Calcium Channel Blocker Class Heterogeneity: Select Aspects of Pharmacokinetics and Pharmacodynamics

Calcium channel blockers (CCBs) comprise a heterogeneous group of compounds with unique structures and pharmacologic characteristics. These agents are employed in the treatment of hypertension, coronary ischemia, and/or supraventricular arrhythmias. CCBs are both substrates for, and in the instance of verapamil and diltiazem inhibitors of, cytochrome P450 3A4. In the case of verapamil and diltiazem, this inhibitory effect increases the likelihood of drug-drug interactions with other compounds similarly metabolized by cytochrome P450 3A4. Much of the debate with reference to a cardiovascular risk for CCBs has been quieted with the advent of sustained-release delivery systems that offer a more gradual rate of drug delivery. The most common side effects with CCBs are vasodilatory in nature and include peripheral edema, flushing, and headache. Despite the potential for side effects with CCBs, their potent blood pressure-lowering effect makes them a prerequisite for blood pressure control in many patients.     

Patient satisfaction and use of Veterans Affairs versus non-Veterans Affairs healthcare services by veterans

OBJECTIVES: Chronically ill patients who are not satisfied with their care may change healthcare providers or systems, which could disrupt continuity of care and impede management of their conditions. We examined whether patient satisfaction affected subsequent use of non-Veterans Affairs (VA) services among chronically ill veterans discharged from VA hospitals. METHODS: The data used in this study came from a multicenter trial of increased access to primary care. We enrolled patients with diabetes, heart failure, and/or chronic obstructive pulmonary disease who were discharged from 1 of 9 VA medical centers. At baseline, we assessed satisfaction using the Patient Satisfaction Questionnaire. VA and non-VA utilization over the subsequent 6 months were assessed using VA and Medicare administrative data, non-VA billing data, and patient interviews. Using multivariable logistic regression analyses, we examined whether baseline patient satisfaction was associated with non-VA inpatient or outpatient utilization during the next 6 months. We conducted the same analysis for Medicare-eligible veterans, a group with better access to non-VA care. RESULTS: Of 1375 study patients, 174 (13%) used non-VA healthcare. Patients with non-VA utilization were older and lived farther from a VA. The odds of non-VA use decreased by 11% as satisfaction increased (odds ratio 0.89; 95% confidence interval 0.83-0.97; P = 0.005). This relationship was strongest among Medicare-eligible veterans (odds ratio 0.85; 95% confidence interval 0.77-0.93; P = 0.001). CONCLUSIONS: Dissatisfied veterans discharged from the hospital were more likely to go outside VA for care. Thus, improvements in patient satisfaction may lead to improvements in continuity of care.     

Diuretic use in renal disease

Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type diuretics, loop diuretics and K(+)-sparing diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na(+) and K(+) axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.     

Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

In the past 2 decades, calcium channel blockers have emerged as important and useful agents for treating hypertension. The safety of this drug class has been vigorously debated for some time, and it has only been in the past few years that such debate has been quieted by favorable outcomes data with these compounds. Calcium channel blockers are a heterogeneous group of compounds as alike as they are dissimilar. Calcium channel blockers can be separated into dihydropyridine and nondihydropyridine subclasses, with representatives of the latter being verapamil and diltiazem. A lengthy treatment experience exists for verapamil, a compound that has progressed from an immediate‐release to a sustained‐release and, more recently, a delayed/sustained‐release formulation designated for administration at bedtime. This latter formulation synchronizes drug delivery with the early morning rise in blood pressure, which is a particularly attractive feature when viewed in the context of the distinctive pharmacokinetic and pharmacodynamic features of verapamil.     

ACE Inhibitor-Related Angioedema: Can Angiotensin-Receptor Blockers Be Safely Used?

Angioedema is a well-recognized side effect of angiotensin-converting enzyme (ACE) inhibitor therapy. Angioedema can also be seen with angiotensin receptor blocker therapy but much less frequently than is the case with ACE inhibitors. For unclear reasons, ACE inhibitor-related angioedema occurs more commonly in black patients. Angioedema can be life threatening but more times than not its occurrence can be managed with conservative treatment measures including discontinuation of the medication and/or administration of an antihistamine. Occasionally, epinephrine and/or steroid therapy may be warranted. In a patient having experienced ACE inhibitor-related angioedema, angiotensin receptor blockers should be used cautiously if at all. If angiotensin receptor blocker therapy is being considered in a patient with prior ACE inhibitor-related angioedema there should be some justification for the use. Such justification might include the presence of heart failure or proteinuric nephropathic states among other considerations.