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Transcript of Jessica Schwenk, Pharm.D. September 14, 2013. Review pharmacologic treatment of hypertension,...
ANTIHYPERTENSIVE DRUG UPDATE
Jessica Schwenk, Pharm.D.September 14, 2013
Objectives Review pharmacologic treatment of
hypertension, including drug combinations and management of hypertension with other disease states
Discuss updates in the use of antihypertensive drugs
Describe medications used for hypertensive urgencies and emergencies
Review of Hypertension
Review of Hypertension How many people in the US have
hypertension?
Review of Hypertension How many people in the US have
hypertension? 58 to 65 million adults (estimated in 2008) 29-31% of US adults
Treatment of hypertension #1 reason for doctor visits (non-pregnant
adults) #1 reason for use of prescription drugs
Review of Hypertension Definitions
Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg
Prehypertension: systolic 120-139 mmHg or diastolic 80-89 mmHg
Hypertension: Stage 1: systolic 140-159 mmHg or diastolic
90-99 mmHg Stage 2: systolic ≥160 or diastolic ≥100
mmHg
Review of Hypertension Definitions
Isolated systolic hypertension: systolic ≥140 mmHg and diastolic <90 mmHg
Isolated diastolic hypertension: systolic <140 mmHg and diastolic ≥90 mmHg
Review of Hypertension Definitions continued
Malignant hypertension: hypertension with retinal hemorrhages, exudates, or papilledema Hypertensive encephalopathy Acute renal failure
Hypertensive urgency: Diastolic blood pressure > 120 mmHg without symptoms
Review of Hypertension Primary (essential) hypertension
Pathogenesis Increased sympathetic neural activity (beta-
adrenergic) Increased angiotensin II activity
Mineralocorticoid excess Genetics
Reduced adult nephron mass
Review of Hypertension Risk Factors
Ethnicity Genetics Diet
Sodium intake Alcohol
Obesity Tobacco use
Decreased physical activity
Hyperlipidemia Age > 65 years Personality Traits Vitamin D
Deficiency
Review of Hypertension Complications
Risk factor for other disease states Heart failure Left ventricular hypertrophy Stroke Intra-cerebral hemorrhage Kidney disease Malignant hypertension
Review of Hypertension Treatment benefits
Reduce risk of cardiovascular events, kidney disease, eye damage, morbidity and mortality
Only 46-51%have blood pressure under control Poor access to healthcare, medications Lack of adherence
Side effects, disadvantages of therapy Benefits not obvious to patients
Treatment of HypertensionLifestyle ModificationsTreatment AlgorithmTreatment GoalMedication Classes
Treatment of Hypertension Lifestyle Modification
Modification Systolic BP reduction
Sodium restriction 4.8 mmHg(2.5 mm HG diastolic)
Weight loss 0.5-2 mmHgper 1 kg weight loss
Diet (DASH) 2-8 mm Hg
Physical activity 4-8 mmHg
Moderation of alcohol consumption
2-4 mmHg
Treatment Goal JNC7 blood pressure goals
Generally <140/<90 mmHg Complications or increased risk factors
<130/<90 Diabetes Chronic kidney disease
Treatment of Hypertension Medications
Monitor Blood pressure Side effects: hypotension, orthostatic
hypotension, dizziness
Thiazide Diuretics Chlorthalidone (generic) 12.5-25 mg
daily Hydrochlorothiazide (Microzide,
HydroDIURIL) 12.5-50 mg daily Indapamide (Lozol) 1.25-2.5 mg daily Metolazone (Zaroxolyn) 2.5-5 mg daily
Thiazide Diuretics Side effects
Hypokalemia Hypomagnesemia Hypercalcemia Hyperuricemia Hyperglycemia Hyperlipidemia Sexual dysfunction
Monitoring Fluid status Electrolytes Renal function
Loses efficacy with ClCr < 40 mL/min
Dose-related side effects Limiting dose to
chlorthalidone or HCTZ 25-50 mg greatly reduces risk of metabolic side effects
Loop Diuretics Bumetanide (Bumex) 0.5-2 mg daily-BID Furosemide (Lasix) 20-80 mg daily-BID Torsemide (Demadex) 2.5-10 mg daily
Loop Diuretics Side Effects
Hypokalemia Hypomagnesemia Hypocalcemia Hyperuricemia Sexual dysfunction
Monitoring Fluid status
Weight loss/gain Electrolytes
Usually need electrolyte supplementation
Renal function Hearing (high doses)
Potassium-Sparing Diuretics Amiloride (Midamor) 5-10 mg daily-BID Triamterene (Dyrenium) 50-100 mg
daily-BIDAldosterone Antagonists Eplerenone (Inspra) 50-100 mg daily Spironolactone (Aldactone) 25-50 mg
daily
Potassium-Sparing Diuretics/Aldosterone Antagonists Side effects
Similar to thiazide diuretics: hypomagnesemia, hypercalcemia, hyperuricemia, sexual dysfunction
Hyperkalemia Especially eplerenone (contraindicated in impaired
renal function or DM II with proteinuria) Gynecomastia (10% with spironolactone)
Monitoring Electrolytes, fluid status, renal function
Angiotensin Converting Enzyme (ACE) Inhibitors Benazepril (Lotensin) 10-40 mg daily Captopril (Capoten) 25-100 mg BID Enalapril (Vasotec) 5-40 mg daily-BID Fosinopril (Monopril) 10-40 mg daily Lisinopril (Prinivil, Zestril) 10-40 mg daily Moexipril (Univasc) 7.5-30 mg daily Perindopril (Aceon) 4-8 mg daily Quinapril (Accupril) 10-80 mg daily Ramipril (Altace) 2.5-20 mg daily Trandolapril (Mavik) 1-4 mg daily
Angiotensin Converting Enzyme (ACE) Inhibitors Side effects
Hyperkalemia Dry cough (20%) Increased serum creatinine/kidney insufficiency Angioedema (2%) Rare (<1%)
Neutropenia and agranulocytosis, proteinuria, glomerulonephritis, acute kidney failure
Monitoring: potassium, kidney function Absolute contraindication in pregnancy
Angiotensin II Receptor Blockers (ARBs) Candesartan (Atacand) 8-32 mg daily Eprosartan (Teveten) 400-800 mg daily-
BID Irbesartan (Avapro) 150-300 mg daily Losartan (Cozaar) 25-100 mg daily-BID Olmesartan (Benicar) 20-40 mg daily Telmisartan (Micardis) 20-80 mg daily Valsartan (Diovan) 80-320 mg daily-BID
Angiotensin II Receptor Blockers (ARBs) Side effects
Hyperkalemia Increased serum creatinine/kidney
insufficiency Possible angioedema (cross-reactivity with
ACEIs reported) No bradykinin-induced dry cough
Monitoring: potassium, kidney function Should not be used in pregnancy
Calcium Channel Blockers Non-Dihydropyridines
Diltiazem Extended release (Cardizem CD, Dilacor XR,
Tiazac) 180-420 mg daily Extended release (Cardizem LA) 120-540 mg dialy
Verapamil Immediate release (Calan, Isoptin †) 80-320 mg BID Long acting (Calan SR, Isoptin SR †) 120-480 mg
daily-BID, (Coer, Covera HS, Verelan PM) 120-360 mg daily
Calcium Channel Blockers Dihydropyridines
Amlodipine (Norvasc) 2.5-10 mg daily Felodipine (Plendil) 2.5-20 mg daily Isradipine (Dynacirc CR) 2.5-10 mg daily Nicardipine sustained release (Cardene
SR) 60-120 mg BID Nifedipine long-acting (Adalat CC,
Procardia XL) 30-60 mg daily Nisoldipine (Sular) 10-40 mg daily
Calcium Channel Blockers Side effects
Flushing, headache, gingival hyperplasia, peripheral edema
Non-dihydropyridines: bradycardia, AV block (high doses), heart failure, anorexia
Precautions/Contraindications Contraindicated in heart failure Multiple drug interactions due to CYP450 3A4
inhibition Combination of non-dihydropyridine with beta
blocker increases chance of heart block
Beta Blockers Beta-1 selective (cardioselective)
Atenolol (Tenormin) 25-100 mg daily Metoprolol (Lopressor, Toprol XL) 50-100 mg daily-BID Betaxolol (Kerlone) 5-10 mg daily Bisaprolol (Zebeta) 2.5-20 mg daily
Non-selective Nadolol (Corgard) 40-120 mg daily Propranolol (Inderal, Inderal LA) 40-160 mg BID (60-
180 mg daily for LA) Timolol (Blocadren) 20-40 mg BID
Beta Blockers Intrinsic sympathomimetic activity
Acebutolol (Sectral) 200-800 mg BID Penbutolol (Levatol) 10-40 mg daily Pindolol (generic) 10-40 mg BID
Combined alpha-1 and beta blockers Carvedilol (Coreg) 12.5-50 mg BID Labetalol (Normodyne, Trandate†) 200-800
mg BID Nebivolol (Bystolic) 5-40 mg daily
Beta Blockers Side effects
Bradycardia, heart block, heart failure Monitoring: HR
Increased blood glucose Sexual dysfunction (impotence) Abrupt cessation: rebound hypertension, unstable
angina/myocardial infarction Specific groups
More CNS effects (dizziness/drowsiness ) with more lipophylic agents (propranolol)
Non-selective agents: β2-receptor activation, bronchospasm
Non-ISA agents: increased triglycerides
Alpha-1 Blockers Doxazosin (Cardura) 1-16 mg daily Prazosin (Minipress) 2-20 mg BID-TID Terazosin (Hytrin) 1-20 mg daily-BID
Side effects 1st dose phenomenon: dizziness, palpitations,
syncope Orthostatic hypotension CNS effects: vivid dreams, depression Sodium and water retention
Central alpha-2 agonists and Other centrally acting drugs Clonidine (Catapres) 0.1-0.8 mg BID
Clonidine patch (Catapres-TTS) 0.1-0.3 weekly
Clonidine (Catapres) 0.1-0.8 mg BID Methyldopa (Aldomet†) 250-1,000 mg
BID Reserpine (generic) 0.1-0.25 mg daily Guanfacine (Tenex†) 0.5-2 mg daily
Central alpha-2 agonists and Other centrally acting drugs Side effects
Sodium and water retention Orthostatic hypotension CNS side effects: depression Anticholinergic: dry mouth, sedation, constipation,
urinary retention, blurred vision Reserpine: parasympathetic activity (increased
secretions, bradycardia) Abrupt cessation: rebound hypertension Clonidine often used for resistant hypertension Methyldopa is a first-line agent in pregnancy
Direct vasodilators Hydralazine (Apresoline) 25-100 mg BID Minoxidil (Loniten) 2.5-80 mg daily-BID
Side effects Sodium and water retention Tachyphylaxis (use with beta blocker) Hydralazine
Lupus-like syndrome, dermatitis, drug fever, peripheral neuropathy, hepatitis, vascular HA
Minoxidil Hypertrichosis (hirsutism of face, arms, back, chest),
pericardial effusion, nonspecific T-wave change
Treatment of HypertensionTreatment of hypertension with
concurrent disease states or compelling indications
Choice of medication for hypertensionTreatment of hypertensive urgency &
emergencyNew Recommendations
Ischemic Heart Disease Stable angina
Beta blocker, or CCB Acute coronary syndrome
Beta blocker (without ISA), ACEI Post-MI
Beta blocker, ACEI, aldosterone antagonist
Heart Failure Asymptomatic heart failure
ACEI (or ARB), beta blocker Symptomatic ventricular dysfunction or
end-stage heart disease Beta blocker, ACEI or ARB, aldosterone
antagonist, loop diuretic
Diabetes ACEI or ARB
Reduce diabetic nephropathy and albuminuria
ARBs reduce progression to macroalbuminuria
Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs Prevent CVD and stroke incidence
Caution with beta blockers Mask signs of hypoglycemia
Chronic Kidney Disease ACEI or ARB
Slow progression of renal disease Limited rise in Scr acceptable (up to 35%
increase) Advanced CKD
Loop diuretics (volume control) Thiazide diuretics lose efficacy with ClCr
< 40
Cerebrovascular Disease Combination of thiazide diuretic and
ACEI Reduce recurrent stroke rate
Left ventricular hypertrophy All classes of antihypertensive agents
except the direct vasodilators hydralazine and minoxidil Regression of LVH
Severe hypertension with ECG evidence of LVH ARB
Only indication where ARB has proven benefit over ACEI
Ethnicity African-American
Monotherapy: thiazide diuretic or CCB Reduced BP responses with BBs, ACEIs, or
ARBs Caution: ACEI-induced angioedema
occurs 2–4 times more frequently Heart failure
Hydralazine/Isosorbide dinitrate (Bidil)
Elderly Follow same principles of therapy Start at lower doses, increase more
slowly Avoid side effects
Classes to avoid Alpha-1 blockers, alpha-2 agonists, centrally
acting agents, direct vasodilators Treatment of HTN may slow progression
of cognitive impairment and dementia
Pregnancy Preferred agents
Methyldopa, beta blockers, and vasodilators Contraindicated:
ACEIs and ARBs
Other indications Atrial tachyarrythmias/fibrillation
Beta blockers or calcium channel blockers (rate control) Migraine, tremor
Beta blockers BPH
Alpha-1 blockers Asthma, reactive airway disease, second or third degree
heart block Avoid beta-blockers (especially non-selective)
Gout, hyponatremia Avoid thiazide diuretics
Hyperkalemia Avoid potassium-sparing diuretics, aldosterone antagonists
Choice of initial medication
Choice of initial medication First line options
Thiazide diuretic Calcium channel blocker (long acting) ACEI or ARB
If treatment with second medication likely (ACCOMPLISH trial) Calcium channel blocker (long acting) ACEI or ARB
Hypertensive Urgency vs. Emergency Hypertensive urgency
Severe hypertension: SBP ≥180 mmHg and/or DBP ≥120 mmHg
Asymptomatic (other than headache) No evidence of acute end-organ damage
Hypertensive emergency Malignant hypertension Marked hypertension with retinal hemorrhages,
exudates, or papilledema Hypertensive encephalopathy Acute renal failure (malignant nephrosclerosis)
Hypertensive Urgency Treatment
Goal: gradual reduction of BP to < 160/100 Previously: rapid reduction of BP, but no
proven benefit Cerebral or myocardial ischemia or infarction
can be induced Sublingual nifedipine now contraindicated
Hypertensive Urgency Treatment: oral medications
Previously treated HTN Increase dose of existing medication or add new
medications Previously untreated HTN
Furosemide 20 mg PO(or higher if renal insufficiency) Clonidine 0.2 mg PO Captopril 6.25-12.5 mg PO Monitor until BP decreases 20-30 mmHg (or < 160/100) Prescribe longer acting agent(s), follow-up with provider
Malignant Hypertension Goal: rapidly reduce DBP to 100-105 mmHg
in 2-6 hours (25% reduction) Treatment: IV medications
Nitroprusside (Nitropress) Arteriolar and venous dilator IV infusion 0.25-0.5 mcg/kg/min
Max 8-10 mcg/kg /min. Onset: seconds. Duration of action: 2-5 minutes Cyanide toxicity possible with prolonged use
Nicardipine IV infusion 5 mg/hr; max 15 mg/hr
Malignant Hypertension Treatment: IV medications
Clevidipine Dihydropyridine calcium channel blocker IV infusion 1 mg/hr; max 21 mg/hr
Labetalol IV bolus 20 mg initially, followed by 20-80 mg every 10 min Infusion: 0.5-2 mg/min Max dose 300 mg in 24 hours
Fenoldopam Peripheral dopamine-1 receptor agonist, IV infusion 0.1 mcg/kg/min, titrate as needed every 15
minutes
Malignant Hypertension Treatment: oral medications
Not recommended unless IV meds not available Uncontrolled hypotensive response
Sublingual nifedipine 10 mg Sublingual captopril 25 mg
Monitoring When BP controlled, switch to oral therapy Decrease DBP to 85-90 mmHg over 2-3
months
What’s to come?
New Recommendations Chlorthalidone preferred over HCTZ
More potent Longer acting Potential lower risk of cardiovascular events
Beta blockers should NOT be used as 1st line therapy In absence of compelling indications Especially for patient’s > 60 years old
Higher SBP goals may be more appropriate Elderly: <150/<60 Diabetes: SBP < 130 may not improve CV risk
References Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-52.
Cupp M. Antihypertensives. Pharmacist’s Letter 2013; 29(4):290401. [Electronic version]. Available at: http://www.pharmacistsletter.com. Accessed April 14, 2013.
DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically.
Kaplan NM. Malignant hypertension and hypertensive encephalopathy in adults. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013.
Kaplan NM, Domino FJ. Overview of hypertension in adults. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013.
Lacy CF, Armstrong LL, Goldman MP, Lance LL. Lexi-Comp’s Drug Information Handbook. 17th ed. Hudson (OH): Lexi-Comp;2008.
Saseen JJ, Carter BL. Hypertension. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 6th ed. New York (NY): McGraw Hill;2005:185-218.
Systematic Evidence Reviews in Development: Cardiovascular Disease Risk Reduction in Adults (June 2013). National Institutes of Health Web site. Available at: http://www.nhlbi.nih.gov/guidelines/indevelop.htm#status. Accessed August 14, 2013.