and previous preeclampsia. The etiology of preeclampsia is complex and incompletely understood.
Preeclampsia poses serious risks for the fetus and mother.
Risks for the fetus include intrauterine growth restriction, premature birth, and even death. The mother is at risk for seizures (eclampsia), renal failure, pulmonary edema, stroke, and death.
Management of preeclampsia is based on the severity of the disease, the status of mother and fetus, and the length of gestation. The objective is to preserve the health of the mother and deliver an infant who will not require intensive and prolonged neonatal care. Success requires close maternal and fetal monitoring. Although drugs can help reduce BP, delivery is the only cure.
Management of mild preeclampsia is controversial and depends on the duration of gestation. If preeclampsia develops near term, and if fetal maturity is certain, induction of labor is advised. However, if mild preeclampsia develops earlier in gestation, experts disagree about what to do. Suggested measures include bed rest, prolonged hospitalization, treatment with antihypertensive drugs, and prophylaxis with an anticonvulsant.
Studies to evaluate these strategies have generally failed to demonstrate benefits from any of them, including treatment with antihypertensive drugs.
The definitive intervention for severe preeclampsia is delivery. However, making the choice to induce labor presents a dilemma. Since preeclampsia can deteriorate rapidly, with grave consequences for the patient and fetus, immediate delivery is recommended. However, if the fetus is not sufficiently mature, immediate delivery could threaten its life. Do we deliver the fetus immediately, which would eliminate risk for the patient but present a serious risk for the fetus—or do we postpone delivery, which would reduce risk for the fetus but greatly increase risk for the patient? If the patient elects to postpone delivery, then BP can be lowered with drugs. Because severe preeclampsia can be life threatening, treatment must be done in a tertiary care center to permit close monitoring. The major objective is to prevent maternal cerebral complications (e.g., hemorrhage, encephalopathy). The drug of choice for lowering
to 0.5 mcg/kg/min. With continuous 24-hour infusion, no tolerance develops to antihypertensive effects, and there is no rebound increase in BP when the infusion is stopped. With a 48-hour infusion, some tolerance may develop.
Oral antihypertensive therapy can be added as soon as BP has stabilized.
Labetalol
Labetalol blocks alpha- and beta-adrenergic receptors. Blood pressure is reduced by arteriolar dilation secondary to alpha blockade. Beta blockade prevents reflex tachycardia in response to reduced arterial pressure, and hence the drug is probably safe for patients with angina or MI. Beta blockade can aggravate bronchial asthma, heart failure, AV block, cardiogenic shock, and bradycardia.
Accordingly, labetalol should not be given to patients with these disorders.
Administration is by slow IV injection.
Clevidipine
Clevidipine [Cleviprex] is a dihydropyridine CCB with an ultrashort half-life (about 1 minute). Administration is by IV infusion. As with nitroprusside, effects begin rapidly and then fade rapidly when the infusion is slowed or stopped. As a result, BP can be easily titrated. For patients with severe hypertension, the infusion rate is 1 to 2 mg/hr initially, and can be doubled every 3 minutes up to a maximum of 32 mg/hr. In clinical trials, the average time to reach the target BP was 10.9 minutes. The most common side effects are headache, nausea, and vomiting. The basic pharmacology of clevidipine is discussed in Chapter 45.
DRUGS FOR HYPERTENSIVE DISORDERS OF PREGNANCY
Hypertension is the most common complication of pregnancy, with an incidence of about 10%. When hypertension develops, it is essential to distinguish between chronic hypertension and preeclampsia. Chronic hypertension is relatively benign, whereas preeclampsia can lead to life-threatening complications for the patient and the fetus.
CHRONIC HYPERTENSION
Chronic hypertension, seen in 5% of pregnancies, is defined as hypertension that was present before pregnancy or that developed before the 20th week of gestation. Persistent severe hypertension carries a risk to both the patient and the fetus.
Potential adverse outcomes include placental abruption, maternal cardiac decompensation, premature birth, fetal growth delay, central nervous system hemorrhage, and renal failure. The goal of treatment is to minimize the risk of hypertension to the patient and fetus while avoiding drug-induced harm to the fetus. With the exception of ACE inhibitors, ARBs, and DRIs, antihypertensive drugs that were being taken before pregnancy can be continued. ACE inhibitors, ARBs, and DRIs are con- traindicated owing to their potential for harm (fetal growth delay, congenital malformations, neonatal renal failure, neonatal death). When drug therapy is initiated during pregnancy, methyldopa or labetalol are the traditional agents of choice.
These drugs have limited effects on uteroplacental and fetal hemodynamics, and do not adversely affect the fetus or neonate.
Regardless of the drug selected, treatment should not be too aggressive because an excessive drop in BP could compromise uteroplacental blood flow.
According to guidelines issued by the American College of Obstetricians and Gynecologists (ACOG), “severe” hyperten- sion requires treatment, whereas “mild” hypertension generally
or 5 gm IM injected into alternating buttocks every 4 hours.
To ensure therapeutic effects and prevent toxicity, blood levels of magnesium, as well as presence of patellar reflex, should be monitored. The target range for serum magnesium is 4 to 7 mEq/L (the normal range for magnesium is 1.5 to 2 mEq/L).
Can drugs help prevent preeclampsia in those at risk?
Yes. When started before 16 weeks of gestation, low-dose aspirin reduces risk by about 50%. Similarly, L-arginine (com- bined with antioxidant vitamins) can also help. By contrast, several other preparations—magnesium, zinc, vitamin C, vitamin E, fish oil, and diuretics—appear to offer no protection at all.
BP is labetalol (20 mg by IV bolus over 2 minutes); dosing may be repeated at 10-minute intervals up to a total of 300 mg.
Because severe preeclampsia can evolve into eclampsia, an antiseizure drug may be given for prophylaxis. Magnesium sulfate is the drug of choice. In one study, prophylaxis with magnesium sulfate reduced the risk of eclampsia by 58% and the risk of death by 45%. Dosing is the same as for treating eclampsia.
If eclampsia develops, magnesium sulfate is the preferred drug for seizure control. Initial dosing consists of a 4- to 6-gm IV loading dose followed by 5 gm IM injected into each buttock.
Maintenance consists of continuous IV infusion of 1 to 2 gm/hr
KEY POINTS
■ Hypertension is defined as SBP greater than 130 mm Hg or DBP greater than 80 mm Hg.
■ Primary hypertension (essential hypertension), defined as hypertension with no identifiable cause, is the most common form of hypertension.
■ Untreated hypertension can lead to heart disease, kidney disease, and stroke.
■ In patients older than 50, elevated systolic BP represents a greater cardiovascular risk than elevated diastolic BP.
■ The goal of antihypertensive therapy is to decrease morbid- ity and mortality without decreasing quality of life. For most patients, this goal is achieved by maintaining BP between 120/80 and 130/80 mm Hg.
■ To reduce BP, two types of treatment may be used: drug therapy and lifestyle modification (smoking cessation, reduction of salt and alcohol intake, following the DASH diet, and increasing aerobic exercise).
■ The baroreceptor reflex, the kidneys, and the RAAS can oppose our attempts to lower BP with drugs. We can counteract the baroreceptor reflex with a beta blocker, the kidneys with a diuretic, and the RAAS with an ACE inhibitor, ARB, DRI, or aldosterone antagonist.
■ Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone) and loop diuretics (e.g., furosemide) reduce BP in two ways: they reduce blood volume (by promoting diuresis) and they reduce arterial resistance (by an unknown mechanism).
■ Loop diuretics should be reserved for (1) patients who need greater diuresis than can be achieved with thiazides and (2) patients with a low GFR (because thiazides don’t work when GFR is low).
■ Beta blockers (e.g., metoprolol) appear to lower BP primar- ily by reducing peripheral vascular resistance; the mecha- nism is unknown. They may also lower BP by decreasing myocardial contractility and suppressing reflex tachycardia (through beta1 blockade in the heart), and by decreasing renin release (through beta1 blockade in the kidney).
■ Calcium channel blockers (e.g., diltiazem, nifedipine) reduce BP by promoting dilation of arterioles.
■ ACE inhibitors, ARBs, and DRIs lower BP by preventing angiotensin II–mediated vasoconstriction and aldosterone- mediated volume expansion. ACE inhibitors work by blocking the formation of angiotensin II, whereas ARBs block the actions of angiotensin II. DRIs prevent formation of angiotensin I and thereby shut down the entire RAAS.
■ Aldosterone antagonists lower BP by preventing aldosterone- mediated retention of sodium and water in the kidney.
■ Thiazide diuretics are preferred drugs for initial therapy of uncomplicated hypertension.
■ When a combination of drugs is used for hypertension, each drug should have a different mechanism of action.
■ Dosages of antihypertensive drugs should be low initially and increased gradually. This approach minimizes adverse effects and permits baroreceptors to reset to a lower pressure.
■ Lack of patient adherence is the major cause of treatment failure in antihypertensive therapy.
■ Adherence is difficult to achieve because (1) hypertension has no symptoms (so drug benefits aren’t obvious); (2) hypertension progresses slowly (so patients think they can postpone treatment); and (3) treatment is complex and expensive, continues lifelong, and can cause adverse effects.
■ A severe hypertensive emergency exists when diastolic BP exceeds 120 mm Hg and there is ongoing end-organ damage.
■ Nitroprusside (IV) is a drug of choice for hypertensive emergencies.
■ Hypertension is the most common complication of pregnancy.
■ Methyldopa and labetalol are drugs of choice for treating chronic hypertension of pregnancy.
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Summary of Major Nursing Implications
aANTIHYPERTENSIVE DRUGS Preadministration Assessment Therapeutic Goal
The goal of antihypertensive therapy is to prevent the long- term sequelae of hypertension (heart disease, kidney disease, stroke) while minimizing drug effects that can reduce quality of life. For most patients, BP should be reduced to less than 130/80 mm Hg.
Baseline Data
The following tests should be done in all patients: BP;
electrocardiogram; complete urinalysis; hemoglobin and hematocrit; and blood levels of sodium, potassium, calcium, creatinine, glucose, uric acid, triglycerides, and cholesterol (total, LDL, and HDL cholesterol).
Identifying High-Risk Patients
When taking the patient’s drug history, attempt to identify drugs that can raise BP or that can interfere with the effects of antihypertensive drugs. Some drugs of concern are listed later under Minimizing Adverse Interactions.
The patient history should identify comorbid conditions that either contraindicate the use of specific agents (e.g., AV block contraindicates use of beta blockers) or require that drugs be used with special caution (e.g., thiazide diuretics must be used with caution in patients with gout or diabetes).
For risk factors that pertain to specific antihypertensive drugs, see the chapters in which those drugs are discussed.
Implementation: Administration Routes
All drugs for chronic hypertension are administered orally.
Dosage
To minimize adverse effects, dosages should be low initially and increased gradually. It is counterproductive to employ high initial dosages that produce a rapid fall in pressure while also producing intense adverse effects that can discourage adherence. After 12 months of successful treatment, dosage reductions should be tried.
Implementation: Measures to Enhance Therapeutic Effects
Lifestyle Modifications
In hypertensive patients, lifestyle changes can reduce BP and increase responsiveness to antihypertensive drugs. These changes should be tried for 6 to 12 months before implement- ing drug therapy and should continue even if drugs are required.
Weight Reduction. Help patients develop an exercise and weight management program if needed.
Sodium Restriction. Encourage patients to consume no more than 2300 mg of salt daily and provide them with information on the salt content of foods.
DASH Diet. Encourage patients to adopt a diet rich in fruits, vegetables, and low-fat dairy products, and low in total fat, unsaturated fat, and cholesterol.
Alcohol Restriction. Encourage patients to limit alcohol consumption to 1 ounce/day (for most men) and 0.5 ounce/
day (for women and lighter weight men). One ounce of ethanol is equivalent to about two mixed drinks, two glasses of wine, or two cans of beer.
Exercise. Encourage patients with a sedentary lifestyle to perform 30 to 45 minutes of aerobic exercise (e.g., walking, swimming, bicycling) most days of the week.
Smoking Cessation. Strongly encourage patients to quit smoking. Teach patients about aids for smoking cessation (e.g., nicotine patch, bupropion, varenicline).
Promoting Adherence
Nonadherence is the major cause of treatment failure. Achiev- ing adherence is difficult for several reasons: hypertension is devoid of overt symptoms; drugs don’t make people feel better (but can make them feel worse); regimens can be complex and expensive; complications of hypertension take years to develop, thereby providing a misguided ratio- nale for postponing treatment; and treatment usually lasts lifelong.
Provide Patient Education. Educate patients about the long-term consequences of hypertension and the ability of lifestyle changes and drug therapy to decrease morbidity and prolong life. Inform patients that drugs do not cure hypertension; therefore, the medication prescribed must usually be taken lifelong.
Encourage Self-Monitoring. Make certain that patients know the treatment goal (usually reduction of BP to less than 130/80 mm Hg), and teach them to monitor and chart their own BP. This will increase their involvement and help them see the benefits of treatment.
Minimize Adverse Effects. Adverse drug effects are an obvious deterrent to adherence. Measures to reduce undesired effects are discussed under Minimizing Adverse Effects.
Establish a Collaborative Relationship. Encourage patients to be active partners in setting treatment goals, creating a treatment program, and evaluating progress.
Simplify the Regimen. An antihypertensive regimen can consist of several drugs taken multiple times a day. Once an effective regimen has been established, attempt to switch to once-a-day or twice-a-day dosing. If an appropriate combina- tion product is available (e.g., a fixed-dose combination of a thiazide diuretic plus an ACE inhibitor), substitute the combination product for its components.
Other Measures. Additional measures to promote adherence include providing positive reinforcement when treatment goals are achieved, involving family members in the treatment program, scheduling office visits at convenient times, following up on patients who miss an appointment, and devising a program that is effective but keeps costs low.
Continued
aPatient education information is highlighted as blue text.
Ongoing Evaluation and Interventions Evaluating Treatment
Monitor BP periodically. The usual goal is to reduce it to less than 130/80 mm Hg. Teach patients to self-monitor their BP and to maintain a BP record.
Minimizing Adverse Effects
General Considerations. The fundamental strategy for decreasing adverse effects is to tailor the regimen to the sensitivities of the patient. If a drug causes objectionable effects, a more acceptable drug should be substituted.
Inform patients about the potential side effects of treat- ment, and encourage them to report objectionable responses.
Avoid drugs that can exacerbate comorbid conditions. For example, don’t give beta blockers to patients who have bradycardia, AV block, or asthma. Table 47.5 lists drugs to avoid in patients with specific disorders.
Initiate therapy with low doses and increase them gradually.
Adverse Effects of Specific Drugs. For measures to minimize adverse effects of specific antihypertensive drugs (e.g., beta blockers, diuretics, ACE inhibitors), see the chapters in which those drugs are discussed.
Minimizing Adverse Interactions
When taking the patient history, identify drugs that can raise BP or interfere with the effects of antihypertensive drugs.
Drugs of concern include oral contraceptives, nonsteroidal anti-inflammatory drugs, glucocorticoids, appetite suppres- sants, tricyclic antidepressants, monoamine oxidase inhibitors, cyclosporine, erythropoietin, alcohol (in large quantities), and nasal decongestants and other cold remedies.
Antihypertensive regimens frequently contain two or more drugs, posing a potential risk of adverse interactions (e.g., ACE inhibitors can increase the risk of hyperkalemia caused by potassium-sparing diuretics). For interactions that pertain to specific antihypertensive drugs, see the chapters in which those drugs are discussed.