Low dose oral minoxidil and the conundrum of cardiovascular complications.

In recent months, the general public has become more cognizant of the potential of oral minoxidil to promote hair growth; this was promulgated, in part, by an article published in the New York Times entitled, "An Old Medicine Grows New Hair for Pennies a Day, Doctors Say." Minoxidil was added to the pharmacologic armamentarium as an antihypertensive nearly 60 years ago and was found to trigger hypertrichosis in many patients, but its use dropped sharply as cardiologists observed a number of adverse cardiovascular events including ischemic heart disease, left ventricular hypertrophy, pleural effusions, and pericardial effusions. Studies in the realm of dermatology have explored the utility and safety of low dose oral minoxidil (LDOM) for management of alopecia. This article highlights potential clinical conundrums posed by these rare but severe cardiovascular complications and the importance of collaboration between cardiologists and dermatologists when employing this agent in patients with cardiorenal or cardiovascular risk factors.

The Usage of Concomitant Beta-Blockers with Vasopressors and Inotropes in Cardiogenic Shock.

Vasopressors and inotropes (Vs/Is) are widely used in the treatment of cardiogenic shock (CS). Despite improvements in hemodynamic variables and end-organ perfusion, these agents have been associated with an increase in mortality, potentially due to the increased risk of tachyarrhythmias-which we hypothesize may be mitigated by beta-blockers (BBs). We conducted a retrospective chart review of patients who received a V/I (dobutamine, milrinone, dopamine, and norepinephrine) for CS. The primary objective was to assess the effect of BB in patients receiving Vs/Is for CS. In our final analysis of 227 patients, those in the BB group were younger, were more likely to have acute coronary syndrome as the reason for admission, had more reduced left ventricular ejection fraction, were more likely to have coronary artery disease and atrial fibrillation as pre-existing co-morbidities, and had a lower rate of in-hospital mortality. Nevertheless, in our multivariable logistic regression analysis, concurrent BB usage with a V/I was not associated with a reduction in in-hospital mortality. Our present study sheds light on the importance and urgency of large, carefully designed clinical studies to optimize inpatient medical therapy, particularly evaluating the combination of V/I and BB, in this high-risk patient population.

Predictors of In-hospital Mortality in Cardiogenic Shock Patients on Vasoactive or Inotropic Support.

BACKGROUND: Though controversial, the short-duration in-patient use of inotropes in cardiogenic shock (CS) remain an ACC/AHA Class IIa indication, and are frequently used in the initial treatment of CS. We evaluated in-patient mortality and effect on mortality risk of commonly used vasoactive inotropic medications for the medical management of SCAI stage B and C cardiogenic shock patients in a tertiary care cardiac care unit: dobutamine, dopamine, milrinone, and norepinephrine. METHODS: We retrospectively evaluated 342 patients who received dobutamine, milrinone, dopamine, norepinephrine or a combination of these medications for SCAI stage B and C cardiogenic shock. Cox proportional hazards were used to form longitudinal mortality predictions. RESULTS: Overall in-patient mortality was 18%. Each 1 µg/kg/minute increase in dobutamine independently corresponded to a 15% increase in risk of mortality. High dose dobutamine >3 µg/kg/minute is associated with 3-fold increased risk compared to ⩽3 µg/kg/minute (P < .001). Use of milrinone, norepinephrine, and dopamine were not independently associated with mortality. CONCLUSION: We demonstrate that the overall in-hospital mortality of SCAI stage B and C cardiogenic shock patients medically managed on inotropes was not in excess of prior studies. Dobutamine was independently associated with mortality, while other vasoactive inotropic medications were not. Inotropes remain a feasible method of managing SCAI stage B and C cardiogenic shock.

Amiodarone: A Comprehensive Guide for Clinicians.

Amiodarone is an effective antiarrhythmic medication frequently used in practice for both ventricular and atrial arrhythmias. Though classified as a class III antiarrhythmic, it affects all phases of the cardiac action potential. However, the drug has several side effects, including thyroid abnormalities, pulmonary fibrosis, and transaminitis, for which routine monitoring is recommended. It also interacts with several medications, such as warfarin, simvastatin, and atorvastatin, and many HIV antiretroviral medications. Given the common use of this medication in medical practice, it is vital that clinicians understand the indications, contraindications, dosing, side effects, and interactions of this medication. A thorough understanding of these topics is essential for clinicians to ensure safe and effective use of amiodarone.

Review of Direct Oral Anticoagulants and Guide for Effective Drug Utilization.

Direct oral anticoagulants (DOACs) have been developed as a viable and in some cases superior alternative to warfarin. These agents have overcome some of the limitations of warfarin, which has a narrow therapeutic window and many food and drug interactions. DOACs have been demonstrated to have a more predictable and reliable pharmacology and, unlike warfarin, do not require frequent monitoring of anticoagulant effect. For these reasons, the use of DOACs is increasing. Despite the many positive attributes of these agents, limitations and contraindications do exist. An understanding of the pharmacology, indications, and contraindications is therefore crucial for effective patient management. We review the available agents to aid in effective drug utilization.

Cardiovascular medications and risk of cancer.

Cardiovascular disease and cancer are 2 of the leading causes of death globally. Certain cardiovascular medications have been linked to an increased risk for cancer. Although individual reviews of specific classes of cardiovascular medications have been published previously, a more complete review of several classes has not been performed. The aim of this review is to evaluate the associations of various cardiovascular agents with the risk for developing cancer and provide guidance for clinicians. A comprehensive search of published research was conducted using MEDLINE from 1994 to 2011. Three trials demonstrated an increased risk for cancer using angiotensin II receptor blockers. Additionally, risk for cancer was shown in a number of trials that included the use of angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors. Five trials suggested that diuretics increased the risk for specific cancers, especially in women and those who had been using diuretics for >4 years. Statins and ezetimibe, in contrast, did not show this increased risk. Prasugrel was shown to be associated with an increased risk for cancer in 1 study. It appears that the use of certain cardiovascular medications is associated with an increased risk for cancer. In conclusion, clinicians need to balance the risks and benefits of the use of these agents and provide the appropriate therapy on an individual basis.

A comparison of regional and systemic humoral immune responses to a nematode infection.

The kinetics of humoral immune response against Trichinella spiralis (TS) was characterized with immunofluorescence assay. The mesenteric lymph nodes (MLN) and the spleen of infected rats were examined for concurrent expression of multiple antibody (Ab) isotypes from day 1 to day 15 after infection. The tissues were processed and stained with either a pan-B cell marker (OX33) conjugated with rhodamine (XRITC) or combinations of dual monoclonal Ab probes plus A secondary Ab conjugated with XRITC or fluorescein (FITC). As compared to the uninfected controls, the spleen and the MLN showed significant proliferation of dual-Ab expressing B cells (Debc) on days 5 and 7, respectively. During the immune response, only minimal numbers of B cells expressed single Ab isotype while most B cells expressed more than one isotypes of Ab. When combining all the numbers of Debc within each tissue for each respective days, and comparing those numbers with the total numbers of B cells that were OX33+ in the serial sections of the same tissue specimens, the combined Debc in the spleen were > 6 times higher than the OX33 labeled B cells on day 10, and the Debc in MLN were > 3 times higher than the OX33+ B cells on day 10. Our results thus indicate that the Debc most likely expressed more than two Ab isotypes during the peak days of the humoral immune response to the parasite and this phenomenon occurred in both regional and systemic lymphoid tissues.

Rapidity and multiplicity of synthesis and expression of immunoglobulin isotypes by B lymphocytes in the small intestine.

An immunofluorescence double labeling assay was used to examine the kinetics of intestinal B lymphocytes with concurrent expression of multiple antibody isotypes in the mucosal tissues of rats infected with Trichinella spiralis (TS) muscle larvae for 1 to 15 days. As compared to the uninfected controls (day 0), the non-Peyer's patch tissues of the small intestine contained a significantly increased number of dual antibody-expressing B cells as early as 3 days after infection with a maximum proliferation of these B cells on days 7 and 10. These results indicate the rapidity of B cell response in the small intestine. Similar results were observed in the germinal centers of the Peyer's patches. The non-germinal centers of the Peyer's patch tissues showed delayed kinetics in B cell activation which occurred 10 days after infection. Quantification of the total number of B cells in these tissues was also carried out by staining the CD45RA marker on B cells with the OX33 monoclonal antibody. When comparing the total numbers of B cells with the numbers of B cells expressing dual isotypes of antibodies, our results showed the numbers of dual-expressing B cells (IgA:IgE, IgM:IgE, IgG1:IgE, IgG2a:IgE, IgG2b:IgE, and IgG2c:IgE), when combined, were over 7 times that of the total number of OX33-labeled B cells on day 7 in the small intestine. The dual-expressing B cells in the Peyer's patch-germinal center were more than 5 times that of the OX33-labeled B cells on day 15. These results therefore suggest that the dual-expressing B cells most likely synthesized and expressed more than two isotypes of antibodies during the peak days of the humoral response. Such phenomenon was not observed in non-germinal centers of the Peyer's patch tissues.