Beta-adrenergic Antagonist Research Articles

Oral pharmacological treatment of congestive heart failure

Congestive heart failure (CHF) is a growing epidemiologic and clinical problem, and is increasing in incidence, prevalence and mortality. Therefore, the optimal treatment of heart failure (HF) is important to reduce hospitalization and mortality. In the treatment of CHF, diuretics are the first-line drug treatment for patients with fluid retention and are necessary to relieve symptoms but cannot halt progression or improve the prognosis of CHF. Angiotensin-converting enzyme inhibitors, beta-adrenergic receptor antagonists and mineralocorticoid/aldosterone receptor antagonist therapy have been shown to decrease mortality and progression of CHF and should be used early in HF with reduced ejection fraction. Angiotensin receptor antagonists are recommended in patients with current or prior symptoms who are angiotensin-converting enzyme inhibitor intolerant, unless contraindicated, to reduce morbidity and mortality. However, no treatment has been shown convincingly to reduce morbidity and mortality in patients with HF with preserved ejection fraction. Adequate treatment of hypertension and myocardial ischemia is also considered to be important, as is control of the ventricular rate in HF with preserved ejection fraction. For chronic HF with reduced ejection fraction, ivabradine and angiotensin receptor-neprilysin inhibition have been tested and may be used in evidence-based medicine in the near future. This review presents the evidence base for current drug treatments and their practical implications in chronic HF.

Is it time to replace propranolol with carvedilol for portal hypertension?

Beta-adrenergic receptor antagonists (β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol.

Effect of esmolol on myocardial protection in pediatrics congenital heart defects

Background:Although it is accepted that inducing cardioplegia is the gold standard in myocardial protection, there is still no consensus on the exact type of the cardioplegia. There are fewer studies on the type of the cardioplegia in hearts of the children than adults and they are contradictory. The effects of esmolol have been reviewed (a type of ultrashort-acting beta-adrenergic antagonist, i.e., ß-blockers) in conjunction with the cardioplegia due to the effect of the β-blockers in reducing the myocardial ischemia and reperfusion.Materials and Methods:The left ventricle ejection fraction (LVEF), systolic blood pressure, central venous pressure (CVP), heart rate, etc., were recorded separately in patients who received the cardioplegia without esmolol (n = 35) and with esmolol (n = 30) and matched for the age and sex.Results:The amount of inotrope used in the group without esmolol (100%) was considerably higher than in the group with esmolol (86.7%). Postoperative arrhythmias did not differ significantly between the two groups. There was no significant difference in the duration of cardiopulmonary bypass (CPB), time of the extubation, length of the ICU stay, the first day EF after surgery, and the first week EF after surgery as well. Creatinine kinase-MB (CKMB) was significantly higher in the group without esmolol during operation than in the group with esmolol.Conclusions:The patients who received cardioplegia along with esmolol had less inotropic requirement after operation, and increase in EF and cardiac output (CO) 1 week after surgery. In addition, it reduced damage to the heart during surgery, and patients may have greater stability in the cardiac conduction system.

Beta-Blocking Agents During Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary.

The effects of beta-2 adrenergic agonist and antagonist on human bone metabolism: A randomized controlled trial

PurposeGenetic knockout or pharmacological inhibition of the beta-2 adrenergic receptor (B2AR) increased bone mass, whereas stimulation decreased bone mass in rodents. In humans, observational studies support sympathetic nervous system regulation of bone metabolism, but intervention studies are lacking. We aimed to determine the effects of a selective beta-2 adrenergic agonist and non-selective antagonist on human bone metabolism. Methods32 healthy postmenopausal women were included in a randomized controlled trial conducted in the Academic Medical Center Amsterdam. Participants were randomized to receive treatment with 17-β estradiol 2mg/day; 17-β estradiol 2mg/day and terbutaline 5mg/day (selective B2AR agonist); propranolol 80mg/day (non-selective B-AR antagonist); or no treatment during 12weeks. Main outcome measure was the change in serum concentrations of procollagen type I N propeptide (P1NP) and C-terminal crosslinking telopeptides of collagen type I (CTx) as markers of bone formation and resorption after 12weeks compared between the treatment groups. Data were analyzed with mixed model analysis. Results17-β estradiol decreased bone turnover compared to control (P1NP p<0.001, CTx p=0.003), but terbutaline combined with 17-β estradiol failed to increase bone turnover compared to 17-β estradiol alone (P1NP p=0.135, CTx p=0.406). Propranolol did not affect bone turnover compared to control (P1NP p=0.709, CTx p=0.981). ConclusionSelective beta-2 adrenergic agonists and non-selective beta-antagonists do not affect human bone turnover although we cannot exclude small changes below the detection limit of this study.

Abstract 641: Renal Denervation does not Lower Blood Pressure in Spontaneously Hypertensive Rats Treated with a Beta-1 Adrenergic Receptor Antagonist.

We have used the SHR as an animal model to understand how renal denervation (RDN) lowers blood pressure. In order to determine how concomitant antihypertensive drug therapy could affect the blood pressure response to RDN, we performed RDN both before and after chronic (several days) treatment via the drinking water with the selective alpha-1 adrenergic antagonist prazosin and the selective beta-1 adrenergic antagonist atenolol. In the presence of prazosin treatment, RDN (n=7) significantly (p&lt;0.05) lowered mean arterial pressure (MAP) compared to sham operated (SO; n=6) SHR (Δ=–4.0±1.7mmHg in RDN-SHR vs +1.5±1.3 in SO-SHR). Subsequent addition of atenolol during prazosin treatment reduced MAP significantly in both groups, but MAP in SO-SHR fell to the same level as in RDN-SHR, i.e. the antihypertensive effect of RDN was lost. After discontinuation of all drug treatment, the change in MAP from pre-treatment baseline was –7.7±3.5mmHg in RDN-SHR and +3.0±4.0mmHg in SO-SHR, p=0.06). To test whether the BP response to RDN would be lost during blockade of beta-1 adrenergic receptors alone, we performed RDN in SHR (n=5) pre-treated with atenolol. Atenolol alone significantly reduced MAP (Δ=-20.7±2.5mmHg). Steady-state MAP was not further reduced by RDN (Δ=+2.1±0.9mmHg). When atenolol was withdrawn MAP rose but remained reduced from baseline (Δ= -9.5±0.9mmHg). This magnitude of BP reduction is comparable to what we have previously observed after RDN in untreated SHR. In summary, in SHR RDN does not lower BP in the presence of an effective antihypertensive dose of a beta-1 antagonist. This indicates that RDN is reducing BP in SHR by interrupting a mechanism also affected by beta-1 adrenergic receptor signaling. Although further investigation is necessary, the data suggest that possibility that patients on clinically effective antihypertensive doses of beta-blockers may not exhibit a good response to RDN.

Fixed-Dose Combination of Tafluprost and Timolol in the Treatment of Open-Angle Glaucoma and Ocular Hypertension: Comparison with Other Fixed-Combination Products

A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin–timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav® (Alcon, Fort Worth, USA) and Ganfort® (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0151-7) contains supplementary material, which is available to authorized users.

Noradrenalin and dopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex.

Noradrenergic fibers innervate the entire cerebral cortex, whereas the cortical distribution of dopaminergic fibers is more restricted. However, the relative functional impact of noradrenalin and dopamine receptors in various cortical regions is largely unknown. Using a specific genetic label, we first confirmed that noradrenergic fibers innervate the entire cortex whereas dopaminergic fibers were present in all layers of restricted medial and lateral areas but only in deep layers of other areas. Imaging of a genetically encoded sensor revealed that noradrenalin and dopamine widely activate PKA in cortical pyramidal neurons of frontal, parietal and occipital regions with scarce dopaminergic fibers. Responses to noradrenalin had higher amplitude, velocity and occurred at more than 10-fold lower dose than those elicited by dopamine, whose amplitude and velocity increased along the antero-posterior axis. The pharmacology of these responses was consistent with the involvement of Gs-coupled beta1 adrenergic and D1/D5 dopaminergic receptors, but the inhibition of both noradrenalin and dopamine responses by beta adrenergic antagonists was suggestive of the existence of beta1-D1/D5 heteromeric receptors. Responses also involved Gi-coupled alpha2 adrenergic and D2-like dopaminergic receptors that markedly reduced their amplitude and velocity and contributed to their cell-to-cell heterogeneity. Our results reveal that noradrenalin and dopamine receptors both control cAMP-PKA signaling throughout the cerebral cortex with moderate regional and laminar differences. These receptors can thus mediate widespread effects of both catecholamines, which are reportedly co-released by cortical noradrenergic fibers beyond the territory of dopaminergic fibers.

Akathisia: Case Presentation and Review of Newer Treatment Agents

Akathisia is a common and potentially debilitating adverse effect of many psychotropic agents. To a physician not specifically screening for this phenomenon, symptoms can appear similar to depression, anxiety, and/or psychosis. Further complicating matters, akathisia may also occur at different points during the treatment period with varying levels of severity in terms of patient distress. Treatment options have been limited by our somewhat poor understanding of akathisia’s neurological basis, but dopamine dysregulation is theorized to play a central role. Most pharmacotherapy regimens focus on beta-adrenergic antagonists (eg, propranolol, the current gold-standard), which are thought to affect noradrenergic inputs into the dopamine pathways of the brain. However, new research suggests a role for serotonin-based pharmacotherapy, particularly those affecting 5-HT2a/c receptors (eg, mirtazapine) in regulating dopamine. [ Psychiatr Ann . 2014; 44(8):391–396.]

Acute Wounding Alters the Beta2-Adrenergic Signaling and Catecholamine Synthetic Pathways in Keratinocytes

Keratinocyte migration is critical for wound re-epithelialization. Previous studies showed that epinephrine activates the beta2-adrenergic receptor (B2AR), impairing keratinocyte migration. Here, we investigated the keratinocyte catecholamine synthetic pathway in response to acute trauma. Cultured keratinocytes were scratch wounded and expression levels of the B2AR and catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were assayed. The binding affinity of the B2AR was measured. Wounding downregulated B2AR, tyrosine hydroxylase, and phenylethanolamine-N-methyltransferase expression, but pre-exposure to timolol, a beta-adrenergic receptor antagonist, delayed this effect. In wounded keratinocytes, B2AR-binding affinity remained depressed even after its expression returned to prewounding levels. Keratinocyte-derived norepinephrine increased after wounding. Norepinephrine impaired keratinocyte migration; this effect was abrogated with B2AR-selective antagonist ICI-118,551 but not with B1AR-selective antagonist bisoprolol. Finally, for clinical relevance, we determined that norepinephrine was present in freshly wounded skin, thus providing a potential mechanism for impaired healing by local B2AR activation in wound-edge keratinocytes. Taken together, the data show that keratinocytes modulate catecholamine synthetic enzymes and release norepinephrine after scratch wounding. Norepinephrine appears to be a stress-related mediator that impairs keratinocyte migration through activation of the B2AR. Future therapeutic strategies evaluating modulation of norepinephrine-related effects in the wound are warranted.

Beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration

Context: Propranolol, atenolol, and ICI118,551 are non-selective β-adrenergic receptor (AR), β1-AR, and β2-AR antagonists, respectively.Objective: We investigated the efficacy of propranolol, atenolol, and ICI118,551 on proliferation, migration, and invasion of non-stimulated breast (MCF7), colon (HT-29), and hepatocellular (HepG2) cancer cells.Materials and methods: β-AR expression profiling of cells was performed by real time PCR. Cell proliferation was determined by MTT. Boyden chamber and scratch assays were performed to evaluate invasion and migration.Results and discussion: All cell lines expressed β-ARs. ICI118,551 was the most cytotoxic, whereas atenolol was the least effective β-AR antagonist for 24, 48, and 72 h. Cell invasion was inhibited by ICI118,551 (45, 46, and 50% for MCF7, HT29, and HepG2, respectively) and propranolol (72, 65, and 90% for MCF7, HT29, and HepG2, respectively). Propranolol, atenolol, and ICI118,551 reduced migration of MCF7, HT-29, and HepG2 cells to varying extents depending on the application concentration and duration. Propranolol and atenolol reduced migration of MCF7 and HT-29 in a concentration-dependent manner, whereas migration of these cells decreased after 48 and 72 h of ICI118,551 applications.Conclusion: Beta2-AR antagonist seemed to be the most cytotoxic β-blocker on non-stimulated cancer cells. Propranolol and ICI118,551 were more effective than atenolol in inhibiting invasion and migration of non-stimulated MCF7 and HT-29 cells; ICI118,551 being the most potent. Concordantly, β2-selective blockage seemed to be more effective for non-stimulated cells. Effect of the selective β-AR antagonists showed variation depending on the concentration, incubation time, and histological origin of cells.

Defeating the fear: New insights into the neurobiology of stress susceptibility

The psychopathological impact of emotional stress on a specific individual varies markedly: while most escape the development of post-traumatic stress disorder and/or major depression, a select group of individuals demonstrate a vulnerability to succumb to these conditions. The past decade has witnessed an explosion in animal research into the underlying neurobiological mechanisms that govern both vulnerability and resilience to such stressors. In the May 2014 issue, Chou and colleagues employ the mouse social defeat model of chronic stress to demonstrate that defeated susceptible mice display an exaggerated conditioned fear response associated with more pronounced autonomic changes. These physiological alterations were found to be mediated via local increases in the levels of brain derived neurotrophic factor (BDNF) within the basolateral amygdala and could be inhibited by the systemic administration of a beta adrenergic antagonist. This mini-review critically examines this manuscript's new mechanistic insights in light of previous results employing similar approaches. The strengths and limitations of the social defeat model, as well as the relevance of these findings to neurologic illness are discussed briefly.

Acute and Chronic Cardiovascular Effects of Hyperkalemia: New Insights Into Prevention and Clinical Management

The plasma pool of potassium is a partial reflection of the overall body, transient cellular shifts, and potassium elimination regulated by the kidneys. Potassium concentrations elevating above the upper limit of normal (> 5.0 mEq/L) have become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad applications of drugs that modulate potassium excretion by either reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, beta-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). In addition, acute kidney injury, critical illness, crush injuries, and massive red blood cell transfusions can result in hyperkalemia. Progressively more severe elevations in potassium are responsible for abnormalities in cardiac depolarization and repolarization and contractility. Untreated severe hyperkalemia results in sudden cardiac death. Traditional management steps have included reducing dietary potassium and discontinuing potassium supplements; withdrawal of exacerbating drugs; acute treatment with intravenous calcium gluconate, insulin, and glucose; nebulized albuterol; correction of acidosis with sodium bicarbonate for short-term shifts out of the plasma pool; and, finally, gastrointestinal ion exchange with oral sodium polystyrene sulfonate in sorbitol, which is mainly used in the hospital and is poorly tolerated due to gastrointestinal adverse effects. This review explores hyperkalemia as a complication in cardiovascular patients and highlights new acute, chronic, and preventative oral therapies (patiromer calcium, cross-linked polyelectrolyte, ZS-9) that could potentially create a greater margin of safety for vulnerable patients with combined heart and kidney disease.

Advances in the Clinical Management of Cardiac Arrest

Cardiac arrest constitutes an extremely life-threatening condition that inevitably and promptly results in death if left untreated. Cardiac arrest outcomes still remain very poor, especially when the presenting cardiac rhythm is nonshockable. Important, recent, clinical research has focused on the quality of cardiopulmonary resuscitation (CPR), the mechanical augmentation of the circulation during CPR, CPR drugs, and therapeutic hypothermia. Chest compression depth of at least 51 mm increases the probability of neurologically favorable survival. Despite initially promising results, a large effectiveness study failed to confirm the efficacy of the mechanical augmentation of the circulation. Epinephrine has finally been shown to slightly improve functional outcome after out-of-hospital cardiac arrest, especially when given early. In a recent, in-hospital study of 268 patients, the addition of vasopressin and methylprednisolone during CPR and the administration of hydrocortisone in postresuscitation shock improved functional outcome after vasopressor-requiring cardiac arrest; however, corticosteroid efficacy still needs to be separately confirmed in a large, international trial. Lastly, preliminary human data may support the conduct of high quality trials evaluating the efficacy of beta adrenergic antagonists in shockable cardiac arrest. The purpose of this paper is to review these potentially important advances in the management of cardiac arrest.

Marketing analysis of the drugs used for the treatment of affected military men with brain injuries

During the research the comparative analysis of protocols of medical care for patients with brain injuries and information of scientific literature and evidence-based medicine has been conducted. It has demonstrated that for the treatment of affected military men with brain injury the following groups of drugs are used: antibacterial agents for systemic use, psychoanaleptics, blood substitutes and perfusion solutions, antiepileptics, vitamins, peripheral vasodilators, cardiac drugs, calcium channel blockers, analgesics, antihemorrhagic drugs, drugs for treating wounds and ulcers, diuretics, antithrombotic agents, antiparkinsonian drugs, psycholeptics, vasoprotectives, beta adrenoreceptor antagonists, etc. Marketing analysis of certain groups of drugs has been conducted according to the following criteria: legal (registration in Ukraine), economic (commercial: country, company), pharmaceutical (types of dosage forms, the composition of active substances, method of application), pharmacotherapeutic (ATC-classification). The analysis of the domestic pharmaceutical market has shown that drugs for treatment of head injuries comprise 1034 drugs manufactured in 39 countries. It has been found that the Ukrainian producers are able to provide the necessary level of rendering medical care in treatment of the traumatic brain injury, they produce 549 names of drugs, and it is almost 53% of the total range of medicines. The first place among the Ukrainian companies manufacturing drugs for treatment of the brain injury has “Darnitsa pharmaceutical company” JSC, the second one – “Yuriа-Farm” Ltd., the third place – Pharmaceutical company “Zdorovye” Ltd. Foreign producers supply 485 drugs (47%). The leaders are India, Germany and Slovenia, which take the first, second and third places in the import of drugs, respectively.

No evidence of nitrate tolerance caused by nebivolol

Continuous long-term treatment with nitrates may cause nitrate tolerance. Nebivolol is a highly selective beta1-adrenergic antagonist with additional nitric oxide (NO)-mediated vasodilatory effects. However, there have been no investigations into whether or not the long-term administration of nebivolol might cause nitrate tolerance. We performed a randomized, double-blind, placebo-controlled, cross-over study in 16 healthy men. Subjects received 5 mg nebivolol or placebo once daily for 8 days in random order divided by a drug-free interval of 2 weeks. Forearm blood flow (FBF) was measured by venous occlusion plethysmography 3 h after oral intake of the first and last doses of nebivolol and placebo, respectively. FBF was measured again following the intravenous administration of 4 μg nitroglycerin/kg body weight/min for 5 min. Following 8 days of continuous intake of placebo, nitroglycerin increased FBF by 54% (p < 0.05), whereas nitroglycerin increased FBF by 96% (p < 0.01) following 8 days of continuous intake of nebivolol, and the increase after 8 days of nebivolol was significantly (p < 0.05) more pronounced than after 8 days of placebo. These findings indicate no evidence of nitrate tolerance caused by long-term administration of nebivolol. On the contrary, long-term intake of nebivolol increases rather than decreases the NO-mediated vasodilating effects.

A Case of Akathisia induced by Escitalopram: Case Report &amp; Review of Literature

Although cases of Selective Serotonin Reuptake Inhibitor (SSRI) induced akathisia have often been reported in literature, this adverse effect has not adequately been mentioned in major pharmacology textbooks. As a result, SSRIinduced akathisia is very frequently under-recognized. A review of literature showed that almost all frequently used SSRIs such as Fluvoxamine, Fluoxetine, Sertraline, Citalopram have been reported to be causing akathisia. SSRI-induced restless legs syndrome and movement disorders have also been reported. However, Escitalopram-induced akathisia is rare. In our review of literature, we could find only one single case of Escitalopram-induced severe akathisia. And this specific SSRI drug has rarely been implicated with occurrence of restless legs syndrome and extra-pyramidal side-effects like dytonia etc. Here, we present a case of Escitalopram-induced severe akathisia - a 53year old female, who had developed severe akathisia after taking Escitalopram for a few days. According to the Barnes Akathisia Rating Scale (BARS), her Global Clinical Assessment of Akathisia Score was 5 i.e. severe akathisia. As per Naronjo Adverse Drug Reaction Scale the probability of association of this adverse reaction with Escitalopram was 7 (i.e. probable). Her symptoms continued in spite of prompt discontinuation of the drug. But, she improved rapidly with the use of Propranolol and Clonazepam. On the last follow-up, she was free from any symptoms. As new generation antidepressants are rarely associated with extra-pyramidal symptoms, the recognition of such adverse effects requires a high index of suspicion. Early recognition of the symptoms and discontinuation of the offending agent along with supportive therapy like a short course of benzodiazepines, beta-adrenergic antagonists or anticholinergics may rapidly relieve the patient from this distressing symptom.

Benefits of Pharmacogenetics in the Management of Hypertension

Introduction: Hypertension, suffered by 35% of the population, stands out as the main risk factor for cardiovascular disorders with the highest death rate worldwide. Only a small number of patients with hypertension gets efficient control over blood pressure (BP) with appropriate drug therapy. Pharmacogenetics, as a tool to identify antihypertensive therapeutic response-associated polymorphisms, could help to reduce this problem. Objectives: We present here an epidemiological study of the prevalence of hypertension and its pharmacological treatment to demonstrate the error rate that physicians can commit when the patient´s pharmacogenetic profile is unknown. Method: The sample consisted of 1115 individuals of which 332 met criteria for hypertension. We recorded each patient´s drug prescription prior to their visit to EuroEspes Biomedical Research Center, and analyzed their pharmacogenetic profile. Results: About 30% of patients were hypertensive, of whom only 40.4% were receiving an active ingredient for hypertension control. Among them, CYP3A4/5 and CYP2C9 were the major metabolizing enzymes. Antagonists of angiotensin II receptors, followed by calcium-blocking agents and beta-adrenergic antagonists were the most commonly-prescribed drug categories. However, 61% of hypertensive patients were not taking suitable antihypertensive agents for their metabolism according to their genetic idiosyncrasy. Furthermore, the highest error rate was determined for CYP2C9. Conclusion: The introduction of changes in the management of hypertension in the Spanish population could be useful to promote the prevention and treatment of high blood pressure in a more efficient way. The integration of pharmacogenetic testing into routine clinical procedures could optimize the therapeutic response, guiding the physician in the choice of the correct antihypertensive drug and the correct dose. The control of BP arises as an area of particular interest in assessing the validity and utility of pharmacogenetic testing/intervention.

Does Long-Term Administration of a Beta-Blocker (Timolol) Induce Fibril-Based Cataract Formation In-vivo?

Timolol is a non-selective beta-adrenergic receptor antagonist administered for treating glaucoma, heart attacks and hypertension. In the present study, we set out to determine whether or not timolol can provoke cataract formation, thus the influence of timolol on the amyloid-type aggregation of crystallin was investigated. We then provided experimental evidence of crystallin aggregation and its induction by timolol using different spectroscopic measurements. Turbidimetric measurements as well as ThT fluorescence data indicated that timolol induce extent of crystallin amyloid formation. The kinetic of protein aggregation was also changed in presence of increasing concentrations of the drug suggesting that long-term drug administration may contribute to the development of cataract. Since the consequence of timolol-crystallin interaction has yet to be identified, additional data on it may help us to postpone amyloid cataract formation.

Three Cases of Infantile Hemanioma Treated with Topical Timolol

Infantile hemangioma is a common, benign tumor of infancy. Although systemic propranolol was found to be effective in the treatment of infantile hemangioma, its use is often challenging for clinicians owing to its potential side effects. Recent small studies have suggested that the topical use of timolol maleate gel, a non-selective beta-adrenergic antagonist, might be effective for the treatment of superficial infantile hemangioma. Here, we report three cases of infantile hemangioma of different sizes and depths treated with the topical timolol maleate gel-forming solution.