David Q. Pham, PharmD, BCPS

Insulin pump therapy and continuous glucose monitoring systems can be invaluable tools for patients with type 1 and type 2 diabetes. 

	Diabetes mellitus is a chronic disease characterized by elevated levels of blood glucose. To prevent diabetes complications, high blood glucose must be controlled with diet, exercise, and medications.

 Type 1 diabetes occurs when the pancreas cannot supply adequate amounts of insulin to regulate blood glucose levels due to a cellular-mediated autoimmune response, which destroys the pancreatic beta-cells.

 The most common diabetes is type 2 diabetes mellitus (T2DM), in which patients no longer produce sufficient amounts of insulin and are insulin resistant.

 Insulin is the key for unlocking the cells to allow glucose to act as a fuel to create energy. Insulin is indicated for all patients with type 1 diabetes, most patients with gestational diabetes when diet is not enough to achieve control, and patients with T2DM who cannot control blood glucose levels with other forms of therapy.

	The Diabetes Control and Complications Trial (DCCT) concluded that intensive insulin therapy was superior to conventional therapy in improving glycemic control and slowing the progression of retinopathy, nephropathy, and neuropathy in patients with type 1 diabetes.

 The study defined conventional therapy as 1 or 2 insulin injections daily. Intensive insulin therapy was considered to be 3 or more insulin injections daily or the use of an insulin pump, which provides continuous subcutaneous insulin infusion.

	The American Diabetes Association (ADA) and American Association of Clinical Endocrinologists’ recommendations for type 1 diabetes concur with the DCCT results.

 Multiple daily injections or insulin pump therapy are the 2 options preferred for patients. Choosing the appropriate regimen is usually dependent upon the patient’s preference, lifestyle, and self-care capabilities, as well as cost.

	According to several major clinical trials, insulin pump therapy was more efficient in reducing blood glucose levels than the multiple daily injections.

 Using an insulin pump can help maintain tighter glycemic control without dramatically hindering the patient’s lifestyle.

 Because of cost differences and the inconvenience of being attached to a device, the use of insulin pumps is less common.

 The pump is a small, programmable device that contains a reservoir of rapid-acting insulin. The reservoir is connected by narrow tubing to a plastic cannula (not a needle, but a soft, flexible tube) that lies under the skin. A fine needle is used to help insert the cannula subcutaneously (usually around the abdomen, thigh, or upper buttocks), but the needle is removed once the cannula is placed. The cannula is replaced every 2 or 3 days; patients will only need to be punctured by a needle every 2 or 3 days compared with when insulin is used multiple times daily. The pump is programmed to deliver a predetermined amount of basal insulin throughout the day. The versatility and simplicity of the pump vary depending on the manufacturer. Typical features include the ability to program and deliver different types of boluses and basal rates, as well as set alarms and reminders. Pumps have bolus calculators as well.

	Although previous studies showed that insulin pump therapy was more effective than multiple daily insulin injections in reducing blood glucose levels,

 a metaanalysis of 15 randomized controlled trials showed marginal benefit (additional 0.2% reduction in A1C) for patients with type 1 diabetes.

 It also concluded there were little to no differences in efficacy for patients with T2DM.

 When deciding between insulin pump therapy and multiple daily injections, one must take into account the advantages and disadvantages of both regimens (Table

). There are definitely times during which insulin pump therapy should be considered over multiple daily injections (Table 2). As pump technology and insulin pharmacokinetics become more advanced, we may approach a clearer picture of which regimen is superior overall.

	The FDA has approved 4 continuous glucose monitoring (CGM) systems (Abbott’s FreeStyle Navigator CGM System, Dexcom’s Seven Plus CGM System, and Medtronic’s Guardian Real- Time CGM and MiniMed Paradigm Revel insulin pump). They can measure and record blood glucose levels continuously and can record up to 288 glucose measurements in a 24-hour period. If using Medtronic’s insulin pump and their CGM together, patients’ data are transmitted from the CGM to the insulin pump. CGM systems have great potential and may help control daily fluctuating blood glucose. Features include recording trends for up to 3 days, alerting patients of high and low glucose levels in real time, and measuring blood glucose every minute then transmitting the 5-minute average reading to the pump.

 A recent study showed that using a CGM for at least 6 days a week can lead to significant decreases in A1C.

Table 2. When to Consider Insulin Pump Therapy

Conditions when insulin pump therapy should be considered:

				2. Wide fluctuations in blood glucose levels regardless of A1C.

				3. Suboptimal diabetes control (ie, A1C exceeds target range for age).

				4. Microvascular complications and/or risk factors for macrovascular complications.

				5. Good metabolic control but insulin regimen that compromises lifestyle.

Populations for whom insulin pump therapy may be beneficial:

				1. Young children, especially infants and neonates.

				2. Adolescents with eating disorders.

				3. Children and adolescents with a pronounced dawn phenomenon.

				5. Pregnant adolescents, ideally before conception

	Currently, CGMs are starting to be used more and may be most valuable in patients with a history of severe hypoglycemia. The caveats of CGMs are that they are expensive ($900 per 10 of the replaceable sensors) and they read blood glucose via the interstitial fluid, causing an approximately 20-minute delay in readings. 

Patients will still need to measure their blood glucose levels via traditional finger sticks due to the delays.

CGMs and pumps working together may perhaps pave the way to closing the loop of insulin delivery and creating a successful artificial pancreas in the near future.

	Of all the agents used for the treatment of diabetes, insulin is the most effective at lowering high blood glucose.

 The ADA recommends that patients with T2DM be prescribed metformin in conjunction with lifestyle interventions at diagnosis.

 Two to 3 months after the initiation of metformin, A1C levels should be retested and additional medication considered if A1C levels are above 7%.

 The consensus regarding the medication to add is either a sulfonylurea if the A1C is 7% to 8.5% or basal insulin if the A1C is above 8.5%.

 Thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors, and incretins are other medications used for T2DM.

	There are 4 major categories of insulin. The rapid-acting insulin analogs, which currently most closely mimic a healthy postprandial pancreas’ response, are lispro, glulisine, and aspart. These 3 agents have been shown to produce less hypoglycemia with a more favorable dosing timeframe than insulin regular. Furthermore, the long-acting insulin analogs, such as glargine and detemir, have allowed for once-daily dosing (occasionally twice daily) of basal insulin compared with intermediate neutral protamine Hagedorn (NPH), which is usually administered twice daily. There is no maximum dose when titrating insulin for pharmacotherapeutic response.

	Patients with T2DM will often require a higher dose of insulin than those with type 1 diabetes due to the insulin resistance that is prominent in patients with T2DM.18 Patients with T2DM will usually initiate insulin use with bedtime intermediate NPH or either bedtime or morning long-acting insulin (glargine, detemir) as adjunctive therapy to their other medication(s).

	Although insulin reservoirs built for insulin pump therapy and the actual pumps are typically ordered directly from the manufacturer, pharmacists must keep abreast of these treatment regimens to provide optimal patient care.

Dr. Pham is a diabetes pharmacist at the Mary & Dick Allen Diabetes Center at Hoag Hospital and assistant professor of pharmacy practice at Western University of Health Sciences, College of Pharmacy. Dr. Iyer is an endocrinologist and medical director of the Mary & Dick Allen Diabetes Center at Hoag Hospital. Mrs. Woodring is a certified diabetes educator and nurse at the Mary & Dick Allen Diabetes Center at Hoag Hospital. Mr. Vuu and Ms. McArthur are PharmD candidates at Western University of Health Sciences, College of Pharmacy. 

	1. The Diabetes Control and Complications Trial Research Group (DCCT). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. 

	2. Rodbard H, Blonde L, Braithwaite S, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus (AACE). 

	3. American Diabetes Association: Standards of medical care in diabetes — 2010. 

	4. UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macro vascular and micro vascular complications in type 2 diabetes (UKPDS 38). 

	5. Jeitler K, Horvath K, Berghold A, et al. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis. 

	6. Sherr J, Tamborlane W. Past, present, and future of insulin pump therapy: better shot at diabetes control. 

	7. DCCT Research Group. Resource utilization and costs of care in the diabetes control and complications trial. 

	8. Neithercott, Tracey. Insulin pumps and infusion sets. 

. January 2010. http://forecast.diabetes.org/insulin-pumps.

	9. Fatourechi, MM, Kudva YC, Murad MH, Elamin MB, Tabini CC, Montori VM. Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections. 

	10. Sindelka G, Heinemann L, Berger M, Frenck W, Chantelau E. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects. 

	11. Mecklenburg RS, Benson EA, Benson JW Jr, et al. Acute complications associated with insulin infusion pump therapy. Report of experience with 161 patients. 

	12. Nicoucci A, Maione A, Franciosis M, et al. Quality of life and treatment satisfaction in adults with type 1 diabetes: a comparison between continuous subcutaneous insulin infusion and multiple daily injections. 

	13. Pankoska E, Skorka A, Szypowska A, Lipka M. Memory of insulin pumps and their record as a source of information about insulin therapy in children and adolescents with type 1 diabetes. 

	14. Jeha GS, Karaviti LP, Anderson B, et al. Insulin pump therapy in preschool children with type 1 diabetes mellitus improves glycemic control and decreases glucose excursions and the risk of hypoglycemia. 

	15. Phillip M,  Battelino T, Rodriguez H, et al. Use of insulin pump therapy in the pediatric age-group: consensus statement from the European Society for

	Paediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society, and the International Society for Pediatric and Adolescent Diabetes, endorsed by the

	American Diabetes Association and the European Association for the Study of Diabetes. 

Articles

Insulin Pump Therapy and Continuous Glucose Monitoring

Dr. Lee is an assistant professor of medicine at New York Medical College and clinical pharmacy manager in infectious diseases with Cardinal Health at Westchester Medical Center in Valhalla, New York. Dr. Pham is an assistant professor of pharmacy practice at Western University of Health Sciences, College of Pharmacy, in Pomona, California. 

Clinical practice guidelines have been adopted by the American Thyroid Association

 and the American Association of Clinical Endocrinologists

 for the evaluation and treatment of patients with hypothyroidism and hyperthyroidism. The treatment of thyroid disorders differs slightly, depending on whether the disease presents acutely or chronically. 

Hypothyroidism results from inadequate secretion of thyroid hormones, which virtually alters the function of every organ system.

The typical nonspecific signs of hypothyroidism include fatigue, cold intolerance, weight gain, constipation, dry skin, brittle nails, hoarse voice, hair loss, and overall body aches. 

Levothyroxine sodium is the drug of choice for thyroid replacement,

 because it is chemically stable, free of antigenicity, has a long half-life, and is relatively inexpensive.

 Dosage must be carefully adjusted according to individual requirements and response.

The average daily dose of levothyroxine in adults up to 50 years of age is 1.6 mcg/kg of actual body weight (100-125 mcg/day for a 70-kg adult). 

 Levothyroxine requirements change with age, preexisting cardiovascular disease, long-standing hypothyroidism, and pregnancy. 

Parenteral levothyroxine sodium is available and is usually reserved for patients with myxedema coma, the condition caused by acute hypothyroidism. Intramuscular injection is discouraged, because absorption is variable. Intravenous doses should be half the oral dosage, because oral doses are only absorbed approximately 40% to 80%.

Hyperthyroidism, also known as thyrotoxicosis, occurs when tissues are exposed to excess thyroid hormone.9 The most common cause of hyperthyroidism is Graves’ disease,

 an autoimmune disorder that produces antibodies against thyroid-stimulating hormone (TSH) receptors.

This process stimulates the thyroid gland to synthesize and secrete excess thyroid hormones (thyroxine [T

 Table 1 lists other causes of hyperthyroidism. 

Signs and symptoms of excess thyroid hormone are dependent on the patient’s age, duration of illness, and extent of hormone excess in the circulation. 

 These signs and symptoms are listed in Table 2. 

When evaluating patients for hyperthyroidism, a thorough physical assessment should be obtained, including weight and blood pressure, pulse rate, and cardiac rhythm, cardiovascular examination, thyroid palpation and auscultation (for size, nodularity, and vascularity), as well as neuromuscular, eye, skin, and lymphatic examination.

In addition to the physical examination listed above, laboratory tests must be performed to confirm the diagnosis of hyperthyroidism. Laboratory abnormalities include decreased TSH levels (<0.25-6.7 mIU/L), high levels of free T

 (<22%- 34%) (determined by resin uptake), and high levels of radioiodine uptake.

The primary goals of treatment for hyperthyroidism are to eliminate excess thyroid hormone and minimize the long-term consequences of hyperthyroidism. 

 Treatments include antithyroid medication, radioactive iodine (RAI), and surgery.

Beta-adrenergic blockers are used to provide symptomatic relief.

The approved thionamides include propylthiouracil (PTU) and methimazole (MMI).

These medications prevent the “organification” of iodine into iodotyrosine and iodothyronin. They also block the coupling reaction of monoiodotyrosine and diiodotyrosine to produce T

, thus effectively preventing synthesis of thyroid hormone.9 Additionally, PTU, but not MMI, inhibits peripheral conversion of T

Initial PTU doses range between 300 and 600 mg daily (maximum daily dose = 1200 mg). Initial doses of MMI, which is 10 times more potent than PTU, range between 30 and 60 mg daily (maximum daily dose = 120 mg).

 Although these medications are traditionally divided into 3 to 4 doses daily, they may be administered as single doses.

 Clinical improvement is usually observed at 4 to 8 weeks, at which time the dose should be tapered on a monthly schedule.

 Typical maintenance doses for each medication are 50 to 300 mg for PTU and 5 to 30 mg for MMI. Treatment should be continued for 12 to 24 months if the goal is to achieve lifelong remission.

In the United States, RAI is the treatment of choice for patients with Graves’ disease. Most patients become hypothyroid, requiring lifelong exogenous thyroid hormone.

 RAI is considered to be safe and can be used in women of childbearing age but not during pregnancy (because of risk for thyroid ablation in the fetus). Also, women should be advised to wait at least 6 months after treatment with RAI if planning for a family.

 The usual initial dose of RAI (131I) is a single dose of 5 to 15 mCi.

 Patients who remain hyperthyroid after RAI may need to repeat the treatment within 6 months.

Surgical removal of the thyroid gland is no longer the preferred intervention for hyperthyroid patients.

 Surgery is reserved for patients with suspected thyroid cancer, pregnant women intolerant to antithyroid drugs, and those refusing RAI.

 Candidates for surgery are required to take antithyroid medications (PTU or MMI) for 6 to 8 weeks, or until euthyroid.

 This is followed by the administration of iodides (500 mg/day) for 10 to 14 days before the surgery to decrease the vascularity of the tissue.

Propranolol is also recommended when preparing for thyroidectomy and to be continued for 7 to 10 days postsurgery to decrease beta-adrenergic activity.

Levothyroxine may be added to provide stabilization during the euthyroid state.

Beta-adrenergic antagonists are widely used as adjuvant therapy for those on antithyroid medications because of their ability to relieve symptoms associated with hyperthyroidism as listed in Table 2.

 Of the beta-blockers, propranolol and nadolol have an additional benefit by blocking peripheral conversion of T

Most patients find symptomatic relief with propranolol doses 20 to 40 mg (administered 4 times daily). Younger patients may require larger doses due to an increased medication clearance.

 Adherence may be improved by using agents only requiring once-daily dosing (ie, nadolol [80 mg] or atenolol [50-100 mg]).

Thyroid storm is a severe, life-threatening form of thyrotoxicosis that develops as a result of a precipitating event, most commonly infection.

 Other causes include trauma, surgery, cerebrovascular accident, recent withdrawal from antithyroid treatment, or post-RAI therapy.

Thyroid storm requires hospitalization. Mortality in these patients ranges from 20% to 50%, even if treated.

When treating patients with thyroid storm, it is critical to prescribe in the following step-wise fashion to prevent worsening of symptoms: (1) antithyroid medications, (2) beta-blockers, (3) corticosteroids, and (4) treatment of associated complications.

Thionamides are used to rapidly eliminate symptoms of thyroid hormone activity. Immediately following is the administration of iodide, which will help block secretion of prestored hormones in thyroid glands.

 If iodide is administered prior to thionamides, it may cause more synthesis and release of thyroid hormones. 

 Beta-blocking agents should be added to reverse the adrenergic effects in high doses. Corticosteroids have the ability to block peripheral conversion of T

, although adrenal insufficiency does not seem to play a role in crisis.

 After all of these medications are initiated, supportive treatment may still be necessary.

How Health Systems Choose Medications for Formulary 

Medications selected for health systems formularies need to include an array of chronic and acute medications for hypothyroidism and hyperthyroidism. For chronic hypothyroidism, oral levothyroxine sodium is the drug of choice. In patients with chronic hyperthyroidism, PTU, MMI, RAI, and propranolol are necessary. For myxedema coma, intravenous levothyroxine should be included on the formulary. For thyroid storm, the use of corticosteroids needs to be considered. 

The pharmacotherapy of thyroid disorders is complex. Health systems need to ensure that appropriate medications are available on formulary in order to treat both the acute and chronic states of hypothyroidism and hyperthyroidism. â–  

	1. Singer PA, Cooper DS, Levy EG, et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. 

	2. Baskin HJ, Cobin RH, Duick, DS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. 

	3. Reasner CA, Talbert RL. Thyroid disorders. In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. 

Pharmacotherapy: A Pathophysiologic Approach

, 5th edition. New York: McGraw-Hill; 2002:1359-1378.

	4. Dong BJ. Thyroid disorders. In: Young LY, Koda-Kimble MA, eds. 

Applied Therapeutics: The Clinical Use of Drugs

, 6th edition. Vancouver: Applied Therapeutics Inc; 1995:47.1-47.28

	5. Mandel SJ, Brent GA, Larsen PR. Levothyroxine therapy in patients with thyroid disease. 

	6. Burmeister LA, Goumaz MO, Mariash CN, Oppenheimer JH. Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer. 

	7. Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. 

	8. McKeown NJ, Tews MC, Gossain VV, et al. Hyperthyroidism. 

	9. Dipiro, JT, Talbert RL, Yee GC., et al. 

Pharmacotherapy: A Pathophysiologic Approach. 

6th ed. New York: McGraw-Hill; 2005:1371-1405.

	10. Woeber, KA. Update on the management of hyperthyroidism and hypothyroidism. 

The pharmacotherapy of thyroid disorders is complex. Health systems need to ensure that appropriate medications are available on formulary to treat both the acute and chronic states of hypothyroidism and hyperthyroidism.  

Pharmacotherapy of Thyroid Disorders in Health Systems 

Since 2003, all accredited schools of pharmacy in the United States have been mandated to provide the Doctor of Pharmacy degree (PharmD) as a national standard. To meet PharmD requirements and obtain their licenses, students must engage in a range of direct pharmacy practice experiences. Although PharmD programs began in teaching hospitals,

 many schools of pharmacy have expanded their rotation sites to include community hospitals.

Student pharmacists can positively impact patient care when trained appropriately by qualified and licensed pharmacists, and several studies have reported that pharmacy student participation in the activities of the health

 In one such study, pharmacy interventions performed by pharmacy students contributed to 29% of all interventions made by the pharmacy department.

 The literature shows that the acceptance rate for interventions initiated by pharmacy students has ranged between 79% and 95%.

 Pharmacy student participation appears to show enhanced clinical services for patients

A study conducted at Indiana University Medical Center evaluated the cost impact of pharmacy students in a health system.

 Pharmacy students were asked to document all interventions made over a period of 10 months. After each month, the director of pharmacy conducted an assessment of impact on patient care and costs. Recommendations were categorized as either cost avoiding or cost saving. Examples of cost-avoidance included the prevention of an allergic drug reaction or clinically significant drug interaction. Cost-saving interventions included a change in frequency of administration or elimination of duplication in therapy. The students provided a total of 1217 pharmacy interventions over the study period. Of the 1217 interventions performed, 98% were accepted and implemented by physicians. This annualized cost benefit was estimated at $354,752, of which $99,332 was a result of cost avoidance and $255,420 a result of cost savings.

In another study evaluating the impact of pharmacy students in a surgical intensive care unit, researchers found that over a 20-month period, 1023 recommendations were made, with an acceptance rate of 98% and cost savings

 In the ambulatory care setting, Slaugher et al reported that involving pharmacy students may result in savings of $275 for each 30-day drug regimen that is ordered for patients.

A preceptor must consider his or her own skill set in order to better prepare the student pharmacist for providing

direct patient care services in a community hospital. Critical thinking and communication skills are important traits for clinical practitioners. For the clinical pharmacist, this means increasing the focus on the ability to integrate patient-specific laboratory data, physical findings, and effects of medication use, and then assessing the patient's

response to therapy. The clinical pharmacist must communicate these needs to other health care providers to promote optimal drug therapy and patient outcomes.

When students participate in an acute care inpatient pharmacy practice rotation, they should be required to interact directly with patients on a daily basis. They should assess patients being managed under collaborative practice protocols approved by medical staff, in such areas as anticoagulation, aminoglycoside and vancomycin dosing, anemia management, total parenteral nutrition, and sepsis bundles, among others. Practicing these skills is very important during a student's clinical rotation. Important to the success of this skill set development is the presence of quality rolemodeling by the site preceptor(s). Preceptors need to be committed to providing an educational experience to all advanced pharmacy practice experience students on a daily basis.

As the shortage of pharmacists continues, the community hospital practitioner must be more

acutely aware of the competition for new graduates. The increasing applicant pool for postgraduate year-1 residency training, expansion of new career options for pharmacists, and the increasing need for pharmacists in community settings make a strong case for community hospital programs to create environments that will attract

Pharmacist Rounds: Making an Impact- Students Improving Patient Care

Dr. Youn is a pharmacy practice resident at Fountain Valley Regional Hospital and Medical Center in Fountain Valley, California. Dr. Pham is assistant professor of pharmacy practice at Western University College of Pharmacy and Health Sciences, in Pomona, California.

Of the 73 million Americans who have hypertension,

 will have severe elevation in blood pressure (BP), known as 

, which requires urgent medical treatment. Hypertensive crisis is an acute condition characterized by diastolic BP >109 mm Hg

The key feature that differentiates the 2 types of hypertensive crisis is evidence of target-organ damage.

 exhibit target-organ damage, whereas those suffering from 

 do not. Examples of target-organ damage include intracerebral hemorrhage, ischemic heart disease (eg, acute myocardial infarction [MI], acute heart failure), aortic dissection, eclampsia, and stroke.

 Hence, hypertensive emergency requires a rapid reduction in BP in hours using intravenous (IV) medications to prevent further organ damage. In contrast, hypertensive urgency does not have any physical findings of target-organ damage and is preferably managed with oral agents within 24 to 48 hours.

 To prevent further patient morbidity, it is important to initiate appropriate patient-directed therapy upon the recognition of hypertensive crisis.

Patients presenting with hypertensive urgency do not mandate admission to a hospital.

 Unfortunately, the term hypertensive "urgency" has led to an overly aggressive approach in treating BP.

 The treatment for hypertensive urgency requires a gradual lowering of BP. In fact, a rapid reduction may be associated with significant morbidity due to a marked reduction in perfusion that can result in ischemia or infarction.

 Patients will benefit from short-acting oral agents such as captopril, labetalol, or clonidine.

Captopril is a short-acting angiotensin-converting enzyme inhibitor that can be administered 12.5 to 25 mg orally as needed to reduce BP. Avoid use in patients with renal artery stenosis, hyperkalemia, and pregnancy. The onset of action takes 15 minutes, and the duration of action is 4 to 6 hours.

Labetalol is an alpha- and beta-adrenergic antagonist that can be administered 200 to 400 mg orally and repeated every 2 to 3 hours to control hypertensive urgency. The onset of action is 30 minutes to 2 hours, and it should be avoided in patients with asthma and bradycardia.

Clonidine is a central alpha agonist that is usually dosed 0.1 to 0.2 mg initially, then 0.1 mg every hour, up to 0.8 mg total. The onset of action also is 30 minutes to 2 hours. Clonidine should be avoided in patients with altered mental status and severe carotid artery stenosis.

The initial treatment goal for hypertensive emergency is to reduce the mean arterial pressure by up to 25% over the first few hours to prevent further progression of target organ damage.

The treatment generally consists of administration of an IV antihypertensive medication titrated to a goal with intraarterial BP monitoring until the patient stabilizes.

 Advantages in using IV medications include a rapid onset of action, usually within a few minutes of infusion, and an ease of dose titration. Too rapid a reduction in BP, however, can lead to end-organ ischemia or infarction, such as acute stroke or MI caused by reflex vasoconstriction and tachycardia.

 For this reason, short-acting nifedipine is contraindicated in hypertensive emergency as it may cause an excessive reduction in BP.

Other oral agents such as clonidine also should be avoided in hypertensive emergency due to its unreliable response and risk of rebound hypertension.

 Following are some of the commonly used medications in the management of hypertensive emergency.

Sodium nitroprusside is the preferred drug of choice for most hypertensive emergencies. It is a direct arterial and venous vasodilator with a very rapid onset of action within seconds to a few minutes. Although nitroprusside itself has a very short half-life, it contains 44% cyanide by weight; cyanide is metabolized to thiocyanate by the liver and is eliminated via the kidneys. Thus, in patients with renal or hepatic dysfunction, metabolites can accumulate to toxic levels.

Symptoms of thiocyanate toxicity include nausea, vomiting, muscle cramps, hyperreflexia, and disorientation. When nitroprusside is continued for more than 48 to 72 hours, monitoring of thiocyanate levels is recommended. If the thiocyanate serum concentration exceeds 12 mg/dL, the infusion should be discontinued. Nitroprusside is contraindicated in severe renal dysfunction and pregnancy. Doses will range between 0.25 and 10 mcg/kg per minute, but the dose should be kept at <2 mcg/ kg per minute to avoid toxicity.

At low doses, nitroglycerin is primarily a venous vasodilator with some vasodilatory effects on the coronary arteries. At high doses, nitroglycerin has been known to vasodilate arteries. Due to its favorable effect on coronary arteries, it is the preferred agent in patients with acute coronary syndrome or acute heart failure. Unlike nitroprusside, nitroglycerin does not exhibit any longterm toxicities and is well tolerated, with the most common adverse effect being headache. Patients may develop tolerance, however, when the agent is used for more than 24 to 48 hours. Doses range from 5 to 60 mcg/hour.

Fenoldopam is a peripheral dopamine-1 agonist that can be used as an alternative to nitroprusside. It may be particularly useful for the management of perioperative hypertension or in patients with renal dysfunction. Fenoldopam may improve renal blood flow through dopamine receptor activation of the renal bed.

 It should be used with caution in patients with glaucoma, however. Usual dose ranges from 0.1 to 1.6 mcg/kg per minute.

Nicardipine is a dihydropyridine calcium channel blocker that is appropriate for most hypertensive emergencies. It can be given orally, but IV administration is preferred for the management of hypertensive emergency. Also, unlike many IV antihypertensive agents, nicardipine can be given independent of the patient's weight. The usual dose ranges from 5 to 15 mg/hour.

Health systems need to educate staff, particularly in the emergency department, to be effective in diagnosing hypertensive crises and differentiating between hypertensive and hypertensive urgency emergencies, because treatment plans are dependent on these findings. Tools that can easily identify target-organ damage will assist in this process.

For treatment, the pharmacy and therapeutics committee should devise a plan in selecting the best agents for hypertensive urgency and hypertensive emergency based on safety data, efficacy data, and cost differences. Oral agents that are fast acting and have a short duration of action are preferred, as they can easily be titrated to achieve adequate BP control. Adverse effects must be factored into this equation, however. Sublingual products or products that require "bite and chew" should be avoided to prevent severe hypotension.

Patients who have a precipitous increase in BP are at significant risk for acute end-organ damage, such as stroke or acute coronary syndrome. Initiating patient appropriate antihypertensive treatment in a timely manner can reduce or prevent patient harm.

Many of these antihypertensive agents have adverse effects that require monitoring, and dangers are associated with too rapid of a reduction in BP; thus, one must balance safety of the medications with benefits gained from using them.

The best management for hypertensive crisis is prevention. Of the known risk factors for hypertensive crisis, the most prevalent is a history of hypertension.

 Considering that many individuals with hypertension have inadequate control of, or are not aware of, their medical condition,

 vigilant screening and reinforcement of the chronic management of hypertension by a pharmacist can significantly reduce a patient's risk for hypertensive crisis.

Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 

Marik PE, Varon J. Hypertensive crises: challenges and management. 

Varon J. Treatment of acute severe hypertension: current and newer agents. 

Feldstein C. Management of hypertensive crises. 

Flanigan JS, Vitberg D. Hypertensive emergency and severe hypertension: what to treat, who to treat, and how to treat. 

Stewart DL, Feinstein SE, Colgan R. Hypertensive urgencies and emergencies. 

Haas AR, Marik PE. Current diagnosis and management of hypertensive emergency. 

Elliott WJ. Clinical features in the management of selected hypertensive emergencies. 

Understanding the difference between hypertensive urgency and hypertensive emergency is essential to initiating patient appropriate treatment in a timely. This article reviews targeted therapies for both.