Robert W. Piepho

Effect of race on hypertension and antihypertensive therapy.

The presence of hypertension in individual patients confers significant risk in terms of coronary artery disease, myocardial infarction, stroke and congestive heart failure. However, it is also a modifiable risk factor, as risk may be decreased through either lifestyle changes or pharmacotherapy to reduce the elevated blood pressure. Over the past 3 decades, there has been strenuous debate among clinical scientists regarding the role played by racial background in both the pathogenesis and response to pharmacotherapy. A number of studies, such as the third National Health and Nutrition Examination Survey (NHANES III) have demonstrated a higher prevalence of hypertension in black populations. The Hispanic Health and Nutrition Examination Survey (HHANES) suggested that the prevalence of hypertension in Hispanics of Caribbean descent was similar to that of African Americans, while Mexican Americans had lower rates of the disease. It appears that the pathophysiological consequences of elevated blood pressure may also be more severe in black patients. Thus, these patients will have a worse prognosis than their white counterparts at any given blood pressure level. The incidence of end-stage renal disease has been reported to be as much as 17 times more common in African American patients. A number of individual factors have been postulated for these differences including increased sodium intake, differences in sodium handling, decreased potassium intake, decreased calcium intake, elevated fasting insulin levels, lower levels of plasma renin activity and urinary kallikrein excretion. These differences in prevalence and pathophysiology have resulted in recommendations for differential therapeutic approaches in the treatment of hypertension. A major trial conducted in the Veteran Affairs Medical Centers in the USA noted that African Americans are generally more responsive to diuretics and calcium channel blockers than to ACE inhibitors or beta-blockers. However, it has been reported that this resistance may be overcome by increasing the dose of these agents. It has been postulated that these differences may be related to lower plasma renin activity noted in the black population, since diuretics and calcium channel blockers appear to be better suited to this population. These differential therapeutic recommendations will be reviewed in light of our current knowledge of the disease.

Methamphetamine toxicity and its implications during HIV-1 infection

Over the past two decades methamphetamine (MA) abuse has seen a dramatic increase. The abuse of MA is particularly high in groups that are at higher risk for HIV-1 infection, especially men who have sex with men (MSM). This review is focused on MA toxicity in the CNS as well as in the periphery. In the CNS, MA toxicity is comprised of numerous effects, including, but not limited to, oxidative stress produced by dysregulation of the dopaminergic system, hyperthermia, apoptosis, and neuroinflammation. Multiple lines of evidence demonstrate that these effects exacerbate the neurodegenerative damage caused by CNS infection of HIV perhaps because both MA and HIV target the frontostriatal regions of the brain. MA has also been demonstrated to increase viral load in the CNS of SIV-infected macaques. Using transgenic animal models, as well as cultured cells, the HIV proteins Tat and gp120 have been demonstrated to have neurotoxic properties that are aggravated by MA. In addition, MA has been shown to exhibit detrimental effects on the blood–brain barrier (BBB) that have the potential to increase the probability of CNS infection by HIV. Although the effects of MA in the periphery have not been as extensively studied as have the effects on the CNS, recent reports demonstrate the potential effects of MA on HIV infection in the periphery including increased expression of HIV co-receptors and increased expression of inflammatory cytokines.

Presenting and Publishing Case Reports

The educational value of case reports and the four main categories of information they include are described. Checklists and directions for effective spoken presentations are detailed, so the presenter knows not only the information the audience is likely to expect, but the techniques that will help convey the information. A typical case as it might be presented during rounds is shown with questions for discussion. Guidelines for writing case reports for publication also are included, such as journal selection, descriptions of the standard and nonstandard case formats, the content of the three main sections of the typical case report, and the directions that journal editors typically ask reviewers to follow.

An Overview of Antihypertensive Therapy in the 20th Century

A s we approach the transition to a new millennium, there have been numerous reviews of the achievements and advancements of the past century. This collection of accomplishments has included everything from indoor plumbing to information technology. Similarly, when therapeutic advances are considered, the treatment approaches to many different diseases are highlighted in different sectors. However, when one considers that three of the top four causes of mortality in the United States are directly associated with hypertension, it is clear that advances in the therapy of this disease both represent a key achievement of the past century and remain a priority for the next one. By looking back at the standard of care at the turn of the past century, it is evident that this disease was virtually unrecognized as a cause of serious medical consequences. During the 19th century, physicians separated patients into those with a hard pulse (presumably those with hypertension) versus those with a soft pulse. Then, just prior to the turn of the century, Scipione Riva-Rocci developed a sphygmomanometer based on the earlier work of Stephen Hales. This new method for actually evaluating the pressure in the arterial system set the stage for a century of progress in the identification and treatment of high blood pressure. Other discoveries in the chemical basis of hypertension also occurred just prior to the new millennium. In 1895, Oliver and Schafer presented their experiments with adrenal gland extracts. They showed that the injection of these suprarenal extracts into experimental animals increased arterial pressure. In 1898, Abel identified the active principle in these extracts as epinephrine. In 1898, Tigerstedt and Bergman began their research on the “effect of a blood pressure raising substance found in the kidneys and passed into the blood.” They noted that the injection of a rabbit kidney extract into recipient rabbits caused a rise in blood pressure. The substance, which they called renin, could be found only in renal veins and not in renal arteries. The rest of this story of discovery had to wait until the 1930s with the subsequent identification of angiotensin II, but the era of neurohormonal research on hemodynamic control had also begun almost simultaneously with the development of instrumentation to measure blood pressure.

Antihypertensive Therapy in the Aged Patient

SummaryThe incidence of both systolic and diastolic hypertension is increased in elderly patients, therefore antihypertensive drugs are commonly used in this population. In addition to changes in blood pressure, the aging process also causes numerous changes in other physiological parameters, resulting in altered pharmacokinetic and pharmacodynamic responses to the drugs.The dosage regimens for thiazide diuretics and amiloride must be individually titrated in the elderly patient, since the elimination of these agents decreases concurrently with decreased renal function, as indicated by compromised creatinine clearance. The initial doses of the calcium antagonists should be decreased in elderly patients, since representative compounds from all 3 chemically heterogeneous classes have been shown to have decreased clearance in these patients which appears to be primarily due to the status of hepatic function in the patient. However, with verapamil, the dosage should be further decreased in association with compromised renal function.The dosage of the angiotensin converting enzyme (ACE) inhibitors should be adjusted according to renal function rather than age. Lisinopril, which is primarily eliminated unchanged, is usually given in lower doses in the elderly, and doses of both captopril and enalapril may need to be reduced, depending on renal function. While there is no need to adjust the dosage regimen for the α-adrenoceptor blocking drugs (prazosin, terazosin), caution should be used with the β-adrenergic blockers, particularly the hydrophilic agents, since they are renally eliminated. Labetalol may be a suitable alternative β-blocker for the elderly patient, since its pharmacodynamic properties of decreased systemic vascular resistance without changes in heart rate or stroke volume are preferential for the elderly patient, and its pharmacokinetics are relatively unchanged in this population.Drugs that act primarily through the central nervous system, such as clonidine, methyldopa and guanfacine, require smaller doses in the presence of renal dysfunction. In contrast, guanabenz is metabolised primarily by the liver, so it would appear to be useful in elderly patients with renal dysfunction despite the lack of studies in this population. Guanadrel, an adrenergic neuron blocking drug, also requires a dosage reduction in patients with impaired renal function.In addition to the pharmacokinetic changes that occur in the elderly patient, pharmacodynamic changes may also be anticipated due to receptor modifications. Older patients have a decrease in β-receptor sensitivity, while α-receptor sensitivity does not change. When designing the dosage regimen for a senior patient with hypertension, the combination of all these variables must be considered.

Antihypertensive Therapy in the Geriatric Patient: II. A Review of the Alpha1-Adrenergic Blocking Agents

The prevalence of hypertension increases with age. Multiple physiologic factors are involved in the development of hypertension in the elderly. Alpha1‐adrenergic blocking agents lower blood pressure through a reduction in total peripheral resistance. Prazosin, terazosin, and doxazosin have been shown to be equally effective in reducing blood pressure in older persons. The bioavailability, terminal elimination half‐life, and volume of distribution of prazosin is increased in the elderly. Hybrid drugs, such as ketanserin, urapidil, and indoramin are also effective in lowering blood pressure. Ketanserin seems to have a greater effect on blood pressure reduction in persons older than 60 years of age. Alpha1‐adrenergic blockers may be used safely in patients with diabetes, asthma, and hyperlipidemia.

Minimizing the Risks Associated with Significant QTc Prolongation in People with Schizophrenia: A Consensus Statement by The Cardiac Safety in Schizophrenia Group

Cardiac Safety in Schizophrenia Group Objectes: This study was designed to help identify and clarify issues associated with cardiac safety in schizophrenia, particularly QTc interval prolongation; to raise awareness among psychiatrists of the cardiac issues involved in prescribing for schizophrenia and help psychiatrists minimise the potential cardiac risks associated with treating schizophrenia. Methods: The currently available literature on cardiac dysfunction associated with antipsychotic treatments was reviewed by an independent panel of international psychiatric and cardiology experts. Following individual review, a joint meeting was held and a consensus statement produced. Results: Prolongation of QTc interval is relatively common among antipsychotic drugs although there is marked variation in the extent to which the different agents exert their effect. If a patient is considered to be at high risk of significantly prolonged QTc interval (e.g. increasing age, female gender, comorbid cardiovascular disease) prescription of an antipsychotic drug with low QTc prolonging potential is recommended. Evaluation of a patients risk factors for significant QTc prolongation is an important part of patient assessment at presentation. To significantly reduce the risk of morbidity and mortality from prolonged QTc interval a team approach involving the hospital emergency psychiatric care team, the office-based psychiatrist, the primary care physician, the cardiologist and the pharmacist is advocated. Conclusions: Significant QTc interval prolongation caused by some antipsychotics is a risk factor that may lead to sudden death in patients with schizophrenia receiving these medications. Not all antipsychotic drugs prolong QTc interval. Careful clinical and pharmacological management of the patient with schizophrenia can significantly reduce the risks of morbidity and mortality from QTc interval prolongation.

Economic Impact of Ramipril on Hospitalization of High-Risk Cardiovascular Patients

OBJECTIVE: To estimate differences in direct costs attributable to avoided hospitalizations and procedures during the years of the HOPE (Heart Outcomes Prevention Evaluation) study after the cost of treatment with ramipril or alternative angiotensin-converting enzyme inhibitor therapy was taken into account. METHODS: A decision analytical model was developed to estimate the economic impact of reductions in hospitalizations and/or procedures both at annual increments and over the first 4 years of the HOPE study. The analysis compared the number of cardiovascular events per endpoint per year in the intervention and placebo group with hospitalization and procedural costs. Cost data were derived from the literature and inflated to the appropriate index year using the consumer price index. RESULTS: For approximately 9000 patients studied, the gross estimated savings in direct costs for 297 events avoided were more than

Web-based sharing of cutting-edge teaching strategies

5 million over 4 years. After the cost of treatment was deducted for both groups, the net estimated savings were

Calcium antagonist use in congestive heart failure : still a bridge too far ?

871 000 over 4 years. CONCLUSIONS: The results demonstrate that the use of ramipril provides cost-effective treatment for high-risk cardiovascular patients with an ejection fraction >40%.