Essential Hypertension

NON-PHARMACOLOGICAL THERAPY

– Weight:

Aim for an ideal Body Mass Index, decrease as little as 4.5 kg in weight significantly reduces BP.

Target: BMI = 18.5 to 24.9 kg/m²

Formula: BMI = weight in kilograms / height in meter ²

– Waist circumference:

– Salt intake:

To decrease BP, consider reducing sodium intake toward 2000 mg (5 g of salt or 87 mmol of sodium) per day.

1,500 mg sodium (Na) = 65 mmol sodium (Na) = 3.75 g of salt (NaCl) = 1/2 level teaspoon of table salt

– Alcohol: Restrict intake to a maximum of

• Two standard drinks per day or 14 drinks per week for men and 9 drinks per week for women

One standard drink is equivalent to:

• 5 oz./142 ml of wine (12% alcohol)
• 1.5 oz./43 ml of spirits (40% alcohol)
• 12 oz./341 ml regular strength beer (5% alcohol)

– Potassium intake:

In patients not at risk of hyperkalemia, increase dietary potassium intake to reduce BP

When appropriate, patients with hypertension should be encouraged to consume foods with higher potassium content (e.g. fresh fruits, vegetables, and legumes)

– Exercise:

Moderate intensity dynamic exercise, such as brisk walking for 30-60 minutes, 4-7 days per week in addition to the routine activities of daily living

– Diet:

A diet rich in fruits, vegetables, and dairy products with reduced saturated and total fat can substantially lower BP – consider the DASH diet.

– Smoking:

Cessation of smoking and smoke-free environment is important to reduce hypertension, stroke, and cardiovascular risk.

PHARMACOLOGICAL THERAPY

Indications:

• Average SBP >160 or DBP >100 mm Hg without TOD or risk factors
• Average  SBP ≥140 and/or DBP ≥90 mm Hg for patients with target organ damage e.g. left ventricular hypertrophy
• Diabetes or chronic kidney disease with BP ≥130/80 mm Hg
• Chronic kidney disease with BP ≥140/90 mm Hg
• Presence of other risk factors (over 90% of Canadians with hypertension have other risk factors)

Treatment Gap Alert: Many younger hypertensive Canadians with multiple cardiovascular risks are currently not treated with pharmacotherapy. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy.

Considerations in the selection of therapy:

• Race: Diuretics preferred over renin-angiotensin system (RAS) inhibitors for African-Americans
• Age
• Coexisting diseases and therapies
• Quality of life (QOL)
• Economic consideration
• Dose per day (compliance factor)

– Diuretics:

• Thiazides are used as 1^st line agents because of effectiveness, compliance, and cost
• Loop diuretics should be used in patients with decreased renal function, defined as CrCl <20-30 mL/min
• Aldosterone antagonists: Prescribed in patients with primary hyperaldosteronism or those with resistant hypertension

– Βeta blockers:

• May be used 1^st line for patients with ischemic heart disease, CHF, those with migraine
• Not indicated 1^st line in patients over the age of 60 years

– ACE inhibitors:

• Should be considered in patients with diabetes, chronic kidney disease, atrial fibrillation, CAD or CHF
• Contraindicated in pregnancy

– Angiotensin receptor blocking agents:

• Considered in patients with diabetes, renal insufficiency, chronic kidney disease, or CHF (when ACE intolerant)
• Contraindicated in pregnancy

– Dihydropyridine calcium channel blockers:

• Considered in patients with isolated systolic hypertension, angina, and those at high CV risk
• Shown to be safe in pregnancy

– Non-dihydropyridine calcium channel blockers:

• Considered in patients with atrial arrhythmia, tachycardia, stable angina, concomitant migraine

– Alpha-adrenoceptor antagonists:

• Non-selective antagonists are usually reserved for use in hypertensive emergencies caused by a pheochromocytoma or as 4^th line agents
• Consider in hypertensive males with BPH

– Direct renin inhibitors:

• Indicated for the treatment of mild to moderate essential hypertension and reduction of proteinuria in addition to ACEIs or ARBs
• Contraindicated in pregnancy

– Drugs with central sympatholytic action (alpha agonists, central):

• Effective in hypertensive patients with renal disease because they do not compromise renal function; considered as 4^th line agents
• Methyldopa is traditionally considered as first-line therapy in pregnancy

– Vasodilators:

• Usually prescribed as adjunct therapy with other BP drugs and rarely are used alone
• Hydralazine also may be used to control high BP in pregnant women
• Nitroglycerin/ nitroprusside can be used in hypertensive emergencies

– Combination drugs:

May be used to:

• Simplify regimen and improve adherence
• Avoid side effects that may occur from high doses of a single agent
• If the BP is >20 mm Hg systolic ± >10 mm Hg diastolic above target – consideration should be given initially to start with 2 drugs from different classes, preferably as a combination product with the exception of beta-blockers with non-DHP-CCBs and ACEI with ARBs

If hypertension is NOT adequately controlled with a single agent, the patient should follow up monthly or more frequently if severe hypertension. Also, consider

• Patient non-adherence: Cost and adverse effects/allergy should be considered
• Suboptimal dose: Increase dose if the patient is considered adherent, however combination therapy is usually preferred to maximal doses of single agents
• If no change in BP and the patient is adherent, 1^st choice option may be ineffective and a new agent should be substituted
• Add in a second drug from another class; to improve control, and minimize adverse effects caused by the maximum dose of single agents

Specific Paradigms for Treatment of Hypertension:

• Isolated hypertension (Non-DM)
• Diabetes with hypertension
• Cardiovascular disease with Hypertension
• Stroke and TIA with hypertension
• Non-DM chronic kidney disease with hypertension
• PAD with hypertension
• Dyslipidemia with hypertension

HYPERTENSIVE EMERGENCY AND URGENCY:

Emergency:

• Initially reduce mean arterial BP by no more than 25% within minutes to an hour, once stable, further stabilization to 160/100-110 mm Hg within the next 2-6 hours to avoid further organ damage

Urgency:

• Avoid precipitous drop in BP. Aggressive dosing with intravenous drugs or even oral agents, to rapidly lower BP is not without risk
• Patients with stage II hypertension with associated symptoms such as severe headache, shortness of breath, epistaxis, or severe anxiety, should have their BP lowered up to 20% over several hours
• Some hypertensive urgencies may benefit from treatment with oral, short-acting agents. Most importantly, patients should not leave the ER without a confirmed follow-up appointment within a few days

Management:

• Monitor for end-organ injury:
  • Abnormal neurologic signs (stroke, seizures)
  • Severe headache
  • Pulmonary edema
  • Chest pain (MI, aortic dissection)
  • Vision difficulty (retinal edema, hemorrhage)
• Hospitalization, IV treatment, and ICU monitoring usually required for hypertension emergency/urgency
• Parenteral antihypertensive agents may include:
  • Vasodilators: e.g. Sodium nitroprusside, nitroglycerin, hydralazine
  • Adrenergic inhibitors: e.g. Labetalol, methyldopa, phentolamine
  • ACEIs: e.g. Enalaprilat
• Diuretics may be used to induce diuresis if required
• Ionotropic pressure support may be required for precipitous drop in BP

Special Considerations:

Hypertension and stroke

• Avoid overzealous BP lowering in acute stroke. Treat extreme BP elevation (systolic >220 mmHg, diastolic >120 mm Hg) by 15-25% over the first 24 hours with gradual reduction thereafter
• If eligible for thrombolytic therapy in acute stroke, treat very high BP (>185/110 mm Hg)
• In secondary prevention, the benefits of BP lowering is seen in both normotensive and hypertensive patients
• ACEI plus diuretic or ARB – based treatment should be considered

Aortic dissection

• Emergent cases, often requiring surgical management, especially in ascending aortic dissection
• Do not use sodium nitroprusside without beta-blockers, (increases the chances of aortic rupture)

Pheochromocytoma

• Alpha and beta-adrenergic receptors are stimulated by excess catecholamine in pheochromocytoma
• Preferred treatment is surgical resection of tumor, following α-adrenergic blockade to avoid catecholamine surge
• β-Adrenergic blockade alone may result in more severe hypertension owing to the unopposed α-adrenergic stimulation

Elderly hypertensive patient (age >60 years)

• May also have coexisting medical conditions
• Dosage should be increased gradually
• Diuretics, CCBs and ACE inhibitors/ARBs are good choices
• Avoid excess BP lowering especially if postural hypotension

Hypertension in patients of African descent

• Beta blockers and ACE inhibitors are less effective
• Calcium channel blockers, diuretics and possibly ARBs are the good choice

Obese hypertensive patient

• Weight reduction is the mainstay of non-pharmacological therapy
• Treatment is similar to isolated hypertension. However, there may be an associated risk of left ventricular hypertrophy, endothelial dysfunction, renal hyperfiltration, microalbuminuria, hence ACEI or ARB may be a reasonable option

The diabetic patient

• Usually require combination therapy to achieve desired levels ≤130/80 mm Hg
• Should start with ACE inhibitors or ARBs, and consider combination therapy if BP is >20 mm Hg systolic ± >10 mm Hg diastolic above target
• Caution with blockers because of their masking hypoglycemic symptoms

Patient with chronic kidney disease

• Most patients with hypertension require combination therapy to achieve optimal BP goals <130/80 mm Hg
• Initially start with diuretics (especially loop diuretics if Clcr <20-30 mL/min) and ACEI or ARBs

Patient with left ventricular hypertrophy (LVH)

• May start with ACEI or ARBs. Long-acting CCB or thiazide diuretics are other options

Patients with coronary artery disease (CAD)

• Increased risk of unstable angina (UA) and myocardial infarction (MI)
• May start with beta-adrenergic antagonist, long-acting CCB or ACE inhibitors
• Cautiously use non-dihydropyridine calcium channel blockers in MI and cardiac conduction system disease

Patients with heart failure (HF)

• ACEI and Beta blocker (ARB if ACEI intolerant)
• Titrate doses of beta-blockers and ACEI/ ARB to those used in clinical trials
• Avoid calcium channel blockers because of negative inotropic effects
• Add aldosterone antagonist in class 2, 3 or 4 HF

Pregnancy and hypertension

• Treatment is recommended for average SBP 140 mm Hg or DBP 90 mm Hg in pregnant women with chronic hypertension, gestational hypertension, or preeclampsia
• Pregnant women receiving antihypertensive therapy with chronic hypertension or gestational hypertension or preeclampsia, a DBP of 85 mm Hg should be targeted
• Avoid non-pharmacologic therapy such as:
  • Weight reduction
  • Exercise
• Oral alpha methyldopa has the largest amount of safety data and is still preferred
• First-line monotherapy drugs to be considered are labetalol, long-acting oral nifedipine, or other oral b-blockers (acebutolol, metoprolol, pindolol, and propranolol)
• Second-line drugs to be considered are clonidine, hydralazine, and thiazide diuretics
• Alpha-methyldopa has the largest amount of safety data and is still preferred
• ACEIs, ARBs, and nitroprusside are contraindicated in the pregnancy

Surgical/ Interventional

Treatment of renovascular hypertension

• Percutaneous transluminal angioplasty
• Stent placement (for fibromuscular hyperplasia and for discrete stenotic arteriosclerotic lesions not involving the renal artery ostium)
• Rarely bypass graft

[/cq_vc_tab_item][cq_vc_tab_item tabtitle=”Medication Dose”]MEDICATIONS

Diuretics

• Thiazide diuretics
• Loop diuretics
• Aldosterone receptor blockers
• Inhibitors of renal epithelial Na⁺ channels

Thiazide diuretics

Mechanism:

• Block Na/Cl transport in the proximal part of renal distal convoluted tubules

Dose:

Hydrochlorothiazide

• Initial 12.5 mg PO daily. Usual dose 25 mg PO daily; minimal benefit for lowering BP beyond 25 mg, however, side effects (such as hypokalemia and hyponatremia) increase

Chlorthalidone

• Initial 12.5 mg PO daily, increase to 25 mg/day if needed. Maximum dose is 50 mg/day, although there is minimal additional BP lowering effect beyond 25 mg/day

Indapamide

• Initial 1.25 mg PO daily; usual 2.5 mg/day, can be used when renal function <30 mL/min

• Titration: Increase by 1.25 mg PO every 4 weeks, according to blood pressure response; Max. 2.5 mg daily

Loop diuretics

Mechanism:

• Loop Diuretics → Block Na/K/Cl transporter in the renal loop of Henle

Dose:

Furosemide

• Initial 20 mg PO BID, it can be given 40 mg PO BID and then adjusted according to the response

Note: Will only consider if eGFR <30 mL/minute

Aldosterone receptor blockers

Mechanism:

• Blocks aldosterone receptors in renal collecting tubule → results in increased excretion of sodium and water and decreased excretion of potassium

Dose:

Spironolactone

• Initial 25-100 mg PO in single or divided doses, should be continued for 2 weeks then adjustments should be made according to the response

Eplerenone

• Initial 50 mg PO Daily for should be continued for 4 weeks, can go up to 50 mg PO BID. No therapeutic benefits observed with >100 mg/day

Inhibitors of renal Epithelial Na⁺ Channels

Mechanism:

• Disrupts sodium ↔ potassium exchange in the distal convoluted tubule and collecting ducts of the nephron
• Inhibits Sodium-Potassium-ATPase
• Decreases calcium excretion
• Increases magnesium loss

Dose:

Amiloride

• Initial 5 mg PO daily, usual 5-10 mg PO daily; Max. 20 mg/day (usually used in combination with another antihypertensive)

Triamterene

• Initial 50 mg PO daily; usual 50-100 mg PO daily (usually used in combination with thiazide diuretic)

Beta-adrenergic blocking agents

Cardioselective:

• Acebutolol
• Atenolol
• Bisoprolol
• Metoprolol
• Nebivolol

Non- Cardioselective:

• Carvedilol
• Nadolol
• Propranolol
• Timolol
• Pindolol
• Labetalol

Mechanism:

• Block beta receptors
• Decrease heart rate and cardiac output
• Decrease renin release

Dose:

Cardioselective:

Acebutolol

• Mild to moderate hypertension 200-400 mg PO daily in 2 divided doses
• Patient with severe hypertension may respond to higher doses

Atenolol

• Initial 25-50 mg PO daily, doses >100 mg/day show no additional benefit

Bisoprolol

• In some case initial 2.5 mg PO daily is preferable (especially in renal and hepatic impairment), usual 5 mg PO daily; may increase up to 20 mg/day if required

Metoprolol

Conventional tablets:

• Initial 25-50 mg/day PO BID; usual 100-200 mg/day in divided doses; Max. 400 mg/day in 2 divided doses

Extended-release tablets:

• Initial 25-100 mg PO daily; usual 100-200 mg PO daily

IV Metoprolol:

May be used to control hypertension/ventricular rate control in patients NPO or nonfunctioning GI tract.

• Initial low dose of 1.25-5 mg IV every 6-12 hrs

Nebivolol

• Initial 5 mg PO once daily, usual 5 to 10 mg once daily; can be increased at two-week intervals up to 20 mg once daily

Non- Cardioselective:

Carvedilol

Extended-release capsules:

• Initial 10 mg PO daily; Max. 80 mg/day

Immediate-release tablets (not indicated in Canada for HTN):

• Initial 6.25 mg PO BID; usual 12.5-25 mg PO BID; Max. 25 mg PO BID

Labetalol

• Initial 100 mg PO BID; usual 200-400 mg PO BID
• In severe hypertension maximum dose 1200 mg/day

• Titration: Increase dosage by 100 mg PO BID every 2-3 days

Hypertensive emergency

• IV: Initial 10-20 mg IV over 2 min x 1
  • Additional doses of up to 40-80 mg at 10-minute intervals may be required to achieve desired BP. Total cumulative dose of 300 mg; Max. 300 mg/day IV
• IV infusion: Initial 0.5-2 mg/minute continuous IV infusion (discontinue after 2.5 hrs of infusion)
• Oral dose following IV: Initial 100 mg PO daily; maintenance dose 200-400 mg PO in 2 divided doses

Nadolol

• Initial 40 mg PO daily; usual 40-80 mg PO daily; Max. 320 mg/day

• Titration: Gradually increase by 40-80 mg/day every 3-7 days

• In renal impairment depending on the CrCl dose interval is increased and doses are reduced

Propranolol

Conventional tablets:

• Not indicated for hypertension

Long acting (extended- release) capsules:

• Initial 80 mg PO; usual 160-320 mg PO daily; Max. 320 mg/day

• Titration: Increase dose 120-160 mg/day every 3-7 days

Timolol

• Initial 10 mg PO BID; usual 20-40 mg/day in 2 divided doses; Max. 60 mg/day

• Titration: May increase dose gradually at 5 mg BID intervals every 14 days

Pindolol

• Initial 5 mg PO twice daily; usual dose is 10-40 mg PO BID; Max. 60 mg/day

• Titration: Increase gradually by 10 mg/day every 3-4 wks

ACE (angiotensin-converting enzyme) inhibitors

• Benazepril
• Captopril
• Cilazapril
• Enalapril
• Fosinopril
• Lisinopril
• Perindopril
• Ramipril
• Quinapril
• Trandolapril

Mechanisms:

• Inhibition of the renin-angiotensin-aldosterone system
• Inhibit bradykinin degradation
• Stimulate vasodilating prostaglandin synthesis
• Reduce sympathetic nervous system activity

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Benazepril

• Initial: 1 mg once daily. Usual: 20 mg once daily; Maximum: 40 mg daily

Captopril

• Initial 12.5-25 mg PO BID or TID; usual 50 mg PO BID or TID; Max. 450 mg/day

• Titration: Increase by 12.5-25 mg/dose every 1-2 week; up to 50 mg 3 times/day

• Usually after 50 mg PO TID, consider adding a diuretic (thiazide)

Cilazapril

• Initial 2.5 mg PO once daily. Usual: 2.5 to 5 mg once daily; Maximum: 10 mg daily
• Elderly: Initial 1.25 mg PO once dailyRenal Impairment: Creatinine Clearance
  • > 40 mL/min: 1 mg once daily; Max. 5 mg once daily
  • 10 – 40 mL/min: 0.5 mg once daily; Max. 2.5 mg once daily
  • < 10 mL/min: 0.25 – 0.5 mg once or twice a week

  Hepatic Impairment:

  Cirrhosis: Initial ≤ 0.5 mg PO once daily

Enalapril

• Initial 2.5-5 mg PO daily; usual 2.5-40 mg/day in 1-2 divided doses; Max: 40 mg/day

Enalaprilat IV

• Initial 1.25 mg IV over 5 minutes every 6 hrs; usual 0.625-1.25 mg IV over 5 minutes given every 6 hrs, up to 36 hrs
• If concomitant diuretic use – begin with 0.625 mg IV over 5 minutes

Fosinopril

• Initial: 10 mg PO once daily. Usual: 20 mg daily as a single dose; Maximum: 40 mg daily

Lisinopril

• Start 10 mg PO daily; usual 10-40 mg PO daily; Max. 80 mg/day

• If concomitant diuretic – use cautiously, begin with 5 mg PO daily

• Moderate renal failure (CrCl 10-30): Begin with 5 mg PO daily; only if the decline/failure is not secondary to bilateral renal stenosis

• Dialysis patients: Begin with 2.5 mg once daily (adjust according to BP response)

Perindopril

• Initial 2-4 mg PO daily; usual 4-8 mg PO daily; Max. 16 mg/day

Ramipril

• Initial 2.5 mg PO daily (Max. 20 mg/day). Adjust at 1-2 week intervals by doubling dose, or 5 mg increments

Quinapril

• Initial: 10 mg once daily. Usual: 10 to 20 mg once daily; Maximum: 40 mg daily

Trandolapril

• Initial 1 mg PO daily or 2 mg PO daily in black patients; usual 2-4 mg PO daily. Adjust dosage at weekly intervals

Angiotensin receptor blocking agents

• Azilsartan
• Candesartan
• Eprosartan
• Telmisartan
• Irbesartan
• Losartan
• Olmesartan
• Valsartan

Mechanisms:

• Block AT1 angiotensin receptors
• Blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II
• Reduce vasoconstriction

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Azilsartan

• Initial 40 mg PO once daily. Max. 80 mg once daily

Candesartan

• Initial 8-16 mg PO daily; Max. 32 mg/day

Eprosartan

• Initial 400-600 mg PO daily. Total daily dose 400-800 mg/day in 1-2 divided doses; Max 800 mg daily

Irbesartan

• Initial 150 mg PO daily; usual 150-300 mg PO daily; Max. 300 mg/day

Note: Starting dose in volume-depleted patients should be 75 mg.

Losartan

• Initial 50 mg PO daily; usual 25-100 mg PO daily in 2 divided doses; Max. 100 mg

Telmisartan

• Initial 40 mg PO daily; usual 20-80 mg PO daily; Max. 80 mg/day

Olmesartan

• Initial: 20 mg once daily. Usual: 20 to 40 mg once daily; Maximum: 40 mg daily and 29 mg in mild to moderate renal impairment

Valsartan

• Initial 80-160 mg PO daily, in non-volume depleted patients; Max. dose is 320 mg PO daily

Direct renin inhibitor

• Aliskiren

Mechanism:

Decrease plasma renin activity → inhibits conversion of angiotensinogen to angiotensin I → results in decreased the formation of angiotensin II

Caveat: Inhibitors of the RAS (ACEI/ARB/DRI) might precipitate acute renal failure in the setting of conditions/illnesses that can be associated with dehydration.

Dose:

Aliskiren

• Initial 150 mg PO daily; Max. 300 mg/day

Calcium channel blocking agents (CCBs)

Non- Dihydropyridines:

• Diltiazem
• Verapamil

Dihydropyridines:

• Amlodipine
• Felodipine
• Nifedipine

Mechanisms:

• Blocks the inward movement of calcium by binding to the L-type calcium channels in the heart and in smooth muscle of the peripheral vasculature
• This decreases intracellular calcium leading to a reduction in muscle contraction
• Significant reduction in afterload but not preload

Dose:

Non- Dihydropyridines:

Diltiazem

• Initial 120-240 mg Po daily, usual 180-360 mg PO in 2 divided doses, Max. 360 mg/day

• Titration: Over 7-14 days

Canadian extended-release formulations

• XC or CD: Initial 120-240 mg PO daily; usual 240-360 mg PO daily

USA extended-release formulations-XR form and LA

• XR: Initial 180-240 mg PO daily; usual 180-480 mg PO daily
• LA: Initial 180-240 mg PO daily; usual 120-540 mg PO daily

Verapamil

Immediate-release form:

• Initial 80 mg TID or, usual 80 mg PO TID; Max. 480 mg/day; Elderly: Initial 40 mg PO TID

Verapamil (SR):

• Initial 180 mg every morning, usual 120-480 mg/day; Max. 480 mg/day; Elderly: Initial 120 mg every morning

Extended-release form (PM):

• Initial 200 mg at night, usual 200 mg at bedtime; Max. 400 mg/day; Elderly: Initial 100 mg at bedtime

Verapamil (HS):

• Initial 180 mg PO at bedtime; usual 240-480 mg PO at bedtime; Max. 480 mg PO at bedtime

Dihydropyridines:

Amlodipine

• Initial 5 mg PO daily or 2.5 mg PO daily in elderly; usual 5-10 mg PO once daily; Max. 10 mg/day

• Titration: Increase 2.5 mg over 1-2 wk (up to a maximum dose)

Felodipine

• Initial 2.5-5 mg PO daily; usual 5-10 mg PO daily; Max. 20 mg/day

Nifedipine – DO NOT USE immediate release formulation

Extended-release:

• Initial 30-60 mg PO daily; usual 30-90 mg PO daily; Max. 120 mg/day

• Titration: Increase dose by every 7-14 days

Nicardipine

• Oral: Initial 20 mg PO TID; usual 20-40 mg PO TID; Max. 120 mg/day

– Other Dihydropyridine NOT available in Canada:

Alpha-adrenoceptor antagonists

Selective alpha-adrenoceptor antagonists

• Prazosin
• Terazosin
• Doxazosin

Non-selective alpha-adrenoceptor antagonists

• Phentolamine

Mechanism:

• Block postsynaptic alpha receptors
• Relax smooth muscle
• Lowers peripheral vascular resistance

Dose:

Prazosin

• Initial 2-3 mg PO TID daily; maintenance 2-20 mg in 2-3 divided doses; Max. 20 mg/day

Terazosin

• Initial 1 mg PO daily at bedtime; usual 1-10 mg daily at bedtime; Max. 20 mg/day

Doxazosin

• Initial 1 mg PO daily at bedtime; may increase dose to 2 mg daily, make subsequent adjustments by doubling dose at intervals of 2-4 weeks until desired effect is achieved; Max. 16 mg/day

• Note: Substantial risk of syncope/postural effects with dosages >4 mg/daily.

Phentolamine

Hypertensive crisis (especially secondary to catecholamine excess)

• IV: Initial 5-15 mg bolus

Agents with central sympatholytic action (alpha agonists, central)

• Clonidine
• Methyldopa

Mechanisms:

• Stimulates alpha-adrenergic receptors in the central nervous system → reduces efferent peripheral sympathetic outflow

Dose:

Clonidine

Oral:

• Initial 0.05 mg PO BID. Usual 0.1 mg/day PO daily

• Titration: May increase by 0.1 mg/day every week until desire response achieved, then taper dose gradually over 2-4 days

Transdermal (available in the US):

• Initial 0.1 mg/week; usual 0.1-0.3 mg/week

• Titration: May increase by 0.1 mg 1-2 week interval

Methyldopa

Oral:

• Initial 250 mg BID or TID; usual 250 mg to 1 g daily in 2-3 divided doses. Max. 3 g/day (divided) in adults; 1 g/day in elderly

• Titration: Adjust dosage every 2 days until an adequate response is achieved

Intravenous (IV):

• 250 mg to 1 g every 6-8 hr, maximum: 1 g every 6 hrs

Vasodilators

• Hydralazine
• Minoxidil
• Nitroglycerin
• Nitroprusside

Mechanisms:

• Relax vascular smooth muscle
• Produce peripheral vasodilatation
• Decrease pre and after-load
• Reduces myocardial oxygen demand
• Nitroglycerin dilates coronary arteries

Dose:

Hydralazine

Oral:

• Initial 10 mg/day every 6 hrs for 2-4 days; usual 25 mg/day QID; Max. 300 mg/day

• Titration: Dosage may increase by 10-25 mg/dose every 2-5 days; up to a maximum dosage

Intravenous (maximum rate: 5 mg/minute):

• 10-20 mg every 4-6 hr

• Titration: May increase to 40 mg/dose

Intramuscular (IM):

• 10-50 mg every 4-6 hr

• Titration: May increase to 40 mg/dose

Minoxidil

• Oral: Initial 5-10 mg PO daily; usual 10-40 mg/day in 1-2 divided doses; Max. 100 mg/day

Nitroglycerin

In hypertensive emergency

• IV: 5 mcg/min; usual range 5-100 mcg/min; Max. 200 mcg/min

• Titration: Increase 5 mcg/minute every 3-5 min to 20 mcg/minute, if no response; increase 10-20 mcg/min every 3-5 min up to maximum dosage

Nitroprusside

In hypertensive emergency

• IV: Initial 0.25-0.3 mcg/kg/min; usual 3-4 mcg/kg/min; Max. 10 mcg/kg/min for 10 min

• Titration: Increase 0.5 mcg/kg/minute to maximum dosage till the desired effect achieved or adverse effect appears

COMBINATION DRUGS:

Examples of some commonly used agents

Diuretic combinations:

Hydrochlorothiazide 25 mg/Spironolactone 25 mg

• Dosage: Initial 1/2 tab/day; Max. 4 tab/day

Hydrochlorothiazide 25 mg/Triamterene 37.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Hydrochlorothiazide 50 mg/Amiloride 5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Ace inhibitors and Diuretics

Benazepril 10 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Captopril 25 mg/Hydrochlorothiazide 15 mg

• Dosage: Initial 1 tab/day; Max. 2 tabs/day

Lisinopril 10 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tabs/day

Enalapril 5 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Angiotensin receptor blockers and Diuretics

Losartan 50 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Candesartan 16 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Irbesartan 150 mg/ Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Valsartan 80 mg/Hydrochlorothiazide 12.5 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Beta-adrenergic blockers and Diuretics

Atenolol 50 mg/Chlorthialidone 25 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Pindolol 10 mg/Hydrochlorothiazide 25 mg

• Dosage: Initial 1 tab/day; Max. 2 tab/day

Metoprolol 50 mg/Hydrochlorothiazide 25 mg

• Dosage: 1 tab once or twice daily; Max. 2 tab

Propranolol 40 mg/Hydrochlorothiazide 25 mg

• Dosage: 2 tab BID; Max. 3 tab

Central alpha/Adrenergic agonist and Diuretics

Methyldopa 250 mg/Hydrochlorothiazide 15 mg

• Dosage: Initial 1 tab PO BID; Max. 4 tab

Calcium channel blockers and Ace inhibitors

Amlodipine 2.5 mg/Benazepril 10 mg

• Dosage: Initial 1 cap daily; Max. 4 cap/day

Felodipine 5 mg/Enalapril 5 mg

• Dosage: Initial 1 tab daily; Max. 3 tab/day

Verapamil extended-release 180 mg/Trandolapril 2 mg

• Dosage: Initial 1 tabs daily; Max. 3 tab/day

Perindopril arginine and Amlodipine

• Dosage: initiated at the recommended starting dose of 3.5 mg/2.5mg once daily; After four weeks of treatment, the dose may be increased to 7 mg/5 mg once daily in adult patients whose blood pressure is not at the appropriate target. If necessary, titration to 14 mg/10 mg once daily may be considered in adult patients insufficiently controlled after four weeks of treatment with 7 mg/5 mg
• Not indicated for the initiation of treatment in elderly patients (> 65 years of age)

Calcium channel blockers and Angiotensin II receptor blocker

Amlodipine (mg)/Telmisartan (mg)

• Dosage: 40/5, 40/10, 80/5 and 80/10 are all available

Direct renin inhibitor and Diuretics

Aliskiren 150/Hydrochlorothiazide 12.5

• Dosage: Initial 1 tab daily; Max. 2 tab/day

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