Drugs

Birkenhäger, W.; Leeuw, P.

doi: 10.2165/00003495-198600314-00002pmid: 3732087

The main demographic transition during the next decade will be a worldwide increase in older and elderly people, both in proportional and absolute terms. Although age itself is the main risk factor for morbidity and disability, additional cardiovascular risk may be brought about by inherent rises of blood pressure in these older age groups. This additional risk factor appears to be a suitable target for corrective measures.

Whelton, Paul; Klag, Michael

doi: 10.2165/00003495-198600314-00003pmid: 3732100

Cardiovascular disease continues to be the principal cause of death in Western countries. Epidemiological studies have repeatedly demonstrated a striking relationship between blood pressure and the risk of cardiovascular disease in that those with the highest levels of blood pressure are at the greatest risk for subsequent disease or death. However, most blood pressure-related cardiovascular complications occur at much lower levels of blood pressure. Any attempt to substantially reduce the frequency of blood pressure-related cardiovascular disease mandates treatment of large numbers of asymptomatic subjects who are, on average, only exposed to a slight increase in risk. Based on current demographic trends, this requirement will become even more striking in the future.

Ribeiro, Artur; Debert Ribeiro, Myriam

doi: 10.2165/00003495-198600314-00004pmid: 3732097

Data obtained from subjects in the city of São Paulo show that hypertension will be an increasing major public health problem as the adult population grows older. Information from over 5000 subjects indicated that males had a prevalence of hypertension almost 3 times that of females, with this difference being significant up to 44 years of age. Although mild and moderate forms of hypertension increased with age among both males and females, black males were noted to have diastolic blood pressures ⩾ 90mm Hg in almost twice the frequency of their white counterparts. In addition, the demographic tendencies in São Paulo of increasing older age groups over the last 2 decades compare similarly with data from other developed Western countries. Thus, the importance of hypertension in underdeveloped countries must not be underestimated.

Francischetti, Emílio; Genelhu, Virgínia; Oigman, Wille

doi: 10.2165/00003495-198600314-00005pmid: 2942388

Interpopulation studies support the hypothesis of a causal relationship between sodium consumption and arterial hypertension. However, although this association has been contradicted by intrapopulation studies, the correlation between sodium and hypertension appears to be genetically determined, as there are both sodium-sensitive and sodium-resistant individuals.

Lant, Ariel

doi: 10.2165/00003495-198600314-00006pmid: 3525089

Oral diuretics are amongst the most widely used drugs in clinical practice today. Their discovery close on thirty years ago remains a major milestone in therapeutic progress. Though originally designed for treating heart failure, diuretics are more commonly prescribed, worldwide, in hypertension than for relief of oedema. Since the introduction of chlorothiazide, diuretic development has passed through a series of distinct stages. The thiazide era was followed by the ‘high-ceiling’ diuretics, the antikaliuretics and, more recently, polyvalent agents that cause both saluresis and uricosuria. Alongside these synthetic achievements, major advances have occurred in the knowledge of nephron function and ion transport mechanisms. These have acted as stimulus to the design of novel categories of diuretics.

Moser, Marvin

doi: 10.2165/00003495-198600314-00007pmid: 3525090

Diuretics are used in first-step antihypertensive monotherapy or in combination with adrenergic-inhibiting agents in the majority of hypertensive patients in the United States. A 30-year experience has demonstrated that blood pressure is lowered to as great or greater a degree with diuretics than when many of the presently available antihypertensive drugs, including converting enzyme inhibitors, calcium entry blockers, β-or α-adrenergic inhibitors, or centrally acting sympatholytic agents, are used. Diuretics appear to be especially effective in the elderly and in black patients. All of the major hypertension clinical trials upon which we base our decisions for treatment have employed diuretics as step-1 therapy —with a reduction in morbidity and mortality. In addition, data suggest that more effective treatment of hypertension has contributed to the decrease of over 45% in deaths from cerebrovascular disease and the overall reduction of cardiovascular deaths over the past 15 to 20 years in the United States.

Ramires, Jose; Pileggi, Fulvio

doi: 10.2165/00003495-198600314-00008pmid: 3732098

Cardiogenic oedema results from an increase in capillary hydrostatic pressure (either pulmonary or systemic). This increase produces a reduction in the plasma colloidosmotic pressure-capillary pressure gradient, facilitating the accumulation of fluid in the interstitial space and reducing the circulating plasmatic volume.

Birkenhäger, W.

doi: 10.2165/00003495-198600314-00009pmid: N/A

Holland, O.

doi: 10.2165/00003495-198600314-00010pmid: 3732099

In the past, potassium depletion in both non-digitalised patients and in patients without cardiac disease was thought to cause no adverse cardiac effects. However, several studies have now demonstrated a significant incidence of ventricular ectopic activity (VEA) with diuretic-induced hypokalaemia, even in hypertensive patients without overt heart disease. Additional evidence suggests that sudden death may occasionally result from this VEA. Potassium repletion with potassium-sparing diuretics or with potassium chloride supplementation has generally demonstrated a beneficial therapeutic effect in reducing VEA. However, after diuretic therapy occasional patients may have persistent VEA which may result from focal myocardial lesions associated with potassium depletion. In contrast, diuretic therapy in which normokalaemia is maintained has only been associated with a very low occurrence of VEA. Thus, with the preservation of normokalaemia, diuretic therapy for hypertension does not appear to be associated with the significant hazards of VEA.

Caralis, Potoula; Perez-Stable, Eliseo

doi: 10.2165/00003495-198600314-00011pmid: 3525091

Investigation of coronary heart disease manifesting as sudden death has highlighted the role of electrolyte disturbances in arrhythmogenesis. The identification of the 3 major cardiac risk factors —hyperlipidaemia, hypertension and smoking —does not fully explain sudden death in asymptomatic patients with an abnormal ECG. Sudden death is usually ascribed to cardiac arrhythmia whose pathogenesis has 3 possible mechanisms affecting the electrical properties of the heart. Thiazide diuretics are known to deplete potassium and magnesium in the body and while magnesium deficiency has been especially associated with cardiac rhythmicity, potassium levels modulate the cellular effects of calcium in the myocardium. In patients with ischaemic heart disease, both hypokalaemia and hypomagnesaemia correlate with the frequency of serious arrhythmias and even in ambulatory hypertensive patients on diuretics, it is important to preserve electrolyte homeostasis. There is, however evidence to suggest that some patients are more susceptible to diuretic-induced arrhythmias and in these patients even mild hypokalaemia can cause ventricular arrhythmias, and age may be a contributory factor. The risk of thiazide-induced arrhythmias has yet to be confirmed.