Pharmacology Update
Pharmacology Update
Dietary Sodium Reduction
Dietary sodium restriction is sometimes helpful in management of hypertension, both as a mechanism to lower blood pressure as a sole intervention, and as a method to enhance responsiveness to some antihypertensive medications. On the other hand, adverse impact on glucose metabolism, probably as a consequence of RAA activation attendant to sodium restriction, is concerning. The literature has been inconclusive, in normotensive and hypertensive patients, about whether sodium restriction worsens insulin resistance. The current study investigated the effect of varying levels of sodium restriction on blood pressure and insulin resistance in hypertensive patients (n = 12).
Subjects were admitted to a research ward and after seven days on a normal diet (200 mmoL sodium), insulin resistance was measured by the euglycemic hyperinsulinemic glucose clamp method. Subsequently, patients were subjected to sodium restriction of either moderate (= 100 mmoL/d) or strict (= 30 mmoL/d) degree.
The change from normal diet to moderate sodium restriction produced only a slight increase in renin levels, but no changes in insulin, glucose, norepinephrine, or aldosterone. Strict sodium restriction, on the other hand, resulted in a 41% increase in fasting insulin, and significant reduction of insulin sensitivity. Moderate sodium restriction is associated with minimal perturbation of glucose homeostasis and neurohumors; strict sodium restriction may result in consequential compensations in norepinephrine and insulin sensitivity.
Gomi T, et al. Am J Hypertens 1998; 11(9):1048-1055.
Intensive Blood-Glucose Control with Metformin
The united kingdom prospective Diabetes Study (UKPDS) has reported recently in its prospective trial (n = 4075) that intensive blood glucose control with sulphonylureas or insulin reduces risk of microvascular complications. A subgroup of this population (n = 753) was followed for over 10 years comparing diet control with metformin; additionally, the metformin recipients were also compared with patients receiving sulfonylureas or insulin for tight control. A final subgroup analysis allowed patients who had not achieved optimum glucose control on maximum sulfonylurea dose to either add metformin, or continue on their same regimen.
The metformin treatment group enjoyed a number of benefits when compared with conventional (standard dose sulfonylurea or insulin) therapy: 36% lower all-cause mortality, 42% lower diabetes-related mortality, and 32% lower incidence of any diabetes-related endpoint. Patients who had metformin added to their regimen of sulfonylurea due to inadequate glucose control did not demonstrate improvements in mortal endpoints, but did trend toward better hemoglobin A-1-C levels, and did not gain as much weight. These data support consideration of metformin as first-line therapy in Type 2 diabetes.
UK Prospective Diabetes Study Group. Lancet 1998;352:854-865.
Low-Dose Hydrocortisone for Treatment of Chronic Fatigue Syndrome
The definition of chronic fatigue syndrome (CFS) includes new onset of severe, unexplained fatigue for at least six months, plus at least four of the following symptoms: memory/concentration deficits, sore throat, tender lymph nodes, muscle pain, multijoint pain, new headaches, unrefreshing sleep, and prolonged postexertional malaise. There has been some literature documentation of reduced cosyntropin responsiveness in CFS patients (30% less cortisol response over 24 hours). Since this aberration suggests a role of insufficient cortisol in CFS patients, McKenzie and associates undertook a randomized trial of low-dose hydrocortisone for CFS (n = 70).
Patients received 20-30 mg hydrocortisone each morning, and 5 mg each evening for 12 weeks. Patients recorded symptoms and well-being on several different scales. The trial was blinded and placebo controlled.
Cortisone therapy was associated with modest symptomatic improvement in some, but not all measurement tools. One-third of cortisone recipients had measurable adrenal suppression secondary to treatment. McKenzie et al conclude that though cortisone treatment did produce some favorable changes, the consequences and frequency of adrenal suppression are too great to consider this therapy appropriate for clinical use.
McKenzie R, et al. JAMA 1998; 280:1061-1066.
Clinical Scenario: The ECG shown in the Figure was obtained from a 42-year-old man complaining of atypical chest discomfort intermittently over the past few weeks. The patient was previously healthy. He was symptomatic at the time this tracing was recorded. What entities should be considered in your differential diagnosis? Is there evidence of atrial activity in the Figure?
Interpretation: There is a regular, supraventricular tachycardia (SVT) at a rate of just under 150 beats/minute. Practically speaking, the differential diagnosis of a regular SVT at this rate consists of three entities: 1) sinus tachycardia; 2) atrial flutter; and 3) PSVT (paroxysmal supraventricular tachycardia). Definitive diagnosis is unfortunately not possible from this single tracing. The rhythm could be sinus tachycardia, with an upright P wave concealed within the T wave seen in lead II. Atrial flutter should always be considered in the differential diagnosis of a regular SVT at a ventricular rate that is close to 150/minute—but the absence of any semblance of flutter activity in all 12 leads on this tracing makes this possibility less likely. Consequently, the most probable diagnosis is PSVT—which we strongly suspect because of the suggestion of subtle retrograde (negative) atrial activity that appears to be notching the terminal portion of the QRS complex in each of the inferior leads, and which produces a terminal positive deflection (simulating an r’) in lead V1.
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