Choice Of Antihypertensive Agent Research Articles

Meeting Report of the International Society of Hypertension Conference on Hypertension and Diabetes

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.

Choosing the correct drug for the individual hypertensive patient.

With the availability of a wide selection of antihypertensive drugs acting by different mechanisms, it should be possible to match the requirement of individual patients with the pharmacological and clinical properties of an appropriate agent. Although the concept of stepped-care therapy is now largely outdated, therapy must be initiated with one agent. Diuretics remain a first-choice option in the elderly and in Black patients, as do calcium antagonists. In patients with ischaemic heart disease or enhanced adrenergic drive, beta-blockers are preferred. Calcium antagonists or ACE inhibitors are finding increasing use as initial therapy when quality of life is important and metabolic neutrality is required. The choice of antihypertensive agent may be limited by adverse effects, e.g. pedal oedema with nifedipine, constipation with verapamil, and cough with ACE inhibitors. Certain advantages are evident for both calcium antagonists and ACE inhibitors. Calcium antagonists are more likely to be effective first-line therapy than ACE inhibitors in Black patients, in those with a high salt intake, in patients with Raynaud's disease, and when angina pectoris is present. ACE inhibitors are preferred for use in combination with diuretic agents, and in the presence of congestive heart failure or low salt intake. Combination therapy between these 2 drug classes is finding increasing acceptance because of its many theoretical advantages, and may provide a means of maximising benefit.

Choice of antihypertensive agents in hemodynamic aspects to match pathophysiology and pharmacology in essential hypertension.

Choice of antihypertensive agents in hemodynamic aspects to match pathophysiology and pharmacology in essential hypertension.

Metabolic changes with antihypertensive therapy of the salt-sensitive patient

Recent evidence suggests that metabolic changes that occur with antihypertensive agents may influence cardiovascular risk. Diuretic therapy is particularly appropriate for the salt-sensitive hypertensive patient. However, diuretic-induced electrolyte abnormalities may lead to ventricular arrhythmias, even in patients with uncomplicated essential hypertension. Antihypertensive drugs may change circulating lipoprotein levels, which may influence the development of atherosclerosis. Therefore, serum cholesterol and triglyceride levels should be monitored when antihypertensive drugs are administered that can cause hyperlipidemia. Weight reduction and diet therapy should be used because these may have a greater effect on reducing hyperlipidemia, though choice of antihypertensive agents is important. In addition, glucose tolerance may worsen with thiazide therapy, perhaps because newer evidence suggests that insulin resistance is common in essential hypertension. This glucose intolerance may be corrected with potassium repletion or substitution of bumetanide for thiazide. The calcium antagonists may be substituted for diuretic therapy, or other classes of antihypertensive drugs may be used with a reduced dose of diuretic drug if these metabolic changes persist. Thus, attention to metabolic changes may be as important as blood pressure reduction in treatment of the salt-sensitive hypertensive patient.

Recent trend in the research of hypertension in Japan. Choice of antihypertensive agents in hemodynamic aspects to match pathophysiology and pharmacology in essential hypertension

Recent trend in the research of hypertension in Japan. Choice of antihypertensive agents in hemodynamic aspects to match pathophysiology and pharmacology in essential hypertension

Diuretic Responsiveness of Blood Pressure in the Elderly

The problem of elevated blood pressure in the elderly is a common and potentially devastating one. Reduction of elevated blood pressure, whether systolic, diastolic, or both, is particularly beneficial in older hypertensive subjects in reducing morbidity and mortality. The older individual presents a unique pathophysiologic situation, one in which a variety of considerations must be given to the safest choice of antihypertensive agents. A consistent response of blood pressure in the elderly is not observed with different antihypertensive agents, and the problems of side effects and as well as life-threatening effects of antihypertensive drugs are of particular concern among older hypertensive subjects. While diuretics, on balance, appear to be more effective in lowering blood pressure in older hypertensive patients than in young individuals, the disadvantages and risks of diuretic therapy make them less than ideal agents. Calcium channel blockers and serotonin antagonists have proven, in preliminary studies, to be useful, effective, and safe alternatives to diuretic therapy in older hypertensive patients.

Cerebral Blood Flow Autoregulation and Hypertension

Hypertension and antihypertensive therapy have clinically important effects on cerebral blood flow. The autoregulatory changes that occur with chronic arterial hypertension should influence the clinician's choice of antihypertensive agents and the rapidity with which the blood pressure is lowered in order to avoid symptoms of focal or global cerebral hypoperfusion.

Treatment of hypertension in diabetic men: Problems with sexual dysfunction

Hypertension occurs 2 to 3 times more frequently in diabetic persons than in nondiabetic persons. Care must be taken in treating hypertension in diabetic patients because the choice of antihypertensive agent may worsen the diabetic state or its complications or cause additional health problems for the patient. Sexual dysfunction is a common problem in diabetic patients; however, diabetes need not be the cause. Diabetic men with hypertension have an increased sensitivity to the side effect of sexual dysfunction, which occurs from the use of centrally acting antihypertensive agents. By using prazosin, an α 1-adrenergic blocking agent, this cause of sexual dysfunction was eliminated. The reasons for the increased prevalence of hypertension in diabetic patients are discussed and a rational approach is given for the treatment of elevated blood pressure in these individuals.

Cardiac factors in response to antihypertensive treatment.

The cardiac status of hypertensive patients will influence not only the indications for and choice of antihypertensive agents but can also alter the effectiveness of antihypertensive therapy. The heart may interfere with adequate blood pressure control either because of marked increases in cardiac output or as result of decompensation activating various pressor mechanisms or through the generation of pressor reflexes. Reflex increases in cardiac output may blunt or even nullify the effect of reduction in peripheral resistance by vasodilators. Cardiac decompensation from incidental disease or secondary to some antihypertensive drugs can lead to hypertension rather than reduction in blood pressure. It is particularly liable to develop from excessive fluid retention, particularly when associated with reduction of cardioadrenergic support. Coronary insufficiency from either coexisting coronary disease or triggered by injudicious antihypertensive treatment can stimulate pressor reflexes leading to marked fluctuations in arterial pressure. Alterations in left ventricular relaxation and rapid filling have been reported with some antihypertensive drugs; these changes could conceivably influence blood pressure responses through their effect on reflexes from low pressure baroceptors.

Renal hemodynamic changes during long-term antihypertensive therapy

Studies of renal hemodynamics were carried out in 84 patients with essential hypertension during long-term antihypertensive therapy with a number of drugs. Renal perfusion was maintained or enhanced despite a fall in mean arterial pressure during therapy with hydrochlorothiazide, furosemide, clonidine, prazosin, and the combination of guanabenz and hydrochlorothiazide. Renal perfusion deteriorated during long-term treatment with propranolol. Renal hemodynamics may be enhanced, maintained, or adversely influenced depending on the choice of antihypertensive agent.