Changing Strategies in the Management of Chronic Congestive Heart Failure

Recent studies have more clearly defined the role of drug therapy in patients with chronic congestive heart failure (CHF). Treatment of patients with asymptomatic left ventricular dysfunction (New York Heart Association [NYHA] class I) cannot be recommended at this time. The benefit of prophylactic treatment with angiotensin-converting enzyme inhibitors (ACEIs) or vasodilators in patients at high risk for developing symptomatic CHF is currently being evaluated. Treatment of patients with symptomatic CHF (NYHA class II-IV) should be initiated with a combination of a diuretic, digoxin, and an ACEI. This combination has been shown to reduce the mortality rate in patients with NYHA class II-IV CHF. Patients who remain symptomatic despite treatment with this combination may benefit from the addition of the direct-acting, nonspecific vasodilators—hydralazine and a nitrate. The addition of the nonspecific vasodilators to an ACEI has not been tested in controlled trials. In patients who remain symptomatic despite treatment with diuretics, digoxin, ACEIs, and nonspecific vasodilators, treatment options are not clear. The use of beta-agonists, phosphodiesterase inhibitors, and intermittent fixed-dose, fixed-interval dobutamine should be avoided as these agents are associated with a high mortality rate. Heart transplantation should be considered early in the course of CHF to allow for preservation of other vital organ systems. Unfortunately, heart transplantation is available to only a very small minority of potential transplant candidates.

Recommendations for Establishing a Drug and Toxicology Information Center in a Developing Country

The purpose of this work was to formulate guidelines to help health professionals in establishing or strengthening the capabilities of drug and toxicology information centers and related facilities in developing countries. These guidelines are based on the experience of an established drug and toxicology information service in Zimbabwe which has been operating for more than ten years and on information obtained from other centers in developed countries. The guidelines provide advice rather than a unique model and should therefore be adapted rather than adopted. We conclude that national drug policies should include provision for establishing drug information centers. The World Health Organization and similar organizations should assist in establishing these centers. We believe that a drug and toxicology information center is more beneficial to the community when it is part of the teaching curriculum and continuing education for health professionals. Therefore, the center should be located in a medical teaching institution.

Steady-State Pharmacokinetics of Hydroxychloroquine in Rheumatoid Arthritis Patients

Steady-state pharmacokinetics of hydroxychloroquine (HC) sulfate (Plaquenil) were studied in five volunteers with rheumatoid arthritis who had taken 6 mg/kg/d of the drug for at least six months. Blood samples were drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following an oral dose. Both whole blood and plasma were assayed by an HPLC method for HC and its metabolites desethylhydroxychloroquine, desethylchloroquine, and didesethylchloroquine. A 24-hour urine collection was obtained and assayed for the same compounds. The pharmacokinetics of HC and its metabolites conformed to the model predicted by single-dose studies. During the 24-hour period the absorption phase and both early and late distribution phases were seen. Variation in mean maximum/minimum concentration was 40 percent. Renal clearance accounted for only 16 percent of unchanged HC (22 percent of total drug and metabolites) and did not correlate with creatinine clearance.

Assessing the Effects of Antihypertensive Medication on Cerebral Blood Flow: Demonstration in Internal Carotid Artery Occlusion

Dynamic cerebral blood flow (CBF) studies using acetazolamide or hypercapnia as a vasodilatory challenge have attempted to evaluate intracranial hemodynamics. We report two patients with asymptomatic internal carotid artery occlusion in whom the vasodilatory stimulus was a single oral dose of antihypertensive medication (prazosin hydrochloride or enalapril maléate). In both patients, changes in regional CBF occurred that were larger than those seen in nine normal controls. One patient experienced an improvement in regional CBF with a reduction in probe pair asymmetry. In the other patient, who had bilateral carotid artery disease, a decrease in regional CBF in all 16 probes (mean decrease 12 percent) and an accentuation of the predose asymmetry were observed. Both patients remained asymptomatic throughout the study. Assessing these effects on cerebral circulation may help identify patients at risk for iatrogenic focal cerebral ischemia and provide information regarding the functional status of the cerebral vasculature.

Medication Usage Patterns in Patients with Human Immunodeficiency Virus Infection: A Comparison of Patient-Reported Medication Usage with Medical Chart Review

Patients infected with the human immunodeficiency virus (HIV) receive numerous medications from multiple providers. As a result, it is important that medication usage is properly documented in each patient's medical record. Lack of adequate documentation may confound a provider's assessment of drug efficacy, potentially leading to an increased incidence of drug interactions and adverse effects. The objective of this study was to determine if discrepancies exist between patient-reported medication usage and that documented in the medical record by healthcare providers. Data were obtained using structured telephone surveys and medical chart review. Study participants were recruited from the University of California, San Francisco Medical Center AIDS Clinic. Results obtained for 41 patients demonstrated discrepancies between patient-reported medication usage and that documented in the medical record ranging from 9 to 92 percent, depending on the class of drug. The largest differences were observed with the “as-needed” class of drugs: benzodiazepines (92 percent), morphine (60 percent), and codeine (56 percent). Differences were also noted for scheduled medications: ketoconazole (54 percent), clotrimazole (45 percent), acyclovir (38 percent), zidovudine (15 percent), and pentamidine (9 percent).These observed discrepancies reaffirm the need for accurate exchange of information between provider and patient to promote the most effective, rational, and safe drug therapy. Careful reviews of medication usage at each visit and use of pharmacy-based medication profiles are potential mechanisms to improve documentation of medication usage in HIV-infected patients.