Hypertension and Its Treatment in Concomitant Conditions
Degenerative Joint Disease, Depression, Alzheimer Disease, and Parkinson Disease
Hypertension occurs in more than 50 million people in the United States, and thus, it is not uncommon for it to be present in patients with other illnesses. This is particularly the case in the elderly in whom several commonly found illnesses, including degenerative joint disease, Parkinson disease, depression, and Alzheimer disease, can make the treatment of hypertension a particularly challenging proposition. This chapter addresses these disease states and their relationship to the treatment of hypertension.
Degenerative joint disease
Hypertension is frequently observed in the setting of degenerative joint disease, in part, because the prevalence of each of these disturbances increases with age. The treatment of hypertension can be complicated in the presence of DJD in that the mainstay of therapy for this disease involves administration of nonsteroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs are well known for their ability to produce de novo hypertension and/or to attenuate the antihypertensive effect of many drugs routinely utilized in the treatment of hypertension. In susceptible subjects such as the elderly or those with diabetes (salt-sensitive hypertensive patients), nonsteroidal anti-inflammatory drug therapy can prompt modest salt and water retention and thereby expand plasma volume. Secondarily, this combination of events results in an increase in mean arterial pressure. Except for a change in blood pressure, the findings of physical examinations are typically insufficiently sensitive to detect what is otherwise modest plasma volume expansion.
Nonsteroidal anti-inflammatory drugs can blunt the antihypertensive effect of most drug classes with the possible exception of calcium channel blockers (calcium channel blockers). Thus, calcium channel blocker therapy may be the preferred mode of therapy in such patients. Diuretics are suitable alternatives to calcium channel blockers but may require higher than normal doses to effect a diuresis in nonsteroidal anti-inflammatory drug-treated patients. This mode of diuretic resistance is most at issue when potent nonsteroidal anti-inflammatory drugs such as indomethacin are administered but may be less problematic with other presumably more “renal friendly” nonsteroidal anti-inflammatory drugs; thus, the adverse renal effects of nonsteroidal anti-inflammatory drugs have been suggested to be less prominent with the nonsteroidal anti-inflammatory drug sulindac. The interaction between nonsteroidal anti-inflammatory drugs and diuretics seems to be less impressive for thiazide-type diuretics than for loop diuretics. In the latter, a significant blunting of diuretic effect can occur and in susceptible subjects such as those with cirrhosis or congestive heart failure, extreme volume excess may develop. If an nonsteroidal anti-inflammatory drug is felt to be associated with a change in either the hypertensive or volume profile of a patient, a switch to an alternative nonsteroidal anti-inflammatory drug class and/or a decrease in dose amount should be considered.
The time of day when an nonsteroidal anti-inflammatory drug is dosed in a degenerative joint disease patient can be very important. Nonsteroidal anti-inflammatory drugs administered at bedtime (if successful in pain relief) can restore normal sleep architecture by diminishing the impact of pain on the integrity of the sleep cycle. This may, in turn, simplify daytime blood pressure control. degenerative joint disease patients also oftentimes adopt a sedentary lifestyle because of pain-related limitations in mobility. The ensuing weight gain secondary to this decreased exercise pattern can result in deterioration in blood pressure control. Accordingly, degenerative joint disease patients should be considered good candidates for lifestyle modifications, such as weight loss and aerobic exercise, in an effort to control hypertension.
Parkinson disease
Hypertension is not uncommonly observed in Parkinson disease patients. Hypertension does not develop as a direct consequence of Parkinson disease; rather, it independently occurs in the same age range, as does most Parkinson disease. The treatment of hypertension in Parkinson disease can be complicated because certain antihypertensive drugs (reserpine or a-methyldopa) can intensify parkinsonian symptomatology or therapies used in this condition exhibit important vasoactive properties. For example, orthostatic hypotension, which occurs frequently in patients with parkinsonism, can be aggravated by levodopa therapy. Fortunately, this phenomenon tends to abate over several months of therapy with levodopa. In addition, monoamine oxidase (Monamine oxidase) inhibitor therapy with drugs such as selegiline (Eldepryl®) can occur as an adjunct to levodopa/carbidopa therapy. At high doses, selegiline loses its МАО В selectivity and has the potential to interact with products containing tyramine or other sympathomimetic amines (see Depression section) with the development of a hypertensive crisis.
Psychiatric side effects including confusion, visual hallucinations, and paranoia are often present in combination with dementia that is related to the disease rather than its treatment. These neuropsychiatric abnormalities along with the natural deteriorative element of this disease make antihypertensive therapy complicated and oftentimes affect medication compliance. Like Alzheimer disease, the risk:benefit ratio of treating hypertension in a patient with Parkinson disease must be carefully examined.
Depression
The relationship between depression and hypertension/cardiovascular disease is becoming increasingly complex. Several well-designed studies have demonstrated that depressed patients have a poorer prognosis from diverse illnesses such as stroke and myocardial infarction. In addition, recent studies now suggest that individuals who report high levels of anxiety or depressive symptoms are at elevated risk for developing hypertension over the ensuing decade. The exact risk gradient for this phenomenon depends on race and age, but the relative risk is on the order of 2.0, or a doubling of the risk.
Depression is also problematic because many antidepressants manifest direct cardiac effects. For example, tricyclic antidepressants exhibit a quinidine-like effect and can decrease cardiac output and/or slow intracardiac conduction. Common adverse reactions to these drugs include orthostatic hypotension (particularly in the elderly) and a variety of supraventricular and ventricular arrhythmias as well as heart block. Patients with significant underlying conduction system disease are at particular risk from these drugs. Fortunately, except in the instance of overdose, major cardiac complications are rare in individuals without underlying cardiac pathology. However, it is advisable to obtain an electrocardiogram before initiating antidepressant therapy in patients older than 40 yr.
Monamine oxidase inhibitors are also used as antidepressants, and in a hypertensive patient carry with their use a substantial likelihood of drug-drug interactions. The most feared cardiovascular complication of Monamine oxidase inhibitor therapy is the precipitation of an adrenergic crisis owing to concomitant ingestion of sympathomimetic drugs or pressor amines such as tyramine, which are found in food and beverages. Among the various Monamine oxidase inhibitors, tranylcypromine (Parnate®) is perceived as the most hazardous. Because of the wide range of substances known to precipitate hypertensive crises in patients treated with Monamine oxidase inhibitors, it is prudent to have ready access to a listing of foodstuffs as well as prescription and over-the-counter medications that can trigger an Monamine oxidase-related hypertensive crisis. Several antihypertensive compounds are best avoided in patients treated with Monamine oxidase inhibitors including a-methyldopa, guanethidine, and reserpine. The best strategy is preventive for this reaction, because it can prove to be lethal. Thus, in the hypertensive patient with preexisting cardiac disease, any new treatment for depression should be introduced cautiously with an understanding that any new symptomatology should warrant a reassessment of a patient’s cardiac profile.
Depression can also be seen as a side effect of a number of different antihypertensive medications including β-blockers, 04-receptor agonists (such as a-methyldopa), and reserpine. Among the β-blockers, propran-olol is particularly sedating and can cause confusional states and nightmares. All β-blockers penetrate the central nervous system, although less lipophilic compounds, such as atenolol and nadolol, penetrate much less so than does propranolol. Despite this hierarchy of central nervous system penetration, there is only minimal evidence to support the notion that the lipophilicity of a β-blocker determines the likelihood of its causing depression. Diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin-receptor antagonists appear to have the lowest associated risk with depression and are therefore the drugs of choice when depression is a consideration.
Depression has to be viewed as an important confounding variable in medication compliance. This is unfortunately an extremely difficult issue, particularly if the depressive symptomatology is intensified by concomitant antihypertensive therapy. Compliance with medication should be carefully evaluated in a depressed patient. In this regard, it is useful to verify patient assertions by crosschecking with information provided by family members. Depression is a broad term under which many disease-state variants are grouped together. Reaching a correct diagnosis (and thereby offering optimal pharmacotherapy) may have a quite favorable influence on what can otherwise be very destructive patterns of medication ingestion. Obviously, in the depressed hypertensive patient, it is prudent to replace any potential offending antihypertensive agents before addressing pharmacologic therapy for depression.
Alzheimer disease
The treatment of hypertension in Alzheimer disease requires a careful assessment of the risk:benefit ratio of such an endeavor. Both the anticipated longevity as well as the functional status of an Alzheimer patient prove to be important determinants in the decision to treat. Thus, it is not at all unreasonable to withhold drug therapy in those hypertensive patients in the borderline -> stage I category, particularly if the onset of hypertension coincides with the later stages of Alzheimer disease.
If the decision is made to either begin or continue antihypertensive therapy in an Alzheimer patient, careful attention should be directed toward the interface between what might otherwise be viewed as trivial day-to-day activities such as eating/swallowing, meal and posture changes, and the prevailing sleep-wake cycle. In the more advanced stage of Alzheimer disease, nutritional needs may be poorly met without the support of a caregiver. If such is the case, every effort should be made to be certain that any long-acting antihypertensive preparations being administered are not inadvertently crushed to facilitate ingestion. If this occurs, a sustained-release preparation will frequently assume immediate released characteristics. This dumping of active drug into the gastrointestinal tract exaggerates medication peak effect (with possible central nervous system symptoms) and diminishes duration of effect.
Also, careful attention should be directed to the possibility of postprandial hypotension in these patients, and, if present, the timing of medication administration should be such to avoid any overlap between meal-related blood pressure decrements and peak medication effect. If postprandial hypotension occurs, decreasing the meal size and spreading total caloric intake more evenly over all three daily meals can lessen its impact. In addition, in certain individuals, caffeine intake may attenuate the meal-related drop in blood pressure. Alzheimer patients should always be evaluated for the possibility of postural hypotension. If bedridden, deconditioning can occur quite rapidly in any subject including an Alzheimer patient. Consequently, this should not be an unexpected phenomenon in the later stages of the disease. Maneuvers that worsen postural hypotension, such as volume contraction from diuretics and pulse rate reduction with β-blockers, should be employed in the management of hypertension only if absolutely indicated and with expressed caution.
As a rule of thumb, nighttime administration of antihypertensive medication should occur cautiously in an Alzheimer patient and only if bedtime blood pressures are documented to be elevated. Blood pressure exhibits a circadian rhythm with a varying degree of drop during sleep. In those older than 60 yr, blood pressure may inordinately drop during sleep (as much as a 30-35% reduction); this has been termed extreme dipping. Those patients prone to arising in the middle of the night may be subject to risk if medication peak effect coincides with the naturally occurring nadir of blood pressure. If nighttime antihypertensive therapy is considered, patients should be advised to gradually shift from the supine to the recumbent position and to ambulate at night only with assistance. Extreme dipping of blood pressure is now believed to be a risk factor for both multi-infarct dementia and other less severe forms of cerebrovascular disease. Thus, Alzheimer’s disease or similar neurologic illnesses may represent a preselected population whose nocturnal blood pressure pattern is phenotypically one of extreme dipping.
Selection of a drug class for the treatment of hypertension in this population should limit use of drugs with significant sedating effects, those that produce clinically relevant volume contraction, or those that significantly decrease cardiac output. angiotensin-converting enzyme inhibitors and calcium channel blockers are reasonably safe compounds in this population, whereas diuretics, centrally acting agents, and β-blockers may carry with their use unnecessary risk. angiotensin-converting enzyme inhibitors may be of particular utility in that they preserve cerebrovascular autoregulatory ability; thus, even if systemic blood pressure is reduced cerebral blood flow is well maintained. The principles of effective antihypertensive therapy in this population should avoid inducing postural hypotension and/or sudden drops in blood pressure; hence, unless medication compliance is an issue, multiple drugs should not be simultaneously administered. This will lessen the unintended risk of an exaggerated drop in blood pressure at the peak effect of several antihypertensive medications. Concomitant medications used in the treatment of Alzheimer’s disease typically do not affect blood pressure. More important, the introduction of any new medication in this population can influence blood pressure as it relates to alterations in cognitive ability. Accordingly, a more effective means of treating hypertension in this population should involve the use of home blood pressure monitoring, a process that is simplified by the availability of a caregiver in the home environment. Home blood pressure monitoring improves decision making for medication adjustment and provides a means of delineating the relationship between side effects and the prevailing blood pressure.
This post has been viewed 785 times.
Comments are closed.
