Benefits of delapril in hypertensive patients along the cardiovascular continuum

Angiotensin-converting enzyme inhibitors (ACEIs) are the first-line therapy for the treatment of hypertension. However, not all ACEIs are equal. Delapril is a nonsulfhydryl ACEI with unique properties. Delapril has a high lipophilicity and weak bradykinin potentiating action. As a result, delapril has a more potent inhibition capacity of vascular wall angiotensin-converting enzyme activity and a lower incidence of cough than enalapril or captopril. With regard to efficacy, delapril has a long-lasting antihypertensive effect with a trough/peak ratio that is in the upper range of different ACEIs and a positively high smoothness index. Thus, delapril effectively and smoothly reduces blood pressure over 24 h. Moreover, the benefits of delapril are not limited to hypertensive patients, but also in those with microalbuminuria, left ventricular hypertrophy, myocardial infarction or heart failure; delapril appears to be effective and well tolerated.     

Status and prospect of current inotropic agents

Critical reassessment of established inotropic drugs such as the phosphodiesterase inhibitors and the digitalis glycosides has reaffirmed the need for novel cardiotonic agents that will not only beneficially affect the haemodynamic and functional impairment of patients with overt congestive heart failure, but also prevent its clinical manifestation and reduce the high mortality. None of the drugs examined in these directions - calcium sensitisers, β-receptor blockers, sodium channel modulators, digitalis derivatives - have been shown to achieve these goals. The research on endogenous digitalis did not, as was hoped, reveal a general strategy for improving the therapeutic index of cardiac glycosides. The proof that Na+/K+-transporting ATPase of cardiac muscle is the molecular point of attack (receptor) for the inotropic and toxic effects of digitalis-like acting C/D-cis and C/D-trans steroids revealed the cyclopentano-perhydrophenanthrene nucleus as their common pharmacophoric lead structure. This has opened a wide field for lead development in the direction of derivatives that favourably discriminate between the inotropy-linked α1-isoform and the toxicity-linked α3-isoform of Na+/K+-ATPase as the basis for the design of inotropic agents with high therapeutic margin.     

IgA nephropathy associated with axial spondyloarthritis responding to treatment by etanercept: A case report

IntroductionImmunoglobulin A (IgA) nephropathy may be associated with spondyloarthritis (SpA). This association raises the possibility of a common pathogenesis. Tumor necrosis factor alpha (TNFα) blockers showed good efficiency in SpA and may be efficient in IgA nephropathy.Case reportA case of a 28-year-old man diagnosed with axial SpA is reported. The patient’s Bath ankylosing spondylitis disease activity index (BASDAI) was 7 and functional index (BASFI) 9. Laboratory investigations revealed: erythrocyte sedimentation rate (ESR) 38 mm/1st hour, C-reactive protein (CRP) 6 mg/L, serum creatinine 72 μmol/L with a clearance of 108 ml/min; proteinuria 1.55 g/24 h, leucocyturia at 60,000 cells/ml and haematuria 80,000 red cells/ml. The serum IgA level was normal (238.8 mg/dL). Salivary gland and subcutaneous fat biopsies were normal. The renal biopsy showed moderate focal interstitial fibrosis. The glomerular basement membranes were not thickened while the mesangium was slightly thickened. There was no vascular damage. Congo red staining was negative. By immunofluorescent microscopy, there were mesangial deposits of IgA mainly; leading to the diagnosis of IgA nephropathy. Infliximab was initially given with limited efficacy and the patient was switched to etanercept which was effective especially in the osteoarticular symptoms. Leucocyturia, haematuria and proteinuria decreased but did not disappear, and the renal function and blood pressure remained normal. After 2 years there remained a persistent efficacy and good profile of tolerance (BASDAI = 2.2, BASFI = 4, CRP = 2, ESR = 21, proteinurua = 0.5 g/24 h).ConclusionEtanercept may be a potentially effective option for treating IgA nephropathy associated with axial SpA.     

The Challenges of Ulcerative Colitis

Much remains to be learned about ulcerative colitis, including the cause. The high morbidity, significant mortality, and variable and unpredictable course make a rather grim picture. Still the potential for reversibility is substantial. Most of these patients can be maintained in satisfactory health under the combined care of their personal physicians and gastroenterologists.     

Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.     

The Road to Eleusis: Unveiling the Secret of the Mysteries

Abstract

Vivid imagery and hallucinations are occasionally reported by patients on beta-adrenergic blocking agents. The authors document this side effect with drawings by a well-known commercial artist.     

Combination therapy with aliskiren and amlodipine in hypertension: treatment rationale and clinical results

Optimal antihypertensive therapy requires a multimodal approach based on lifestyle modification and, for most individuals, combination drug therapy. Recommendations from experts suggest that a combination of an agent that blocks the renin–angiotensin system (RAS), together with a vasodilator (generally a calcium-channel blocker or a thiazide-type diuretic), is most likely to control blood pressure and provide the widest overall cardiovascular protection. Understanding the opportunities afforded by the combination of RAS blockade with a calcium-channel blocker requires a discussion of basic and clinical science data. One new concept is that of ‘global’ or total RAS blockade. The impact of the RAS can be diminished or blocked by several different classes of drugs (central sympatholytics, β-blockers, renin inhibitors, ACE inhibitors or ARBs); what is most important is how effectively the overall impact of angiotensin II is blunted. A second new concept is that the complementary actions of RAS blockers and calcium-channel blockers are best explained on the basis of diminished intracellular calcium availability in excitable tissue (sympathetic neurons and vascular smooth muscle cells) via parallel actions that reduce angiotensin II type-1 receptor stimulation and L-channel-mediated calcium flux. Aliskiren is the first of the direct renin inhibitors, the newest subclass of RAS blockers. In both short- and long-term studies, aliskiren has been shown to be similar in efficacy and tolerability compared with other RAS blockers, with the added benefit that its effects persist longer. Outcome studies with aliskiren are currently underway.     

Hospital Management of Acute Iron Ingestion

Abstract

This overview summarizes the major and minor side effects and drug interactions of fluoxetine. The adverse reactions include the “serotonin syndrome”, cardiovascular complications, extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual disorders are evaluated along with minor symptoms of allergic reactions, stuttering, hematological changes, psoriasis, and inappropriate secretion of the antidiuretic hormone. The major fluoxetine-drug interactions involve the amino acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants, anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs of abuse. The underlying mechanism and the paradoxical effects of fluoxetine are addressed.