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Think outside the box when faced with difficult hypertension

From the June ACP Observer, copyright © 2007 by the American College of Physicians.

By Janet Colwell

SAN DIEGO—Consider the case of a 38-year-old Caucasian female with a several-year history of difficult-to-control hypertension and multiple medication intolerances. Her blood pressure readings typically are in the 160/100 mm Hg range and her physician has tried several medications without success: hydrochlorothiazide, amlodipine, doxazosin, oral clonidine and metoprolol.

Instead of prescribing more medication, the physician might investigate whether this is a case of white coat hypertension, advised Dominic Sica, FACP, chair of the section of Clinical Pharmacology and Hypertension at Virginia Commonwealth University Health System in Richmond, Va. If white coat hypertension is at play, for example, the physician might consider different treatment options, such as transdermal clonidine and non-drug options such as biofeedback and synchronized breathing.

When hypertension resists standard treatments, internists should look beyond simply increasing drug dosages, said Dr. Sica during a presentation at Internal Medicine 2007. For example, was the patient's blood pressure (BP) measured correctly? Do their readings fluctuate according to time of day? Is the patient suffering from other underlying conditions—such as sleep apnea or panic disorder—that might be contributing to their "resistant" hypertension?

Early morning BP changes can also be a red flag to adjust a patient's medication regimen, especially when there is a history of stroke, he said. For example, a 62-year-old man with a 10-year history of hypertension and a recent stroke had BP readings of about 160/100 mm Hg in the early morning after awakening but his BP dropped to 120-130/75-85 mm Hg during the rest of the day.

The man had been on a daily regimen of 25 mg hydrochlorothiazide, 50 mg atenolol, 10 mg ramipril, 325 mg acetylsalicylic acid and 40 mg atorvastatin. Because the risk of stroke is higher in the early morning, Dr. Sica recommended medication regimen adjustments that might include adding 4 mg of doxazosin at night to the man's regimen, or 5 mg of amlodipine at bedtime. In either case, more medication effect would be present the next morning.

In other difficult-to-treat cases, look for symptoms of conditions that may be contributing to the patient's hypertension, said Dr. Sica. He cited the case of a 54-year-old Caucasian woman with a past history of multiple medication failures, high anxiety and occasional panic. She reported sleeping only two to three hours a night and had a typical office BP reading of 160/105 mm Hg. The patient had been prescribed the following:

  • 25 mg hydrochlorothiazide once daily
  • 32 mg candesartan daily
  • 10 mg amlodipine once daily
  • 4 mg doxazosin at bedtime
  • 40 mg simvastatin at night
  • 0.5 mg alprazolam twice daily

Should the physician change the patient's diuretic or increase the dose of amlodipine? Try an ACE inhibitor in addition to the angiotensin-receptor blocker? What about converting alprazolam to the more long-acting 0.5 mg clonazepam twice a day?

In this case, Dr. Sica opted to substitute 12.5 mg chlorthalidone once a day for the hydrochlorothiazide and switch from alprazolam to 0.5 mg of clonazepam twice daily. After these adjustments, the patient reported sleeping for five to six hours a night and feeling considerably less anxious, and her daytime BP dropped to 150/90-95 mm Hg. Her BP dropped even lower to 130/85 mm Hg after amlodipine was shifted to nighttime dosing and the diuretic was increased to 25 mg of chlorthalidone once daily.

While every patient should be treated individually, there are some proven combinations that should be considered in the individual patient. Such combinations should also be mindful of the need to control for volume, pulse-rate, RAAS and SNS activation, said Dr. Sica. Here are some to note:

  • Minoxidil, beta-blocker (alone or combined with alpha blocker), diuretic, and ACE inhibitor (or ARB);
  • ACE inhibitor (or ARB), diuretic, calcium channel blocker (CCB), and peripheral alpha blocker or spironolactone;
  • ACE inhibitor (or ARB), non-dihydropyridine CCB and dihydropyridine CCB, with or without a diuretic, and
  • ACE inhibitor (or ARB), diuretic, CCB, and transdermal clonidine.

In treating the resistant hypertensive a number of adjunctive treatment measures should be considered: restoring sleep architecture, effectively treating anxiety and panic disorder, managing depression, limiting alcohol intake, smoking cessation, weight control and avoidance of medications associated with increases in BP, such as non-steroidal anti-inflammatory drugs.

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Considerations in blood pressure measurement:

  • Measure BP in both arms,
  • Measure in the sitting and upright position to determine if orthostatic change in present,
  • Make sure the cuff bladder has a length equal to at least 80% of the measured arm circumference,
  • Make sure the cuff bladder has a width equal to at least 40% of the measured arm circumference,
  • During measurement, the arm should be at the level of the heart, and
  • Do not round the BP reading—report it as close to the obtained reading as possible.

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