block
• systolic HF

• orthostatic hypotension
• 1st dose phenomenon: transient dizziness, faintness, palpitations, syncope within 1 to 3 hours of 1st dose
• lassitude, vivid dreams, depression
• priapism
• Na+/H2O retention

• 1st dose at bedtime
• Used with diuretics to minimize edema Caution in elderly patients
• Reduce benign prostatic hypertrophy symptoms
• block postsynaptic α1-adrenergic receptors on the prostate
• relaxation
• decreased urinary outflow resistance

• Adverse effects: sodium/water retention
• abrupt discontinuation may cause rebound HTN
• depression
• orthostatic hypotension
• dizziness
• Clonidine: anticholinergic side effects
• Methyldopa: can cause hepatitis, hemolytic anemia (rare)

-lol

-pine

-pril

• -tan
• -tin

• -sin
• -mine

• sodium/water retention
• angina
• Hydralazine can cause lupus-like syndrome
• Minoxidil can cause hypertrichosis

• Peripheral adrenergic antagonist
• depletes norephinephrine from sympathetic nerve endings; blocks norephinephrine transport into storage granules
• reduces norephinephrine release into synapse following nerve stimulation
• reduced sympathetic tone
• peripheral vascular resistance reduction
• decreased BP
• depletes catecholamines from brain & myocardium

• sedation
• depression
• decreased CO
• sodium/water retention
• increased gastric acid secretion
• diarrhea
• bradycardia
• Use with diuretic (preferably thiazide) to avoid fluid retention

Decrease in SBP > 20 mmHg or DBP > 10 mmHg when changing from supine to standing position

• BP > 180/120 mmHg
• reduce gradually

• elevated BP
• no acute or progressing target-organ injury

• acute or progressing target-organ damage
• encephalopathy, intracranial hemorrhage, acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, unstable angina, eclampsia

Nausea, vomiting, muscle twitching, sweating, thiocyanate and cyanide intoxication

Most hypertensive emergencies; caution with high intracranial pressure, azotemia, or in chronic kidney disease

Tachycardia, headache, flushing, local phlebitis

Most hypertensive emergencies except acute heart failure; caution with coronary ischemia

Headache, syncope, dyspnea, nausea, vomiting

Most hypertensive emergencies except severe aortic stenosis; caution with heart failure

Tachycardia, headache, nausea, flushing

Most hypertensive emergencies; caution with glaucoma

Headache, vomiting, methemoglobinemia, tolerance with prolonged use

Coronary ischemia

Tachycardia, flushing, headache vomiting, aggravation of angina

Eclampsia (In Hypertensive Emergency)

Vomiting, scalp tingling, bronchoconstriction, dizziness, nausea, heart block, orthostatic hypotension

Most hypertensive emergencies except acute heart failure

Hypotension, nausea, asthma, first-degree heart block, heart failure

Aortic dissection; perioperative

• Parameters:
• blood pressure
• BUN/serum creatinine
• serum electrolytes (K+, Mg2+, Na+)
• uric acid (for thiazides)

• Parameters:
• blood pressure
• heart rate

• Parameters:
• blood pressure
• BUN/serum creatinine
• serum potassium

• Parameters:
• blood pressure
• heart rate

failure to achieve BP goal on full doses of 3 drug regimen including a diuretic